User login
‘How could he?’
The headline in a Portland, Maine, newspaper read, “Standish man sentenced to serve 15 years in prison for death of his 3-month-old son” (Edward Murphy, May 23, 2017). I suspect that many of the folks who read the story under the headline feel that the sentence was too light. Others are asking themselves how a 21-year-old man could beat a fragile 5-pound infant to death. What kind of evil monster is this guy?
However, even with the snatches of information provided in the 500-word newspaper story, the unfortunate scenario makes sense, and the child’s death is a tragic culmination of a series of events that shouldn’t surprise any pediatrician. It turns out the infant was a twin who, with his sister, had been born at 30 weeks’ gestation. He had spent a month or more in the hospital, and his sister was still in neonatal ICU at the time of his death. While it is unclear from the newspaper article whether the twins’ parents were married, they were living in a house with eight other adults and some other children. The mother was out of the home working while the father was left to care for his son.
I am sure that the neonatologists and social workers at the hospital where the twins were born were aware of at least some of the red flags that waved over this unfortunate family. I also am confident that they did what they could to assure this infant a safe home environment when it was time for his discharge from the NICU. However, risks factors may have been missed that now seem obvious in retrospect. We should all realize by now from our experience with domestic terrorism that simply appearing on someone’s radar doesn’t mean that preemptive action can or will be taken. Short of keeping the parents of high-risk neonates under constant surveillance for a year or 2, there are few other workable options to prevent every tragedy like this one.
This case is another example of the erosive power of a baby’s cry. Most pediatricians have developed a filtering mechanism that allows us to function in a cacophonous environment dominated by a screaming infant. However, even adults without this young father’s deprived background crack under the stress when they are confined in a space with a crying child. The risk of decompensation is compounded when the adult also feels some responsibility for the child’s welfare. I don’t think we can condone what the father did in this tragic scenario, but we can certainly understand how the dominoes fell.
We are all potential child abusers. When faced with the right, or I guess the wrong, set of circumstances we might lash out to stop the crying. Luckily, most of us are several body lengths from the end of that rope.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
The headline in a Portland, Maine, newspaper read, “Standish man sentenced to serve 15 years in prison for death of his 3-month-old son” (Edward Murphy, May 23, 2017). I suspect that many of the folks who read the story under the headline feel that the sentence was too light. Others are asking themselves how a 21-year-old man could beat a fragile 5-pound infant to death. What kind of evil monster is this guy?
However, even with the snatches of information provided in the 500-word newspaper story, the unfortunate scenario makes sense, and the child’s death is a tragic culmination of a series of events that shouldn’t surprise any pediatrician. It turns out the infant was a twin who, with his sister, had been born at 30 weeks’ gestation. He had spent a month or more in the hospital, and his sister was still in neonatal ICU at the time of his death. While it is unclear from the newspaper article whether the twins’ parents were married, they were living in a house with eight other adults and some other children. The mother was out of the home working while the father was left to care for his son.
I am sure that the neonatologists and social workers at the hospital where the twins were born were aware of at least some of the red flags that waved over this unfortunate family. I also am confident that they did what they could to assure this infant a safe home environment when it was time for his discharge from the NICU. However, risks factors may have been missed that now seem obvious in retrospect. We should all realize by now from our experience with domestic terrorism that simply appearing on someone’s radar doesn’t mean that preemptive action can or will be taken. Short of keeping the parents of high-risk neonates under constant surveillance for a year or 2, there are few other workable options to prevent every tragedy like this one.
This case is another example of the erosive power of a baby’s cry. Most pediatricians have developed a filtering mechanism that allows us to function in a cacophonous environment dominated by a screaming infant. However, even adults without this young father’s deprived background crack under the stress when they are confined in a space with a crying child. The risk of decompensation is compounded when the adult also feels some responsibility for the child’s welfare. I don’t think we can condone what the father did in this tragic scenario, but we can certainly understand how the dominoes fell.
We are all potential child abusers. When faced with the right, or I guess the wrong, set of circumstances we might lash out to stop the crying. Luckily, most of us are several body lengths from the end of that rope.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
The headline in a Portland, Maine, newspaper read, “Standish man sentenced to serve 15 years in prison for death of his 3-month-old son” (Edward Murphy, May 23, 2017). I suspect that many of the folks who read the story under the headline feel that the sentence was too light. Others are asking themselves how a 21-year-old man could beat a fragile 5-pound infant to death. What kind of evil monster is this guy?
However, even with the snatches of information provided in the 500-word newspaper story, the unfortunate scenario makes sense, and the child’s death is a tragic culmination of a series of events that shouldn’t surprise any pediatrician. It turns out the infant was a twin who, with his sister, had been born at 30 weeks’ gestation. He had spent a month or more in the hospital, and his sister was still in neonatal ICU at the time of his death. While it is unclear from the newspaper article whether the twins’ parents were married, they were living in a house with eight other adults and some other children. The mother was out of the home working while the father was left to care for his son.
I am sure that the neonatologists and social workers at the hospital where the twins were born were aware of at least some of the red flags that waved over this unfortunate family. I also am confident that they did what they could to assure this infant a safe home environment when it was time for his discharge from the NICU. However, risks factors may have been missed that now seem obvious in retrospect. We should all realize by now from our experience with domestic terrorism that simply appearing on someone’s radar doesn’t mean that preemptive action can or will be taken. Short of keeping the parents of high-risk neonates under constant surveillance for a year or 2, there are few other workable options to prevent every tragedy like this one.
This case is another example of the erosive power of a baby’s cry. Most pediatricians have developed a filtering mechanism that allows us to function in a cacophonous environment dominated by a screaming infant. However, even adults without this young father’s deprived background crack under the stress when they are confined in a space with a crying child. The risk of decompensation is compounded when the adult also feels some responsibility for the child’s welfare. I don’t think we can condone what the father did in this tragic scenario, but we can certainly understand how the dominoes fell.
We are all potential child abusers. When faced with the right, or I guess the wrong, set of circumstances we might lash out to stop the crying. Luckily, most of us are several body lengths from the end of that rope.
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at [email protected].
Not better late ...
You all know the statistics or at least have a sense of the scope of the problem. While 85% of mothers in this country intend to breastfeed their infants exclusively for at least 3 months, only slightly more than 30% achieve this goal. Among the dozens of reasons for this unfortunate shortfall is what some experts view as inadequate support by primary care physicians and their offices. In the May 2017 Pediatrics, two members of the American Academy of Pediatrics Section on Breastfeeding offer a clinical report that hopes to remedy this situation (“The Breastfeeding-Friendly Pediatric Office Practice.” Pediatrics. 2017 May. 139[5]:e20170647). It is a document that begins with an excellent review of the background and epidemiology of breastfeeding in the United States and a survey of the current initiatives targeted at improving our dismal performance. What follows is an extensive set of 19 evidence-based recommendations for the pediatric outpatient practice that hopes to “meet or exceed the AAP recommendations.”
A large part of the problem is the failure of the point person in the office, usually the receptionist, to realize that a tearful call from a new mother who is struggling with breastfeeding is an emergency, one that demands a response in minutes … not hours. Even when the call is eventually routed to someone with a compassionate voice who will call back with the right answers, if that process takes just an hour or two, that is enough time for a mother with a screaming and hungry newborn to reach for a bottle of formula.
I urge you to read this exhaustive clinical report in Pediatrics because it is very likely you will come across some things that you can include in your office practice to make it more breastfeeding friendly. However, Even if you and your staff have the right advice, this is not a situation of “better late than never.”
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”
You all know the statistics or at least have a sense of the scope of the problem. While 85% of mothers in this country intend to breastfeed their infants exclusively for at least 3 months, only slightly more than 30% achieve this goal. Among the dozens of reasons for this unfortunate shortfall is what some experts view as inadequate support by primary care physicians and their offices. In the May 2017 Pediatrics, two members of the American Academy of Pediatrics Section on Breastfeeding offer a clinical report that hopes to remedy this situation (“The Breastfeeding-Friendly Pediatric Office Practice.” Pediatrics. 2017 May. 139[5]:e20170647). It is a document that begins with an excellent review of the background and epidemiology of breastfeeding in the United States and a survey of the current initiatives targeted at improving our dismal performance. What follows is an extensive set of 19 evidence-based recommendations for the pediatric outpatient practice that hopes to “meet or exceed the AAP recommendations.”
A large part of the problem is the failure of the point person in the office, usually the receptionist, to realize that a tearful call from a new mother who is struggling with breastfeeding is an emergency, one that demands a response in minutes … not hours. Even when the call is eventually routed to someone with a compassionate voice who will call back with the right answers, if that process takes just an hour or two, that is enough time for a mother with a screaming and hungry newborn to reach for a bottle of formula.
I urge you to read this exhaustive clinical report in Pediatrics because it is very likely you will come across some things that you can include in your office practice to make it more breastfeeding friendly. However, Even if you and your staff have the right advice, this is not a situation of “better late than never.”
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”
You all know the statistics or at least have a sense of the scope of the problem. While 85% of mothers in this country intend to breastfeed their infants exclusively for at least 3 months, only slightly more than 30% achieve this goal. Among the dozens of reasons for this unfortunate shortfall is what some experts view as inadequate support by primary care physicians and their offices. In the May 2017 Pediatrics, two members of the American Academy of Pediatrics Section on Breastfeeding offer a clinical report that hopes to remedy this situation (“The Breastfeeding-Friendly Pediatric Office Practice.” Pediatrics. 2017 May. 139[5]:e20170647). It is a document that begins with an excellent review of the background and epidemiology of breastfeeding in the United States and a survey of the current initiatives targeted at improving our dismal performance. What follows is an extensive set of 19 evidence-based recommendations for the pediatric outpatient practice that hopes to “meet or exceed the AAP recommendations.”
A large part of the problem is the failure of the point person in the office, usually the receptionist, to realize that a tearful call from a new mother who is struggling with breastfeeding is an emergency, one that demands a response in minutes … not hours. Even when the call is eventually routed to someone with a compassionate voice who will call back with the right answers, if that process takes just an hour or two, that is enough time for a mother with a screaming and hungry newborn to reach for a bottle of formula.
I urge you to read this exhaustive clinical report in Pediatrics because it is very likely you will come across some things that you can include in your office practice to make it more breastfeeding friendly. However, Even if you and your staff have the right advice, this is not a situation of “better late than never.”
Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.”
Infant mortality down in most states
Infant mortality in the United States was down by 15% from 2005 to 2014, with 33 states reporting significant declines, according to the National Center for Health Statistics.
The overall rate for 2014 was 5.82 infant deaths per 1,000 live births, compared with 6.84 per 1,000 in 2005. The data for individual states were grouped into 3-year periods, so between the periods of 2005-2007 and 2012-2014, there were 33 states (and the District of Columbia) with a significant decline and 17 states with no significant change. Three states – Maine, South Dakota, and Utah – had increased infant mortality, but the changes did not reach significance, the NCHS reported, using data from the National Vital Statistics System.
Infant mortality in the United States was down by 15% from 2005 to 2014, with 33 states reporting significant declines, according to the National Center for Health Statistics.
The overall rate for 2014 was 5.82 infant deaths per 1,000 live births, compared with 6.84 per 1,000 in 2005. The data for individual states were grouped into 3-year periods, so between the periods of 2005-2007 and 2012-2014, there were 33 states (and the District of Columbia) with a significant decline and 17 states with no significant change. Three states – Maine, South Dakota, and Utah – had increased infant mortality, but the changes did not reach significance, the NCHS reported, using data from the National Vital Statistics System.
Infant mortality in the United States was down by 15% from 2005 to 2014, with 33 states reporting significant declines, according to the National Center for Health Statistics.
The overall rate for 2014 was 5.82 infant deaths per 1,000 live births, compared with 6.84 per 1,000 in 2005. The data for individual states were grouped into 3-year periods, so between the periods of 2005-2007 and 2012-2014, there were 33 states (and the District of Columbia) with a significant decline and 17 states with no significant change. Three states – Maine, South Dakota, and Utah – had increased infant mortality, but the changes did not reach significance, the NCHS reported, using data from the National Vital Statistics System.
Should convicted sex offender get penile prosthetic implant?
SAN DIEGO – Should a man with a distant history of pedophilia be allowed to get a penile prosthetic implant to treat his erectile dysfunction? Mental health professionals at a Veterans Affairs medical center in San Diego recently faced this question and decided the risk was too great. They denied his request.
“This kind of dilemma occurs throughout all health systems, and it’s very challenging. It obviously puts the physician in a very ethically challenging situation,” said Kristin Beizai, MD, a psychiatrist and coauthor of a case report presented at the annual meeting of the American Psychiatric Association.
Yash B. Joshi, MD, PhD, and Dr. Beizai, both psychiatrists at the University of California, San Diego, and the VA San Diego Healthcare System, reported the penile prosthetic implant case in a poster at APA.
According to them, a married veteran sought treatment for erectile dysfunction (ED) from VA hospital urologists after oral treatment had failed. The elderly man, who had been imprisoned for 3 years some 25-30 years previously, sought a penile prosthetic implant – an alternative to treatments for ED when drugs have failed. Other options include self-injections and vacuum devices.
Men with the implants trigger erections by squeezing a pump in the scrotum that allows fluid to flow from a reservoir into the cylinder.
The man had been imprisoned in his 40s for 3 years because of a single incident of sexually abusing a toddler. According to the case report, his primary care doctors previously had offered him ED treatments “without acknowledging this history in their clinical-decision making process.”
A psychologist determined the man to be at low risk of committing a sexual offense again and cleared him for an implant. But his urologists requested an ethics consultation, which was provided by a team that included representatives from the fields of psychiatry, internal medicine, nursing, and social work.
“The ethics team determined that the most appropriate course of action hinged on a thorough and individualized risk-benefit assessment to determine if providing the treatment was ethically justifiable,” Dr. Beizai said in an interview.
An on-site psychologist and an outside expert evaluated the patient using a tool known as the Violence Risk Assessment Instrument–Sexual and determined the man was at moderate to severe risk of committing a sexual offense again.
“It was also discovered that the patient never completed treatment for pedophilia in the community as previously recommended,” the psychiatrists reported. “He was offered a plan for reevaluation and rehabilitation by subspecialists but declined this option.”
The man subsequently died of natural causes.
Dr. Beizai said those kinds of cases present numerous challenges. “This case involves surgery/urology, but this is an issue with primary care as well, and they likely do not have the time, resources, or protocol to address fully, particularly when legal information may be withheld and there are confidentiality issues.”
In regard to a risk-benefit analysis, she said, “a general mental health practitioner may not be comfortable completing this kind of assessment, and there may be an indication to refer to a forensic psychiatrist or psychologist. But this can be an expensive and scarce resource.”
There’s also the potential for political storms if the news gets out that a convicted sex offender received ED treatment. News reports in the mid-2000s about this kind of care persuaded several states to ban government payments for ED treatment for convicted sex offenders, and Medicaid funding was eliminated.
Two researchers who study pedophilia said in an interview that these decisions are far from simple and must take several factors into account.
Fred S. Berlin, MD, PhD, director of the Sexual Behavior Consultation Unit, and associate professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, said a sexual offense background isn’t necessarily enough of a reason to deny ED treatment to a patient. Important factors for decision making, he said, include the nature of the previous offenses (such as whether they involved penile penetration, or the use of drugs or alcohol) and the state of an offender’s current relationship.
He added that it’s important to understand that the lack of functioning genitals isn’t a barrier to sexual abuse. “There shouldn’t be a narrow focus on the capacity of the penis to have an erection,” he said.
Treatment for ED in convicted sex offenders can be helpful in some cases, said Richard B. Krueger, MD, an associate clinical professor of psychiatry at Columbia University, New York, and medical director of the Sexual Behavior Clinic at New York State Psychiatric Institute. “The general sense is that it would be a benefit to enable an appropriate, peer-related relationship with a spouse, significant other, or adults,” Dr. Krueger said.
Red flags regarding ED treatment in sex offenders, he said, include high scores on predictive tests, a history of extreme sadism or sociopathy, and challenges regarding monitoring of the offender.
Dr. Beizai, Dr. Joshi, Dr. Krueger, and Dr. Berlin reported no relevant disclosures.
[polldaddy:9767052]
SAN DIEGO – Should a man with a distant history of pedophilia be allowed to get a penile prosthetic implant to treat his erectile dysfunction? Mental health professionals at a Veterans Affairs medical center in San Diego recently faced this question and decided the risk was too great. They denied his request.
“This kind of dilemma occurs throughout all health systems, and it’s very challenging. It obviously puts the physician in a very ethically challenging situation,” said Kristin Beizai, MD, a psychiatrist and coauthor of a case report presented at the annual meeting of the American Psychiatric Association.
Yash B. Joshi, MD, PhD, and Dr. Beizai, both psychiatrists at the University of California, San Diego, and the VA San Diego Healthcare System, reported the penile prosthetic implant case in a poster at APA.
According to them, a married veteran sought treatment for erectile dysfunction (ED) from VA hospital urologists after oral treatment had failed. The elderly man, who had been imprisoned for 3 years some 25-30 years previously, sought a penile prosthetic implant – an alternative to treatments for ED when drugs have failed. Other options include self-injections and vacuum devices.
Men with the implants trigger erections by squeezing a pump in the scrotum that allows fluid to flow from a reservoir into the cylinder.
The man had been imprisoned in his 40s for 3 years because of a single incident of sexually abusing a toddler. According to the case report, his primary care doctors previously had offered him ED treatments “without acknowledging this history in their clinical-decision making process.”
A psychologist determined the man to be at low risk of committing a sexual offense again and cleared him for an implant. But his urologists requested an ethics consultation, which was provided by a team that included representatives from the fields of psychiatry, internal medicine, nursing, and social work.
“The ethics team determined that the most appropriate course of action hinged on a thorough and individualized risk-benefit assessment to determine if providing the treatment was ethically justifiable,” Dr. Beizai said in an interview.
An on-site psychologist and an outside expert evaluated the patient using a tool known as the Violence Risk Assessment Instrument–Sexual and determined the man was at moderate to severe risk of committing a sexual offense again.
“It was also discovered that the patient never completed treatment for pedophilia in the community as previously recommended,” the psychiatrists reported. “He was offered a plan for reevaluation and rehabilitation by subspecialists but declined this option.”
The man subsequently died of natural causes.
Dr. Beizai said those kinds of cases present numerous challenges. “This case involves surgery/urology, but this is an issue with primary care as well, and they likely do not have the time, resources, or protocol to address fully, particularly when legal information may be withheld and there are confidentiality issues.”
In regard to a risk-benefit analysis, she said, “a general mental health practitioner may not be comfortable completing this kind of assessment, and there may be an indication to refer to a forensic psychiatrist or psychologist. But this can be an expensive and scarce resource.”
There’s also the potential for political storms if the news gets out that a convicted sex offender received ED treatment. News reports in the mid-2000s about this kind of care persuaded several states to ban government payments for ED treatment for convicted sex offenders, and Medicaid funding was eliminated.
Two researchers who study pedophilia said in an interview that these decisions are far from simple and must take several factors into account.
Fred S. Berlin, MD, PhD, director of the Sexual Behavior Consultation Unit, and associate professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, said a sexual offense background isn’t necessarily enough of a reason to deny ED treatment to a patient. Important factors for decision making, he said, include the nature of the previous offenses (such as whether they involved penile penetration, or the use of drugs or alcohol) and the state of an offender’s current relationship.
He added that it’s important to understand that the lack of functioning genitals isn’t a barrier to sexual abuse. “There shouldn’t be a narrow focus on the capacity of the penis to have an erection,” he said.
Treatment for ED in convicted sex offenders can be helpful in some cases, said Richard B. Krueger, MD, an associate clinical professor of psychiatry at Columbia University, New York, and medical director of the Sexual Behavior Clinic at New York State Psychiatric Institute. “The general sense is that it would be a benefit to enable an appropriate, peer-related relationship with a spouse, significant other, or adults,” Dr. Krueger said.
Red flags regarding ED treatment in sex offenders, he said, include high scores on predictive tests, a history of extreme sadism or sociopathy, and challenges regarding monitoring of the offender.
Dr. Beizai, Dr. Joshi, Dr. Krueger, and Dr. Berlin reported no relevant disclosures.
[polldaddy:9767052]
SAN DIEGO – Should a man with a distant history of pedophilia be allowed to get a penile prosthetic implant to treat his erectile dysfunction? Mental health professionals at a Veterans Affairs medical center in San Diego recently faced this question and decided the risk was too great. They denied his request.
“This kind of dilemma occurs throughout all health systems, and it’s very challenging. It obviously puts the physician in a very ethically challenging situation,” said Kristin Beizai, MD, a psychiatrist and coauthor of a case report presented at the annual meeting of the American Psychiatric Association.
Yash B. Joshi, MD, PhD, and Dr. Beizai, both psychiatrists at the University of California, San Diego, and the VA San Diego Healthcare System, reported the penile prosthetic implant case in a poster at APA.
According to them, a married veteran sought treatment for erectile dysfunction (ED) from VA hospital urologists after oral treatment had failed. The elderly man, who had been imprisoned for 3 years some 25-30 years previously, sought a penile prosthetic implant – an alternative to treatments for ED when drugs have failed. Other options include self-injections and vacuum devices.
Men with the implants trigger erections by squeezing a pump in the scrotum that allows fluid to flow from a reservoir into the cylinder.
The man had been imprisoned in his 40s for 3 years because of a single incident of sexually abusing a toddler. According to the case report, his primary care doctors previously had offered him ED treatments “without acknowledging this history in their clinical-decision making process.”
A psychologist determined the man to be at low risk of committing a sexual offense again and cleared him for an implant. But his urologists requested an ethics consultation, which was provided by a team that included representatives from the fields of psychiatry, internal medicine, nursing, and social work.
“The ethics team determined that the most appropriate course of action hinged on a thorough and individualized risk-benefit assessment to determine if providing the treatment was ethically justifiable,” Dr. Beizai said in an interview.
An on-site psychologist and an outside expert evaluated the patient using a tool known as the Violence Risk Assessment Instrument–Sexual and determined the man was at moderate to severe risk of committing a sexual offense again.
“It was also discovered that the patient never completed treatment for pedophilia in the community as previously recommended,” the psychiatrists reported. “He was offered a plan for reevaluation and rehabilitation by subspecialists but declined this option.”
The man subsequently died of natural causes.
Dr. Beizai said those kinds of cases present numerous challenges. “This case involves surgery/urology, but this is an issue with primary care as well, and they likely do not have the time, resources, or protocol to address fully, particularly when legal information may be withheld and there are confidentiality issues.”
In regard to a risk-benefit analysis, she said, “a general mental health practitioner may not be comfortable completing this kind of assessment, and there may be an indication to refer to a forensic psychiatrist or psychologist. But this can be an expensive and scarce resource.”
There’s also the potential for political storms if the news gets out that a convicted sex offender received ED treatment. News reports in the mid-2000s about this kind of care persuaded several states to ban government payments for ED treatment for convicted sex offenders, and Medicaid funding was eliminated.
Two researchers who study pedophilia said in an interview that these decisions are far from simple and must take several factors into account.
Fred S. Berlin, MD, PhD, director of the Sexual Behavior Consultation Unit, and associate professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, said a sexual offense background isn’t necessarily enough of a reason to deny ED treatment to a patient. Important factors for decision making, he said, include the nature of the previous offenses (such as whether they involved penile penetration, or the use of drugs or alcohol) and the state of an offender’s current relationship.
He added that it’s important to understand that the lack of functioning genitals isn’t a barrier to sexual abuse. “There shouldn’t be a narrow focus on the capacity of the penis to have an erection,” he said.
Treatment for ED in convicted sex offenders can be helpful in some cases, said Richard B. Krueger, MD, an associate clinical professor of psychiatry at Columbia University, New York, and medical director of the Sexual Behavior Clinic at New York State Psychiatric Institute. “The general sense is that it would be a benefit to enable an appropriate, peer-related relationship with a spouse, significant other, or adults,” Dr. Krueger said.
Red flags regarding ED treatment in sex offenders, he said, include high scores on predictive tests, a history of extreme sadism or sociopathy, and challenges regarding monitoring of the offender.
Dr. Beizai, Dr. Joshi, Dr. Krueger, and Dr. Berlin reported no relevant disclosures.
[polldaddy:9767052]
AT APA
Crossing the personal quality chasm: QI enthusiast to QI leader
Editor’s Note: This new series highlights the professional pathways of quality improvement leaders. This month features the story of Eric Howell, MD, MHM, professor of medicine at Johns Hopkins University, Baltimore.
For Eric Howell, MD, MHM, the journey to becoming a professor of medicine at Johns Hopkins University, past president of SHM, and director of SHM’s Leadership Academies commenced with a major quality improvement (QI) challenge.
Johns Hopkins Bayview Medical Center was struggling with throughput from the emergency department when Dr. Howell began practicing there in the early days of hospital medicine. “The ED said the medicine service was too slow, and the hospitalists said, ‘We’re working as fast as we can,’ ” Dr. Howell recalled of his real-world introduction to implementation science. “So, I took on triage oversight in 2000 and began streamlining flow.”
With a growing reputation for finding solutions to reduce readmissions and improve care transitions, Dr. Howell joined the Better Outcomes by Optimizing Safe Transitions (Project BOOST) project team in 2007 to codevelop one of SHM’s most successful programs. He humbly attributes some of this success to luck. “I happened to be at the right place at the right time. There was a problem, opportunity knocked, and I opened the door,” he said.
After some reflection, he pinpoints more tangible factors – a gift for innovative thinking and finding options that unify, rather than polarize, people and departments.
“I always ensure a solution makes the pie bigger, so that everyone benefits from it,” he said. “I don’t approach a problem like a sporting event, where one group wins and another loses.”
Dr. Howell says that an inclusive mindset is an important characteristic for anyone on a QI track because “it encourages buy-in from everyone who is impacted by a problem, and their investment in making the outcome successful.”
Skill development in areas such as leadership principles and processes such as lean will benefit those on a QI pathway, but finding the right mentors is just as critical. Dr. Howell looked to multiple people from diverse backgrounds, none of which included QI, to “help me move my skill set forward,” he said. “A clinical educator helped me to interact with other people, learn to facilitate an educational initiative, and lead people to change.”
Another mentor, he recalled, was an engineer who helped him figure out how to measure the success of his projects. And a third mentor cleared the pathway of obstructions, providing access to the people who would make his projects successful.
Being able to pivot is also important, Dr. Howell said. “Whether it is looking at data or the people you need to approach to solve a problem, be able to change your approach. Flip-flopping is a good thing in QI, because you’re always adjusting your tactics based on new information.”
Today, as SHM’s senior physician advisor to its Center for Quality Improvement, Dr. Howell holds multiple roles within the Johns Hopkins system and has received numerous awards for excellence in teaching and practice. The core principles that he started with on the path remain the same: “Be humble,” he said, “and give away credit. We are often collaborating with other professionals, so shining a light on the great work that they do will make projects more successful and improve the likelihood that they will want to collaborate with you in the future.”
Claudia Stahl is a content manager for the Society of Hospital Medicine.
Editor’s Note: This new series highlights the professional pathways of quality improvement leaders. This month features the story of Eric Howell, MD, MHM, professor of medicine at Johns Hopkins University, Baltimore.
For Eric Howell, MD, MHM, the journey to becoming a professor of medicine at Johns Hopkins University, past president of SHM, and director of SHM’s Leadership Academies commenced with a major quality improvement (QI) challenge.
Johns Hopkins Bayview Medical Center was struggling with throughput from the emergency department when Dr. Howell began practicing there in the early days of hospital medicine. “The ED said the medicine service was too slow, and the hospitalists said, ‘We’re working as fast as we can,’ ” Dr. Howell recalled of his real-world introduction to implementation science. “So, I took on triage oversight in 2000 and began streamlining flow.”
With a growing reputation for finding solutions to reduce readmissions and improve care transitions, Dr. Howell joined the Better Outcomes by Optimizing Safe Transitions (Project BOOST) project team in 2007 to codevelop one of SHM’s most successful programs. He humbly attributes some of this success to luck. “I happened to be at the right place at the right time. There was a problem, opportunity knocked, and I opened the door,” he said.
After some reflection, he pinpoints more tangible factors – a gift for innovative thinking and finding options that unify, rather than polarize, people and departments.
“I always ensure a solution makes the pie bigger, so that everyone benefits from it,” he said. “I don’t approach a problem like a sporting event, where one group wins and another loses.”
Dr. Howell says that an inclusive mindset is an important characteristic for anyone on a QI track because “it encourages buy-in from everyone who is impacted by a problem, and their investment in making the outcome successful.”
Skill development in areas such as leadership principles and processes such as lean will benefit those on a QI pathway, but finding the right mentors is just as critical. Dr. Howell looked to multiple people from diverse backgrounds, none of which included QI, to “help me move my skill set forward,” he said. “A clinical educator helped me to interact with other people, learn to facilitate an educational initiative, and lead people to change.”
Another mentor, he recalled, was an engineer who helped him figure out how to measure the success of his projects. And a third mentor cleared the pathway of obstructions, providing access to the people who would make his projects successful.
Being able to pivot is also important, Dr. Howell said. “Whether it is looking at data or the people you need to approach to solve a problem, be able to change your approach. Flip-flopping is a good thing in QI, because you’re always adjusting your tactics based on new information.”
Today, as SHM’s senior physician advisor to its Center for Quality Improvement, Dr. Howell holds multiple roles within the Johns Hopkins system and has received numerous awards for excellence in teaching and practice. The core principles that he started with on the path remain the same: “Be humble,” he said, “and give away credit. We are often collaborating with other professionals, so shining a light on the great work that they do will make projects more successful and improve the likelihood that they will want to collaborate with you in the future.”
Claudia Stahl is a content manager for the Society of Hospital Medicine.
Editor’s Note: This new series highlights the professional pathways of quality improvement leaders. This month features the story of Eric Howell, MD, MHM, professor of medicine at Johns Hopkins University, Baltimore.
For Eric Howell, MD, MHM, the journey to becoming a professor of medicine at Johns Hopkins University, past president of SHM, and director of SHM’s Leadership Academies commenced with a major quality improvement (QI) challenge.
Johns Hopkins Bayview Medical Center was struggling with throughput from the emergency department when Dr. Howell began practicing there in the early days of hospital medicine. “The ED said the medicine service was too slow, and the hospitalists said, ‘We’re working as fast as we can,’ ” Dr. Howell recalled of his real-world introduction to implementation science. “So, I took on triage oversight in 2000 and began streamlining flow.”
With a growing reputation for finding solutions to reduce readmissions and improve care transitions, Dr. Howell joined the Better Outcomes by Optimizing Safe Transitions (Project BOOST) project team in 2007 to codevelop one of SHM’s most successful programs. He humbly attributes some of this success to luck. “I happened to be at the right place at the right time. There was a problem, opportunity knocked, and I opened the door,” he said.
After some reflection, he pinpoints more tangible factors – a gift for innovative thinking and finding options that unify, rather than polarize, people and departments.
“I always ensure a solution makes the pie bigger, so that everyone benefits from it,” he said. “I don’t approach a problem like a sporting event, where one group wins and another loses.”
Dr. Howell says that an inclusive mindset is an important characteristic for anyone on a QI track because “it encourages buy-in from everyone who is impacted by a problem, and their investment in making the outcome successful.”
Skill development in areas such as leadership principles and processes such as lean will benefit those on a QI pathway, but finding the right mentors is just as critical. Dr. Howell looked to multiple people from diverse backgrounds, none of which included QI, to “help me move my skill set forward,” he said. “A clinical educator helped me to interact with other people, learn to facilitate an educational initiative, and lead people to change.”
Another mentor, he recalled, was an engineer who helped him figure out how to measure the success of his projects. And a third mentor cleared the pathway of obstructions, providing access to the people who would make his projects successful.
Being able to pivot is also important, Dr. Howell said. “Whether it is looking at data or the people you need to approach to solve a problem, be able to change your approach. Flip-flopping is a good thing in QI, because you’re always adjusting your tactics based on new information.”
Today, as SHM’s senior physician advisor to its Center for Quality Improvement, Dr. Howell holds multiple roles within the Johns Hopkins system and has received numerous awards for excellence in teaching and practice. The core principles that he started with on the path remain the same: “Be humble,” he said, “and give away credit. We are often collaborating with other professionals, so shining a light on the great work that they do will make projects more successful and improve the likelihood that they will want to collaborate with you in the future.”
Claudia Stahl is a content manager for the Society of Hospital Medicine.
FDA asks drug maker to shelve Opana ER
The Food and Drug Administration has asked Endo Pharmaceuticals to voluntarily remove its opioid pain medication, reformulated Opana ER (oxymorphone hydrochloride), from the market in the United States, citing the potential for its abuse as a concern.
“We are facing an opioid epidemic – a public health crisis, and we must take all necessary steps to reduce the scope of opioid misuse and abuse,” FDA Commissioner Scott Gottlieb, MD, said in a June 8 press release . “We will continue to take regulatory steps when we see situations where an opioid product’s risks outweigh its benefits, not only for its intended patient population but also in regard to its potential for misuse and abuse.”
Opana ER was first approved in 2006 for the management of moderate to severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. It was reformulated in 2012, with the intent of making it “resistant to physical and chemical manipulation for abuse by snorting or injecting,” according to the FDA release.
The Food and Drug Administration has asked Endo Pharmaceuticals to voluntarily remove its opioid pain medication, reformulated Opana ER (oxymorphone hydrochloride), from the market in the United States, citing the potential for its abuse as a concern.
“We are facing an opioid epidemic – a public health crisis, and we must take all necessary steps to reduce the scope of opioid misuse and abuse,” FDA Commissioner Scott Gottlieb, MD, said in a June 8 press release . “We will continue to take regulatory steps when we see situations where an opioid product’s risks outweigh its benefits, not only for its intended patient population but also in regard to its potential for misuse and abuse.”
Opana ER was first approved in 2006 for the management of moderate to severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. It was reformulated in 2012, with the intent of making it “resistant to physical and chemical manipulation for abuse by snorting or injecting,” according to the FDA release.
The Food and Drug Administration has asked Endo Pharmaceuticals to voluntarily remove its opioid pain medication, reformulated Opana ER (oxymorphone hydrochloride), from the market in the United States, citing the potential for its abuse as a concern.
“We are facing an opioid epidemic – a public health crisis, and we must take all necessary steps to reduce the scope of opioid misuse and abuse,” FDA Commissioner Scott Gottlieb, MD, said in a June 8 press release . “We will continue to take regulatory steps when we see situations where an opioid product’s risks outweigh its benefits, not only for its intended patient population but also in regard to its potential for misuse and abuse.”
Opana ER was first approved in 2006 for the management of moderate to severe pain when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. It was reformulated in 2012, with the intent of making it “resistant to physical and chemical manipulation for abuse by snorting or injecting,” according to the FDA release.
EU label for nilotinib now includes info on stopping therapy
The European Commission has approved the inclusion of treatment-free remission (TFR) data in the European Union (EU) product information for nilotinib (Tasigna®).
TFR is the ability to maintain molecular response after stopping tyrosine kinase inhibitor (TKI) therapy in patients with Ph+ chronic myeloid leukemia in chronic phase (CML-CP).
Nilotinib is approved for the treatment of CML-CP in adults resistant or intolerant to at least one prior therapy, including imatinib, and for the treatment of adults with newly diagnosed Ph+ CML.
Nilotinib is the first and only TKI to include TFR data in its product information in the EU, according to Novartis, developer of the drug.
Two large international Ph+ CML trials assessing nilotinib discontinuation—ENESTfreedom and ENESTop—formed the basis of the decision.
The two open-label trials showed that half of Ph+ CML-CP patients who met rigorous predefined response criteria maintained TFR after stopping nilotinib, both in the frontline setting and after switching from imatinib.
Both trials included regular and frequent molecular monitoring of BCR-ABL levels with an assay that could measure transcript levels down to a molecular response (MR) of 4.5. Frequent monitoring after discontinuation helped determine loss of MR 4.0 and major molecular response, indicating the need to re-initiate treatment.
This phase 2 trial (Evaluating Nilotinib Efficacy and Safety in Clinical Trials - Following REsponsE in De nOvo CML-CP Patients) involved 215 patients with Ph+ CML-CP treated at 132 sites across 19 countries.
The trial evaluated whether treatment could be stopped in 190 of the patients after they had achieved a response of MR 4.5 and a sustained deep molecular response for 1 year as first-line treatment.
The results showed that 51.6% of the patients in the trial could discontinue therapy and remain in TFR at the 48-week analysis.
However, ENESTfreedom did not meet its primary endpoint of 50% or more of patients in MMR at 48 weeks in the TFR phase. The median treatment duration was 3.6 years.
Adverse events in the trial included musculoskeletal pain (24.7%) during the first years of the TFR phase compared with 16.3% in those still on nilotinib.
No patient progressed to advanced phase/blast crisis.
This phase 2 trial (Evaluating Nilotinib Efficacy and Safety Trial) involved 163 patients with Ph+ CML-CP treated at 63 sites across 18 countries. Investigators evaluated 126 patients who had been treated with imatinib and then switched to nilotinib and had achieved a sustained deep molecular response for 1 year while on nilotinib.
The trial demonstrated that 57.9% of patients maintained a molecular resonse at 48 weeks after stopping treatment. The trial met its primary endpoint—the proportion of patients who did not lose MR 4.0 or MMR within 48 weeks of discontinuing nilotinib in the TFR phase.
Again, the rates of musuloskeletal pain were higher in the first year of TFR than in patients still on nilotinib in the consolidation phase, 42.1% and 14.3%, respectively.
Results of the EURO-SKI trial also support the idea that certain CML patients can safely stop TKI therapy.
For full prescribing information, see the product insert. 
The European Commission has approved the inclusion of treatment-free remission (TFR) data in the European Union (EU) product information for nilotinib (Tasigna®).
TFR is the ability to maintain molecular response after stopping tyrosine kinase inhibitor (TKI) therapy in patients with Ph+ chronic myeloid leukemia in chronic phase (CML-CP).
Nilotinib is approved for the treatment of CML-CP in adults resistant or intolerant to at least one prior therapy, including imatinib, and for the treatment of adults with newly diagnosed Ph+ CML.
Nilotinib is the first and only TKI to include TFR data in its product information in the EU, according to Novartis, developer of the drug.
Two large international Ph+ CML trials assessing nilotinib discontinuation—ENESTfreedom and ENESTop—formed the basis of the decision.
The two open-label trials showed that half of Ph+ CML-CP patients who met rigorous predefined response criteria maintained TFR after stopping nilotinib, both in the frontline setting and after switching from imatinib.
Both trials included regular and frequent molecular monitoring of BCR-ABL levels with an assay that could measure transcript levels down to a molecular response (MR) of 4.5. Frequent monitoring after discontinuation helped determine loss of MR 4.0 and major molecular response, indicating the need to re-initiate treatment.
This phase 2 trial (Evaluating Nilotinib Efficacy and Safety in Clinical Trials - Following REsponsE in De nOvo CML-CP Patients) involved 215 patients with Ph+ CML-CP treated at 132 sites across 19 countries.
The trial evaluated whether treatment could be stopped in 190 of the patients after they had achieved a response of MR 4.5 and a sustained deep molecular response for 1 year as first-line treatment.
The results showed that 51.6% of the patients in the trial could discontinue therapy and remain in TFR at the 48-week analysis.
However, ENESTfreedom did not meet its primary endpoint of 50% or more of patients in MMR at 48 weeks in the TFR phase. The median treatment duration was 3.6 years.
Adverse events in the trial included musculoskeletal pain (24.7%) during the first years of the TFR phase compared with 16.3% in those still on nilotinib.
No patient progressed to advanced phase/blast crisis.
This phase 2 trial (Evaluating Nilotinib Efficacy and Safety Trial) involved 163 patients with Ph+ CML-CP treated at 63 sites across 18 countries. Investigators evaluated 126 patients who had been treated with imatinib and then switched to nilotinib and had achieved a sustained deep molecular response for 1 year while on nilotinib.
The trial demonstrated that 57.9% of patients maintained a molecular resonse at 48 weeks after stopping treatment. The trial met its primary endpoint—the proportion of patients who did not lose MR 4.0 or MMR within 48 weeks of discontinuing nilotinib in the TFR phase.
Again, the rates of musuloskeletal pain were higher in the first year of TFR than in patients still on nilotinib in the consolidation phase, 42.1% and 14.3%, respectively.
Results of the EURO-SKI trial also support the idea that certain CML patients can safely stop TKI therapy.
For full prescribing information, see the product insert.
The European Commission has approved the inclusion of treatment-free remission (TFR) data in the European Union (EU) product information for nilotinib (Tasigna®).
TFR is the ability to maintain molecular response after stopping tyrosine kinase inhibitor (TKI) therapy in patients with Ph+ chronic myeloid leukemia in chronic phase (CML-CP).
Nilotinib is approved for the treatment of CML-CP in adults resistant or intolerant to at least one prior therapy, including imatinib, and for the treatment of adults with newly diagnosed Ph+ CML.
Nilotinib is the first and only TKI to include TFR data in its product information in the EU, according to Novartis, developer of the drug.
Two large international Ph+ CML trials assessing nilotinib discontinuation—ENESTfreedom and ENESTop—formed the basis of the decision.
The two open-label trials showed that half of Ph+ CML-CP patients who met rigorous predefined response criteria maintained TFR after stopping nilotinib, both in the frontline setting and after switching from imatinib.
Both trials included regular and frequent molecular monitoring of BCR-ABL levels with an assay that could measure transcript levels down to a molecular response (MR) of 4.5. Frequent monitoring after discontinuation helped determine loss of MR 4.0 and major molecular response, indicating the need to re-initiate treatment.
This phase 2 trial (Evaluating Nilotinib Efficacy and Safety in Clinical Trials - Following REsponsE in De nOvo CML-CP Patients) involved 215 patients with Ph+ CML-CP treated at 132 sites across 19 countries.
The trial evaluated whether treatment could be stopped in 190 of the patients after they had achieved a response of MR 4.5 and a sustained deep molecular response for 1 year as first-line treatment.
The results showed that 51.6% of the patients in the trial could discontinue therapy and remain in TFR at the 48-week analysis.
However, ENESTfreedom did not meet its primary endpoint of 50% or more of patients in MMR at 48 weeks in the TFR phase. The median treatment duration was 3.6 years.
Adverse events in the trial included musculoskeletal pain (24.7%) during the first years of the TFR phase compared with 16.3% in those still on nilotinib.
No patient progressed to advanced phase/blast crisis.
This phase 2 trial (Evaluating Nilotinib Efficacy and Safety Trial) involved 163 patients with Ph+ CML-CP treated at 63 sites across 18 countries. Investigators evaluated 126 patients who had been treated with imatinib and then switched to nilotinib and had achieved a sustained deep molecular response for 1 year while on nilotinib.
The trial demonstrated that 57.9% of patients maintained a molecular resonse at 48 weeks after stopping treatment. The trial met its primary endpoint—the proportion of patients who did not lose MR 4.0 or MMR within 48 weeks of discontinuing nilotinib in the TFR phase.
Again, the rates of musuloskeletal pain were higher in the first year of TFR than in patients still on nilotinib in the consolidation phase, 42.1% and 14.3%, respectively.
Results of the EURO-SKI trial also support the idea that certain CML patients can safely stop TKI therapy.
For full prescribing information, see the product insert.
Dasatinib potentially a new SOC for children with CML-CP
CHICAGO—The largest ongoing and prospective trial of pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP), according to the best knowledge of the investigators, has found dasatinib to be safe and effective as first- or second-line therapy for these children.
Patients refractory to or intolerant of imatinib had a major cytogenetic response (MCyR) by 3 months and responses at 12 and 24 months exceeded 90%.
Newly diagnosed patients had a complete cytogenetic response (CCyR) by 6 months.
“We believe our data suggests that dasatinib could be considered as a new standard of care (SOC) for children with CML in chronic phase,” said study author Lia Gore, MD, of the University of Colorado School of Medicine/Children’s Hospital Colorado in Aurora.
She presented the findings of the study at the ASCO 2017 Annual Meeting (abstract 10511).
Study design
CA 180-226 is a phase 2, open-label, nonrandomized, prospective study conducted in 18 countries. Patients younger than 18 years with newly diagnosed CML-CP, or imatinib-resistant/intolerant (R/I) CML-CP, or CML in accelerated phase, or Ph+ acute lymphoblastic leukemia (ALL) were enrolled on the study between March 2009 and September 2014.
Dr Gore’s presentation focused on the CML-CP patients in the study, both the newly diagnosed and the imatinib-R/I patients.
The imatinib-R/I patients received dasatinib 60 mg/m2 tablets once daily, and the newly diagnosed patients received the same tablet dosage daily or a powdered formulation for oral suspension (PFOS) of dasatinib at 72 mg/m2 daily.
Dr Gore noted the different dosage in the oral suspension formulation is based on bioavailability studies performed in adults, which was determined to be equivalent to the 60 mg/m2 tablet formulation.
Once accrual was reached in the tablet cohort, newly diagnosed patients were accrued to the PFOS cohort. The patients on PFOS could switch to tablets after a year or more on the oral suspension.
Patients remained on treatment until disease progression, unacceptable toxicity occurred, or the patient/physician preference.
All patients had a minimum follow-up of 2 years. The longest follow-up was more than 90 months.
Primary objectives of the study were MCyR greater than 30% for imatinib-R/I patients and complete CCyR greater than 55% for newly diagnosed patients.
Secondary objectives included time to and duration of response, major molecular response (MMR), progression-free survival (PFS), overall survival (OS), and safety.
Baseline patient characteristics
One hundred thirteen patients were treated across the 3 cohorts—29 in the imatinib-R/I receiving tablets, 51 newly diagnosed patients receiving tablets, and 33 newly diagnosed patients in the PFOS arm. A total of 84 patients had newly diagnosed disease.
Of the 29 imatinib-R/I patients, 25 were resistant, 2 intolerant, and 2 undetermined. And 6 of the 25 resistant patients had defined imatinib-resistance mutations.
Median age was 13.8 years in the imatinib-R/I cohort, 12.9 years in the newly diagnosed on tablets, and 11.7 years in the PFOS group. Other baseline characteristics were similar among the cohorts.
“Importantly, there were 3 patients less than 2 years of age, and a substantial proportion of patients were actually less than 12 years of age,” Dr Gore pointed out.
Dasatinib exposure
The median duration of therapy was 50 months and 42 months in the R/I and newly diagnosed cohorts, respectively.
Forty-eight percent of the imatinib-R/I patients and 73% of the newly diagnosed patients are still on treatment. A relatively small number of patients discontinued therapy.
The median duration of therapy was shorter in the PFOS cohort because they were enrolled only after accrual to the tablet cohort. However, they were also followed up for more than 2 years.
Of the 33 patients on PFOS, 22 eventually switched to tablet formulation.
Results
The primary endpoint for imatinib-R/I patients—MCyR greater than 30%—was reached by 3 months, and MCyR at 12 and 24 months exceeded 90%. The median time to response was 3.1 months (range, 2.8 – 4.1), and median duration of response was not yet reached (range, 54.9 – not estimable).
For newly diagnosed patients, the preset defined rate of interest of 55% for CCyR was reached as early as 6 months, and exceeded 90% by 12 and 24 months.
Dr Gore pointed out that intolerant patients also reached CCyR relatively quickly, although it was not a specified endpoint.
Data indicate that responses occurred relatively quickly and continued to increase over time of follow-up.
MMR also continued to increase over time and showed no difference between formulation and response rate.
Median PFS has not been reached, as only 7 patients in each cohort had disease progression.
One imatinib-R/I patient died 1 year after stopping treatment. The patient, who had a GI bleed unrelated to dasatinib, had discontinued therapy for progressive disease with loss of MCyR.
Safety
Overall safety was very similar to the dasatinib exposure and experience in adults, Dr Gore said, and there were no differences in events between PFOS and tablets.
One patient in the PFOS cohort had a dasatinib-related grade 3 hypersensitivity reaction, which resolved after discontinuation of dasatinib.
“What’s important here,” she said, “is that there were almost no adverse events of severity in either cohort, only 1 in the imatinib refractory and intolerant and 1 in the newly diagnosed cohorts.”
“Most importantly for those of us with a lot of experience in this field,” she added, “there were no occurrences of pleural effusion, pericardial effusion, pulmonary edema, pulmonary hypertension, or any vascular occlusive events in patients noted on this trial.”
“Additionally, for pediatricians, we care a lot about what happens to growth in these patients and prospectively we collected a lot of data related to growth parameters in bone growth and development."
Of the dasatinib-related adverse events occurring in 10% or more of patients, there were only 5 growth and development events noted out of the 113 patients treated and all were grade 1 or 2 events, Dr Gore pointed out.
In the R/I cohort, one patient had osteopenia and gynecomastia. At the time of data analysis, this event had resolved even though the patient continued on dasatinib.
“We believe our data suggests that dasatinib could be considered as a new standard of care for children with CML in chronic phase,” she said.
“It includes the advantage of a liquid formulation as well as the advantages of once daily dosing and administration without regard to fed or fasting state,” she added, “which for all of us who treat children know could be quite important.”
The study was funded by Bristol-Myers Squibb.
CHICAGO—The largest ongoing and prospective trial of pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP), according to the best knowledge of the investigators, has found dasatinib to be safe and effective as first- or second-line therapy for these children.
Patients refractory to or intolerant of imatinib had a major cytogenetic response (MCyR) by 3 months and responses at 12 and 24 months exceeded 90%.
Newly diagnosed patients had a complete cytogenetic response (CCyR) by 6 months.
“We believe our data suggests that dasatinib could be considered as a new standard of care (SOC) for children with CML in chronic phase,” said study author Lia Gore, MD, of the University of Colorado School of Medicine/Children’s Hospital Colorado in Aurora.
She presented the findings of the study at the ASCO 2017 Annual Meeting (abstract 10511).
Study design
CA 180-226 is a phase 2, open-label, nonrandomized, prospective study conducted in 18 countries. Patients younger than 18 years with newly diagnosed CML-CP, or imatinib-resistant/intolerant (R/I) CML-CP, or CML in accelerated phase, or Ph+ acute lymphoblastic leukemia (ALL) were enrolled on the study between March 2009 and September 2014.
Dr Gore’s presentation focused on the CML-CP patients in the study, both the newly diagnosed and the imatinib-R/I patients.
The imatinib-R/I patients received dasatinib 60 mg/m2 tablets once daily, and the newly diagnosed patients received the same tablet dosage daily or a powdered formulation for oral suspension (PFOS) of dasatinib at 72 mg/m2 daily.
Dr Gore noted the different dosage in the oral suspension formulation is based on bioavailability studies performed in adults, which was determined to be equivalent to the 60 mg/m2 tablet formulation.
Once accrual was reached in the tablet cohort, newly diagnosed patients were accrued to the PFOS cohort. The patients on PFOS could switch to tablets after a year or more on the oral suspension.
Patients remained on treatment until disease progression, unacceptable toxicity occurred, or the patient/physician preference.
All patients had a minimum follow-up of 2 years. The longest follow-up was more than 90 months.
Primary objectives of the study were MCyR greater than 30% for imatinib-R/I patients and complete CCyR greater than 55% for newly diagnosed patients.
Secondary objectives included time to and duration of response, major molecular response (MMR), progression-free survival (PFS), overall survival (OS), and safety.
Baseline patient characteristics
One hundred thirteen patients were treated across the 3 cohorts—29 in the imatinib-R/I receiving tablets, 51 newly diagnosed patients receiving tablets, and 33 newly diagnosed patients in the PFOS arm. A total of 84 patients had newly diagnosed disease.
Of the 29 imatinib-R/I patients, 25 were resistant, 2 intolerant, and 2 undetermined. And 6 of the 25 resistant patients had defined imatinib-resistance mutations.
Median age was 13.8 years in the imatinib-R/I cohort, 12.9 years in the newly diagnosed on tablets, and 11.7 years in the PFOS group. Other baseline characteristics were similar among the cohorts.
“Importantly, there were 3 patients less than 2 years of age, and a substantial proportion of patients were actually less than 12 years of age,” Dr Gore pointed out.
Dasatinib exposure
The median duration of therapy was 50 months and 42 months in the R/I and newly diagnosed cohorts, respectively.
Forty-eight percent of the imatinib-R/I patients and 73% of the newly diagnosed patients are still on treatment. A relatively small number of patients discontinued therapy.
The median duration of therapy was shorter in the PFOS cohort because they were enrolled only after accrual to the tablet cohort. However, they were also followed up for more than 2 years.
Of the 33 patients on PFOS, 22 eventually switched to tablet formulation.
Results
The primary endpoint for imatinib-R/I patients—MCyR greater than 30%—was reached by 3 months, and MCyR at 12 and 24 months exceeded 90%. The median time to response was 3.1 months (range, 2.8 – 4.1), and median duration of response was not yet reached (range, 54.9 – not estimable).
For newly diagnosed patients, the preset defined rate of interest of 55% for CCyR was reached as early as 6 months, and exceeded 90% by 12 and 24 months.
Dr Gore pointed out that intolerant patients also reached CCyR relatively quickly, although it was not a specified endpoint.
Data indicate that responses occurred relatively quickly and continued to increase over time of follow-up.
MMR also continued to increase over time and showed no difference between formulation and response rate.
Median PFS has not been reached, as only 7 patients in each cohort had disease progression.
One imatinib-R/I patient died 1 year after stopping treatment. The patient, who had a GI bleed unrelated to dasatinib, had discontinued therapy for progressive disease with loss of MCyR.
Safety
Overall safety was very similar to the dasatinib exposure and experience in adults, Dr Gore said, and there were no differences in events between PFOS and tablets.
One patient in the PFOS cohort had a dasatinib-related grade 3 hypersensitivity reaction, which resolved after discontinuation of dasatinib.
“What’s important here,” she said, “is that there were almost no adverse events of severity in either cohort, only 1 in the imatinib refractory and intolerant and 1 in the newly diagnosed cohorts.”
“Most importantly for those of us with a lot of experience in this field,” she added, “there were no occurrences of pleural effusion, pericardial effusion, pulmonary edema, pulmonary hypertension, or any vascular occlusive events in patients noted on this trial.”
“Additionally, for pediatricians, we care a lot about what happens to growth in these patients and prospectively we collected a lot of data related to growth parameters in bone growth and development."
Of the dasatinib-related adverse events occurring in 10% or more of patients, there were only 5 growth and development events noted out of the 113 patients treated and all were grade 1 or 2 events, Dr Gore pointed out.
In the R/I cohort, one patient had osteopenia and gynecomastia. At the time of data analysis, this event had resolved even though the patient continued on dasatinib.
“We believe our data suggests that dasatinib could be considered as a new standard of care for children with CML in chronic phase,” she said.
“It includes the advantage of a liquid formulation as well as the advantages of once daily dosing and administration without regard to fed or fasting state,” she added, “which for all of us who treat children know could be quite important.”
The study was funded by Bristol-Myers Squibb.
CHICAGO—The largest ongoing and prospective trial of pediatric patients with chronic myeloid leukemia in chronic phase (CML-CP), according to the best knowledge of the investigators, has found dasatinib to be safe and effective as first- or second-line therapy for these children.
Patients refractory to or intolerant of imatinib had a major cytogenetic response (MCyR) by 3 months and responses at 12 and 24 months exceeded 90%.
Newly diagnosed patients had a complete cytogenetic response (CCyR) by 6 months.
“We believe our data suggests that dasatinib could be considered as a new standard of care (SOC) for children with CML in chronic phase,” said study author Lia Gore, MD, of the University of Colorado School of Medicine/Children’s Hospital Colorado in Aurora.
She presented the findings of the study at the ASCO 2017 Annual Meeting (abstract 10511).
Study design
CA 180-226 is a phase 2, open-label, nonrandomized, prospective study conducted in 18 countries. Patients younger than 18 years with newly diagnosed CML-CP, or imatinib-resistant/intolerant (R/I) CML-CP, or CML in accelerated phase, or Ph+ acute lymphoblastic leukemia (ALL) were enrolled on the study between March 2009 and September 2014.
Dr Gore’s presentation focused on the CML-CP patients in the study, both the newly diagnosed and the imatinib-R/I patients.
The imatinib-R/I patients received dasatinib 60 mg/m2 tablets once daily, and the newly diagnosed patients received the same tablet dosage daily or a powdered formulation for oral suspension (PFOS) of dasatinib at 72 mg/m2 daily.
Dr Gore noted the different dosage in the oral suspension formulation is based on bioavailability studies performed in adults, which was determined to be equivalent to the 60 mg/m2 tablet formulation.
Once accrual was reached in the tablet cohort, newly diagnosed patients were accrued to the PFOS cohort. The patients on PFOS could switch to tablets after a year or more on the oral suspension.
Patients remained on treatment until disease progression, unacceptable toxicity occurred, or the patient/physician preference.
All patients had a minimum follow-up of 2 years. The longest follow-up was more than 90 months.
Primary objectives of the study were MCyR greater than 30% for imatinib-R/I patients and complete CCyR greater than 55% for newly diagnosed patients.
Secondary objectives included time to and duration of response, major molecular response (MMR), progression-free survival (PFS), overall survival (OS), and safety.
Baseline patient characteristics
One hundred thirteen patients were treated across the 3 cohorts—29 in the imatinib-R/I receiving tablets, 51 newly diagnosed patients receiving tablets, and 33 newly diagnosed patients in the PFOS arm. A total of 84 patients had newly diagnosed disease.
Of the 29 imatinib-R/I patients, 25 were resistant, 2 intolerant, and 2 undetermined. And 6 of the 25 resistant patients had defined imatinib-resistance mutations.
Median age was 13.8 years in the imatinib-R/I cohort, 12.9 years in the newly diagnosed on tablets, and 11.7 years in the PFOS group. Other baseline characteristics were similar among the cohorts.
“Importantly, there were 3 patients less than 2 years of age, and a substantial proportion of patients were actually less than 12 years of age,” Dr Gore pointed out.
Dasatinib exposure
The median duration of therapy was 50 months and 42 months in the R/I and newly diagnosed cohorts, respectively.
Forty-eight percent of the imatinib-R/I patients and 73% of the newly diagnosed patients are still on treatment. A relatively small number of patients discontinued therapy.
The median duration of therapy was shorter in the PFOS cohort because they were enrolled only after accrual to the tablet cohort. However, they were also followed up for more than 2 years.
Of the 33 patients on PFOS, 22 eventually switched to tablet formulation.
Results
The primary endpoint for imatinib-R/I patients—MCyR greater than 30%—was reached by 3 months, and MCyR at 12 and 24 months exceeded 90%. The median time to response was 3.1 months (range, 2.8 – 4.1), and median duration of response was not yet reached (range, 54.9 – not estimable).
For newly diagnosed patients, the preset defined rate of interest of 55% for CCyR was reached as early as 6 months, and exceeded 90% by 12 and 24 months.
Dr Gore pointed out that intolerant patients also reached CCyR relatively quickly, although it was not a specified endpoint.
Data indicate that responses occurred relatively quickly and continued to increase over time of follow-up.
MMR also continued to increase over time and showed no difference between formulation and response rate.
Median PFS has not been reached, as only 7 patients in each cohort had disease progression.
One imatinib-R/I patient died 1 year after stopping treatment. The patient, who had a GI bleed unrelated to dasatinib, had discontinued therapy for progressive disease with loss of MCyR.
Safety
Overall safety was very similar to the dasatinib exposure and experience in adults, Dr Gore said, and there were no differences in events between PFOS and tablets.
One patient in the PFOS cohort had a dasatinib-related grade 3 hypersensitivity reaction, which resolved after discontinuation of dasatinib.
“What’s important here,” she said, “is that there were almost no adverse events of severity in either cohort, only 1 in the imatinib refractory and intolerant and 1 in the newly diagnosed cohorts.”
“Most importantly for those of us with a lot of experience in this field,” she added, “there were no occurrences of pleural effusion, pericardial effusion, pulmonary edema, pulmonary hypertension, or any vascular occlusive events in patients noted on this trial.”
“Additionally, for pediatricians, we care a lot about what happens to growth in these patients and prospectively we collected a lot of data related to growth parameters in bone growth and development."
Of the dasatinib-related adverse events occurring in 10% or more of patients, there were only 5 growth and development events noted out of the 113 patients treated and all were grade 1 or 2 events, Dr Gore pointed out.
In the R/I cohort, one patient had osteopenia and gynecomastia. At the time of data analysis, this event had resolved even though the patient continued on dasatinib.
“We believe our data suggests that dasatinib could be considered as a new standard of care for children with CML in chronic phase,” she said.
“It includes the advantage of a liquid formulation as well as the advantages of once daily dosing and administration without regard to fed or fasting state,” she added, “which for all of us who treat children know could be quite important.”
The study was funded by Bristol-Myers Squibb.
E. coli, GBS account for majority of neonatal bacterial meningitis in Canada
No major shifts appear to have occurred in the bacteria that cause meningitis in Canada, said Lynda Ouchenir, MD, University of Montreal, and her associates.
“There is a paucity of information on the characteristics of neonatal meningitis in the era of infant Haemophilus influenzae type B (Hib) and pneumococcal immunization, maternal group B Streptococcus (GBS) prophylaxis, and emerging antimicrobial resistance,” the researchers said. So, they undertook a retrospective study of infants with onset of bacterial meningitis in the first 90 days of life at seven Canadian hospitals to find out the major pathogens involved and best empirical antibiotics to use.
This substitution of a carbapenem for the cephalosporin was considered prudent if the birth hospitalization was complicated and if the cerebrospinal fluid Gram-stain or the blood culture was suggestive of Gram-negative meningitis, Dr. Ouchenir and her associates said.
Read more at (Pediatrics. 2017;140[1)]:e20170476).
No major shifts appear to have occurred in the bacteria that cause meningitis in Canada, said Lynda Ouchenir, MD, University of Montreal, and her associates.
“There is a paucity of information on the characteristics of neonatal meningitis in the era of infant Haemophilus influenzae type B (Hib) and pneumococcal immunization, maternal group B Streptococcus (GBS) prophylaxis, and emerging antimicrobial resistance,” the researchers said. So, they undertook a retrospective study of infants with onset of bacterial meningitis in the first 90 days of life at seven Canadian hospitals to find out the major pathogens involved and best empirical antibiotics to use.
This substitution of a carbapenem for the cephalosporin was considered prudent if the birth hospitalization was complicated and if the cerebrospinal fluid Gram-stain or the blood culture was suggestive of Gram-negative meningitis, Dr. Ouchenir and her associates said.
Read more at (Pediatrics. 2017;140[1)]:e20170476).
No major shifts appear to have occurred in the bacteria that cause meningitis in Canada, said Lynda Ouchenir, MD, University of Montreal, and her associates.
“There is a paucity of information on the characteristics of neonatal meningitis in the era of infant Haemophilus influenzae type B (Hib) and pneumococcal immunization, maternal group B Streptococcus (GBS) prophylaxis, and emerging antimicrobial resistance,” the researchers said. So, they undertook a retrospective study of infants with onset of bacterial meningitis in the first 90 days of life at seven Canadian hospitals to find out the major pathogens involved and best empirical antibiotics to use.
This substitution of a carbapenem for the cephalosporin was considered prudent if the birth hospitalization was complicated and if the cerebrospinal fluid Gram-stain or the blood culture was suggestive of Gram-negative meningitis, Dr. Ouchenir and her associates said.
Read more at (Pediatrics. 2017;140[1)]:e20170476).
FROM PEDIATRICS
Fighting Fatigue in MS
Q) Why do my patients with multiple sclerosis experience so much fatigue, and what can I do to help them?
Fatigue is an extremely common symptom of multiple sclerosis (MS) and one of the most disabling complications of the disease.1 More than 75% of patients with MS experience fatigue, which can worsen motor function, sleep quality, mood, and overall quality of life.1,2 Fatigue can also adversely affect employment; among patients with MS who reduce their work hours from full- to part-time, 90% do so because of fatigue.3
The
Patients with MS may have primary or secondary causes of fatigue. Primary fatigue is believed to result from the disease itself. Although it is not well understood, one hypothesis suggests that it is caused by an immune-related process involving inflammation and immune-mediated neurodegeneration.7 Another theory relates it to impaired nerve conduction.8
Secondary fatigue is unrelated to MS itself, and it is often treatable. Common causes include anemia, infection, or insomnia (see Table 1).9,10 These possibilities should be considered and ruled out in all patients with MS who complain of fatigue. A comprehensive history, exam, and evaluation performed by the clinician may help identify alternative reasons for fatigue.
Once any secondary causes have been addressed, primary fatigue should be evaluated and managed. One method for assessing the severity of fatigue and its impact on functional disability is to discuss it with the patient. The Fatigue Severity Scale can also be used as a measure; this self-assessment is quick, easy, and can be downloaded for free at www.saintalphonsus.org/documents/boise/sleep-Fatigue-Severity-Scale.pdf.11Identifying potential triggers of fatigue can help clinicians develop appropriate interventions. Heat intolerance is common and can precipitate or contribute to fatigue; cooling equipment can be a helpful solution (see Figure). Urinary tract infections frequently cause fatigue and can exacerbate many symptoms of MS. Bladder dysfunction and subsequent nocturnal wakening may contribute to the problem. Psychological stress is another common trigger; managing it can reduce fatigue.1,12 Screening for depression in patients with MS who complain of fatigue is imperative; if diagnosed, it must be addressed as the first line of treatment.1
Other clinician-initiated intervention strategies include exercise, therapy, and medication. Modafinil is frequently prescribed for MS fatigue; small trials have demonstrated dramatic improvements with its use.13 Interestingly, aspirin has been shown to reduce fatigue in randomized controlled trials.14 This may be due to its indirect effects on neuroendocrine and autonomic responses, both of which are involved in the perception of fatigue.14 Additional interventions are listed in Table 2. As always, before prescribing any new medication, ensure that it is appropriate and that the patient’s other medical providers agree to the plan.
Counsel patients by emphasizing the importance of good sleep hygiene, a healthy diet, and avoidance of unhealthy habits. Taking an interdisciplinary approach can help patients with MS receive the best possible health care. While you may not be treating your patient’s disease, you will be managing much of his or her health care; treating the underlying causes of fatigue can significantly improve quality of life. —SA
Stephanie Agrella, MSN, RN, APRN, ANP-BC, MSCN
Director of Clinical Services, Multiple Scerlosis Clinic of Central Texas, Round Rock
1. Krupp B, Serafin D, Christodoulou C. Multiple sclerosis-associated fatigue. Expert Rev Neurother. 2010;10(9):1437-1447.
2. Krupp L. Fatigue is intrinsic to multiple sclerosis (MS) and is the most commonly reported symptom of the disease. Mult Scler. 2006;12(4):367-368.
3. Dennett SL, Castelli-Haley J, Oleen-Burkey MK. The impact of multiple sclerosis on patient employment: a review of the medical literature. J Health Productivity. 2007;2(2):12-18.
4. Fatigue Guidelines Development Panel of the Multiple Sclerosis Council for Clinical Practice Guidelines. Fatigue and Multiple Sclerosis: Evidence-based Management Strategies for Fatigue in Multiple Sclerosis. Washington, DC: Paralyzed Veterans of America; 1998.
5. Kalb R. Multiple Sclerosis: The Questions You Have—The Answers You Need. New York, NY: Demos; 2012.
6. Krupp LB, Alvarez LA, LaRocca NG, Scheinberg LC. Fatigue in multiple sclerosis. Arch Neurol. 1988;45(4):435-437.
7. Patejdl R, Penner IK, Noack TK, Zettl UK. Multiple sclerosis and fatigue: a review on the contribution of inflammation and immune-mediated neurodegeneration. Autoimmun Rev. 2016;15(3):210-220.
8. Davis S, Wilson T, White A, Frohman E. Thermoregulation in multiple sclerosis. J Appl Physiol. 2016;109(5):1531-1537.
9. Ponka D, Kirlew M. Top 10 differential diagnoses in family medicine: fatigue. Can Fam Physician. 2007;53(5):892.
10. Rosenthal TC, Majeroni BA, Pretorius R, Malik K. Fatigue: an overview. Am Fam Physician. 2008;78(10):1173-1179.
11. Saint Alphonsus. Fatigue severity scale. www.saintalphonsus.org/documents/boise/sleep-Fatigue-Severity-Scale.pdf. Accessed May 16, 2017.
12. Motl RW, McAuley E, Snook EM. Physical activity and multiple sclerosis: a meta-analysis. Mult Scler. 2005;11(4):459-463.
13. Lange R, Volkmer M, Heesen C, Liepert J. Modafinil effects in multiple sclerosis patients with fatigue. J Neurol. 2009; 256(4):645-650.
14. Wingerchuk DM, Benarroch EE, O’Brien PC, et al. A randomized controlled crossover trial of aspirin for fatigue in multiple sclerosis. Neurology. 2005;64(7):1267-1269.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Stephanie Agrella, MSN, RN, APRN, ANP-BC, MSCN, Director of Clinical Services at the Multiple Sclerosis Clinic of Central Texas, Round Rock, and Patricia Pagnotta, ARNP, MSN, CNRN, MSCN, who is with Neurology Associates, PA, and the MS Center of Greater Orlando.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Stephanie Agrella, MSN, RN, APRN, ANP-BC, MSCN, Director of Clinical Services at the Multiple Sclerosis Clinic of Central Texas, Round Rock, and Patricia Pagnotta, ARNP, MSN, CNRN, MSCN, who is with Neurology Associates, PA, and the MS Center of Greater Orlando.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month's responses were authored by Stephanie Agrella, MSN, RN, APRN, ANP-BC, MSCN, Director of Clinical Services at the Multiple Sclerosis Clinic of Central Texas, Round Rock, and Patricia Pagnotta, ARNP, MSN, CNRN, MSCN, who is with Neurology Associates, PA, and the MS Center of Greater Orlando.
Q) Why do my patients with multiple sclerosis experience so much fatigue, and what can I do to help them?
Fatigue is an extremely common symptom of multiple sclerosis (MS) and one of the most disabling complications of the disease.1 More than 75% of patients with MS experience fatigue, which can worsen motor function, sleep quality, mood, and overall quality of life.1,2 Fatigue can also adversely affect employment; among patients with MS who reduce their work hours from full- to part-time, 90% do so because of fatigue.3
The
Patients with MS may have primary or secondary causes of fatigue. Primary fatigue is believed to result from the disease itself. Although it is not well understood, one hypothesis suggests that it is caused by an immune-related process involving inflammation and immune-mediated neurodegeneration.7 Another theory relates it to impaired nerve conduction.8
Secondary fatigue is unrelated to MS itself, and it is often treatable. Common causes include anemia, infection, or insomnia (see Table 1).9,10 These possibilities should be considered and ruled out in all patients with MS who complain of fatigue. A comprehensive history, exam, and evaluation performed by the clinician may help identify alternative reasons for fatigue.
Once any secondary causes have been addressed, primary fatigue should be evaluated and managed. One method for assessing the severity of fatigue and its impact on functional disability is to discuss it with the patient. The Fatigue Severity Scale can also be used as a measure; this self-assessment is quick, easy, and can be downloaded for free at www.saintalphonsus.org/documents/boise/sleep-Fatigue-Severity-Scale.pdf.11Identifying potential triggers of fatigue can help clinicians develop appropriate interventions. Heat intolerance is common and can precipitate or contribute to fatigue; cooling equipment can be a helpful solution (see Figure). Urinary tract infections frequently cause fatigue and can exacerbate many symptoms of MS. Bladder dysfunction and subsequent nocturnal wakening may contribute to the problem. Psychological stress is another common trigger; managing it can reduce fatigue.1,12 Screening for depression in patients with MS who complain of fatigue is imperative; if diagnosed, it must be addressed as the first line of treatment.1
Other clinician-initiated intervention strategies include exercise, therapy, and medication. Modafinil is frequently prescribed for MS fatigue; small trials have demonstrated dramatic improvements with its use.13 Interestingly, aspirin has been shown to reduce fatigue in randomized controlled trials.14 This may be due to its indirect effects on neuroendocrine and autonomic responses, both of which are involved in the perception of fatigue.14 Additional interventions are listed in Table 2. As always, before prescribing any new medication, ensure that it is appropriate and that the patient’s other medical providers agree to the plan.
Counsel patients by emphasizing the importance of good sleep hygiene, a healthy diet, and avoidance of unhealthy habits. Taking an interdisciplinary approach can help patients with MS receive the best possible health care. While you may not be treating your patient’s disease, you will be managing much of his or her health care; treating the underlying causes of fatigue can significantly improve quality of life. —SA
Stephanie Agrella, MSN, RN, APRN, ANP-BC, MSCN
Director of Clinical Services, Multiple Scerlosis Clinic of Central Texas, Round Rock
Q) Why do my patients with multiple sclerosis experience so much fatigue, and what can I do to help them?
Fatigue is an extremely common symptom of multiple sclerosis (MS) and one of the most disabling complications of the disease.1 More than 75% of patients with MS experience fatigue, which can worsen motor function, sleep quality, mood, and overall quality of life.1,2 Fatigue can also adversely affect employment; among patients with MS who reduce their work hours from full- to part-time, 90% do so because of fatigue.3
The
Patients with MS may have primary or secondary causes of fatigue. Primary fatigue is believed to result from the disease itself. Although it is not well understood, one hypothesis suggests that it is caused by an immune-related process involving inflammation and immune-mediated neurodegeneration.7 Another theory relates it to impaired nerve conduction.8
Secondary fatigue is unrelated to MS itself, and it is often treatable. Common causes include anemia, infection, or insomnia (see Table 1).9,10 These possibilities should be considered and ruled out in all patients with MS who complain of fatigue. A comprehensive history, exam, and evaluation performed by the clinician may help identify alternative reasons for fatigue.
Once any secondary causes have been addressed, primary fatigue should be evaluated and managed. One method for assessing the severity of fatigue and its impact on functional disability is to discuss it with the patient. The Fatigue Severity Scale can also be used as a measure; this self-assessment is quick, easy, and can be downloaded for free at www.saintalphonsus.org/documents/boise/sleep-Fatigue-Severity-Scale.pdf.11Identifying potential triggers of fatigue can help clinicians develop appropriate interventions. Heat intolerance is common and can precipitate or contribute to fatigue; cooling equipment can be a helpful solution (see Figure). Urinary tract infections frequently cause fatigue and can exacerbate many symptoms of MS. Bladder dysfunction and subsequent nocturnal wakening may contribute to the problem. Psychological stress is another common trigger; managing it can reduce fatigue.1,12 Screening for depression in patients with MS who complain of fatigue is imperative; if diagnosed, it must be addressed as the first line of treatment.1
Other clinician-initiated intervention strategies include exercise, therapy, and medication. Modafinil is frequently prescribed for MS fatigue; small trials have demonstrated dramatic improvements with its use.13 Interestingly, aspirin has been shown to reduce fatigue in randomized controlled trials.14 This may be due to its indirect effects on neuroendocrine and autonomic responses, both of which are involved in the perception of fatigue.14 Additional interventions are listed in Table 2. As always, before prescribing any new medication, ensure that it is appropriate and that the patient’s other medical providers agree to the plan.
Counsel patients by emphasizing the importance of good sleep hygiene, a healthy diet, and avoidance of unhealthy habits. Taking an interdisciplinary approach can help patients with MS receive the best possible health care. While you may not be treating your patient’s disease, you will be managing much of his or her health care; treating the underlying causes of fatigue can significantly improve quality of life. —SA
Stephanie Agrella, MSN, RN, APRN, ANP-BC, MSCN
Director of Clinical Services, Multiple Scerlosis Clinic of Central Texas, Round Rock
1. Krupp B, Serafin D, Christodoulou C. Multiple sclerosis-associated fatigue. Expert Rev Neurother. 2010;10(9):1437-1447.
2. Krupp L. Fatigue is intrinsic to multiple sclerosis (MS) and is the most commonly reported symptom of the disease. Mult Scler. 2006;12(4):367-368.
3. Dennett SL, Castelli-Haley J, Oleen-Burkey MK. The impact of multiple sclerosis on patient employment: a review of the medical literature. J Health Productivity. 2007;2(2):12-18.
4. Fatigue Guidelines Development Panel of the Multiple Sclerosis Council for Clinical Practice Guidelines. Fatigue and Multiple Sclerosis: Evidence-based Management Strategies for Fatigue in Multiple Sclerosis. Washington, DC: Paralyzed Veterans of America; 1998.
5. Kalb R. Multiple Sclerosis: The Questions You Have—The Answers You Need. New York, NY: Demos; 2012.
6. Krupp LB, Alvarez LA, LaRocca NG, Scheinberg LC. Fatigue in multiple sclerosis. Arch Neurol. 1988;45(4):435-437.
7. Patejdl R, Penner IK, Noack TK, Zettl UK. Multiple sclerosis and fatigue: a review on the contribution of inflammation and immune-mediated neurodegeneration. Autoimmun Rev. 2016;15(3):210-220.
8. Davis S, Wilson T, White A, Frohman E. Thermoregulation in multiple sclerosis. J Appl Physiol. 2016;109(5):1531-1537.
9. Ponka D, Kirlew M. Top 10 differential diagnoses in family medicine: fatigue. Can Fam Physician. 2007;53(5):892.
10. Rosenthal TC, Majeroni BA, Pretorius R, Malik K. Fatigue: an overview. Am Fam Physician. 2008;78(10):1173-1179.
11. Saint Alphonsus. Fatigue severity scale. www.saintalphonsus.org/documents/boise/sleep-Fatigue-Severity-Scale.pdf. Accessed May 16, 2017.
12. Motl RW, McAuley E, Snook EM. Physical activity and multiple sclerosis: a meta-analysis. Mult Scler. 2005;11(4):459-463.
13. Lange R, Volkmer M, Heesen C, Liepert J. Modafinil effects in multiple sclerosis patients with fatigue. J Neurol. 2009; 256(4):645-650.
14. Wingerchuk DM, Benarroch EE, O’Brien PC, et al. A randomized controlled crossover trial of aspirin for fatigue in multiple sclerosis. Neurology. 2005;64(7):1267-1269.
1. Krupp B, Serafin D, Christodoulou C. Multiple sclerosis-associated fatigue. Expert Rev Neurother. 2010;10(9):1437-1447.
2. Krupp L. Fatigue is intrinsic to multiple sclerosis (MS) and is the most commonly reported symptom of the disease. Mult Scler. 2006;12(4):367-368.
3. Dennett SL, Castelli-Haley J, Oleen-Burkey MK. The impact of multiple sclerosis on patient employment: a review of the medical literature. J Health Productivity. 2007;2(2):12-18.
4. Fatigue Guidelines Development Panel of the Multiple Sclerosis Council for Clinical Practice Guidelines. Fatigue and Multiple Sclerosis: Evidence-based Management Strategies for Fatigue in Multiple Sclerosis. Washington, DC: Paralyzed Veterans of America; 1998.
5. Kalb R. Multiple Sclerosis: The Questions You Have—The Answers You Need. New York, NY: Demos; 2012.
6. Krupp LB, Alvarez LA, LaRocca NG, Scheinberg LC. Fatigue in multiple sclerosis. Arch Neurol. 1988;45(4):435-437.
7. Patejdl R, Penner IK, Noack TK, Zettl UK. Multiple sclerosis and fatigue: a review on the contribution of inflammation and immune-mediated neurodegeneration. Autoimmun Rev. 2016;15(3):210-220.
8. Davis S, Wilson T, White A, Frohman E. Thermoregulation in multiple sclerosis. J Appl Physiol. 2016;109(5):1531-1537.
9. Ponka D, Kirlew M. Top 10 differential diagnoses in family medicine: fatigue. Can Fam Physician. 2007;53(5):892.
10. Rosenthal TC, Majeroni BA, Pretorius R, Malik K. Fatigue: an overview. Am Fam Physician. 2008;78(10):1173-1179.
11. Saint Alphonsus. Fatigue severity scale. www.saintalphonsus.org/documents/boise/sleep-Fatigue-Severity-Scale.pdf. Accessed May 16, 2017.
12. Motl RW, McAuley E, Snook EM. Physical activity and multiple sclerosis: a meta-analysis. Mult Scler. 2005;11(4):459-463.
13. Lange R, Volkmer M, Heesen C, Liepert J. Modafinil effects in multiple sclerosis patients with fatigue. J Neurol. 2009; 256(4):645-650.
14. Wingerchuk DM, Benarroch EE, O’Brien PC, et al. A randomized controlled crossover trial of aspirin for fatigue in multiple sclerosis. Neurology. 2005;64(7):1267-1269.