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.

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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.

[email protected]

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.

[email protected]

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]

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.”

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.”

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.”

Claudia Stahl is a content manager for the Society of Hospital Medicine.

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.”

[email protected]

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.”

[email protected]

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.”

[email protected]

Image by Difu Wu

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.

ENESTfreedom

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.

ENESTop

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.

Image by Difu Wu

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.

ENESTfreedom

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.

ENESTop

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.

Image by Difu Wu

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.

ENESTfreedom

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.

ENESTop

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.

Photo by Bill Branson

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.

Photo by Bill Branson

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.

Photo by Bill Branson

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.

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.

© Janice Haney Carr/CDC

[email protected]

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.

© Janice Haney Carr/CDC

[email protected]

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.

© Janice Haney Carr/CDC

[email protected]

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 Multiple Sclerosis Clinical Council Guidelines define MS-related fatigue as a “significant lack of physical and/or mental energy that is perceived by the individual or caretaker to interfere with usual or desired activity.”⁴ Described as “overwhelming,” this type of fatigue is generally unrelated to activity level.⁵ It differs from fatigue experienced by patients without MS in that it generally comes on suddenly, impairs functioning, and prevents patients from attending to responsibilities.^1,5,6

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 Multiple Sclerosis Clinical Council Guidelines define MS-related fatigue as a “significant lack of physical and/or mental energy that is perceived by the individual or caretaker to interfere with usual or desired activity.”⁴ Described as “overwhelming,” this type of fatigue is generally unrelated to activity level.⁵ It differs from fatigue experienced by patients without MS in that it generally comes on suddenly, impairs functioning, and prevents patients from attending to responsibilities.^1,5,6

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 Multiple Sclerosis Clinical Council Guidelines define MS-related fatigue as a “significant lack of physical and/or mental energy that is perceived by the individual or caretaker to interfere with usual or desired activity.”⁴ Described as “overwhelming,” this type of fatigue is generally unrelated to activity level.⁵ It differs from fatigue experienced by patients without MS in that it generally comes on suddenly, impairs functioning, and prevents patients from attending to responsibilities.^1,5,6

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

CHICAGO – The oral PARP inhibitor olaparib likely offers a new treatment option for patients with BRCA-related HER2-negative metastatic breast cancer, according to results of the randomized phase III OlympiAD trial reported at the annual meeting of the American Society of Clinical Oncology.

Inhibitors of PARP, or poly(ADP-ribose) polymerase, exploit defective DNA repair due to BRCA mutations, lead author Mark E. Robson, MD, clinic director of the clinical genetics service and medical oncologist at Memorial Sloan Kettering Cancer Center in New York, noted in a press briefing.

“PARP inhibitors have already been approved for the treatment of ovarian cancer in patients with mutations of BRCA1 or BRCA2, and recently in other circumstances. And there have been a couple of small studies that have suggested that breast cancer in BRCA mutation carriers could also be responsive to PARP inhibitors,” he said.

Findings going forward

Although the trial was positive, the absolute difference in progression-free survival was just 2.8 months, and the curves converged over time, raising questions about potentially more efficacious PARP inhibitors or strategies for getting greater benefit out of olaparib.

“There are three PARP inhibitors in the developmental stage in breast cancer, and there are noncomparative trials and no really good ways to make a decision about which one is better,” Dr. Robson commented.

Several strategies are being explored for enhancing the benefit of these drugs, he continued. “One is combining it with a conventional chemotherapy agent, which is hard to do because of overlapping bone marrow toxicity, so it’s tough to get full doses of chemotherapy and full doses of PARP inhibitor in. Another is to combine it with other targeted agents that interact with components of the DNA damage repair pathway … and there are certainly combination therapy trials that are underway. And then third is … a combination of olaparib with an immuno-oncology agent.”

Additionally, some studies are evaluating expansion of PARP inhibitors to populations such as patients with triple-negative breast cancer who do not have an identifiable BRCA mutation, on the assumption that they have similar, somatic DNA defects that might be susceptible to this class of agents, according to Dr. Robson.

“The studies have been small and at least the initial ones have not been particularly encouraging,” he said. “But as mentioned, combination approaches now are being evaluated as a way to potentially ‘soup up’ the effect in a broader group of patients.”

Expert perspective

The OlympiAD trial represents a “major step forward in breast cancer” in terms of both translational medicine and precision medicine, according to ASCO President Daniel F. Hayes, MD, FACP, FASCO.

Study details

OlympiAD, which was funded by AstraZeneca, enrolled patients with HER2-negative metastatic breast cancer and a centrally confirmed germline (inherited) BRCA mutation who had received anthracyclines and taxanes, and up to two lines of chemotherapy for metastases.

They were randomized 2:1 to open-label treatment with either olaparib (300 mg., twice daily) or single-agent chemotherapy of the treating physician’s choice among three options (capecitabine, eribulin, or vinorelbine). A tablet formulation and dose of olaparib were used that differ from the currently approved capsule formulation and dose to reduce pill burden, Dr. Robson noted.

The patients were about equally split between BRCA1 and BRCA2 mutations, and between hormone receptor–positive disease and triple-negative disease, he reported. The majority (71%) had received chemotherapy for metastases, and a sizable minority (28%) had received prior platinum in the (neo)adjuvant or metastatic setting.

With a median follow-up of about 14.5 months, median progression-free survival assessed by central radiologic review was 7.0 months with olaparib and 4.2 months with chemotherapy (hazard ratio, 0.58; P = .0009).

The median time to investigator-reported second progression or death was also longer with olaparib (13.2 vs. 9.3 months; HR, 0.57; P = .0033).

Median overall survival was about 19-20 months in each group and not significantly different in an interim analysis.

The olaparib group had lower rates of grade 3 or worse adverse events (36.6% vs. 50.5%) and treatment discontinuation because of adverse events (4.9% vs. 7.7%).

The main adverse event of any grade with olaparib was nausea, which was usually mild; only about a quarter of affected patients required antiemetics, according to Dr. Robson. Patients also commonly experienced anemia, requiring transfusion in some cases, and fatigue.

Dr. Robson disclosed that he has a consulting or advisory role with McKesson and AstraZeneca; receives honoraria, travel, accommodations, and/or expenses from AstraZeneca; rand receives research funding (institutional) from AstraZeneca, Abbvie, Myriad Genetics, Biomarin, Medivation, and Tesaro.
 

CHICAGO – The oral PARP inhibitor olaparib likely offers a new treatment option for patients with BRCA-related HER2-negative metastatic breast cancer, according to results of the randomized phase III OlympiAD trial reported at the annual meeting of the American Society of Clinical Oncology.

Inhibitors of PARP, or poly(ADP-ribose) polymerase, exploit defective DNA repair due to BRCA mutations, lead author Mark E. Robson, MD, clinic director of the clinical genetics service and medical oncologist at Memorial Sloan Kettering Cancer Center in New York, noted in a press briefing.

“PARP inhibitors have already been approved for the treatment of ovarian cancer in patients with mutations of BRCA1 or BRCA2, and recently in other circumstances. And there have been a couple of small studies that have suggested that breast cancer in BRCA mutation carriers could also be responsive to PARP inhibitors,” he said.

Findings going forward

Although the trial was positive, the absolute difference in progression-free survival was just 2.8 months, and the curves converged over time, raising questions about potentially more efficacious PARP inhibitors or strategies for getting greater benefit out of olaparib.

“There are three PARP inhibitors in the developmental stage in breast cancer, and there are noncomparative trials and no really good ways to make a decision about which one is better,” Dr. Robson commented.

Several strategies are being explored for enhancing the benefit of these drugs, he continued. “One is combining it with a conventional chemotherapy agent, which is hard to do because of overlapping bone marrow toxicity, so it’s tough to get full doses of chemotherapy and full doses of PARP inhibitor in. Another is to combine it with other targeted agents that interact with components of the DNA damage repair pathway … and there are certainly combination therapy trials that are underway. And then third is … a combination of olaparib with an immuno-oncology agent.”

Additionally, some studies are evaluating expansion of PARP inhibitors to populations such as patients with triple-negative breast cancer who do not have an identifiable BRCA mutation, on the assumption that they have similar, somatic DNA defects that might be susceptible to this class of agents, according to Dr. Robson.

“The studies have been small and at least the initial ones have not been particularly encouraging,” he said. “But as mentioned, combination approaches now are being evaluated as a way to potentially ‘soup up’ the effect in a broader group of patients.”

Expert perspective

The OlympiAD trial represents a “major step forward in breast cancer” in terms of both translational medicine and precision medicine, according to ASCO President Daniel F. Hayes, MD, FACP, FASCO.

Study details

OlympiAD, which was funded by AstraZeneca, enrolled patients with HER2-negative metastatic breast cancer and a centrally confirmed germline (inherited) BRCA mutation who had received anthracyclines and taxanes, and up to two lines of chemotherapy for metastases.

They were randomized 2:1 to open-label treatment with either olaparib (300 mg., twice daily) or single-agent chemotherapy of the treating physician’s choice among three options (capecitabine, eribulin, or vinorelbine). A tablet formulation and dose of olaparib were used that differ from the currently approved capsule formulation and dose to reduce pill burden, Dr. Robson noted.

The patients were about equally split between BRCA1 and BRCA2 mutations, and between hormone receptor–positive disease and triple-negative disease, he reported. The majority (71%) had received chemotherapy for metastases, and a sizable minority (28%) had received prior platinum in the (neo)adjuvant or metastatic setting.

With a median follow-up of about 14.5 months, median progression-free survival assessed by central radiologic review was 7.0 months with olaparib and 4.2 months with chemotherapy (hazard ratio, 0.58; P = .0009).

The median time to investigator-reported second progression or death was also longer with olaparib (13.2 vs. 9.3 months; HR, 0.57; P = .0033).

Median overall survival was about 19-20 months in each group and not significantly different in an interim analysis.

The olaparib group had lower rates of grade 3 or worse adverse events (36.6% vs. 50.5%) and treatment discontinuation because of adverse events (4.9% vs. 7.7%).

The main adverse event of any grade with olaparib was nausea, which was usually mild; only about a quarter of affected patients required antiemetics, according to Dr. Robson. Patients also commonly experienced anemia, requiring transfusion in some cases, and fatigue.

Dr. Robson disclosed that he has a consulting or advisory role with McKesson and AstraZeneca; receives honoraria, travel, accommodations, and/or expenses from AstraZeneca; rand receives research funding (institutional) from AstraZeneca, Abbvie, Myriad Genetics, Biomarin, Medivation, and Tesaro.
 

CHICAGO – The oral PARP inhibitor olaparib likely offers a new treatment option for patients with BRCA-related HER2-negative metastatic breast cancer, according to results of the randomized phase III OlympiAD trial reported at the annual meeting of the American Society of Clinical Oncology.

Inhibitors of PARP, or poly(ADP-ribose) polymerase, exploit defective DNA repair due to BRCA mutations, lead author Mark E. Robson, MD, clinic director of the clinical genetics service and medical oncologist at Memorial Sloan Kettering Cancer Center in New York, noted in a press briefing.

“PARP inhibitors have already been approved for the treatment of ovarian cancer in patients with mutations of BRCA1 or BRCA2, and recently in other circumstances. And there have been a couple of small studies that have suggested that breast cancer in BRCA mutation carriers could also be responsive to PARP inhibitors,” he said.

Findings going forward

Although the trial was positive, the absolute difference in progression-free survival was just 2.8 months, and the curves converged over time, raising questions about potentially more efficacious PARP inhibitors or strategies for getting greater benefit out of olaparib.

“There are three PARP inhibitors in the developmental stage in breast cancer, and there are noncomparative trials and no really good ways to make a decision about which one is better,” Dr. Robson commented.

Several strategies are being explored for enhancing the benefit of these drugs, he continued. “One is combining it with a conventional chemotherapy agent, which is hard to do because of overlapping bone marrow toxicity, so it’s tough to get full doses of chemotherapy and full doses of PARP inhibitor in. Another is to combine it with other targeted agents that interact with components of the DNA damage repair pathway … and there are certainly combination therapy trials that are underway. And then third is … a combination of olaparib with an immuno-oncology agent.”

Additionally, some studies are evaluating expansion of PARP inhibitors to populations such as patients with triple-negative breast cancer who do not have an identifiable BRCA mutation, on the assumption that they have similar, somatic DNA defects that might be susceptible to this class of agents, according to Dr. Robson.

“The studies have been small and at least the initial ones have not been particularly encouraging,” he said. “But as mentioned, combination approaches now are being evaluated as a way to potentially ‘soup up’ the effect in a broader group of patients.”

Expert perspective

The OlympiAD trial represents a “major step forward in breast cancer” in terms of both translational medicine and precision medicine, according to ASCO President Daniel F. Hayes, MD, FACP, FASCO.

Study details

OlympiAD, which was funded by AstraZeneca, enrolled patients with HER2-negative metastatic breast cancer and a centrally confirmed germline (inherited) BRCA mutation who had received anthracyclines and taxanes, and up to two lines of chemotherapy for metastases.

They were randomized 2:1 to open-label treatment with either olaparib (300 mg., twice daily) or single-agent chemotherapy of the treating physician’s choice among three options (capecitabine, eribulin, or vinorelbine). A tablet formulation and dose of olaparib were used that differ from the currently approved capsule formulation and dose to reduce pill burden, Dr. Robson noted.

The patients were about equally split between BRCA1 and BRCA2 mutations, and between hormone receptor–positive disease and triple-negative disease, he reported. The majority (71%) had received chemotherapy for metastases, and a sizable minority (28%) had received prior platinum in the (neo)adjuvant or metastatic setting.

With a median follow-up of about 14.5 months, median progression-free survival assessed by central radiologic review was 7.0 months with olaparib and 4.2 months with chemotherapy (hazard ratio, 0.58; P = .0009).

The median time to investigator-reported second progression or death was also longer with olaparib (13.2 vs. 9.3 months; HR, 0.57; P = .0033).

Median overall survival was about 19-20 months in each group and not significantly different in an interim analysis.

The olaparib group had lower rates of grade 3 or worse adverse events (36.6% vs. 50.5%) and treatment discontinuation because of adverse events (4.9% vs. 7.7%).

The main adverse event of any grade with olaparib was nausea, which was usually mild; only about a quarter of affected patients required antiemetics, according to Dr. Robson. Patients also commonly experienced anemia, requiring transfusion in some cases, and fatigue.

Dr. Robson disclosed that he has a consulting or advisory role with McKesson and AstraZeneca; receives honoraria, travel, accommodations, and/or expenses from AstraZeneca; rand receives research funding (institutional) from AstraZeneca, Abbvie, Myriad Genetics, Biomarin, Medivation, and Tesaro.
 

Novel treatments involving the interleukin-17, IL-23, and Janus kinase (JAK) pathways and the growing importance of early diagnosis and treatment will be some of the key themes covered in the scientific program at this year’s EULAR congress in Madrid, June 14-17.

The annual EULAR congress’ traditional spirit of giving congress attendees a thorough scientific update of the evidence published in peer-reviewed journals across the broad spectrum of rheumatic diseases is reflected in the wide range of state-of-the-art lectures, clinical and basic science symposia, practical workshops, and special interest sessions running throughout the packed 4-day congress, said João Eurico Cabral da Fonseca, MD, PhD, chair of the Scientific Programme Committee.

Novel treatments involving the interleukin-17, IL-23, and Janus kinase (JAK) pathways and the growing importance of early diagnosis and treatment will be some of the key themes covered in the scientific program at this year’s EULAR congress in Madrid, June 14-17.

The annual EULAR congress’ traditional spirit of giving congress attendees a thorough scientific update of the evidence published in peer-reviewed journals across the broad spectrum of rheumatic diseases is reflected in the wide range of state-of-the-art lectures, clinical and basic science symposia, practical workshops, and special interest sessions running throughout the packed 4-day congress, said João Eurico Cabral da Fonseca, MD, PhD, chair of the Scientific Programme Committee.

Novel treatments involving the interleukin-17, IL-23, and Janus kinase (JAK) pathways and the growing importance of early diagnosis and treatment will be some of the key themes covered in the scientific program at this year’s EULAR congress in Madrid, June 14-17.

The annual EULAR congress’ traditional spirit of giving congress attendees a thorough scientific update of the evidence published in peer-reviewed journals across the broad spectrum of rheumatic diseases is reflected in the wide range of state-of-the-art lectures, clinical and basic science symposia, practical workshops, and special interest sessions running throughout the packed 4-day congress, said João Eurico Cabral da Fonseca, MD, PhD, chair of the Scientific Programme Committee.