The 2015-2016 flu season was less severe than the last three seasons, with a lower hospitalization rate and fewer pediatric deaths.

Cases of influenza appeared later in the season than typically seen, and activity didn’t peak until March, Stacy L. Davlin, Ph.D., wrote in the June 10 issue of the Morbidity and Mortality Weekly Report (MMWR 2016;22:567-75)

“During the most recent 18 influenza seasons, only two other seasons have peaked in March (2011-2012 and 2005-2006),” wrote Dr. Davlin, an epidemiologist at the Centers for Disease Control and Prevention, Atlanta. This serves as a reminder that influenza can and does occur outside the traditionally expected season, and that clinicians shouldn’t discount the possibility of flu when a patient presents with typical symptoms.

Cynthia Goldsmith/CDC photo #10073

“Although summer influenza activity in the United States typically is low, influenza cases and outbreaks have occurred during summer months, and clinicians should remain vigilant in considering influenza in the differential diagnosis of summer respiratory illnesses,” Dr. Davlin said.

The most common influenza virus of the last season was A(H1N1), which accounted for about half of cases in those aged 5-24 years, and about 70% of cases in those younger than 5 years and those 65 years and older.

Three novel viruses were seen as well: variants of A(H1N1), A(H1N2), and A(H3N2). The A(H1N1) variant occurred in a Minnesota resident who lived and worked in an area of swine farming, but who denied direct contact with pigs. The A(H3N2) variant occurred in a New Jersey resident who reported visiting a farm shortly before symptom onset. There was no evidence of human-to-human transmission. Both recovered fully without hospitalization. The A(H1N2) variant occurred in a Minnesota resident who was hospitalized but who recovered. This person was not interviewed so no possible source of infection was identified.

The CDC tested 2,408 viral specimens for susceptibility to antiviral medications. Among the 2,193 A(H1N1) specimens, less than 1% were resistant to oseltamivir and peramivir. All were susceptible to zanamivir. However, the testing found persistent high levels of resistance to amantadine and rimantadine in the A viruses. Amantadine is not effective on the B strains at all. Therefore, CDC does not recommend the use of amantadine as an anti-influenza medication.

Reports of influenza first exceeded the 2.1% baseline level in the week ending Dec. 26, 2015, according to the U.S. Outpatient Influenza-Like Illness Surveillance Network (ILINet). They remained elevated for the next 17 weeks, with a peak of 3.6% of all outpatient visits in the week ending March 12. From October 2015-April 2016, the overall hospitalization rate for influenza-like illness was 31 per 100,000. This was highest in those aged 65 years and older (85/100,000), and lowest in those aged 5-17 years (10/100,000). About 92% of adults hospitalized for flu-like illness had at least one underlying medical comorbidity, including obesity (42%), cardiovascular disease (40%), and metabolic disorders (38%). Almost half of children (48%) also had medical comorbidities, including asthma or other reactive airway disease (22%) and neurologic disorders (18%).

CDC’s National Center for Health Statistics Mortality Surveillance System found that the percentage of deaths attributed to pneumonia and influenza peaked at 8% during the week ending March 19. This is slightly lower than the death rate seen in the last 5 years, which ranged from 9% in 2011-2012 to 11% in 2012-2013.

Of this season’s deaths, 74 occurred in children. The mean and median ages of these patients were 7 years and 6 years, respectively; the range was 2 months-16 years. This total was lower than that recorded in any of the past three influenza seasons: 171 pediatric deaths in 2012-2013, 111 in 2013-2014, and 148 in 2014-2015.

Dr. Davlin also announced the Food and Drug Administration’s recommendations for composition of the 2016-2017 influenza vaccine.

Trivalent vaccines should contain an A/California/7/2009 (H1N1) pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage). Quadrivalent vaccines, which have two influenza B viruses, should include the viruses recommended for the trivalent vaccines, as well as a B/Phuket/3073/2013-like virus (B/Yamagata lineage).

“The vaccine viruses recommended for inclusion in the 2016-2017 Northern Hemisphere influenza vaccines are the same vaccine viruses that were chosen for inclusion in 2016 Southern Hemisphere seasonal influenza vaccines,” Dr. Davlin noted. “These vaccine recommendations were based on a number of factors, including global influenza virologic and epidemiologic surveillance, genetic and antigenic characterization, antiviral susceptibility, and the availability of candidate vaccine viruses for production.”

As a CDC employee, Dr. Davlin had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

The 2015-2016 flu season was less severe than the last three seasons, with a lower hospitalization rate and fewer pediatric deaths.

Cases of influenza appeared later in the season than typically seen, and activity didn’t peak until March, Stacy L. Davlin, Ph.D., wrote in the June 10 issue of the Morbidity and Mortality Weekly Report (MMWR 2016;22:567-75)

“During the most recent 18 influenza seasons, only two other seasons have peaked in March (2011-2012 and 2005-2006),” wrote Dr. Davlin, an epidemiologist at the Centers for Disease Control and Prevention, Atlanta. This serves as a reminder that influenza can and does occur outside the traditionally expected season, and that clinicians shouldn’t discount the possibility of flu when a patient presents with typical symptoms.

Cynthia Goldsmith/CDC photo #10073

“Although summer influenza activity in the United States typically is low, influenza cases and outbreaks have occurred during summer months, and clinicians should remain vigilant in considering influenza in the differential diagnosis of summer respiratory illnesses,” Dr. Davlin said.

The most common influenza virus of the last season was A(H1N1), which accounted for about half of cases in those aged 5-24 years, and about 70% of cases in those younger than 5 years and those 65 years and older.

Three novel viruses were seen as well: variants of A(H1N1), A(H1N2), and A(H3N2). The A(H1N1) variant occurred in a Minnesota resident who lived and worked in an area of swine farming, but who denied direct contact with pigs. The A(H3N2) variant occurred in a New Jersey resident who reported visiting a farm shortly before symptom onset. There was no evidence of human-to-human transmission. Both recovered fully without hospitalization. The A(H1N2) variant occurred in a Minnesota resident who was hospitalized but who recovered. This person was not interviewed so no possible source of infection was identified.

The CDC tested 2,408 viral specimens for susceptibility to antiviral medications. Among the 2,193 A(H1N1) specimens, less than 1% were resistant to oseltamivir and peramivir. All were susceptible to zanamivir. However, the testing found persistent high levels of resistance to amantadine and rimantadine in the A viruses. Amantadine is not effective on the B strains at all. Therefore, CDC does not recommend the use of amantadine as an anti-influenza medication.

Reports of influenza first exceeded the 2.1% baseline level in the week ending Dec. 26, 2015, according to the U.S. Outpatient Influenza-Like Illness Surveillance Network (ILINet). They remained elevated for the next 17 weeks, with a peak of 3.6% of all outpatient visits in the week ending March 12. From October 2015-April 2016, the overall hospitalization rate for influenza-like illness was 31 per 100,000. This was highest in those aged 65 years and older (85/100,000), and lowest in those aged 5-17 years (10/100,000). About 92% of adults hospitalized for flu-like illness had at least one underlying medical comorbidity, including obesity (42%), cardiovascular disease (40%), and metabolic disorders (38%). Almost half of children (48%) also had medical comorbidities, including asthma or other reactive airway disease (22%) and neurologic disorders (18%).

CDC’s National Center for Health Statistics Mortality Surveillance System found that the percentage of deaths attributed to pneumonia and influenza peaked at 8% during the week ending March 19. This is slightly lower than the death rate seen in the last 5 years, which ranged from 9% in 2011-2012 to 11% in 2012-2013.

Of this season’s deaths, 74 occurred in children. The mean and median ages of these patients were 7 years and 6 years, respectively; the range was 2 months-16 years. This total was lower than that recorded in any of the past three influenza seasons: 171 pediatric deaths in 2012-2013, 111 in 2013-2014, and 148 in 2014-2015.

Dr. Davlin also announced the Food and Drug Administration’s recommendations for composition of the 2016-2017 influenza vaccine.

Trivalent vaccines should contain an A/California/7/2009 (H1N1) pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage). Quadrivalent vaccines, which have two influenza B viruses, should include the viruses recommended for the trivalent vaccines, as well as a B/Phuket/3073/2013-like virus (B/Yamagata lineage).

“The vaccine viruses recommended for inclusion in the 2016-2017 Northern Hemisphere influenza vaccines are the same vaccine viruses that were chosen for inclusion in 2016 Southern Hemisphere seasonal influenza vaccines,” Dr. Davlin noted. “These vaccine recommendations were based on a number of factors, including global influenza virologic and epidemiologic surveillance, genetic and antigenic characterization, antiviral susceptibility, and the availability of candidate vaccine viruses for production.”

As a CDC employee, Dr. Davlin had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

The 2015-2016 flu season was less severe than the last three seasons, with a lower hospitalization rate and fewer pediatric deaths.

Cases of influenza appeared later in the season than typically seen, and activity didn’t peak until March, Stacy L. Davlin, Ph.D., wrote in the June 10 issue of the Morbidity and Mortality Weekly Report (MMWR 2016;22:567-75)

“During the most recent 18 influenza seasons, only two other seasons have peaked in March (2011-2012 and 2005-2006),” wrote Dr. Davlin, an epidemiologist at the Centers for Disease Control and Prevention, Atlanta. This serves as a reminder that influenza can and does occur outside the traditionally expected season, and that clinicians shouldn’t discount the possibility of flu when a patient presents with typical symptoms.

Cynthia Goldsmith/CDC photo #10073

“Although summer influenza activity in the United States typically is low, influenza cases and outbreaks have occurred during summer months, and clinicians should remain vigilant in considering influenza in the differential diagnosis of summer respiratory illnesses,” Dr. Davlin said.

The most common influenza virus of the last season was A(H1N1), which accounted for about half of cases in those aged 5-24 years, and about 70% of cases in those younger than 5 years and those 65 years and older.

Three novel viruses were seen as well: variants of A(H1N1), A(H1N2), and A(H3N2). The A(H1N1) variant occurred in a Minnesota resident who lived and worked in an area of swine farming, but who denied direct contact with pigs. The A(H3N2) variant occurred in a New Jersey resident who reported visiting a farm shortly before symptom onset. There was no evidence of human-to-human transmission. Both recovered fully without hospitalization. The A(H1N2) variant occurred in a Minnesota resident who was hospitalized but who recovered. This person was not interviewed so no possible source of infection was identified.

The CDC tested 2,408 viral specimens for susceptibility to antiviral medications. Among the 2,193 A(H1N1) specimens, less than 1% were resistant to oseltamivir and peramivir. All were susceptible to zanamivir. However, the testing found persistent high levels of resistance to amantadine and rimantadine in the A viruses. Amantadine is not effective on the B strains at all. Therefore, CDC does not recommend the use of amantadine as an anti-influenza medication.

Reports of influenza first exceeded the 2.1% baseline level in the week ending Dec. 26, 2015, according to the U.S. Outpatient Influenza-Like Illness Surveillance Network (ILINet). They remained elevated for the next 17 weeks, with a peak of 3.6% of all outpatient visits in the week ending March 12. From October 2015-April 2016, the overall hospitalization rate for influenza-like illness was 31 per 100,000. This was highest in those aged 65 years and older (85/100,000), and lowest in those aged 5-17 years (10/100,000). About 92% of adults hospitalized for flu-like illness had at least one underlying medical comorbidity, including obesity (42%), cardiovascular disease (40%), and metabolic disorders (38%). Almost half of children (48%) also had medical comorbidities, including asthma or other reactive airway disease (22%) and neurologic disorders (18%).

CDC’s National Center for Health Statistics Mortality Surveillance System found that the percentage of deaths attributed to pneumonia and influenza peaked at 8% during the week ending March 19. This is slightly lower than the death rate seen in the last 5 years, which ranged from 9% in 2011-2012 to 11% in 2012-2013.

Of this season’s deaths, 74 occurred in children. The mean and median ages of these patients were 7 years and 6 years, respectively; the range was 2 months-16 years. This total was lower than that recorded in any of the past three influenza seasons: 171 pediatric deaths in 2012-2013, 111 in 2013-2014, and 148 in 2014-2015.

Dr. Davlin also announced the Food and Drug Administration’s recommendations for composition of the 2016-2017 influenza vaccine.

Trivalent vaccines should contain an A/California/7/2009 (H1N1) pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage). Quadrivalent vaccines, which have two influenza B viruses, should include the viruses recommended for the trivalent vaccines, as well as a B/Phuket/3073/2013-like virus (B/Yamagata lineage).

“The vaccine viruses recommended for inclusion in the 2016-2017 Northern Hemisphere influenza vaccines are the same vaccine viruses that were chosen for inclusion in 2016 Southern Hemisphere seasonal influenza vaccines,” Dr. Davlin noted. “These vaccine recommendations were based on a number of factors, including global influenza virologic and epidemiologic surveillance, genetic and antigenic characterization, antiviral susceptibility, and the availability of candidate vaccine viruses for production.”

As a CDC employee, Dr. Davlin had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

The 2015-2016 flu season was less severe than the last three seasons, with a lower hospitalization rate and fewer pediatric deaths.

Cases of influenza appeared later in the season that typically seen, and activity didn’t peak until March, Stacy L. Davlin, Ph.D., wrote in the June 10 issue of the Morbidity and Mortality report (MMWR 2016; 22:567-75)

“During the most recent 18 influenza seasons, only two other seasons have peaked in March (2011-2012 and 2005-2006),” wrote Dr. Davlin, an epidemiologist at the Centers for Disease Control and Prevention, Atlanta. This serves as a reminder that influenza can and does occur outside the traditionally expected season, and that clinicians shouldn’t discount the possibility of flu when a patient presents with typical symptoms.

Cynthia Goldsmith/CDC photo #10073

“Although summer influenza activity in the United States typically is low, influenza cases and outbreaks have occurred during summer months, and clinicians should remain vigilant in considering influenza in the differential diagnosis of summer respiratory illnesses,” Dr. Davlin said.

The most common influenza virus of the last season was A(H1N1), which accounted for about half of cases in those aged 5-24 years, and about 70% of cases in those younger than 5 years and those 65 years and older.

Three novel viruses were seen as well: variants of A(H1N1), A(H1N2), and A(H3N2). The A(H1N1) variant occurred in a Minnesota resident who lived and worked in an area of swine farming, but who denied direct contact with pigs. The A(H3N2) variant occurred in a New Jersey resident who reported visiting a farm shortly before symptom onset. There was no evidence of human-to-human transmission. Both recovered fully without hospitalization. The A(H1N2) variant occurred in a Minnesota resident who was hospitalized but who recovered. This person was not interviewed so no possible source of infection was identified.

The CDC tested 2,408 viral specimens for susceptibility to antiviral medications. Among the 2,193 A(H1N1) specimens, less than 1% were resistant to oseltamivir and peramivir. All were susceptible to zanamivir. However, the testing found persistent high levels of resistant to amantadine and rimantadine in the A viruses. Amantadine is not effective on the B strains at all. Therefore, CDC does not recommend the use of amantadine as an anti-influenza medication.

Reports of influenza first exceeded the 2.1% baseline level in the week ending Dec. 26, 2015, according to the U.S. Outpatient Influenza-Like Illness Surveillance Network (ILINet). They remained elevated for the next 17 weeks, with a peak of 3.6% of all outpatient visits in the week ending March 12. From October 2015-April 2016, the overall hospitalization rate for influenza-like illness was 31 per 100,000. This was highest in those aged 65 years and older (85/100,000), and lowest in those aged 5-17 years (10/100,000). About 92% of adults hospitalized for flu-like illness had at least one underlying medical comorbidity, including obesity (42%), cardiovascular disease (40%), and metabolic disorders (38%). Almost half of children (48%) also had medical comorbidities, including asthma or other reactive airway disease (22%) and neurologic disorders (18%).

CDC’s National Center for Health Statistics Mortality Surveillance System found that the percentage of deaths attributed to pneumonia and influenza peaked at 8% during the week ending March 19. This is slightly lower than the death rate seen in the last 5 years, which ranged from 9% in 2011-2012 to 11% in 2012-2013.

Of this season’s deaths, 74 occurred in children. The mean and median ages of these patients were 7 years and 6 years, respectively; the range was 2 months-16 years. This total was lower than that recorded in any of the past three influenza seasons: 171 pediatric deaths in 2012-2013, 111 in 2013-2014, and 148 in 2014-2015.

Dr. Davlin also announced the Food and Drug Administration’s recommendations for composition of the 2016-2017 influenza vaccine.

Trivalent vaccines should contain an A/California/7/2009 (H1N1) pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage). Quadrivalent vaccines, which have two influenza B viruses, should include the viruses recommended for the trivalent vaccines, as well as a B/Phuket/3073/2013-like virus (B/Yamagata lineage).

“The vaccine viruses recommended for inclusion in the 2016-2017 Northern Hemisphere influenza vaccines are the same vaccine viruses that were chosen for inclusion in 2016 Southern Hemisphere seasonal influenza vaccines,” Dr. Davlin noted. “These vaccine recommendations were based on a number of factors, including global influenza virologic and epidemiologic surveillance, genetic and antigenic characterization, antiviral susceptibility, and the availability of candidate vaccine viruses for production.”

As a CDC employee, Dr. Davlin had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

The 2015-2016 flu season was less severe than the last three seasons, with a lower hospitalization rate and fewer pediatric deaths.

Cases of influenza appeared later in the season that typically seen, and activity didn’t peak until March, Stacy L. Davlin, Ph.D., wrote in the June 10 issue of the Morbidity and Mortality report (MMWR 2016; 22:567-75)

“During the most recent 18 influenza seasons, only two other seasons have peaked in March (2011-2012 and 2005-2006),” wrote Dr. Davlin, an epidemiologist at the Centers for Disease Control and Prevention, Atlanta. This serves as a reminder that influenza can and does occur outside the traditionally expected season, and that clinicians shouldn’t discount the possibility of flu when a patient presents with typical symptoms.

Cynthia Goldsmith/CDC photo #10073

“Although summer influenza activity in the United States typically is low, influenza cases and outbreaks have occurred during summer months, and clinicians should remain vigilant in considering influenza in the differential diagnosis of summer respiratory illnesses,” Dr. Davlin said.

The most common influenza virus of the last season was A(H1N1), which accounted for about half of cases in those aged 5-24 years, and about 70% of cases in those younger than 5 years and those 65 years and older.

Three novel viruses were seen as well: variants of A(H1N1), A(H1N2), and A(H3N2). The A(H1N1) variant occurred in a Minnesota resident who lived and worked in an area of swine farming, but who denied direct contact with pigs. The A(H3N2) variant occurred in a New Jersey resident who reported visiting a farm shortly before symptom onset. There was no evidence of human-to-human transmission. Both recovered fully without hospitalization. The A(H1N2) variant occurred in a Minnesota resident who was hospitalized but who recovered. This person was not interviewed so no possible source of infection was identified.

The CDC tested 2,408 viral specimens for susceptibility to antiviral medications. Among the 2,193 A(H1N1) specimens, less than 1% were resistant to oseltamivir and peramivir. All were susceptible to zanamivir. However, the testing found persistent high levels of resistant to amantadine and rimantadine in the A viruses. Amantadine is not effective on the B strains at all. Therefore, CDC does not recommend the use of amantadine as an anti-influenza medication.

Reports of influenza first exceeded the 2.1% baseline level in the week ending Dec. 26, 2015, according to the U.S. Outpatient Influenza-Like Illness Surveillance Network (ILINet). They remained elevated for the next 17 weeks, with a peak of 3.6% of all outpatient visits in the week ending March 12. From October 2015-April 2016, the overall hospitalization rate for influenza-like illness was 31 per 100,000. This was highest in those aged 65 years and older (85/100,000), and lowest in those aged 5-17 years (10/100,000). About 92% of adults hospitalized for flu-like illness had at least one underlying medical comorbidity, including obesity (42%), cardiovascular disease (40%), and metabolic disorders (38%). Almost half of children (48%) also had medical comorbidities, including asthma or other reactive airway disease (22%) and neurologic disorders (18%).

CDC’s National Center for Health Statistics Mortality Surveillance System found that the percentage of deaths attributed to pneumonia and influenza peaked at 8% during the week ending March 19. This is slightly lower than the death rate seen in the last 5 years, which ranged from 9% in 2011-2012 to 11% in 2012-2013.

Of this season’s deaths, 74 occurred in children. The mean and median ages of these patients were 7 years and 6 years, respectively; the range was 2 months-16 years. This total was lower than that recorded in any of the past three influenza seasons: 171 pediatric deaths in 2012-2013, 111 in 2013-2014, and 148 in 2014-2015.

Dr. Davlin also announced the Food and Drug Administration’s recommendations for composition of the 2016-2017 influenza vaccine.

Trivalent vaccines should contain an A/California/7/2009 (H1N1) pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage). Quadrivalent vaccines, which have two influenza B viruses, should include the viruses recommended for the trivalent vaccines, as well as a B/Phuket/3073/2013-like virus (B/Yamagata lineage).

“The vaccine viruses recommended for inclusion in the 2016-2017 Northern Hemisphere influenza vaccines are the same vaccine viruses that were chosen for inclusion in 2016 Southern Hemisphere seasonal influenza vaccines,” Dr. Davlin noted. “These vaccine recommendations were based on a number of factors, including global influenza virologic and epidemiologic surveillance, genetic and antigenic characterization, antiviral susceptibility, and the availability of candidate vaccine viruses for production.”

As a CDC employee, Dr. Davlin had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

The 2015-2016 flu season was less severe than the last three seasons, with a lower hospitalization rate and fewer pediatric deaths.

Cases of influenza appeared later in the season that typically seen, and activity didn’t peak until March, Stacy L. Davlin, Ph.D., wrote in the June 10 issue of the Morbidity and Mortality report (MMWR 2016; 22:567-75)

“During the most recent 18 influenza seasons, only two other seasons have peaked in March (2011-2012 and 2005-2006),” wrote Dr. Davlin, an epidemiologist at the Centers for Disease Control and Prevention, Atlanta. This serves as a reminder that influenza can and does occur outside the traditionally expected season, and that clinicians shouldn’t discount the possibility of flu when a patient presents with typical symptoms.

Cynthia Goldsmith/CDC photo #10073

“Although summer influenza activity in the United States typically is low, influenza cases and outbreaks have occurred during summer months, and clinicians should remain vigilant in considering influenza in the differential diagnosis of summer respiratory illnesses,” Dr. Davlin said.

The most common influenza virus of the last season was A(H1N1), which accounted for about half of cases in those aged 5-24 years, and about 70% of cases in those younger than 5 years and those 65 years and older.

Three novel viruses were seen as well: variants of A(H1N1), A(H1N2), and A(H3N2). The A(H1N1) variant occurred in a Minnesota resident who lived and worked in an area of swine farming, but who denied direct contact with pigs. The A(H3N2) variant occurred in a New Jersey resident who reported visiting a farm shortly before symptom onset. There was no evidence of human-to-human transmission. Both recovered fully without hospitalization. The A(H1N2) variant occurred in a Minnesota resident who was hospitalized but who recovered. This person was not interviewed so no possible source of infection was identified.

The CDC tested 2,408 viral specimens for susceptibility to antiviral medications. Among the 2,193 A(H1N1) specimens, less than 1% were resistant to oseltamivir and peramivir. All were susceptible to zanamivir. However, the testing found persistent high levels of resistant to amantadine and rimantadine in the A viruses. Amantadine is not effective on the B strains at all. Therefore, CDC does not recommend the use of amantadine as an anti-influenza medication.

Reports of influenza first exceeded the 2.1% baseline level in the week ending Dec. 26, 2015, according to the U.S. Outpatient Influenza-Like Illness Surveillance Network (ILINet). They remained elevated for the next 17 weeks, with a peak of 3.6% of all outpatient visits in the week ending March 12. From October 2015-April 2016, the overall hospitalization rate for influenza-like illness was 31 per 100,000. This was highest in those aged 65 years and older (85/100,000), and lowest in those aged 5-17 years (10/100,000). About 92% of adults hospitalized for flu-like illness had at least one underlying medical comorbidity, including obesity (42%), cardiovascular disease (40%), and metabolic disorders (38%). Almost half of children (48%) also had medical comorbidities, including asthma or other reactive airway disease (22%) and neurologic disorders (18%).

CDC’s National Center for Health Statistics Mortality Surveillance System found that the percentage of deaths attributed to pneumonia and influenza peaked at 8% during the week ending March 19. This is slightly lower than the death rate seen in the last 5 years, which ranged from 9% in 2011-2012 to 11% in 2012-2013.

Of this season’s deaths, 74 occurred in children. The mean and median ages of these patients were 7 years and 6 years, respectively; the range was 2 months-16 years. This total was lower than that recorded in any of the past three influenza seasons: 171 pediatric deaths in 2012-2013, 111 in 2013-2014, and 148 in 2014-2015.

Dr. Davlin also announced the Food and Drug Administration’s recommendations for composition of the 2016-2017 influenza vaccine.

Trivalent vaccines should contain an A/California/7/2009 (H1N1) pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, and a B/Brisbane/60/2008-like virus (B/Victoria lineage). Quadrivalent vaccines, which have two influenza B viruses, should include the viruses recommended for the trivalent vaccines, as well as a B/Phuket/3073/2013-like virus (B/Yamagata lineage).

“The vaccine viruses recommended for inclusion in the 2016-2017 Northern Hemisphere influenza vaccines are the same vaccine viruses that were chosen for inclusion in 2016 Southern Hemisphere seasonal influenza vaccines,” Dr. Davlin noted. “These vaccine recommendations were based on a number of factors, including global influenza virologic and epidemiologic surveillance, genetic and antigenic characterization, antiviral susceptibility, and the availability of candidate vaccine viruses for production.”

As a CDC employee, Dr. Davlin had no financial disclosures.

[email protected]

On Twitter @Alz_Gal

Copenhagen – Investigators in Italy have found that a recently identified form of inherited thrombocytopenia related to mutations in the gene ETV6 (ETV6-RT) appears to be largely asymptomatic, but puts patients at significantly increased risk for hematologic malignancies, particularly childhood B-cell acute lymphoblastic leukemia (ALL).

“When we are talking about ETV6-related thrombocytopenia patients, we must pay more attention to this hidden but very dangerous risk of developing blood cancer – so that we can define prognosis and plan a personalized follow-up – [rather] than to bleeding complications, which are rare and usually do not affect the quality of life,” said Dr. Federica Melazzini from the University of Pavia, Italy.

Neil Osterweil/Frontline Medical News

At a briefing at the annual congress of the European Hematology Association, Dr. Melazzini described a prospective study of the clinical and laboratory features of the newly identified disorder, with a focus on its association with hematologic cancers.

They enrolled 130 unrelated consecutive patients with inherited thrombocytopenias (IT) who did not have definitive diagnoses because they did exhibit criteria for any of the known forms of IT.

The investigators used whole exome sequencing or Sanger sequencing to look for mutations in ETV6, and when a mutation was identified, all available relatives of the affected participant (proband) also were evaluated. The authors also included data on five patients from two families known to have ETV6-RT from previous studies.

The participants were evaluated with complete blood counts, platelet sizing, flow cytometry studies of platelet membrane glycoproteins, as well as platelet aggregation, activation, adhesion and spreading. Other evaluations included differentiation of human megakaryocytes, morphological analysis of megakaryocytes, megakaryocytes flow cytometry, and evaluation of pro-platelet formation by megakaryocytes differentiated in vitro.

The investigators identified a total of 20 patients from 7 families bearing 5 different mutations in ETV6. Although these patients had only mild thrombocytopenias and a low bleeding tendency, 4 of the 20 had childhood ALL, supporting the association between ETV6 mutations and early leukemic transformation.

This translated into an incidence rate for hematologic malignancies of nearly 1 in 100 persons per year, compared with 1 in 10,000 per year in the general population, Dr. Melazzini said.

The investigators also noted that one patient developed Janus kinase 2 (JAK2)-positive polycythemia vera at age 37 years, “suggesting that this disease should be added to the list of malignancies to which the ETV6-RT predisposes.”

Dr. Melazzini said that clinicians should suspect ETV6-RT when a patient presents with an autosomal inherited thrombocytopenia without platelet macrocytosis, and should confirm the diagnosis with genetic analysis.

Patients also should be followed with whole blood cell counts and peripheral blood smear evaluations every 6-12 months, she recommended.

Dr Anton Hagenbeek, professor of hematology at the University of Amsterdam, who moderated the briefing but was not involved in the study, asked how clinicians should communicate the increased risk of hematologic malignancies to the patients.

Dr. Melazzini replied that patients need counseling about the risks of developing ALL or of passing on the trait if they plan to have children. Additionally, if patients develop ALL, the family should be cautioned against using a related donor for any allogeneic stem cell transplants, she said.

The study funding source was not disclosed. Dr. Melazzini and Dr. Hagenbeek reported no relevant disclosures.

Copenhagen – Investigators in Italy have found that a recently identified form of inherited thrombocytopenia related to mutations in the gene ETV6 (ETV6-RT) appears to be largely asymptomatic, but puts patients at significantly increased risk for hematologic malignancies, particularly childhood B-cell acute lymphoblastic leukemia (ALL).

“When we are talking about ETV6-related thrombocytopenia patients, we must pay more attention to this hidden but very dangerous risk of developing blood cancer – so that we can define prognosis and plan a personalized follow-up – [rather] than to bleeding complications, which are rare and usually do not affect the quality of life,” said Dr. Federica Melazzini from the University of Pavia, Italy.

Neil Osterweil/Frontline Medical News

At a briefing at the annual congress of the European Hematology Association, Dr. Melazzini described a prospective study of the clinical and laboratory features of the newly identified disorder, with a focus on its association with hematologic cancers.

They enrolled 130 unrelated consecutive patients with inherited thrombocytopenias (IT) who did not have definitive diagnoses because they did exhibit criteria for any of the known forms of IT.

The investigators used whole exome sequencing or Sanger sequencing to look for mutations in ETV6, and when a mutation was identified, all available relatives of the affected participant (proband) also were evaluated. The authors also included data on five patients from two families known to have ETV6-RT from previous studies.

The participants were evaluated with complete blood counts, platelet sizing, flow cytometry studies of platelet membrane glycoproteins, as well as platelet aggregation, activation, adhesion and spreading. Other evaluations included differentiation of human megakaryocytes, morphological analysis of megakaryocytes, megakaryocytes flow cytometry, and evaluation of pro-platelet formation by megakaryocytes differentiated in vitro.

The investigators identified a total of 20 patients from 7 families bearing 5 different mutations in ETV6. Although these patients had only mild thrombocytopenias and a low bleeding tendency, 4 of the 20 had childhood ALL, supporting the association between ETV6 mutations and early leukemic transformation.

This translated into an incidence rate for hematologic malignancies of nearly 1 in 100 persons per year, compared with 1 in 10,000 per year in the general population, Dr. Melazzini said.

The investigators also noted that one patient developed Janus kinase 2 (JAK2)-positive polycythemia vera at age 37 years, “suggesting that this disease should be added to the list of malignancies to which the ETV6-RT predisposes.”

Dr. Melazzini said that clinicians should suspect ETV6-RT when a patient presents with an autosomal inherited thrombocytopenia without platelet macrocytosis, and should confirm the diagnosis with genetic analysis.

Patients also should be followed with whole blood cell counts and peripheral blood smear evaluations every 6-12 months, she recommended.

Dr Anton Hagenbeek, professor of hematology at the University of Amsterdam, who moderated the briefing but was not involved in the study, asked how clinicians should communicate the increased risk of hematologic malignancies to the patients.

Dr. Melazzini replied that patients need counseling about the risks of developing ALL or of passing on the trait if they plan to have children. Additionally, if patients develop ALL, the family should be cautioned against using a related donor for any allogeneic stem cell transplants, she said.

The study funding source was not disclosed. Dr. Melazzini and Dr. Hagenbeek reported no relevant disclosures.

Copenhagen – Investigators in Italy have found that a recently identified form of inherited thrombocytopenia related to mutations in the gene ETV6 (ETV6-RT) appears to be largely asymptomatic, but puts patients at significantly increased risk for hematologic malignancies, particularly childhood B-cell acute lymphoblastic leukemia (ALL).

“When we are talking about ETV6-related thrombocytopenia patients, we must pay more attention to this hidden but very dangerous risk of developing blood cancer – so that we can define prognosis and plan a personalized follow-up – [rather] than to bleeding complications, which are rare and usually do not affect the quality of life,” said Dr. Federica Melazzini from the University of Pavia, Italy.

Neil Osterweil/Frontline Medical News

At a briefing at the annual congress of the European Hematology Association, Dr. Melazzini described a prospective study of the clinical and laboratory features of the newly identified disorder, with a focus on its association with hematologic cancers.

They enrolled 130 unrelated consecutive patients with inherited thrombocytopenias (IT) who did not have definitive diagnoses because they did exhibit criteria for any of the known forms of IT.

The investigators used whole exome sequencing or Sanger sequencing to look for mutations in ETV6, and when a mutation was identified, all available relatives of the affected participant (proband) also were evaluated. The authors also included data on five patients from two families known to have ETV6-RT from previous studies.

The participants were evaluated with complete blood counts, platelet sizing, flow cytometry studies of platelet membrane glycoproteins, as well as platelet aggregation, activation, adhesion and spreading. Other evaluations included differentiation of human megakaryocytes, morphological analysis of megakaryocytes, megakaryocytes flow cytometry, and evaluation of pro-platelet formation by megakaryocytes differentiated in vitro.

The investigators identified a total of 20 patients from 7 families bearing 5 different mutations in ETV6. Although these patients had only mild thrombocytopenias and a low bleeding tendency, 4 of the 20 had childhood ALL, supporting the association between ETV6 mutations and early leukemic transformation.

This translated into an incidence rate for hematologic malignancies of nearly 1 in 100 persons per year, compared with 1 in 10,000 per year in the general population, Dr. Melazzini said.

The investigators also noted that one patient developed Janus kinase 2 (JAK2)-positive polycythemia vera at age 37 years, “suggesting that this disease should be added to the list of malignancies to which the ETV6-RT predisposes.”

Dr. Melazzini said that clinicians should suspect ETV6-RT when a patient presents with an autosomal inherited thrombocytopenia without platelet macrocytosis, and should confirm the diagnosis with genetic analysis.

Patients also should be followed with whole blood cell counts and peripheral blood smear evaluations every 6-12 months, she recommended.

Dr Anton Hagenbeek, professor of hematology at the University of Amsterdam, who moderated the briefing but was not involved in the study, asked how clinicians should communicate the increased risk of hematologic malignancies to the patients.

Dr. Melazzini replied that patients need counseling about the risks of developing ALL or of passing on the trait if they plan to have children. Additionally, if patients develop ALL, the family should be cautioned against using a related donor for any allogeneic stem cell transplants, she said.

The study funding source was not disclosed. Dr. Melazzini and Dr. Hagenbeek reported no relevant disclosures.

Copenhagen – Relapse of acute myeloid leukemia among older adults may be caused by pre-leukemic stem cells lurking after treatment.

Among 107 adults with AML treated in a German multicenter clinical trial, 36% were found to have pre-treatment mutations that persisted after therapy, reported Dr. Klaus Metzeler of the University of Munich.

“Mutation persistence after chemotherapy was way more common in older patients, and importantly, patients with persisting mutations had a significantly higher risk of AML recurrence,” he said at a briefing prior to presentation of the data at the annual congress of the European Hematology Association.

Neil Osterweil/Frontline Medical News

The higher relapse risk associated with persistent mutations remained even after adjustment for patient age, cytogenetics, and other risk factors, he noted.

AML can arise from a clone of pre-leukemic stem cells, and it is known that pre-leukemic clones carry genetic mutations that can later be found in leukemic cells. The investigators hypothesized that pre-leukemic clones persisting after chemotherapy could be related treatment outcomes and survival.

To test this idea, they analyzed samples collected from bone marrow or peripheral blood of 107 adults with AML (median age 53 years, range 20-80 years) both before chemotherapy and during the first remission. The majority of remission samples (92%) were collected within the first 180 days of remission.

The investigators looked for the presence of 68 genes known to be recurrently mutated in myeloid malignancies, and identified any sequence alterations with a variant allele frequency of 2% or greater as either known or possible driver mutations, variants of unknown significance, or known germline polymorphisms.

A total of 426 driver mutations in 42 genes were detected in samples collected at diagnosis. In all, 69 patients (64%) had no mutations following chemotherapy. Among the remaining 38 patients, there were 66 persistent mutations in 15 genes. The most common persistent mutations were in the genes DNMT3A, TET2, SRF2, and ASXL1.

“Those are precisely those mutations that are known to occur in these pre-leukemic clones,” Dr. Metzeler said.

Mutations found in the pre-treatment but not the remission samples included those in NMP1, FLT3, WT1, and NRAS.

As noted, patients with one or more persistent mutations tended to be older than those with no mutations, with a median age of 63 years vs. 48 years (P less than .001). Persistence of one or more driver mutations in remission was associated with both significantly shorter relapse-free survival (median 14.3 months vs. 58.0 months, P = .009) and shorter overall survival (median, 39.6 months vs. more than 72 months; P = .005).

In multivariate analyses controlling for age, European LeukemiaNet genetic risk groups, and remission status (complete remission vs. complete remission with incomplete recovery of counts), any persistent mutations was associated with significantly worse relapse-free survival (hazard ratio, 2.2, P =.02) and overall survival (HR, 3.0, P = .008). 

“It is well known that older AML patients have a poor prognosis, but the reasons for that aren’t fully understood yet. So the hypothesis that would come from our data is that frequent persistence of pre-leukemic clones may be one potential explanation for the higher relapse risk that we found in older patients,” Dr. Metzeler said.

Asked how clinicians might go about targeting the escaped mutations, Dr. Metzeler noted that the incidence of pre-leukemic somatic mutations among healthy 70-year-olds is about 10%.

“So the challenge will be to identify those patients who will actually relapse, and then an option in fit patients would be an allogeneic transplant. We don’t have targeted agents at the moment where we can target these specific mutations, and it would be relatively hard to justify giving those patients additional chemotherapy at this point,” he said.

Neil Osterweil/Frontline Medical News

“What this is showing for the first time is a clue as to why a subset will relapse, and now we know that this group exists with these pre-leukemic clones, we can begin to ask questions about why it is they relapse or don’t relapse. Is it something to do with the immune system in those patients who don’t relapse?” commented EHA president Tony Green, M.D., who was not involved in the study, but attended the briefing. Dr. Green is a professor in the department of hematology at the Cambridge Stem Cell Institute, University of Cambridge, U.K.

The study was funded by European Hematology Association research fellowships. Dr. Metzeler and Dr. Green reported no relevant disclosures.

Copenhagen – Relapse of acute myeloid leukemia among older adults may be caused by pre-leukemic stem cells lurking after treatment.

Among 107 adults with AML treated in a German multicenter clinical trial, 36% were found to have pre-treatment mutations that persisted after therapy, reported Dr. Klaus Metzeler of the University of Munich.

“Mutation persistence after chemotherapy was way more common in older patients, and importantly, patients with persisting mutations had a significantly higher risk of AML recurrence,” he said at a briefing prior to presentation of the data at the annual congress of the European Hematology Association.

Neil Osterweil/Frontline Medical News

The higher relapse risk associated with persistent mutations remained even after adjustment for patient age, cytogenetics, and other risk factors, he noted.

AML can arise from a clone of pre-leukemic stem cells, and it is known that pre-leukemic clones carry genetic mutations that can later be found in leukemic cells. The investigators hypothesized that pre-leukemic clones persisting after chemotherapy could be related treatment outcomes and survival.

To test this idea, they analyzed samples collected from bone marrow or peripheral blood of 107 adults with AML (median age 53 years, range 20-80 years) both before chemotherapy and during the first remission. The majority of remission samples (92%) were collected within the first 180 days of remission.

The investigators looked for the presence of 68 genes known to be recurrently mutated in myeloid malignancies, and identified any sequence alterations with a variant allele frequency of 2% or greater as either known or possible driver mutations, variants of unknown significance, or known germline polymorphisms.

A total of 426 driver mutations in 42 genes were detected in samples collected at diagnosis. In all, 69 patients (64%) had no mutations following chemotherapy. Among the remaining 38 patients, there were 66 persistent mutations in 15 genes. The most common persistent mutations were in the genes DNMT3A, TET2, SRF2, and ASXL1.

“Those are precisely those mutations that are known to occur in these pre-leukemic clones,” Dr. Metzeler said.

Mutations found in the pre-treatment but not the remission samples included those in NMP1, FLT3, WT1, and NRAS.

As noted, patients with one or more persistent mutations tended to be older than those with no mutations, with a median age of 63 years vs. 48 years (P less than .001). Persistence of one or more driver mutations in remission was associated with both significantly shorter relapse-free survival (median 14.3 months vs. 58.0 months, P = .009) and shorter overall survival (median, 39.6 months vs. more than 72 months; P = .005).

In multivariate analyses controlling for age, European LeukemiaNet genetic risk groups, and remission status (complete remission vs. complete remission with incomplete recovery of counts), any persistent mutations was associated with significantly worse relapse-free survival (hazard ratio, 2.2, P =.02) and overall survival (HR, 3.0, P = .008). 

“It is well known that older AML patients have a poor prognosis, but the reasons for that aren’t fully understood yet. So the hypothesis that would come from our data is that frequent persistence of pre-leukemic clones may be one potential explanation for the higher relapse risk that we found in older patients,” Dr. Metzeler said.

Asked how clinicians might go about targeting the escaped mutations, Dr. Metzeler noted that the incidence of pre-leukemic somatic mutations among healthy 70-year-olds is about 10%.

“So the challenge will be to identify those patients who will actually relapse, and then an option in fit patients would be an allogeneic transplant. We don’t have targeted agents at the moment where we can target these specific mutations, and it would be relatively hard to justify giving those patients additional chemotherapy at this point,” he said.

Neil Osterweil/Frontline Medical News

“What this is showing for the first time is a clue as to why a subset will relapse, and now we know that this group exists with these pre-leukemic clones, we can begin to ask questions about why it is they relapse or don’t relapse. Is it something to do with the immune system in those patients who don’t relapse?” commented EHA president Tony Green, M.D., who was not involved in the study, but attended the briefing. Dr. Green is a professor in the department of hematology at the Cambridge Stem Cell Institute, University of Cambridge, U.K.

The study was funded by European Hematology Association research fellowships. Dr. Metzeler and Dr. Green reported no relevant disclosures.

Copenhagen – Relapse of acute myeloid leukemia among older adults may be caused by pre-leukemic stem cells lurking after treatment.

Among 107 adults with AML treated in a German multicenter clinical trial, 36% were found to have pre-treatment mutations that persisted after therapy, reported Dr. Klaus Metzeler of the University of Munich.

“Mutation persistence after chemotherapy was way more common in older patients, and importantly, patients with persisting mutations had a significantly higher risk of AML recurrence,” he said at a briefing prior to presentation of the data at the annual congress of the European Hematology Association.

Neil Osterweil/Frontline Medical News

The higher relapse risk associated with persistent mutations remained even after adjustment for patient age, cytogenetics, and other risk factors, he noted.

AML can arise from a clone of pre-leukemic stem cells, and it is known that pre-leukemic clones carry genetic mutations that can later be found in leukemic cells. The investigators hypothesized that pre-leukemic clones persisting after chemotherapy could be related treatment outcomes and survival.

To test this idea, they analyzed samples collected from bone marrow or peripheral blood of 107 adults with AML (median age 53 years, range 20-80 years) both before chemotherapy and during the first remission. The majority of remission samples (92%) were collected within the first 180 days of remission.

The investigators looked for the presence of 68 genes known to be recurrently mutated in myeloid malignancies, and identified any sequence alterations with a variant allele frequency of 2% or greater as either known or possible driver mutations, variants of unknown significance, or known germline polymorphisms.

A total of 426 driver mutations in 42 genes were detected in samples collected at diagnosis. In all, 69 patients (64%) had no mutations following chemotherapy. Among the remaining 38 patients, there were 66 persistent mutations in 15 genes. The most common persistent mutations were in the genes DNMT3A, TET2, SRF2, and ASXL1.

“Those are precisely those mutations that are known to occur in these pre-leukemic clones,” Dr. Metzeler said.

Mutations found in the pre-treatment but not the remission samples included those in NMP1, FLT3, WT1, and NRAS.

As noted, patients with one or more persistent mutations tended to be older than those with no mutations, with a median age of 63 years vs. 48 years (P less than .001). Persistence of one or more driver mutations in remission was associated with both significantly shorter relapse-free survival (median 14.3 months vs. 58.0 months, P = .009) and shorter overall survival (median, 39.6 months vs. more than 72 months; P = .005).

In multivariate analyses controlling for age, European LeukemiaNet genetic risk groups, and remission status (complete remission vs. complete remission with incomplete recovery of counts), any persistent mutations was associated with significantly worse relapse-free survival (hazard ratio, 2.2, P =.02) and overall survival (HR, 3.0, P = .008). 

“It is well known that older AML patients have a poor prognosis, but the reasons for that aren’t fully understood yet. So the hypothesis that would come from our data is that frequent persistence of pre-leukemic clones may be one potential explanation for the higher relapse risk that we found in older patients,” Dr. Metzeler said.

Asked how clinicians might go about targeting the escaped mutations, Dr. Metzeler noted that the incidence of pre-leukemic somatic mutations among healthy 70-year-olds is about 10%.

“So the challenge will be to identify those patients who will actually relapse, and then an option in fit patients would be an allogeneic transplant. We don’t have targeted agents at the moment where we can target these specific mutations, and it would be relatively hard to justify giving those patients additional chemotherapy at this point,” he said.

Neil Osterweil/Frontline Medical News

“What this is showing for the first time is a clue as to why a subset will relapse, and now we know that this group exists with these pre-leukemic clones, we can begin to ask questions about why it is they relapse or don’t relapse. Is it something to do with the immune system in those patients who don’t relapse?” commented EHA president Tony Green, M.D., who was not involved in the study, but attended the briefing. Dr. Green is a professor in the department of hematology at the Cambridge Stem Cell Institute, University of Cambridge, U.K.

The study was funded by European Hematology Association research fellowships. Dr. Metzeler and Dr. Green reported no relevant disclosures.

DNA helix
Image courtesy Spencer Phillips

Using next-generation sequencing (NGS) technology, a team of researchers has discovered 2 new subtypes of pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL).

The 2 new subtypes, called DUX4-rearranged and ETV6/RUNX1-like, may improve risk stratification and targeted therapeutic options for treatment of the disease, the researchers say.

Previous studies have defined 6 major groups of ALL in children. The 2 new types can now be added to these groups.

The research team performed RNA sequencing in a population-based series of 195 pediatric BCP ALL cases, all under 18 years.

They found gene fusions present in 65% of BCP ALL cases. They also identified several new fusions along with the 2 novel subtypes.

The DUX4-rearranged subtype occurs “when a gene called DUX4, which is normally inactive in blood cells, becomes activated when the gene is relocated in the genome,” corresponding author Henrik Lilljebjörn, of Lund University in Sweden, said.

The DUX4-rearranged subtype was represented in 4% of the cases. It led to overexpression of DUX4 and frequently occurred together with intragenic ERG deletions.

The team observed a borderline significance (P=0.051) for age in cases with DUX4 rearrangements. Those with DUX4 rearrangements tended to be from older patients compared to cases lacking the fusion, with a median age of 6.5 year versus 4 years, respectively. The authors noted that this association needs to be confirmed in larger cohorts.

The ETV6/RUNX1-like subtype “resembles a previously known type of childhood leukemia,”Lilljebjörn said, “but is caused by other genetic mutations."

The ETV6/RUNX1-like subtype was represented in 3% of the BCP ALL cases.

According to the team, if all known subtypes are taken into consideration, “98% of the BCP ALL cases could be classified into distinct genetic subtypes with a known underlying driver mutation, or, less commonly, with a rare in-frame gene fusion,” they wrote.

“Finding the critical mutations in the diseased cells,” principal investigator Thoas Fioretos, MD, PhD, of Lund University, explained, “is an important condition for understanding the mechanisms of the disease and ultimately discovering new therapies.”

The investigators published their work in Nature Communications.

The research was funded mainly by The Swedish Childhood Cancer Foundation, The Swedish Cancer Society, The Swedish Research Council, the Faculty of Medicine at Lund University and Region Skåne.

DNA helix
Image courtesy Spencer Phillips

Using next-generation sequencing (NGS) technology, a team of researchers has discovered 2 new subtypes of pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL).

The 2 new subtypes, called DUX4-rearranged and ETV6/RUNX1-like, may improve risk stratification and targeted therapeutic options for treatment of the disease, the researchers say.

Previous studies have defined 6 major groups of ALL in children. The 2 new types can now be added to these groups.

The research team performed RNA sequencing in a population-based series of 195 pediatric BCP ALL cases, all under 18 years.

They found gene fusions present in 65% of BCP ALL cases. They also identified several new fusions along with the 2 novel subtypes.

The DUX4-rearranged subtype occurs “when a gene called DUX4, which is normally inactive in blood cells, becomes activated when the gene is relocated in the genome,” corresponding author Henrik Lilljebjörn, of Lund University in Sweden, said.

The DUX4-rearranged subtype was represented in 4% of the cases. It led to overexpression of DUX4 and frequently occurred together with intragenic ERG deletions.

The team observed a borderline significance (P=0.051) for age in cases with DUX4 rearrangements. Those with DUX4 rearrangements tended to be from older patients compared to cases lacking the fusion, with a median age of 6.5 year versus 4 years, respectively. The authors noted that this association needs to be confirmed in larger cohorts.

The ETV6/RUNX1-like subtype “resembles a previously known type of childhood leukemia,”Lilljebjörn said, “but is caused by other genetic mutations."

The ETV6/RUNX1-like subtype was represented in 3% of the BCP ALL cases.

According to the team, if all known subtypes are taken into consideration, “98% of the BCP ALL cases could be classified into distinct genetic subtypes with a known underlying driver mutation, or, less commonly, with a rare in-frame gene fusion,” they wrote.

“Finding the critical mutations in the diseased cells,” principal investigator Thoas Fioretos, MD, PhD, of Lund University, explained, “is an important condition for understanding the mechanisms of the disease and ultimately discovering new therapies.”

The investigators published their work in Nature Communications.

The research was funded mainly by The Swedish Childhood Cancer Foundation, The Swedish Cancer Society, The Swedish Research Council, the Faculty of Medicine at Lund University and Region Skåne.

DNA helix
Image courtesy Spencer Phillips

Using next-generation sequencing (NGS) technology, a team of researchers has discovered 2 new subtypes of pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL).

The 2 new subtypes, called DUX4-rearranged and ETV6/RUNX1-like, may improve risk stratification and targeted therapeutic options for treatment of the disease, the researchers say.

Previous studies have defined 6 major groups of ALL in children. The 2 new types can now be added to these groups.

The research team performed RNA sequencing in a population-based series of 195 pediatric BCP ALL cases, all under 18 years.

They found gene fusions present in 65% of BCP ALL cases. They also identified several new fusions along with the 2 novel subtypes.

The DUX4-rearranged subtype occurs “when a gene called DUX4, which is normally inactive in blood cells, becomes activated when the gene is relocated in the genome,” corresponding author Henrik Lilljebjörn, of Lund University in Sweden, said.

The DUX4-rearranged subtype was represented in 4% of the cases. It led to overexpression of DUX4 and frequently occurred together with intragenic ERG deletions.

The team observed a borderline significance (P=0.051) for age in cases with DUX4 rearrangements. Those with DUX4 rearrangements tended to be from older patients compared to cases lacking the fusion, with a median age of 6.5 year versus 4 years, respectively. The authors noted that this association needs to be confirmed in larger cohorts.

The ETV6/RUNX1-like subtype “resembles a previously known type of childhood leukemia,”Lilljebjörn said, “but is caused by other genetic mutations."

The ETV6/RUNX1-like subtype was represented in 3% of the BCP ALL cases.

According to the team, if all known subtypes are taken into consideration, “98% of the BCP ALL cases could be classified into distinct genetic subtypes with a known underlying driver mutation, or, less commonly, with a rare in-frame gene fusion,” they wrote.

“Finding the critical mutations in the diseased cells,” principal investigator Thoas Fioretos, MD, PhD, of Lund University, explained, “is an important condition for understanding the mechanisms of the disease and ultimately discovering new therapies.”

The investigators published their work in Nature Communications.

The research was funded mainly by The Swedish Childhood Cancer Foundation, The Swedish Cancer Society, The Swedish Research Council, the Faculty of Medicine at Lund University and Region Skåne.

NEW ORLEANS — Two researchers shared innovative ideas at the annual scientific sessions of the American Diabetes Association for tapping virtually unlimited supplies of islet cells with less risk of an immune reaction.

Transplanting pancreatic islet stem cells from deceased donors into patients with type 1 diabetes has long been known to be an effective way of improve blood-glucose levels and temporarily eliminate the need for insulin injections, but getting an adequate supply of islet cells to treat the 1 million-2 million Americans with Type 1 diabetes, not to mention the risk of rejection and the need for long-term immunosuppressive therapy, makes this approach challenging.

©Tashatuvango/Thinkstockphotos.com

At the University of Pittsburgh, investigators have developed a way to harvest islet cells from genetically engineered pigs and implant them into monkeys, while at the Harvard Stem Cell Institute in Boston, researchers have used gene editing to grow islet cells from blood cells.

“Human islet cells are in very scarce supply and will never solve the problem of diabetes,” said Dr. David K.C. Cooper, professor at the Thomas E. Starzi Transplantation Institute at the University of Pittsburgh. But growing evidence has shown that islet cells harvested from pigs could provide a viable source.

The challenge with stem cells from deceased human donors is that they require long term immunosuppression therapy to prevent the host body from rejecting them. When Dr. Cooper and his team injected islet cells from genetically engineered pigs into the stomachs of monkeys, they found the monkeys were able to maintain blood glucose control for about a year while on “fairly basic immunosuppressive therapy.” Dr. Cooper explained that the immunosuppressive regimen is a nonthrombogenic, monoclonal antibody not yet approved by the Food and Drug Administration. He noted that work at the Seoul National University in Korea has found similar results in monkeys out to 2 years.

The concept involves raising genetically engineered pigs in a biosecure facility, of which there are “two or three” in the United States, to ensure the cells are infection free. “The pig will be the answer to our problems,” Dr. Cooper said.

At Harvard, meanwhile, researchers are developing a way to produce pluripotent stem cells using an individual’s own blood cells that function like embryonic stem cells, but can multiply in a virtually unlimited fashion, Chad Cowan, PhD, reported. The challenge with using stem cells produced from an individual’s own cells has been the “immune barrier” – that is, the person’s immune system would attack the new cells.

However, Dr. Cowan and his team have found a way around this so-called “immune barrier” by producing “universal donor” pluripotent stem cell lines.

“You have an unlimited supply of cells,” Dr. Cowan said. “The key, though, is to teach these cells to do something, and because they come from a very early stage in development, they have the ability to become any of the adult cells in the human body. Our mission has been to teach them to become insulin-producing beta cells.”

The idea is to grow an “off-the-shelf, quality-controlled” product that can be produced in large numbers. By editing the genes, the researchers aim to reduce the immunogenicity of these cells and induce tolerance.

The work is some time away from human trials. “Once created, the next step would be to test these universal donor pluripotent stem cell lines in a humanized mouse model of type 1 diabetes,” Dr. Cowan said.

This type of gene editing also could have implications beyond diabetes, Dr. Cowan said. “If successful, our proposed work could have an enormous impact on regenerative medicine,” he said. “It could lead the way to rigorously tested universal donor stem cells that could be grown and differentiated into very large numbers of cells, made widely available to all medical institutions and used on demand to treat patients suffering from type 1 diabetes and a variety of degenerative illnesses,” including Parkinson’s disease.

Dr. Cowan and Dr. Cooper reported having no financial disclosures.

NEW ORLEANS — Two researchers shared innovative ideas at the annual scientific sessions of the American Diabetes Association for tapping virtually unlimited supplies of islet cells with less risk of an immune reaction.

Transplanting pancreatic islet stem cells from deceased donors into patients with type 1 diabetes has long been known to be an effective way of improve blood-glucose levels and temporarily eliminate the need for insulin injections, but getting an adequate supply of islet cells to treat the 1 million-2 million Americans with Type 1 diabetes, not to mention the risk of rejection and the need for long-term immunosuppressive therapy, makes this approach challenging.

©Tashatuvango/Thinkstockphotos.com

At the University of Pittsburgh, investigators have developed a way to harvest islet cells from genetically engineered pigs and implant them into monkeys, while at the Harvard Stem Cell Institute in Boston, researchers have used gene editing to grow islet cells from blood cells.

“Human islet cells are in very scarce supply and will never solve the problem of diabetes,” said Dr. David K.C. Cooper, professor at the Thomas E. Starzi Transplantation Institute at the University of Pittsburgh. But growing evidence has shown that islet cells harvested from pigs could provide a viable source.

The challenge with stem cells from deceased human donors is that they require long term immunosuppression therapy to prevent the host body from rejecting them. When Dr. Cooper and his team injected islet cells from genetically engineered pigs into the stomachs of monkeys, they found the monkeys were able to maintain blood glucose control for about a year while on “fairly basic immunosuppressive therapy.” Dr. Cooper explained that the immunosuppressive regimen is a nonthrombogenic, monoclonal antibody not yet approved by the Food and Drug Administration. He noted that work at the Seoul National University in Korea has found similar results in monkeys out to 2 years.

The concept involves raising genetically engineered pigs in a biosecure facility, of which there are “two or three” in the United States, to ensure the cells are infection free. “The pig will be the answer to our problems,” Dr. Cooper said.

At Harvard, meanwhile, researchers are developing a way to produce pluripotent stem cells using an individual’s own blood cells that function like embryonic stem cells, but can multiply in a virtually unlimited fashion, Chad Cowan, PhD, reported. The challenge with using stem cells produced from an individual’s own cells has been the “immune barrier” – that is, the person’s immune system would attack the new cells.

However, Dr. Cowan and his team have found a way around this so-called “immune barrier” by producing “universal donor” pluripotent stem cell lines.

“You have an unlimited supply of cells,” Dr. Cowan said. “The key, though, is to teach these cells to do something, and because they come from a very early stage in development, they have the ability to become any of the adult cells in the human body. Our mission has been to teach them to become insulin-producing beta cells.”

The idea is to grow an “off-the-shelf, quality-controlled” product that can be produced in large numbers. By editing the genes, the researchers aim to reduce the immunogenicity of these cells and induce tolerance.

The work is some time away from human trials. “Once created, the next step would be to test these universal donor pluripotent stem cell lines in a humanized mouse model of type 1 diabetes,” Dr. Cowan said.

This type of gene editing also could have implications beyond diabetes, Dr. Cowan said. “If successful, our proposed work could have an enormous impact on regenerative medicine,” he said. “It could lead the way to rigorously tested universal donor stem cells that could be grown and differentiated into very large numbers of cells, made widely available to all medical institutions and used on demand to treat patients suffering from type 1 diabetes and a variety of degenerative illnesses,” including Parkinson’s disease.

Dr. Cowan and Dr. Cooper reported having no financial disclosures.

NEW ORLEANS — Two researchers shared innovative ideas at the annual scientific sessions of the American Diabetes Association for tapping virtually unlimited supplies of islet cells with less risk of an immune reaction.

Transplanting pancreatic islet stem cells from deceased donors into patients with type 1 diabetes has long been known to be an effective way of improve blood-glucose levels and temporarily eliminate the need for insulin injections, but getting an adequate supply of islet cells to treat the 1 million-2 million Americans with Type 1 diabetes, not to mention the risk of rejection and the need for long-term immunosuppressive therapy, makes this approach challenging.

©Tashatuvango/Thinkstockphotos.com

At the University of Pittsburgh, investigators have developed a way to harvest islet cells from genetically engineered pigs and implant them into monkeys, while at the Harvard Stem Cell Institute in Boston, researchers have used gene editing to grow islet cells from blood cells.

“Human islet cells are in very scarce supply and will never solve the problem of diabetes,” said Dr. David K.C. Cooper, professor at the Thomas E. Starzi Transplantation Institute at the University of Pittsburgh. But growing evidence has shown that islet cells harvested from pigs could provide a viable source.

The challenge with stem cells from deceased human donors is that they require long term immunosuppression therapy to prevent the host body from rejecting them. When Dr. Cooper and his team injected islet cells from genetically engineered pigs into the stomachs of monkeys, they found the monkeys were able to maintain blood glucose control for about a year while on “fairly basic immunosuppressive therapy.” Dr. Cooper explained that the immunosuppressive regimen is a nonthrombogenic, monoclonal antibody not yet approved by the Food and Drug Administration. He noted that work at the Seoul National University in Korea has found similar results in monkeys out to 2 years.

The concept involves raising genetically engineered pigs in a biosecure facility, of which there are “two or three” in the United States, to ensure the cells are infection free. “The pig will be the answer to our problems,” Dr. Cooper said.

At Harvard, meanwhile, researchers are developing a way to produce pluripotent stem cells using an individual’s own blood cells that function like embryonic stem cells, but can multiply in a virtually unlimited fashion, Chad Cowan, PhD, reported. The challenge with using stem cells produced from an individual’s own cells has been the “immune barrier” – that is, the person’s immune system would attack the new cells.

However, Dr. Cowan and his team have found a way around this so-called “immune barrier” by producing “universal donor” pluripotent stem cell lines.

“You have an unlimited supply of cells,” Dr. Cowan said. “The key, though, is to teach these cells to do something, and because they come from a very early stage in development, they have the ability to become any of the adult cells in the human body. Our mission has been to teach them to become insulin-producing beta cells.”

The idea is to grow an “off-the-shelf, quality-controlled” product that can be produced in large numbers. By editing the genes, the researchers aim to reduce the immunogenicity of these cells and induce tolerance.

The work is some time away from human trials. “Once created, the next step would be to test these universal donor pluripotent stem cell lines in a humanized mouse model of type 1 diabetes,” Dr. Cowan said.

This type of gene editing also could have implications beyond diabetes, Dr. Cowan said. “If successful, our proposed work could have an enormous impact on regenerative medicine,” he said. “It could lead the way to rigorously tested universal donor stem cells that could be grown and differentiated into very large numbers of cells, made widely available to all medical institutions and used on demand to treat patients suffering from type 1 diabetes and a variety of degenerative illnesses,” including Parkinson’s disease.

Dr. Cowan and Dr. Cooper reported having no financial disclosures.

CHICAGO – Extending adjuvant aromatase inhibitor (AI) therapy from 5 years to 10 years further reduces the risk of recurrence and new breast cancer in postmenopausal women treated for early disease, according to findings of the MA17.R trial.

In the phase III trial conducted by the Canadian Cancer Trials Group and the North American Breast Cancer Group, 1,918 postmenopausal women who had completed about 5 years of AI therapy (preceded by tamoxifen in the majority of cases) were randomized to take the AI letrozole or to stop therapy by taking placebo for an additional 5 years.

Compared with peers who stopped, women who continued AI therapy for 5 more years had a 34% lower risk of recurrence or contralateral breast cancer, investigators reported in sessions and a press briefing at the annual meeting of the American Society of Clinical Oncology. The trade-off was a small increase in the rates of skeletal adverse events such as fractures; quality of life was essentially unaffected.

“MA17.R is the first study to show the benefit of extending an adjuvant aromatase inhibitor beyond 5 years,” commented lead investigator Paul E. Goss, M.D., director of the Breast Cancer Research Program at the Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston. “Unlike many anticancer therapies, aromatase inhibitors are readily accessible around the world, and therefore, our results will further improve the outcome of many women with breast cancer.”

The disease-free survival curves will likely separate further, given a “legacy effect” of endocrine therapy that persists after it ends, he predicted. “And I think overall survival will eventually become positive in MA.17R. … The Food and Drug Administration has taken the opinion that overall survival follows disease-free survival like night follows day for endocrine therapies, and I think they are correct, I think that’s what we see in all the trials.”

Implications

It remains unclear how patients should be managed after 10 years of an AI, according to Dr. Goss. “That’s uncharted waters,” he elaborated. “We know from the curve of the natural history of this disease that it chronically relapses, and we continue to see patients 25 years after their primary diagnosis with a recurrence.” Some data in mice suggest there may be benefit from continuing the AI until recurrence. “I don’t think that would be entered into in clinical practice as a rule, because there is no clinical trial of that,” he said. “But this data will now take the aromatase inhibitors out to 10 years.”

The MA.17R trial’s findings show that extended duration of AI therapy is “clinically valuable,” according to ASCO expert Harold J. Burstein, M.D., Ph.D., a senior physician at the Dana-Farber Cancer Institute and an associate professor of medicine at the Harvard Medical School in Boston. He predicted the findings will have at least two consequences.

“One is tremendous interest in longer durations of therapy with the AI, but also some tailoring of treatment based on how the patient has fared with their therapy and on their baseline risk of recurrence. So women who have less risky cancer will probably be less inclined to pursue these longer durations, and women who have higher-risk cancers will be more inclined,” he explained.

Also, “women who have finished 5 years of an AI without any prior tamoxifen I think are going to be very compelled by these data, whereas women who have had 5 years of tamoxifen, 5 years of an AI, and are already 10 years out probably get less benefit numerically from yet longer duration of therapy,” he added. “And we are certainly not at the point of saying that women should be on these drugs for the rest of their lives.”

MA.17R design

Postmenopausal women were eligible for MA.17R if they had undergone resection of hormone receptor–positive early breast cancer and had already completed about 5 years of therapy with any of the three AIs currently on the market. In the large majority of cases, they also had previously received tamoxifen.

Many of the women came from the parent MA.17 trial, which tested an initial 5 years of letrozole (brand name Femara) against placebo after tamoxifen therapy. Longer-term results of that trial, previously reported (J Clin Oncol. 2012;30:718-21), showed that this duration of letrozole had a significant disease-free survival benefit (hazard ratio, .52) and overall survival benefit (HR, .61).

In the MA.17R trial, the women were randomized to letrozole or a placebo for an additional 5 years, with a primary endpoint of disease-free survival and secondary endpoints including safety and quality of life.

Efficacy and safety

After a median follow-up of 6.3 years, the 5-year rate of disease-free survival was 95% with letrozole and 91% with placebo, according to results reported by Dr. Goss in a plenary session at the meeting and simultaneously published (N Engl J Med. 2016. June 5 doi: 10.1056/NEJMoa1604700).

The difference translated to a more than one-third reduction in the risk of disease recurrence or the occurrence of contralateral breast cancer (HR, .66; P = .01). Roughly three-fourths of recurrences were distant.

The groups did not differ significantly with respect to the rate of overall survival, which was 93% with letrozole and 94% with placebo.

The annual incidence of contralateral breast cancer was sharply lower in the letrozole group, at 0.21%, than in the placebo group, at 0.49%, translating to a more than one-half reduction in this risk of this outcome (HR, .42; P = .007).

No new toxicities or emergent symptoms were noted from extending AI therapy, according to Dr. Goss. However, the letrozole group significantly more commonly experienced bone pain (18% vs. 14%), bone fractures (14% vs. 9%), and new-onset osteoporosis (11% vs. 6%). Therefore, “bone health remains important for risk-benefit consideration,” he said.

Patient-reported outcomes

In a separate session and the press briefing, Dr. Julie Lemieux, a researcher at the Centre Hospitalier affilié Universitaire de Québec, reported the trial’s patient-reported outcomes, ascertained from questionnaires completed at baseline and annually out to 5 years.

In general, both the letrozole and placebo groups had small deteriorations over time in global quality of life as assessed from summary scores on the mental and physical scales of the 36-item Short Form Health Survey (SF-36). But both also had small improvements over time in scores on the Menopause-Specific Quality of Life (MENQOL) scale.

When compared, the two groups were statistically indistinguishable on most of these measures. The only significant difference was greater worsening in the letrozole group on the role function-physical subscale of the SF-36, which pertains to difficulty performing work or physical activity due to physical health. However, the difference averaged just 3.2 points, which fell short of the 5 points that the investigators considered clinically important.

“The limitation of this analysis was that it was a highly selected population. All of these women had already tolerated 5 years of an aromatase inhibitor, and about 70% had received 5 years of tamoxifen before,” Dr. Lemieux commented. “Also, they were clinical trial participants.”

Nonetheless, these findings “are very reassuring for those women who want a longer duration of adjuvant endocrine therapy that they can expect a preserved quality of life,” she concluded.

Dr. Goss disclosed that he had no relevant conflicts of interest. Dr. Lemieux disclosed that she had no relevant conflicts of interest. The trial received support from Novartis.

CHICAGO – Extending adjuvant aromatase inhibitor (AI) therapy from 5 years to 10 years further reduces the risk of recurrence and new breast cancer in postmenopausal women treated for early disease, according to findings of the MA17.R trial.

In the phase III trial conducted by the Canadian Cancer Trials Group and the North American Breast Cancer Group, 1,918 postmenopausal women who had completed about 5 years of AI therapy (preceded by tamoxifen in the majority of cases) were randomized to take the AI letrozole or to stop therapy by taking placebo for an additional 5 years.

Compared with peers who stopped, women who continued AI therapy for 5 more years had a 34% lower risk of recurrence or contralateral breast cancer, investigators reported in sessions and a press briefing at the annual meeting of the American Society of Clinical Oncology. The trade-off was a small increase in the rates of skeletal adverse events such as fractures; quality of life was essentially unaffected.

“MA17.R is the first study to show the benefit of extending an adjuvant aromatase inhibitor beyond 5 years,” commented lead investigator Paul E. Goss, M.D., director of the Breast Cancer Research Program at the Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston. “Unlike many anticancer therapies, aromatase inhibitors are readily accessible around the world, and therefore, our results will further improve the outcome of many women with breast cancer.”

The disease-free survival curves will likely separate further, given a “legacy effect” of endocrine therapy that persists after it ends, he predicted. “And I think overall survival will eventually become positive in MA.17R. … The Food and Drug Administration has taken the opinion that overall survival follows disease-free survival like night follows day for endocrine therapies, and I think they are correct, I think that’s what we see in all the trials.”

Implications

It remains unclear how patients should be managed after 10 years of an AI, according to Dr. Goss. “That’s uncharted waters,” he elaborated. “We know from the curve of the natural history of this disease that it chronically relapses, and we continue to see patients 25 years after their primary diagnosis with a recurrence.” Some data in mice suggest there may be benefit from continuing the AI until recurrence. “I don’t think that would be entered into in clinical practice as a rule, because there is no clinical trial of that,” he said. “But this data will now take the aromatase inhibitors out to 10 years.”

The MA.17R trial’s findings show that extended duration of AI therapy is “clinically valuable,” according to ASCO expert Harold J. Burstein, M.D., Ph.D., a senior physician at the Dana-Farber Cancer Institute and an associate professor of medicine at the Harvard Medical School in Boston. He predicted the findings will have at least two consequences.

“One is tremendous interest in longer durations of therapy with the AI, but also some tailoring of treatment based on how the patient has fared with their therapy and on their baseline risk of recurrence. So women who have less risky cancer will probably be less inclined to pursue these longer durations, and women who have higher-risk cancers will be more inclined,” he explained.

Also, “women who have finished 5 years of an AI without any prior tamoxifen I think are going to be very compelled by these data, whereas women who have had 5 years of tamoxifen, 5 years of an AI, and are already 10 years out probably get less benefit numerically from yet longer duration of therapy,” he added. “And we are certainly not at the point of saying that women should be on these drugs for the rest of their lives.”

MA.17R design

Postmenopausal women were eligible for MA.17R if they had undergone resection of hormone receptor–positive early breast cancer and had already completed about 5 years of therapy with any of the three AIs currently on the market. In the large majority of cases, they also had previously received tamoxifen.

Many of the women came from the parent MA.17 trial, which tested an initial 5 years of letrozole (brand name Femara) against placebo after tamoxifen therapy. Longer-term results of that trial, previously reported (J Clin Oncol. 2012;30:718-21), showed that this duration of letrozole had a significant disease-free survival benefit (hazard ratio, .52) and overall survival benefit (HR, .61).

In the MA.17R trial, the women were randomized to letrozole or a placebo for an additional 5 years, with a primary endpoint of disease-free survival and secondary endpoints including safety and quality of life.

Efficacy and safety

After a median follow-up of 6.3 years, the 5-year rate of disease-free survival was 95% with letrozole and 91% with placebo, according to results reported by Dr. Goss in a plenary session at the meeting and simultaneously published (N Engl J Med. 2016. June 5 doi: 10.1056/NEJMoa1604700).

The difference translated to a more than one-third reduction in the risk of disease recurrence or the occurrence of contralateral breast cancer (HR, .66; P = .01). Roughly three-fourths of recurrences were distant.

The groups did not differ significantly with respect to the rate of overall survival, which was 93% with letrozole and 94% with placebo.

The annual incidence of contralateral breast cancer was sharply lower in the letrozole group, at 0.21%, than in the placebo group, at 0.49%, translating to a more than one-half reduction in this risk of this outcome (HR, .42; P = .007).

No new toxicities or emergent symptoms were noted from extending AI therapy, according to Dr. Goss. However, the letrozole group significantly more commonly experienced bone pain (18% vs. 14%), bone fractures (14% vs. 9%), and new-onset osteoporosis (11% vs. 6%). Therefore, “bone health remains important for risk-benefit consideration,” he said.

Patient-reported outcomes

In a separate session and the press briefing, Dr. Julie Lemieux, a researcher at the Centre Hospitalier affilié Universitaire de Québec, reported the trial’s patient-reported outcomes, ascertained from questionnaires completed at baseline and annually out to 5 years.

In general, both the letrozole and placebo groups had small deteriorations over time in global quality of life as assessed from summary scores on the mental and physical scales of the 36-item Short Form Health Survey (SF-36). But both also had small improvements over time in scores on the Menopause-Specific Quality of Life (MENQOL) scale.

When compared, the two groups were statistically indistinguishable on most of these measures. The only significant difference was greater worsening in the letrozole group on the role function-physical subscale of the SF-36, which pertains to difficulty performing work or physical activity due to physical health. However, the difference averaged just 3.2 points, which fell short of the 5 points that the investigators considered clinically important.

“The limitation of this analysis was that it was a highly selected population. All of these women had already tolerated 5 years of an aromatase inhibitor, and about 70% had received 5 years of tamoxifen before,” Dr. Lemieux commented. “Also, they were clinical trial participants.”

Nonetheless, these findings “are very reassuring for those women who want a longer duration of adjuvant endocrine therapy that they can expect a preserved quality of life,” she concluded.

Dr. Goss disclosed that he had no relevant conflicts of interest. Dr. Lemieux disclosed that she had no relevant conflicts of interest. The trial received support from Novartis.

CHICAGO – Extending adjuvant aromatase inhibitor (AI) therapy from 5 years to 10 years further reduces the risk of recurrence and new breast cancer in postmenopausal women treated for early disease, according to findings of the MA17.R trial.

In the phase III trial conducted by the Canadian Cancer Trials Group and the North American Breast Cancer Group, 1,918 postmenopausal women who had completed about 5 years of AI therapy (preceded by tamoxifen in the majority of cases) were randomized to take the AI letrozole or to stop therapy by taking placebo for an additional 5 years.

Compared with peers who stopped, women who continued AI therapy for 5 more years had a 34% lower risk of recurrence or contralateral breast cancer, investigators reported in sessions and a press briefing at the annual meeting of the American Society of Clinical Oncology. The trade-off was a small increase in the rates of skeletal adverse events such as fractures; quality of life was essentially unaffected.

“MA17.R is the first study to show the benefit of extending an adjuvant aromatase inhibitor beyond 5 years,” commented lead investigator Paul E. Goss, M.D., director of the Breast Cancer Research Program at the Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston. “Unlike many anticancer therapies, aromatase inhibitors are readily accessible around the world, and therefore, our results will further improve the outcome of many women with breast cancer.”

The disease-free survival curves will likely separate further, given a “legacy effect” of endocrine therapy that persists after it ends, he predicted. “And I think overall survival will eventually become positive in MA.17R. … The Food and Drug Administration has taken the opinion that overall survival follows disease-free survival like night follows day for endocrine therapies, and I think they are correct, I think that’s what we see in all the trials.”

Implications

It remains unclear how patients should be managed after 10 years of an AI, according to Dr. Goss. “That’s uncharted waters,” he elaborated. “We know from the curve of the natural history of this disease that it chronically relapses, and we continue to see patients 25 years after their primary diagnosis with a recurrence.” Some data in mice suggest there may be benefit from continuing the AI until recurrence. “I don’t think that would be entered into in clinical practice as a rule, because there is no clinical trial of that,” he said. “But this data will now take the aromatase inhibitors out to 10 years.”

The MA.17R trial’s findings show that extended duration of AI therapy is “clinically valuable,” according to ASCO expert Harold J. Burstein, M.D., Ph.D., a senior physician at the Dana-Farber Cancer Institute and an associate professor of medicine at the Harvard Medical School in Boston. He predicted the findings will have at least two consequences.

“One is tremendous interest in longer durations of therapy with the AI, but also some tailoring of treatment based on how the patient has fared with their therapy and on their baseline risk of recurrence. So women who have less risky cancer will probably be less inclined to pursue these longer durations, and women who have higher-risk cancers will be more inclined,” he explained.

Also, “women who have finished 5 years of an AI without any prior tamoxifen I think are going to be very compelled by these data, whereas women who have had 5 years of tamoxifen, 5 years of an AI, and are already 10 years out probably get less benefit numerically from yet longer duration of therapy,” he added. “And we are certainly not at the point of saying that women should be on these drugs for the rest of their lives.”

MA.17R design

Postmenopausal women were eligible for MA.17R if they had undergone resection of hormone receptor–positive early breast cancer and had already completed about 5 years of therapy with any of the three AIs currently on the market. In the large majority of cases, they also had previously received tamoxifen.

Many of the women came from the parent MA.17 trial, which tested an initial 5 years of letrozole (brand name Femara) against placebo after tamoxifen therapy. Longer-term results of that trial, previously reported (J Clin Oncol. 2012;30:718-21), showed that this duration of letrozole had a significant disease-free survival benefit (hazard ratio, .52) and overall survival benefit (HR, .61).

In the MA.17R trial, the women were randomized to letrozole or a placebo for an additional 5 years, with a primary endpoint of disease-free survival and secondary endpoints including safety and quality of life.

Efficacy and safety

After a median follow-up of 6.3 years, the 5-year rate of disease-free survival was 95% with letrozole and 91% with placebo, according to results reported by Dr. Goss in a plenary session at the meeting and simultaneously published (N Engl J Med. 2016. June 5 doi: 10.1056/NEJMoa1604700).

The difference translated to a more than one-third reduction in the risk of disease recurrence or the occurrence of contralateral breast cancer (HR, .66; P = .01). Roughly three-fourths of recurrences were distant.

The groups did not differ significantly with respect to the rate of overall survival, which was 93% with letrozole and 94% with placebo.

The annual incidence of contralateral breast cancer was sharply lower in the letrozole group, at 0.21%, than in the placebo group, at 0.49%, translating to a more than one-half reduction in this risk of this outcome (HR, .42; P = .007).

No new toxicities or emergent symptoms were noted from extending AI therapy, according to Dr. Goss. However, the letrozole group significantly more commonly experienced bone pain (18% vs. 14%), bone fractures (14% vs. 9%), and new-onset osteoporosis (11% vs. 6%). Therefore, “bone health remains important for risk-benefit consideration,” he said.

Patient-reported outcomes

In a separate session and the press briefing, Dr. Julie Lemieux, a researcher at the Centre Hospitalier affilié Universitaire de Québec, reported the trial’s patient-reported outcomes, ascertained from questionnaires completed at baseline and annually out to 5 years.

In general, both the letrozole and placebo groups had small deteriorations over time in global quality of life as assessed from summary scores on the mental and physical scales of the 36-item Short Form Health Survey (SF-36). But both also had small improvements over time in scores on the Menopause-Specific Quality of Life (MENQOL) scale.

When compared, the two groups were statistically indistinguishable on most of these measures. The only significant difference was greater worsening in the letrozole group on the role function-physical subscale of the SF-36, which pertains to difficulty performing work or physical activity due to physical health. However, the difference averaged just 3.2 points, which fell short of the 5 points that the investigators considered clinically important.

“The limitation of this analysis was that it was a highly selected population. All of these women had already tolerated 5 years of an aromatase inhibitor, and about 70% had received 5 years of tamoxifen before,” Dr. Lemieux commented. “Also, they were clinical trial participants.”

Nonetheless, these findings “are very reassuring for those women who want a longer duration of adjuvant endocrine therapy that they can expect a preserved quality of life,” she concluded.

Dr. Goss disclosed that he had no relevant conflicts of interest. Dr. Lemieux disclosed that she had no relevant conflicts of interest. The trial received support from Novartis.

NEW ORLEANS – Recurrent episodes of diabetic ketoacidosis (DKA) resulted in altered brain metabolite concentration, as well as differences in mental processing speed, compared with healthy controls, judging from the results from a small pilot study.

While previous work examining the relationship of DKA to cognition and neural structure has focused upon children and adolescents, researchers at Emory University and the Georgia Institute of Technology, both in Atlanta, set out of evaluate for the first time acute neuroanatomical and cognitive changes in adult patients with first and recurrent episodes of DKA. In an interview in advance of the annual scientific sessions of the American Diabetes Association, one of the researchers, Gilda E. Ennis, Ph.D., said that DKA is the most serious diabetic emergency in patients with type 1 and 2 diabetes and results in an estimated health care cost of $2.4 billion annually. “While we know that one of the major precipitating causes of DKA in adult patients is poor adherence to insulin therapy, we do not understand why patients are noncompliant,” said Dr. Ennis, who is a postdoctoral fellow in the Georgia Institute of Technology’s school of psychology.

She and her associates conducted a pilot study examining advanced MRI metrics and cognitive measures 72 hours after resolution of DKA in 10 patients with a first episode of DKA and 11 patients with three or more episodes of DKA. The same MRI and cognitive measures were collected from 10 healthy controls and 10 patients with type 1 diabetes and no history of DKA.

MRI spectroscopy revealed reduced N-acetylaspartate concentrations in diabetes patients with multiple episodes of DKA, compared with healthy controls, but no significant differences were seen between diabetes patients with and without DKA. Cognitive testing revealed that patients with recurrent DKA had significantly worse processing speed, compared with healthy controls (P = .02), while processing speed deficits in patients with a single DKA and those with diabetes and no DKA was intermediate between healthy controls and those with recurrent DKA.

“We were surprised to find significant cognitive and neural deficits in the recurrent DKA group relative to healthy controls in such a small sample,” Dr. Ennis said. “This suggests that statistical differences in cognition and neural structure between patients with recurrent DKA and healthy controls may be large. We found that recurrent DKA was associated with significant deficits in processing speed and memory, decreases in right putamen volume, regionally decreased white matter integrity, and altered brain metabolite concentrations, suggestive of CNS inflammatory changes and neuronal injury.”

The findings may explain the high rates of medication noncompliance commonly seen in this patient population. “If this proposition is true, conventional education and standard care approaches to the treatment of type 1 diabetes, especially in patients with a history of DKA, may need to change,” she said. “Strategies to improve insulin adherence may require a special insulin compliance intervention that includes persistent medication adherence reminders, such as text messaging and nurse-telephone follow-up.”

Dr. Ennis acknowledged that the findings require replication in a prospective longitudinal study with a larger sample size. “It will be important to determine if acute neuroanatomical and cognitive deficits in patients with recurrent DKA persist over time,” she said. “Duration of type 1 diabetes could produce similar findings and would need to be controlled in future research.” She reported having no financial disclosures.

[email protected]

NEW ORLEANS – Recurrent episodes of diabetic ketoacidosis (DKA) resulted in altered brain metabolite concentration, as well as differences in mental processing speed, compared with healthy controls, judging from the results from a small pilot study.

While previous work examining the relationship of DKA to cognition and neural structure has focused upon children and adolescents, researchers at Emory University and the Georgia Institute of Technology, both in Atlanta, set out of evaluate for the first time acute neuroanatomical and cognitive changes in adult patients with first and recurrent episodes of DKA. In an interview in advance of the annual scientific sessions of the American Diabetes Association, one of the researchers, Gilda E. Ennis, Ph.D., said that DKA is the most serious diabetic emergency in patients with type 1 and 2 diabetes and results in an estimated health care cost of $2.4 billion annually. “While we know that one of the major precipitating causes of DKA in adult patients is poor adherence to insulin therapy, we do not understand why patients are noncompliant,” said Dr. Ennis, who is a postdoctoral fellow in the Georgia Institute of Technology’s school of psychology.

She and her associates conducted a pilot study examining advanced MRI metrics and cognitive measures 72 hours after resolution of DKA in 10 patients with a first episode of DKA and 11 patients with three or more episodes of DKA. The same MRI and cognitive measures were collected from 10 healthy controls and 10 patients with type 1 diabetes and no history of DKA.

MRI spectroscopy revealed reduced N-acetylaspartate concentrations in diabetes patients with multiple episodes of DKA, compared with healthy controls, but no significant differences were seen between diabetes patients with and without DKA. Cognitive testing revealed that patients with recurrent DKA had significantly worse processing speed, compared with healthy controls (P = .02), while processing speed deficits in patients with a single DKA and those with diabetes and no DKA was intermediate between healthy controls and those with recurrent DKA.

“We were surprised to find significant cognitive and neural deficits in the recurrent DKA group relative to healthy controls in such a small sample,” Dr. Ennis said. “This suggests that statistical differences in cognition and neural structure between patients with recurrent DKA and healthy controls may be large. We found that recurrent DKA was associated with significant deficits in processing speed and memory, decreases in right putamen volume, regionally decreased white matter integrity, and altered brain metabolite concentrations, suggestive of CNS inflammatory changes and neuronal injury.”

The findings may explain the high rates of medication noncompliance commonly seen in this patient population. “If this proposition is true, conventional education and standard care approaches to the treatment of type 1 diabetes, especially in patients with a history of DKA, may need to change,” she said. “Strategies to improve insulin adherence may require a special insulin compliance intervention that includes persistent medication adherence reminders, such as text messaging and nurse-telephone follow-up.”

Dr. Ennis acknowledged that the findings require replication in a prospective longitudinal study with a larger sample size. “It will be important to determine if acute neuroanatomical and cognitive deficits in patients with recurrent DKA persist over time,” she said. “Duration of type 1 diabetes could produce similar findings and would need to be controlled in future research.” She reported having no financial disclosures.

[email protected]

NEW ORLEANS – Recurrent episodes of diabetic ketoacidosis (DKA) resulted in altered brain metabolite concentration, as well as differences in mental processing speed, compared with healthy controls, judging from the results from a small pilot study.

While previous work examining the relationship of DKA to cognition and neural structure has focused upon children and adolescents, researchers at Emory University and the Georgia Institute of Technology, both in Atlanta, set out of evaluate for the first time acute neuroanatomical and cognitive changes in adult patients with first and recurrent episodes of DKA. In an interview in advance of the annual scientific sessions of the American Diabetes Association, one of the researchers, Gilda E. Ennis, Ph.D., said that DKA is the most serious diabetic emergency in patients with type 1 and 2 diabetes and results in an estimated health care cost of $2.4 billion annually. “While we know that one of the major precipitating causes of DKA in adult patients is poor adherence to insulin therapy, we do not understand why patients are noncompliant,” said Dr. Ennis, who is a postdoctoral fellow in the Georgia Institute of Technology’s school of psychology.

She and her associates conducted a pilot study examining advanced MRI metrics and cognitive measures 72 hours after resolution of DKA in 10 patients with a first episode of DKA and 11 patients with three or more episodes of DKA. The same MRI and cognitive measures were collected from 10 healthy controls and 10 patients with type 1 diabetes and no history of DKA.

MRI spectroscopy revealed reduced N-acetylaspartate concentrations in diabetes patients with multiple episodes of DKA, compared with healthy controls, but no significant differences were seen between diabetes patients with and without DKA. Cognitive testing revealed that patients with recurrent DKA had significantly worse processing speed, compared with healthy controls (P = .02), while processing speed deficits in patients with a single DKA and those with diabetes and no DKA was intermediate between healthy controls and those with recurrent DKA.

“We were surprised to find significant cognitive and neural deficits in the recurrent DKA group relative to healthy controls in such a small sample,” Dr. Ennis said. “This suggests that statistical differences in cognition and neural structure between patients with recurrent DKA and healthy controls may be large. We found that recurrent DKA was associated with significant deficits in processing speed and memory, decreases in right putamen volume, regionally decreased white matter integrity, and altered brain metabolite concentrations, suggestive of CNS inflammatory changes and neuronal injury.”

The findings may explain the high rates of medication noncompliance commonly seen in this patient population. “If this proposition is true, conventional education and standard care approaches to the treatment of type 1 diabetes, especially in patients with a history of DKA, may need to change,” she said. “Strategies to improve insulin adherence may require a special insulin compliance intervention that includes persistent medication adherence reminders, such as text messaging and nurse-telephone follow-up.”

Dr. Ennis acknowledged that the findings require replication in a prospective longitudinal study with a larger sample size. “It will be important to determine if acute neuroanatomical and cognitive deficits in patients with recurrent DKA persist over time,” she said. “Duration of type 1 diabetes could produce similar findings and would need to be controlled in future research.” She reported having no financial disclosures.

[email protected]

NATIONAL HARBOR, MD. – Delayed-release dimethyl fumarate (DMF) coadministered with norgestimate/ethinyl estradiol, a commonly used progesterone-estrogen combination oral contraceptive, did not alter the OC’s pharmacokinetics or pharmacodynamics, according to the results of a small study.

The safety profile of the coadministered preparation is similar to the profile of DMF (Tecfidera, Biogen) alone, Dr. Bing Zhu said in a poster session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The findings indicate that women with relapsing-remitting multiple sclerosis (RRMS) who are of childbearing age and who are being treated with DMF can use OCs without having to modify the contraceptive dose, said Dr. Zhu, who is an employee of Biogen, Cambridge, Mass.

The study involved healthy women aged 18-45 years (mean age about 31 years) who were able to conceive. All received a daily OC (Ortho-Cyclen; 250 mcg norgestimate, 35 mcg ethinyl estradiol). After 28 days, those with progesterone levels less than 3 ng/mL were randomized to a 28-day regimen of either the daily dose of OC (n = 39) or OC along with DMF (240 mg twice daily), designated period 1, with crossover to the other treatment for a further 28 days (period 2). Blood samples were collected during the first 24 hours for pharmacokinetic measurements and at 2, 3, and 4 weeks for pharmacodynamic determinations.

The primary objective was the pharmacokinetics of norgestimate, as determined by measuring the levels of its main metabolite, norelgestromin. Secondary objectives included pharmacodynamics, as determined by the levels of serum progesterone and the safety/tolerability of DMF.

©areeya_ann/Thinkstock.com

Plasma concentrations of norelgestromin and ethinyl estradiol were identical over time in the OC and OC + DMF groups in period 1, as was serum progesterone.

Treatment-emergent adverse events were similar in type and severity in both groups. Most were mild. The prevalent adverse events included flushing and gastrointestinal disorders accompanied by nausea and vomiting. Adverse events occurred in 10 of the 39 (26%) subjects who received the OC and in 26 of the 39 (67%) subjects who received the OC + DMF. Discontinuation because of adverse events occurred in 8% and 15% of subjects who received the OC and the OC + DMF, respectively. There were no deaths.

“The results suggest that women of childbearing potential treated with DMF are able to use a combined OC for contraception without dose modification,” said Dr. Zhu.

The study findings were recently published (Neurology. 2016 Apr 5;86:Suppl P2.097).

The study was funded by Biogen. Dr. Zhu is a Biogen employee.

[email protected]

NATIONAL HARBOR, MD. – Delayed-release dimethyl fumarate (DMF) coadministered with norgestimate/ethinyl estradiol, a commonly used progesterone-estrogen combination oral contraceptive, did not alter the OC’s pharmacokinetics or pharmacodynamics, according to the results of a small study.

The safety profile of the coadministered preparation is similar to the profile of DMF (Tecfidera, Biogen) alone, Dr. Bing Zhu said in a poster session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The findings indicate that women with relapsing-remitting multiple sclerosis (RRMS) who are of childbearing age and who are being treated with DMF can use OCs without having to modify the contraceptive dose, said Dr. Zhu, who is an employee of Biogen, Cambridge, Mass.

The study involved healthy women aged 18-45 years (mean age about 31 years) who were able to conceive. All received a daily OC (Ortho-Cyclen; 250 mcg norgestimate, 35 mcg ethinyl estradiol). After 28 days, those with progesterone levels less than 3 ng/mL were randomized to a 28-day regimen of either the daily dose of OC (n = 39) or OC along with DMF (240 mg twice daily), designated period 1, with crossover to the other treatment for a further 28 days (period 2). Blood samples were collected during the first 24 hours for pharmacokinetic measurements and at 2, 3, and 4 weeks for pharmacodynamic determinations.

The primary objective was the pharmacokinetics of norgestimate, as determined by measuring the levels of its main metabolite, norelgestromin. Secondary objectives included pharmacodynamics, as determined by the levels of serum progesterone and the safety/tolerability of DMF.

©areeya_ann/Thinkstock.com

Plasma concentrations of norelgestromin and ethinyl estradiol were identical over time in the OC and OC + DMF groups in period 1, as was serum progesterone.

Treatment-emergent adverse events were similar in type and severity in both groups. Most were mild. The prevalent adverse events included flushing and gastrointestinal disorders accompanied by nausea and vomiting. Adverse events occurred in 10 of the 39 (26%) subjects who received the OC and in 26 of the 39 (67%) subjects who received the OC + DMF. Discontinuation because of adverse events occurred in 8% and 15% of subjects who received the OC and the OC + DMF, respectively. There were no deaths.

“The results suggest that women of childbearing potential treated with DMF are able to use a combined OC for contraception without dose modification,” said Dr. Zhu.

The study findings were recently published (Neurology. 2016 Apr 5;86:Suppl P2.097).

The study was funded by Biogen. Dr. Zhu is a Biogen employee.

[email protected]

NATIONAL HARBOR, MD. – Delayed-release dimethyl fumarate (DMF) coadministered with norgestimate/ethinyl estradiol, a commonly used progesterone-estrogen combination oral contraceptive, did not alter the OC’s pharmacokinetics or pharmacodynamics, according to the results of a small study.

The safety profile of the coadministered preparation is similar to the profile of DMF (Tecfidera, Biogen) alone, Dr. Bing Zhu said in a poster session at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The findings indicate that women with relapsing-remitting multiple sclerosis (RRMS) who are of childbearing age and who are being treated with DMF can use OCs without having to modify the contraceptive dose, said Dr. Zhu, who is an employee of Biogen, Cambridge, Mass.

The study involved healthy women aged 18-45 years (mean age about 31 years) who were able to conceive. All received a daily OC (Ortho-Cyclen; 250 mcg norgestimate, 35 mcg ethinyl estradiol). After 28 days, those with progesterone levels less than 3 ng/mL were randomized to a 28-day regimen of either the daily dose of OC (n = 39) or OC along with DMF (240 mg twice daily), designated period 1, with crossover to the other treatment for a further 28 days (period 2). Blood samples were collected during the first 24 hours for pharmacokinetic measurements and at 2, 3, and 4 weeks for pharmacodynamic determinations.

The primary objective was the pharmacokinetics of norgestimate, as determined by measuring the levels of its main metabolite, norelgestromin. Secondary objectives included pharmacodynamics, as determined by the levels of serum progesterone and the safety/tolerability of DMF.

©areeya_ann/Thinkstock.com

Plasma concentrations of norelgestromin and ethinyl estradiol were identical over time in the OC and OC + DMF groups in period 1, as was serum progesterone.

Treatment-emergent adverse events were similar in type and severity in both groups. Most were mild. The prevalent adverse events included flushing and gastrointestinal disorders accompanied by nausea and vomiting. Adverse events occurred in 10 of the 39 (26%) subjects who received the OC and in 26 of the 39 (67%) subjects who received the OC + DMF. Discontinuation because of adverse events occurred in 8% and 15% of subjects who received the OC and the OC + DMF, respectively. There were no deaths.

“The results suggest that women of childbearing potential treated with DMF are able to use a combined OC for contraception without dose modification,” said Dr. Zhu.

The study findings were recently published (Neurology. 2016 Apr 5;86:Suppl P2.097).

The study was funded by Biogen. Dr. Zhu is a Biogen employee.

[email protected]

NEW ORLEANS – In the first known controlled study of its kind, researchers demonstrated the reliability of trained dogs to alert hypoglycemia in human companions with type 1 diabetes, but at the cost of a high false-positive rate, compared with continuous glucose monitoring.

“The use of trained dogs to alert to changes in blood glucose in human companions with diabetes is increasing yet we don’t know how effective they are,” lead author Dr. Evan Los said in an interview in advance of the annual scientific sessions of the American Diabetes Association. “Enthusiastic anecdotal reports and limited in vitro studies are promising but rigorous studies have not been done. Clinicians are unable to provide informed advice when patients ask, ‘What do you think about diabetes alert dogs?’”

Dr. Los, a pediatric endocrinology fellow at Oregon Health and Science University, Portland, and his associates set out to conduct a controlled study of the reliability of diabetes alert dogs to detect hypoglycemia in their human companions with type 1 diabetes under real-life conditions. Capillary blood glucose (CBG) and continuous glucose monitoring (CGM) were used as comparators, and the study participants consisted of eight dog-human pairs. The human subjects ranged in age from 4 to 48 years old. Hypoglycemia was defined as CBG and/or CGM below 70 mg/dL and the human subjects answered survey questions regarding their impressions of the dog’s reliability and reasons for obtaining a diabetes alert dog. A timely alert was defined as occurring within 10 minutes before to 30 minutes after onset of hypoglycemia.

On a 10-point Likert scale, the dog users reported being “very satisfied” and “largely confident” in their dog’s ability to detect hypoglycemia (scores of 8.9 and 7.9, respectively), and they universally cited detection of hypoglycemia as the chief reason for obtaining a trained service dog. The researchers found that spontaneous dog alerts occurred 3.2 times more often than the rate of alerts during euglycemia, which was defined as 70-180 mg/dL, but the positive predictive value of dog alerts for hypoglycemia was only 12%. When Dr. Los and his associates reviewed event diaries and blinded CGM data, they observed that trained dogs provided a timely alert in 36% of all 45 hypoglycemia events. In the 30 events when both the dog-alerted and the blinded-CGM reached the hypoglycemia threshold, CGM would have alerted prior to the dog in 73% of events, which translated into a median difference of 22 minutes sooner.

“Trained dogs often alert a human companion to otherwise unknown hypoglycemia,” Dr. Los said. “However, due to high false-positive rates, a dog alert alone is unlikely to be helpful in differentiating hypo-/hyper-/euglycemia. CGM often detects hypoglycemia before a trained dog by a clinically significant margin.”

He acknowledged the study’s small sample size as a limitation. “Dog breeds and training methods were not universal, so there are likely to be variation in the reliability between dogs,” Dr. Los added. “This is not the final word on whether trained dogs might be helpful for patients with diabetes and there may be other benefits not assessed by this study such as having a positive partner in the daily management of a chronic disease.” He reported having no financial disclosures.

[email protected]

NEW ORLEANS – In the first known controlled study of its kind, researchers demonstrated the reliability of trained dogs to alert hypoglycemia in human companions with type 1 diabetes, but at the cost of a high false-positive rate, compared with continuous glucose monitoring.

“The use of trained dogs to alert to changes in blood glucose in human companions with diabetes is increasing yet we don’t know how effective they are,” lead author Dr. Evan Los said in an interview in advance of the annual scientific sessions of the American Diabetes Association. “Enthusiastic anecdotal reports and limited in vitro studies are promising but rigorous studies have not been done. Clinicians are unable to provide informed advice when patients ask, ‘What do you think about diabetes alert dogs?’”

Dr. Los, a pediatric endocrinology fellow at Oregon Health and Science University, Portland, and his associates set out to conduct a controlled study of the reliability of diabetes alert dogs to detect hypoglycemia in their human companions with type 1 diabetes under real-life conditions. Capillary blood glucose (CBG) and continuous glucose monitoring (CGM) were used as comparators, and the study participants consisted of eight dog-human pairs. The human subjects ranged in age from 4 to 48 years old. Hypoglycemia was defined as CBG and/or CGM below 70 mg/dL and the human subjects answered survey questions regarding their impressions of the dog’s reliability and reasons for obtaining a diabetes alert dog. A timely alert was defined as occurring within 10 minutes before to 30 minutes after onset of hypoglycemia.

On a 10-point Likert scale, the dog users reported being “very satisfied” and “largely confident” in their dog’s ability to detect hypoglycemia (scores of 8.9 and 7.9, respectively), and they universally cited detection of hypoglycemia as the chief reason for obtaining a trained service dog. The researchers found that spontaneous dog alerts occurred 3.2 times more often than the rate of alerts during euglycemia, which was defined as 70-180 mg/dL, but the positive predictive value of dog alerts for hypoglycemia was only 12%. When Dr. Los and his associates reviewed event diaries and blinded CGM data, they observed that trained dogs provided a timely alert in 36% of all 45 hypoglycemia events. In the 30 events when both the dog-alerted and the blinded-CGM reached the hypoglycemia threshold, CGM would have alerted prior to the dog in 73% of events, which translated into a median difference of 22 minutes sooner.

“Trained dogs often alert a human companion to otherwise unknown hypoglycemia,” Dr. Los said. “However, due to high false-positive rates, a dog alert alone is unlikely to be helpful in differentiating hypo-/hyper-/euglycemia. CGM often detects hypoglycemia before a trained dog by a clinically significant margin.”

He acknowledged the study’s small sample size as a limitation. “Dog breeds and training methods were not universal, so there are likely to be variation in the reliability between dogs,” Dr. Los added. “This is not the final word on whether trained dogs might be helpful for patients with diabetes and there may be other benefits not assessed by this study such as having a positive partner in the daily management of a chronic disease.” He reported having no financial disclosures.

[email protected]

NEW ORLEANS – In the first known controlled study of its kind, researchers demonstrated the reliability of trained dogs to alert hypoglycemia in human companions with type 1 diabetes, but at the cost of a high false-positive rate, compared with continuous glucose monitoring.

“The use of trained dogs to alert to changes in blood glucose in human companions with diabetes is increasing yet we don’t know how effective they are,” lead author Dr. Evan Los said in an interview in advance of the annual scientific sessions of the American Diabetes Association. “Enthusiastic anecdotal reports and limited in vitro studies are promising but rigorous studies have not been done. Clinicians are unable to provide informed advice when patients ask, ‘What do you think about diabetes alert dogs?’”

Dr. Los, a pediatric endocrinology fellow at Oregon Health and Science University, Portland, and his associates set out to conduct a controlled study of the reliability of diabetes alert dogs to detect hypoglycemia in their human companions with type 1 diabetes under real-life conditions. Capillary blood glucose (CBG) and continuous glucose monitoring (CGM) were used as comparators, and the study participants consisted of eight dog-human pairs. The human subjects ranged in age from 4 to 48 years old. Hypoglycemia was defined as CBG and/or CGM below 70 mg/dL and the human subjects answered survey questions regarding their impressions of the dog’s reliability and reasons for obtaining a diabetes alert dog. A timely alert was defined as occurring within 10 minutes before to 30 minutes after onset of hypoglycemia.

On a 10-point Likert scale, the dog users reported being “very satisfied” and “largely confident” in their dog’s ability to detect hypoglycemia (scores of 8.9 and 7.9, respectively), and they universally cited detection of hypoglycemia as the chief reason for obtaining a trained service dog. The researchers found that spontaneous dog alerts occurred 3.2 times more often than the rate of alerts during euglycemia, which was defined as 70-180 mg/dL, but the positive predictive value of dog alerts for hypoglycemia was only 12%. When Dr. Los and his associates reviewed event diaries and blinded CGM data, they observed that trained dogs provided a timely alert in 36% of all 45 hypoglycemia events. In the 30 events when both the dog-alerted and the blinded-CGM reached the hypoglycemia threshold, CGM would have alerted prior to the dog in 73% of events, which translated into a median difference of 22 minutes sooner.

“Trained dogs often alert a human companion to otherwise unknown hypoglycemia,” Dr. Los said. “However, due to high false-positive rates, a dog alert alone is unlikely to be helpful in differentiating hypo-/hyper-/euglycemia. CGM often detects hypoglycemia before a trained dog by a clinically significant margin.”

He acknowledged the study’s small sample size as a limitation. “Dog breeds and training methods were not universal, so there are likely to be variation in the reliability between dogs,” Dr. Los added. “This is not the final word on whether trained dogs might be helpful for patients with diabetes and there may be other benefits not assessed by this study such as having a positive partner in the daily management of a chronic disease.” He reported having no financial disclosures.

[email protected]