During a particularly busy day in my inpatient and outpatient practice, I realized that nearly every one of the patients had been given the diagnosis of bipolar disorder at one point or another. The interesting thing is this wasn’t an unusual day.

Tassii/E+/Getty Images

Nearly all of my patients and their family members have been given the diagnosis of bipolar disorder. Because prevalence of bipolar affective disorders is a little over 2%, this seemed a little odd. Could there be an epidemic of bipolar disorder in the area? Should someone sound the alarm on this unique cluster and get Julia Roberts ready? Unfortunately, the story behind this mystery is a little less sexy but nevertheless interesting.

When I probe more into what symptoms might have led to the diagnosis of bipolar disorder, I most often get some sort of answer about being easily angered (“I’m fine 1 minute and the next minute I’m yelling at my mom”) or mood changing from 1 minute to the next. Rarely do they tell me about sleeping less, increased energy, change in mood (elation, anger, irritability), increase in activity level, and increased pleasurable though dangerous activities all happening around the same time(s). So what is going on?

Beginning in the 1990s, a debate about the phenotypic presentation of pediatric bipolar disorder polarized the field. It was theorized that mania could present with severe nonepisodic irritability with extended periods of very rapid mood cycling within the day as opposed to discrete episodic mood cycles in children and adolescents. With this broader conceptualization in the United States, the rate of bipolar diagnosis increased by over 40 times in less than a decade.¹ Similarly, the use of mood stabilizers and atypical antipsychotics in children also rose substantially.²

To help assess if severe nonepisodic irritability belongs in the spectrum of bipolar disorders, the National Institutes of Mental Health proposed a syndrome called “Severe Mood Dysregulation” or SMD, to promote the study of children with this phenotype. In longitudinal studies, Stringaris et al. compared rates of manic episodes in youth with SMD versus bipolar disorder over 2 years and found only one youth (1%) with SMD who presented with manic, hypomanic, or mixed episodes, compared with 58 (62%) with bipolar disorder.³ Leibenluft et al.showed that chronic irritability during early adolescence predicted ADHD at late adolescence and major depressive disorder in early adulthood whereas episodic irritability predicted mania.⁴ Twenty-year follow-up of the same sample showed chronic irritability in adolescence predicted dysthymia, generalized anxiety disorders, and major depressive disorder.⁵ Other longitudinal studies essentially have shown the same results.⁶

At this point, the question of whether chronic irritability is a part of the bipolar spectrum disorder is largely resolved – the consensus is that chronic irritability, no matter how severe, is not sufficient for a diagnosis of bipolar disorder.⁷ The diagnosis emphasizes the episodic nature of the illness, and that irritability would wax and wane with other manic symptoms such as changes in energy and sleep. And the ultrarapid mood changes (mood changes within the day) appear to describe mood fluctuations within a manic episode as opposed to each change being a separate episode.

So, most likely, my patients were caught in a time of uncertainty before data were able to clarify their phenotype.
 

Dr. Chung is a child and adolescent psychiatrist at the University of Vermont Medical Center, Burlington, and practices at Champlain Valley Physician’s Hospital in Plattsburgh, N.Y. Email him at pdnews@mdedge.com.

References

1. Biol Psychiatry. 2007 Jul 15;62(2):107–14.

2. JAMA Psychiatry. 2015 Sep;72(9):859-60.

3. J Am Acad Child Adolesc Psychiatry. 2010 Apr;49(4):397-405.

4. J Child Adolesc Psychopharmacol 2006;16(4):456-66.

5. Am J Psychiatry. 2009 Sep;166(9):1048-54.

6. Biol Psychiatry. 2006 Nov 1;60(9):991-7.

7. Bipolar Disord. 2017 Nov;19(7):524-43.

During a particularly busy day in my inpatient and outpatient practice, I realized that nearly every one of the patients had been given the diagnosis of bipolar disorder at one point or another. The interesting thing is this wasn’t an unusual day.

Tassii/E+/Getty Images

Nearly all of my patients and their family members have been given the diagnosis of bipolar disorder. Because prevalence of bipolar affective disorders is a little over 2%, this seemed a little odd. Could there be an epidemic of bipolar disorder in the area? Should someone sound the alarm on this unique cluster and get Julia Roberts ready? Unfortunately, the story behind this mystery is a little less sexy but nevertheless interesting.

When I probe more into what symptoms might have led to the diagnosis of bipolar disorder, I most often get some sort of answer about being easily angered (“I’m fine 1 minute and the next minute I’m yelling at my mom”) or mood changing from 1 minute to the next. Rarely do they tell me about sleeping less, increased energy, change in mood (elation, anger, irritability), increase in activity level, and increased pleasurable though dangerous activities all happening around the same time(s). So what is going on?

Beginning in the 1990s, a debate about the phenotypic presentation of pediatric bipolar disorder polarized the field. It was theorized that mania could present with severe nonepisodic irritability with extended periods of very rapid mood cycling within the day as opposed to discrete episodic mood cycles in children and adolescents. With this broader conceptualization in the United States, the rate of bipolar diagnosis increased by over 40 times in less than a decade.¹ Similarly, the use of mood stabilizers and atypical antipsychotics in children also rose substantially.²

To help assess if severe nonepisodic irritability belongs in the spectrum of bipolar disorders, the National Institutes of Mental Health proposed a syndrome called “Severe Mood Dysregulation” or SMD, to promote the study of children with this phenotype. In longitudinal studies, Stringaris et al. compared rates of manic episodes in youth with SMD versus bipolar disorder over 2 years and found only one youth (1%) with SMD who presented with manic, hypomanic, or mixed episodes, compared with 58 (62%) with bipolar disorder.³ Leibenluft et al.showed that chronic irritability during early adolescence predicted ADHD at late adolescence and major depressive disorder in early adulthood whereas episodic irritability predicted mania.⁴ Twenty-year follow-up of the same sample showed chronic irritability in adolescence predicted dysthymia, generalized anxiety disorders, and major depressive disorder.⁵ Other longitudinal studies essentially have shown the same results.⁶

At this point, the question of whether chronic irritability is a part of the bipolar spectrum disorder is largely resolved – the consensus is that chronic irritability, no matter how severe, is not sufficient for a diagnosis of bipolar disorder.⁷ The diagnosis emphasizes the episodic nature of the illness, and that irritability would wax and wane with other manic symptoms such as changes in energy and sleep. And the ultrarapid mood changes (mood changes within the day) appear to describe mood fluctuations within a manic episode as opposed to each change being a separate episode.

So, most likely, my patients were caught in a time of uncertainty before data were able to clarify their phenotype.
 

Dr. Chung is a child and adolescent psychiatrist at the University of Vermont Medical Center, Burlington, and practices at Champlain Valley Physician’s Hospital in Plattsburgh, N.Y. Email him at pdnews@mdedge.com.

References

1. Biol Psychiatry. 2007 Jul 15;62(2):107–14.

2. JAMA Psychiatry. 2015 Sep;72(9):859-60.

3. J Am Acad Child Adolesc Psychiatry. 2010 Apr;49(4):397-405.

4. J Child Adolesc Psychopharmacol 2006;16(4):456-66.

5. Am J Psychiatry. 2009 Sep;166(9):1048-54.

6. Biol Psychiatry. 2006 Nov 1;60(9):991-7.

7. Bipolar Disord. 2017 Nov;19(7):524-43.

During a particularly busy day in my inpatient and outpatient practice, I realized that nearly every one of the patients had been given the diagnosis of bipolar disorder at one point or another. The interesting thing is this wasn’t an unusual day.

Tassii/E+/Getty Images

Nearly all of my patients and their family members have been given the diagnosis of bipolar disorder. Because prevalence of bipolar affective disorders is a little over 2%, this seemed a little odd. Could there be an epidemic of bipolar disorder in the area? Should someone sound the alarm on this unique cluster and get Julia Roberts ready? Unfortunately, the story behind this mystery is a little less sexy but nevertheless interesting.

When I probe more into what symptoms might have led to the diagnosis of bipolar disorder, I most often get some sort of answer about being easily angered (“I’m fine 1 minute and the next minute I’m yelling at my mom”) or mood changing from 1 minute to the next. Rarely do they tell me about sleeping less, increased energy, change in mood (elation, anger, irritability), increase in activity level, and increased pleasurable though dangerous activities all happening around the same time(s). So what is going on?

Beginning in the 1990s, a debate about the phenotypic presentation of pediatric bipolar disorder polarized the field. It was theorized that mania could present with severe nonepisodic irritability with extended periods of very rapid mood cycling within the day as opposed to discrete episodic mood cycles in children and adolescents. With this broader conceptualization in the United States, the rate of bipolar diagnosis increased by over 40 times in less than a decade.¹ Similarly, the use of mood stabilizers and atypical antipsychotics in children also rose substantially.²

To help assess if severe nonepisodic irritability belongs in the spectrum of bipolar disorders, the National Institutes of Mental Health proposed a syndrome called “Severe Mood Dysregulation” or SMD, to promote the study of children with this phenotype. In longitudinal studies, Stringaris et al. compared rates of manic episodes in youth with SMD versus bipolar disorder over 2 years and found only one youth (1%) with SMD who presented with manic, hypomanic, or mixed episodes, compared with 58 (62%) with bipolar disorder.³ Leibenluft et al.showed that chronic irritability during early adolescence predicted ADHD at late adolescence and major depressive disorder in early adulthood whereas episodic irritability predicted mania.⁴ Twenty-year follow-up of the same sample showed chronic irritability in adolescence predicted dysthymia, generalized anxiety disorders, and major depressive disorder.⁵ Other longitudinal studies essentially have shown the same results.⁶

At this point, the question of whether chronic irritability is a part of the bipolar spectrum disorder is largely resolved – the consensus is that chronic irritability, no matter how severe, is not sufficient for a diagnosis of bipolar disorder.⁷ The diagnosis emphasizes the episodic nature of the illness, and that irritability would wax and wane with other manic symptoms such as changes in energy and sleep. And the ultrarapid mood changes (mood changes within the day) appear to describe mood fluctuations within a manic episode as opposed to each change being a separate episode.

So, most likely, my patients were caught in a time of uncertainty before data were able to clarify their phenotype.
 

Dr. Chung is a child and adolescent psychiatrist at the University of Vermont Medical Center, Burlington, and practices at Champlain Valley Physician’s Hospital in Plattsburgh, N.Y. Email him at pdnews@mdedge.com.

References

1. Biol Psychiatry. 2007 Jul 15;62(2):107–14.

2. JAMA Psychiatry. 2015 Sep;72(9):859-60.

3. J Am Acad Child Adolesc Psychiatry. 2010 Apr;49(4):397-405.

4. J Child Adolesc Psychopharmacol 2006;16(4):456-66.

5. Am J Psychiatry. 2009 Sep;166(9):1048-54.

6. Biol Psychiatry. 2006 Nov 1;60(9):991-7.

7. Bipolar Disord. 2017 Nov;19(7):524-43.

As I’m writing, my Twitter feed announces yet another public shooting, this one at a Walmart in Oklahoma. It’s a problem that gets worse as it gets more attention and the argument over how to approach the issue of mass shootings still continues down two separate and distinct pathways: Is this the result of too-easy access to firearms or is it one of untreated mental illness?

flownaksala/Thinkstock

Sen. John Cornyn (R-Tex.) spoke on the Senate floor on Oct. 23, 2019, about new legislation he is cosponsoring in the aftermath of two mass shootings in Texas this past August. The Restoring, Enhancing, Strengthening, and Promoting Our Nation’s Safety Efforts Act of 2019 (S. 2690), or the RESPONSE Act, is designed to “reduce mass violence, strengthen mental health collaboration in communities, improve school safety, and for other purposes.” Sen. Cornyn notes that in the aftermath of those shootings he met with his constituents and he heard a common refrain: Please do something.

“Unfortunately, there is no quick fix, no simple answer, instead we are left to look at the factors that led to these attacks and to try to do something to prevent the sequence of events from playing out again in the future,” Sen. Cornyn said.

“While mental illness is not the prevailing cause of mass violence, enhanced mental health resources are critical to saving lives,” he said, adding that most gun deaths are from suicide. In his speech, he outlined the issues it would address – and despite his statement that mental illness is not the cause of mass violence – he went on to elaborate on the issues that the bill would address.

“First, this legislation takes aim at unlicensed firearms dealers who are breaking the law,” he said. This legislation would create a task force to prosecute those who buy and sell firearms through unlicensed dealers, and he notes that one of the Texas shooters was denied a gun by a licensed firearms dealer before purchasing one from an unlicensed dealer. That Sen. Cornyn’s proposed legislation would not create any new gun legislation is not a surprise: he has an A+ rating from the National Rifle Association and his website’s fun facts include the statement: “Sen. Cornyn owns several firearms and hunts as often as he can.”

The rest of the RESPONSE Act takes aim at those who have or might have psychiatric disorders or a tendency toward violence. Sen. Cornyn noted that the act would expand assisted outpatient treatment (AOT, or outpatient civil commitment). He referenced this as a way for families to get care for their loved ones in the community rather than in a hospital and did not allude to the involuntary nature of the treatment.

Marvin Swartz, MD, is professor of psychiatry at Duke University, Durham, N.C., and lead investigator on outcome studies following the implementation of outpatient civil commitment legislation.

“AOT may be justified in improving treatment adherence and service provision,” Dr. Swartz noted, “but there is no direct line to serious violence. The violence we documented as reduced were mainly minor acts of interpersonal violence – pushing and shoving – what we call minor acts of violence. There is no evidence that AOT is a remedy to serious acts of violence – mass shootings included.”

In addition, Sen. Cornyn noted there would be expanded crisis intervention teams and increased coordination between mental health providers and law enforcement. Furthermore, the bill would make schools safer by identifying students whose behavior indicated a threat of violence and providing those students with the services they need. This would be done “by promoting best practices within our schools and promoting Internet safety.”

Finally, Sen. Cornyn talked about using social media as a means to identify those who might be a danger. “Because so often these shooters advertise on social media ... this legislation includes provisions to [ensure] that law enforcement can receive timely information about threats made online.”

The bill already has garnered both support and opposition. It has been supported by the National Council for Behavioral Health, the National Alliance on Mental Illness (NAMI), and the Treatment Advocacy Center. Those opposed to the legislation include the National Disability Rights Network, the American Association of People with Disabilities, the National Council on Independent Living, the Disability Rights Education & Defense Fund, the Bazelon Center for Mental Health Law, and the Autistic Self Advocacy Network. The American Psychiatric Association has not made a statement on the proposed legislation as of this writing.

The National Council for Behavioral Health posted an endorsement on its website. It notes: “The RESPONSE Act authorizes up to $10 million of existing funds in the Department of Justice for partnership between law enforcement and mental health providers to increase access to long-acting medically assisted treatment. Additionally, it requires the Department of Health and Human Services (HHS) to develop and disseminate guidance for states to fund mental health programs and crisis intervention teams through Medicaid as well as to issue a report to Congress on best practices to expand the mental health workforce. These provisions aim to divert more individuals from incarceration and will create more opportunities for community-based treatment and recovery.”

There is no question that psychiatric treatment for those with mental illness is underfunded and often inaccessible. But while it is true that some individuals become violent when they are ill, most do not, and targeting those one in five Americans who suffer from a psychiatric disorder each year in an effort to identify, then thwart, the rare mass murderer among us makes no sense.

Acts of mass violence remain rare. In 2018, the year we had a record-breaking number of mass shootings, there were 12 mass murders in the United States, according to the criteria used by Mother Jones, and 27 active shooter incidents using the FBI’s criteria. Approximately half of all mass shooters showed signs of mental illness prior to the shooting and of those, some had never come to the attention of mental health professionals in a way that would have predicted violence. While linking mass violence to mental illness may seem reasonable, the numbers just don’t make sense and targeting this presumed link between mental illness and mass violence is stigmatizing.

The text of the RESPONSE Act reveals proposed legislation that is perhaps more thoughtful than Sen. Cornyn’s speech suggested; the bill starts with funding services for those with psychiatric disorders who are being released from the correctional system, a population that may be at higher risk for acts of violence. The funding for outpatient civil commitment is worded in such a way that it is hard to know exactly what is required. The bill starts by mandating that each state must use 10% of the funding it gets from this bill for court-ordered treatment (AOT), but then lists alternative ways states may use that 10%, including “otherwise support evidence-based programs that address the needs of eligible patients.” In all, the proposed legislation is long and complex and attempts to address issues related to terrorism, the Internet, mental health, and the educational system. It’s an ambitious use of $10 million a year for our entire country.

At a time when mental health care is desperately underfunded and many are unable to access treatment, it is tempting to endorse any legislation that improves funding. But does it serve society to endorse legislation that suggests psychiatrists can prevent mass shootings? Does that ultimately serve our patients? My best guess is that we should aim legislation at preventing mass murders toward limiting access to firearms and banning weapons designed to kill many people quickly.
 

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle of Inpatient Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016), and has a private practice in Baltimore.

As I’m writing, my Twitter feed announces yet another public shooting, this one at a Walmart in Oklahoma. It’s a problem that gets worse as it gets more attention and the argument over how to approach the issue of mass shootings still continues down two separate and distinct pathways: Is this the result of too-easy access to firearms or is it one of untreated mental illness?

flownaksala/Thinkstock

Sen. John Cornyn (R-Tex.) spoke on the Senate floor on Oct. 23, 2019, about new legislation he is cosponsoring in the aftermath of two mass shootings in Texas this past August. The Restoring, Enhancing, Strengthening, and Promoting Our Nation’s Safety Efforts Act of 2019 (S. 2690), or the RESPONSE Act, is designed to “reduce mass violence, strengthen mental health collaboration in communities, improve school safety, and for other purposes.” Sen. Cornyn notes that in the aftermath of those shootings he met with his constituents and he heard a common refrain: Please do something.

“Unfortunately, there is no quick fix, no simple answer, instead we are left to look at the factors that led to these attacks and to try to do something to prevent the sequence of events from playing out again in the future,” Sen. Cornyn said.

“While mental illness is not the prevailing cause of mass violence, enhanced mental health resources are critical to saving lives,” he said, adding that most gun deaths are from suicide. In his speech, he outlined the issues it would address – and despite his statement that mental illness is not the cause of mass violence – he went on to elaborate on the issues that the bill would address.

“First, this legislation takes aim at unlicensed firearms dealers who are breaking the law,” he said. This legislation would create a task force to prosecute those who buy and sell firearms through unlicensed dealers, and he notes that one of the Texas shooters was denied a gun by a licensed firearms dealer before purchasing one from an unlicensed dealer. That Sen. Cornyn’s proposed legislation would not create any new gun legislation is not a surprise: he has an A+ rating from the National Rifle Association and his website’s fun facts include the statement: “Sen. Cornyn owns several firearms and hunts as often as he can.”

The rest of the RESPONSE Act takes aim at those who have or might have psychiatric disorders or a tendency toward violence. Sen. Cornyn noted that the act would expand assisted outpatient treatment (AOT, or outpatient civil commitment). He referenced this as a way for families to get care for their loved ones in the community rather than in a hospital and did not allude to the involuntary nature of the treatment.

Marvin Swartz, MD, is professor of psychiatry at Duke University, Durham, N.C., and lead investigator on outcome studies following the implementation of outpatient civil commitment legislation.

“AOT may be justified in improving treatment adherence and service provision,” Dr. Swartz noted, “but there is no direct line to serious violence. The violence we documented as reduced were mainly minor acts of interpersonal violence – pushing and shoving – what we call minor acts of violence. There is no evidence that AOT is a remedy to serious acts of violence – mass shootings included.”

In addition, Sen. Cornyn noted there would be expanded crisis intervention teams and increased coordination between mental health providers and law enforcement. Furthermore, the bill would make schools safer by identifying students whose behavior indicated a threat of violence and providing those students with the services they need. This would be done “by promoting best practices within our schools and promoting Internet safety.”

Finally, Sen. Cornyn talked about using social media as a means to identify those who might be a danger. “Because so often these shooters advertise on social media ... this legislation includes provisions to [ensure] that law enforcement can receive timely information about threats made online.”

The bill already has garnered both support and opposition. It has been supported by the National Council for Behavioral Health, the National Alliance on Mental Illness (NAMI), and the Treatment Advocacy Center. Those opposed to the legislation include the National Disability Rights Network, the American Association of People with Disabilities, the National Council on Independent Living, the Disability Rights Education & Defense Fund, the Bazelon Center for Mental Health Law, and the Autistic Self Advocacy Network. The American Psychiatric Association has not made a statement on the proposed legislation as of this writing.

The National Council for Behavioral Health posted an endorsement on its website. It notes: “The RESPONSE Act authorizes up to $10 million of existing funds in the Department of Justice for partnership between law enforcement and mental health providers to increase access to long-acting medically assisted treatment. Additionally, it requires the Department of Health and Human Services (HHS) to develop and disseminate guidance for states to fund mental health programs and crisis intervention teams through Medicaid as well as to issue a report to Congress on best practices to expand the mental health workforce. These provisions aim to divert more individuals from incarceration and will create more opportunities for community-based treatment and recovery.”

There is no question that psychiatric treatment for those with mental illness is underfunded and often inaccessible. But while it is true that some individuals become violent when they are ill, most do not, and targeting those one in five Americans who suffer from a psychiatric disorder each year in an effort to identify, then thwart, the rare mass murderer among us makes no sense.

Acts of mass violence remain rare. In 2018, the year we had a record-breaking number of mass shootings, there were 12 mass murders in the United States, according to the criteria used by Mother Jones, and 27 active shooter incidents using the FBI’s criteria. Approximately half of all mass shooters showed signs of mental illness prior to the shooting and of those, some had never come to the attention of mental health professionals in a way that would have predicted violence. While linking mass violence to mental illness may seem reasonable, the numbers just don’t make sense and targeting this presumed link between mental illness and mass violence is stigmatizing.

The text of the RESPONSE Act reveals proposed legislation that is perhaps more thoughtful than Sen. Cornyn’s speech suggested; the bill starts with funding services for those with psychiatric disorders who are being released from the correctional system, a population that may be at higher risk for acts of violence. The funding for outpatient civil commitment is worded in such a way that it is hard to know exactly what is required. The bill starts by mandating that each state must use 10% of the funding it gets from this bill for court-ordered treatment (AOT), but then lists alternative ways states may use that 10%, including “otherwise support evidence-based programs that address the needs of eligible patients.” In all, the proposed legislation is long and complex and attempts to address issues related to terrorism, the Internet, mental health, and the educational system. It’s an ambitious use of $10 million a year for our entire country.

At a time when mental health care is desperately underfunded and many are unable to access treatment, it is tempting to endorse any legislation that improves funding. But does it serve society to endorse legislation that suggests psychiatrists can prevent mass shootings? Does that ultimately serve our patients? My best guess is that we should aim legislation at preventing mass murders toward limiting access to firearms and banning weapons designed to kill many people quickly.
 

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle of Inpatient Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016), and has a private practice in Baltimore.

As I’m writing, my Twitter feed announces yet another public shooting, this one at a Walmart in Oklahoma. It’s a problem that gets worse as it gets more attention and the argument over how to approach the issue of mass shootings still continues down two separate and distinct pathways: Is this the result of too-easy access to firearms or is it one of untreated mental illness?

flownaksala/Thinkstock

Sen. John Cornyn (R-Tex.) spoke on the Senate floor on Oct. 23, 2019, about new legislation he is cosponsoring in the aftermath of two mass shootings in Texas this past August. The Restoring, Enhancing, Strengthening, and Promoting Our Nation’s Safety Efforts Act of 2019 (S. 2690), or the RESPONSE Act, is designed to “reduce mass violence, strengthen mental health collaboration in communities, improve school safety, and for other purposes.” Sen. Cornyn notes that in the aftermath of those shootings he met with his constituents and he heard a common refrain: Please do something.

“Unfortunately, there is no quick fix, no simple answer, instead we are left to look at the factors that led to these attacks and to try to do something to prevent the sequence of events from playing out again in the future,” Sen. Cornyn said.

“While mental illness is not the prevailing cause of mass violence, enhanced mental health resources are critical to saving lives,” he said, adding that most gun deaths are from suicide. In his speech, he outlined the issues it would address – and despite his statement that mental illness is not the cause of mass violence – he went on to elaborate on the issues that the bill would address.

“First, this legislation takes aim at unlicensed firearms dealers who are breaking the law,” he said. This legislation would create a task force to prosecute those who buy and sell firearms through unlicensed dealers, and he notes that one of the Texas shooters was denied a gun by a licensed firearms dealer before purchasing one from an unlicensed dealer. That Sen. Cornyn’s proposed legislation would not create any new gun legislation is not a surprise: he has an A+ rating from the National Rifle Association and his website’s fun facts include the statement: “Sen. Cornyn owns several firearms and hunts as often as he can.”

The rest of the RESPONSE Act takes aim at those who have or might have psychiatric disorders or a tendency toward violence. Sen. Cornyn noted that the act would expand assisted outpatient treatment (AOT, or outpatient civil commitment). He referenced this as a way for families to get care for their loved ones in the community rather than in a hospital and did not allude to the involuntary nature of the treatment.

Marvin Swartz, MD, is professor of psychiatry at Duke University, Durham, N.C., and lead investigator on outcome studies following the implementation of outpatient civil commitment legislation.

“AOT may be justified in improving treatment adherence and service provision,” Dr. Swartz noted, “but there is no direct line to serious violence. The violence we documented as reduced were mainly minor acts of interpersonal violence – pushing and shoving – what we call minor acts of violence. There is no evidence that AOT is a remedy to serious acts of violence – mass shootings included.”

In addition, Sen. Cornyn noted there would be expanded crisis intervention teams and increased coordination between mental health providers and law enforcement. Furthermore, the bill would make schools safer by identifying students whose behavior indicated a threat of violence and providing those students with the services they need. This would be done “by promoting best practices within our schools and promoting Internet safety.”

Finally, Sen. Cornyn talked about using social media as a means to identify those who might be a danger. “Because so often these shooters advertise on social media ... this legislation includes provisions to [ensure] that law enforcement can receive timely information about threats made online.”

The bill already has garnered both support and opposition. It has been supported by the National Council for Behavioral Health, the National Alliance on Mental Illness (NAMI), and the Treatment Advocacy Center. Those opposed to the legislation include the National Disability Rights Network, the American Association of People with Disabilities, the National Council on Independent Living, the Disability Rights Education & Defense Fund, the Bazelon Center for Mental Health Law, and the Autistic Self Advocacy Network. The American Psychiatric Association has not made a statement on the proposed legislation as of this writing.

The National Council for Behavioral Health posted an endorsement on its website. It notes: “The RESPONSE Act authorizes up to $10 million of existing funds in the Department of Justice for partnership between law enforcement and mental health providers to increase access to long-acting medically assisted treatment. Additionally, it requires the Department of Health and Human Services (HHS) to develop and disseminate guidance for states to fund mental health programs and crisis intervention teams through Medicaid as well as to issue a report to Congress on best practices to expand the mental health workforce. These provisions aim to divert more individuals from incarceration and will create more opportunities for community-based treatment and recovery.”

There is no question that psychiatric treatment for those with mental illness is underfunded and often inaccessible. But while it is true that some individuals become violent when they are ill, most do not, and targeting those one in five Americans who suffer from a psychiatric disorder each year in an effort to identify, then thwart, the rare mass murderer among us makes no sense.

Acts of mass violence remain rare. In 2018, the year we had a record-breaking number of mass shootings, there were 12 mass murders in the United States, according to the criteria used by Mother Jones, and 27 active shooter incidents using the FBI’s criteria. Approximately half of all mass shooters showed signs of mental illness prior to the shooting and of those, some had never come to the attention of mental health professionals in a way that would have predicted violence. While linking mass violence to mental illness may seem reasonable, the numbers just don’t make sense and targeting this presumed link between mental illness and mass violence is stigmatizing.

The text of the RESPONSE Act reveals proposed legislation that is perhaps more thoughtful than Sen. Cornyn’s speech suggested; the bill starts with funding services for those with psychiatric disorders who are being released from the correctional system, a population that may be at higher risk for acts of violence. The funding for outpatient civil commitment is worded in such a way that it is hard to know exactly what is required. The bill starts by mandating that each state must use 10% of the funding it gets from this bill for court-ordered treatment (AOT), but then lists alternative ways states may use that 10%, including “otherwise support evidence-based programs that address the needs of eligible patients.” In all, the proposed legislation is long and complex and attempts to address issues related to terrorism, the Internet, mental health, and the educational system. It’s an ambitious use of $10 million a year for our entire country.

At a time when mental health care is desperately underfunded and many are unable to access treatment, it is tempting to endorse any legislation that improves funding. But does it serve society to endorse legislation that suggests psychiatrists can prevent mass shootings? Does that ultimately serve our patients? My best guess is that we should aim legislation at preventing mass murders toward limiting access to firearms and banning weapons designed to kill many people quickly.
 

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle of Inpatient Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016), and has a private practice in Baltimore.

To the Editor:

Papulonecrotic tuberculid (PNT) is a cutaneous hypersensitivity reaction to antigenic components of Mycobacterium species, most commonly Mycobacterium tuberculosis. According to a PubMed search of articles indexed for MEDLINE using the terms papulonecrotic tuberculid, Mycobacterium avium complex, and Mycobacterium, only 1 case of PNT secondary to infection with Mycobacterium avium complex (MAC) has been reported.^1,2 Papulonecrotic tuberculid classically presents with symmetrical, dusky red papules with necrosis on the extremities.³ Patients may or may not have associated symptoms of fever and weight loss. It is diagnosed through skin biopsy as well as identification of a distant source of mycobacterial infection. Papulonecrotic tuberculid is considered a reactive process to a distant site of mycobacterial infection, and skin lesions contain few, if any, mycobacteria.⁴

A 65-year-old man was admitted to the hospital for expedited workup of chronic fevers, 20-lb weight loss, and night sweats of 8 months’ duration. He had a medical history of myelodysplastic syndrome and autoimmune hemolytic anemia. During hospitalization, positron emission tomography revealed multilevel vertebral lytic and sclerotic lesions. Subsequent T10 vertebral biopsy showed necrotizing granulomatous inflammation with extensive necrosis and acid-fast bacilli–positive organisms. The patient was empirically started on rifampicin, isoniazid, pyrazinamide, ethambutol, and pyridoxine for presumed M tuberculosis and placed on respiratory isolation.

Dermatology was consulted for a recurrent tender rash on the bilateral upper and lower extremities of 5 years’ duration. Physical examination revealed numerous erythematous papulonecrotic lesions in various states of healing on the bilateral upper and lower extremities (Figure 1). Three years prior to the current presentation, 2 lesions were biopsied and demonstrated leukocytoclastic vasculitis with neutrophilic panniculitis and vasculopathy. A presumptive diagnosis of Sweet syndrome was made given the history of myelodysplastic syndrome, though an infectious etiology could not be ruled out at that time. Concurrently, the patient was diagnosed with autoimmune hemolytic anemia and was started on prednisone. Initially, the skin lesions improved with prednisone but never fully resolved; however, as the dosage of oral steroids decreased, the skin lesions worsened and presented in larger numbers with more frequency. The patient was titrated down to prednisone 5 mg daily with no additional treatment of the skin lesions at that time.

Disseminated MAC infection also was on the differential for our patient; however, we felt it was less likely than PNT for several reasons. First, disseminated infection rarely presents with cutaneous involvement and is associated with pulmonary involvement in 90% of cases.^7-9 Second, the granuloma formation noted on our patient’s skin biopsy was not typical for disseminated MAC but is well described in cases of PNT.^4,8,9 Finally, in the rare cases in which cutaneous involvement has occurred with disseminated mycobacterial infections, skin biopsies typically revealed numerous Mycobacterium organisms.^8,10 In contrast, skin lesions associated with PNT usually reveal few, if any, organisms, as was seen with our patient.²

The patient’s initial biopsies also supported a diagnosis of PNT, as early lesions of PNT typically show leukocytoclastic vasculitis. His response to low and high doses of prednisone also fit well with a PNT diagnosis. In fact, a case of PNT secondary to Mycobacterium bovis similarly showed an improvement in the rash with high-dose steroids but progression with lower doses.¹¹ It is possible that our patient’s response to steroids complicated the diagnosis of his rash.

The treatment of PNT is clearance of the underlying infection. Macrolide antibiotics, such as clarithromycin and azithromycin, have the best efficacy against MAC, in combination with ethambutol and/or rifabutin.^6,12 Treatment duration should be 1 year. Amikacin or streptomycin may be added to this regimen during early treatment.⁶ Mycobacterium avium complex is resistant to many antibiotics, including typical antituberculosis drugs, and sensitivities should be identified at the onset of treatment.^11,12

Albeit rare, clinicians should be aware of PNT secondary to MAC or other mycobacterial infections. Because this condition is difficult to diagnose with varying histologic findings and often negative tissue cultures, a high index of suspicion is necessary when a patient presents with recurrent papulonecrotic lesions, especially in immunocompromised hosts and patients with exposure to mycobacteria.

To the Editor:

Papulonecrotic tuberculid (PNT) is a cutaneous hypersensitivity reaction to antigenic components of Mycobacterium species, most commonly Mycobacterium tuberculosis. According to a PubMed search of articles indexed for MEDLINE using the terms papulonecrotic tuberculid, Mycobacterium avium complex, and Mycobacterium, only 1 case of PNT secondary to infection with Mycobacterium avium complex (MAC) has been reported.^1,2 Papulonecrotic tuberculid classically presents with symmetrical, dusky red papules with necrosis on the extremities.³ Patients may or may not have associated symptoms of fever and weight loss. It is diagnosed through skin biopsy as well as identification of a distant source of mycobacterial infection. Papulonecrotic tuberculid is considered a reactive process to a distant site of mycobacterial infection, and skin lesions contain few, if any, mycobacteria.⁴

A 65-year-old man was admitted to the hospital for expedited workup of chronic fevers, 20-lb weight loss, and night sweats of 8 months’ duration. He had a medical history of myelodysplastic syndrome and autoimmune hemolytic anemia. During hospitalization, positron emission tomography revealed multilevel vertebral lytic and sclerotic lesions. Subsequent T10 vertebral biopsy showed necrotizing granulomatous inflammation with extensive necrosis and acid-fast bacilli–positive organisms. The patient was empirically started on rifampicin, isoniazid, pyrazinamide, ethambutol, and pyridoxine for presumed M tuberculosis and placed on respiratory isolation.

Dermatology was consulted for a recurrent tender rash on the bilateral upper and lower extremities of 5 years’ duration. Physical examination revealed numerous erythematous papulonecrotic lesions in various states of healing on the bilateral upper and lower extremities (Figure 1). Three years prior to the current presentation, 2 lesions were biopsied and demonstrated leukocytoclastic vasculitis with neutrophilic panniculitis and vasculopathy. A presumptive diagnosis of Sweet syndrome was made given the history of myelodysplastic syndrome, though an infectious etiology could not be ruled out at that time. Concurrently, the patient was diagnosed with autoimmune hemolytic anemia and was started on prednisone. Initially, the skin lesions improved with prednisone but never fully resolved; however, as the dosage of oral steroids decreased, the skin lesions worsened and presented in larger numbers with more frequency. The patient was titrated down to prednisone 5 mg daily with no additional treatment of the skin lesions at that time.

Disseminated MAC infection also was on the differential for our patient; however, we felt it was less likely than PNT for several reasons. First, disseminated infection rarely presents with cutaneous involvement and is associated with pulmonary involvement in 90% of cases.^7-9 Second, the granuloma formation noted on our patient’s skin biopsy was not typical for disseminated MAC but is well described in cases of PNT.^4,8,9 Finally, in the rare cases in which cutaneous involvement has occurred with disseminated mycobacterial infections, skin biopsies typically revealed numerous Mycobacterium organisms.^8,10 In contrast, skin lesions associated with PNT usually reveal few, if any, organisms, as was seen with our patient.²

The patient’s initial biopsies also supported a diagnosis of PNT, as early lesions of PNT typically show leukocytoclastic vasculitis. His response to low and high doses of prednisone also fit well with a PNT diagnosis. In fact, a case of PNT secondary to Mycobacterium bovis similarly showed an improvement in the rash with high-dose steroids but progression with lower doses.¹¹ It is possible that our patient’s response to steroids complicated the diagnosis of his rash.

The treatment of PNT is clearance of the underlying infection. Macrolide antibiotics, such as clarithromycin and azithromycin, have the best efficacy against MAC, in combination with ethambutol and/or rifabutin.^6,12 Treatment duration should be 1 year. Amikacin or streptomycin may be added to this regimen during early treatment.⁶ Mycobacterium avium complex is resistant to many antibiotics, including typical antituberculosis drugs, and sensitivities should be identified at the onset of treatment.^11,12

Albeit rare, clinicians should be aware of PNT secondary to MAC or other mycobacterial infections. Because this condition is difficult to diagnose with varying histologic findings and often negative tissue cultures, a high index of suspicion is necessary when a patient presents with recurrent papulonecrotic lesions, especially in immunocompromised hosts and patients with exposure to mycobacteria.

To the Editor:

Papulonecrotic tuberculid (PNT) is a cutaneous hypersensitivity reaction to antigenic components of Mycobacterium species, most commonly Mycobacterium tuberculosis. According to a PubMed search of articles indexed for MEDLINE using the terms papulonecrotic tuberculid, Mycobacterium avium complex, and Mycobacterium, only 1 case of PNT secondary to infection with Mycobacterium avium complex (MAC) has been reported.^1,2 Papulonecrotic tuberculid classically presents with symmetrical, dusky red papules with necrosis on the extremities.³ Patients may or may not have associated symptoms of fever and weight loss. It is diagnosed through skin biopsy as well as identification of a distant source of mycobacterial infection. Papulonecrotic tuberculid is considered a reactive process to a distant site of mycobacterial infection, and skin lesions contain few, if any, mycobacteria.⁴

A 65-year-old man was admitted to the hospital for expedited workup of chronic fevers, 20-lb weight loss, and night sweats of 8 months’ duration. He had a medical history of myelodysplastic syndrome and autoimmune hemolytic anemia. During hospitalization, positron emission tomography revealed multilevel vertebral lytic and sclerotic lesions. Subsequent T10 vertebral biopsy showed necrotizing granulomatous inflammation with extensive necrosis and acid-fast bacilli–positive organisms. The patient was empirically started on rifampicin, isoniazid, pyrazinamide, ethambutol, and pyridoxine for presumed M tuberculosis and placed on respiratory isolation.

Dermatology was consulted for a recurrent tender rash on the bilateral upper and lower extremities of 5 years’ duration. Physical examination revealed numerous erythematous papulonecrotic lesions in various states of healing on the bilateral upper and lower extremities (Figure 1). Three years prior to the current presentation, 2 lesions were biopsied and demonstrated leukocytoclastic vasculitis with neutrophilic panniculitis and vasculopathy. A presumptive diagnosis of Sweet syndrome was made given the history of myelodysplastic syndrome, though an infectious etiology could not be ruled out at that time. Concurrently, the patient was diagnosed with autoimmune hemolytic anemia and was started on prednisone. Initially, the skin lesions improved with prednisone but never fully resolved; however, as the dosage of oral steroids decreased, the skin lesions worsened and presented in larger numbers with more frequency. The patient was titrated down to prednisone 5 mg daily with no additional treatment of the skin lesions at that time.

Disseminated MAC infection also was on the differential for our patient; however, we felt it was less likely than PNT for several reasons. First, disseminated infection rarely presents with cutaneous involvement and is associated with pulmonary involvement in 90% of cases.^7-9 Second, the granuloma formation noted on our patient’s skin biopsy was not typical for disseminated MAC but is well described in cases of PNT.^4,8,9 Finally, in the rare cases in which cutaneous involvement has occurred with disseminated mycobacterial infections, skin biopsies typically revealed numerous Mycobacterium organisms.^8,10 In contrast, skin lesions associated with PNT usually reveal few, if any, organisms, as was seen with our patient.²

The patient’s initial biopsies also supported a diagnosis of PNT, as early lesions of PNT typically show leukocytoclastic vasculitis. His response to low and high doses of prednisone also fit well with a PNT diagnosis. In fact, a case of PNT secondary to Mycobacterium bovis similarly showed an improvement in the rash with high-dose steroids but progression with lower doses.¹¹ It is possible that our patient’s response to steroids complicated the diagnosis of his rash.

The treatment of PNT is clearance of the underlying infection. Macrolide antibiotics, such as clarithromycin and azithromycin, have the best efficacy against MAC, in combination with ethambutol and/or rifabutin.^6,12 Treatment duration should be 1 year. Amikacin or streptomycin may be added to this regimen during early treatment.⁶ Mycobacterium avium complex is resistant to many antibiotics, including typical antituberculosis drugs, and sensitivities should be identified at the onset of treatment.^11,12

Albeit rare, clinicians should be aware of PNT secondary to MAC or other mycobacterial infections. Because this condition is difficult to diagnose with varying histologic findings and often negative tissue cultures, a high index of suspicion is necessary when a patient presents with recurrent papulonecrotic lesions, especially in immunocompromised hosts and patients with exposure to mycobacteria.

The incidence of melanoma in the United States dropped significantly among adolescents and young adults aged 10 to 29 years between 2006 and 2015, according to results of a population-based registry study of 988,103 cases of invasive melanoma.

These data are observational, “and thus cannot conclusively determine the cause of this statistically and clinically significant decrease,” wrote Kelly G. Paulson, MD, PhD, of the Fred Hutchinson Cancer Research Center, Seattle, and colleagues. However, they added, “a likely explanation for the reduced melanoma incidence in adolescents and young adults is success at increased UV exposure protection. These data provide an impetus to further improve multimodal efforts aimed at reducing the burden of melanoma and encourage ongoing UV exposure protection efforts throughout the lifetime of individuals.”

Public health measures to promote sun-protective behaviors including sunscreen use, protective clothing, and seeking shade were initiated in the United States in the late 1990s and early 2000s, but the public health impact remains unknown, they noted in the study, published in JAMA Dermatology.

For the study, they reviewed data from the National Program of Cancer Registries – Surveillance Epidemiology and End Results combined database for the years 2001-2015. Overall, the incidence of invasive melanoma among people of all ages in the United States increased from 50,272 cases in 2001 to 83,362 in 2015. However, in 2015 only 67 cases were reported in children younger than 10 years, 251 in adolescents aged 10-19 years, and 1,973 in young adults (aged 20-29 years).

Between 2006 and 2015, the annual percentage change in melanoma incidence decreased by 4.4% for male adolescents, 5.4% for female adolescents, 3.7% for male young adults, and 3.6% for female young adults; these changes were statistically significant. The trends in incidence was similar when the population was limited to non-Hispanic whites, considered a high-risk group for melanoma.

By contrast, melanoma incidence increased by an annual percentage change of 1.8% for both men and women aged 40 years and older during the same period of time. Young adult women had a greater incidence of melanoma compared with young adult men (about twofold greater), but older men had a greater incidence of melanoma compared with older women, the researchers said.

The findings were limited by a lack of data about potential confounders, such as skin pigmentation, UV light exposure, sunburn history, sunscreen use, sun avoidance, protective clothing, and tanning bed use; and the absence of information kept the researchers from estimating an association between increased sun-protective behaviors and decreased incidence of melanoma.

“However, this change in behavior remains a plausible explanation for decreased melanoma rates in adolescent and young adult populations,” and the data support continued strategies to promote UV protection throughout life, they said.

The study was supported in part by the National Institutes of Health, the Fred Hutchinson Cancer Research Center Integrated Immunotherapy Research Core, and a Society for Immunotherapy of Cancer–Merck fellowship. Dr. Paulson disclosed grants from the Society for Immunotherapy of Cancer–Merck, bluebird biosciences, EMD Serono; she also disclosed an issued and licensed patent for a Merkel cell carcinoma T cell receptor.

SOURCE: Paulson KG et al. JAMA Dermatol. 2019. Nov 13. doi: 10.1001/jamadermatol.2019.3353.

The incidence of melanoma in the United States dropped significantly among adolescents and young adults aged 10 to 29 years between 2006 and 2015, according to results of a population-based registry study of 988,103 cases of invasive melanoma.

These data are observational, “and thus cannot conclusively determine the cause of this statistically and clinically significant decrease,” wrote Kelly G. Paulson, MD, PhD, of the Fred Hutchinson Cancer Research Center, Seattle, and colleagues. However, they added, “a likely explanation for the reduced melanoma incidence in adolescents and young adults is success at increased UV exposure protection. These data provide an impetus to further improve multimodal efforts aimed at reducing the burden of melanoma and encourage ongoing UV exposure protection efforts throughout the lifetime of individuals.”

Public health measures to promote sun-protective behaviors including sunscreen use, protective clothing, and seeking shade were initiated in the United States in the late 1990s and early 2000s, but the public health impact remains unknown, they noted in the study, published in JAMA Dermatology.

For the study, they reviewed data from the National Program of Cancer Registries – Surveillance Epidemiology and End Results combined database for the years 2001-2015. Overall, the incidence of invasive melanoma among people of all ages in the United States increased from 50,272 cases in 2001 to 83,362 in 2015. However, in 2015 only 67 cases were reported in children younger than 10 years, 251 in adolescents aged 10-19 years, and 1,973 in young adults (aged 20-29 years).

Between 2006 and 2015, the annual percentage change in melanoma incidence decreased by 4.4% for male adolescents, 5.4% for female adolescents, 3.7% for male young adults, and 3.6% for female young adults; these changes were statistically significant. The trends in incidence was similar when the population was limited to non-Hispanic whites, considered a high-risk group for melanoma.

By contrast, melanoma incidence increased by an annual percentage change of 1.8% for both men and women aged 40 years and older during the same period of time. Young adult women had a greater incidence of melanoma compared with young adult men (about twofold greater), but older men had a greater incidence of melanoma compared with older women, the researchers said.

The findings were limited by a lack of data about potential confounders, such as skin pigmentation, UV light exposure, sunburn history, sunscreen use, sun avoidance, protective clothing, and tanning bed use; and the absence of information kept the researchers from estimating an association between increased sun-protective behaviors and decreased incidence of melanoma.

“However, this change in behavior remains a plausible explanation for decreased melanoma rates in adolescent and young adult populations,” and the data support continued strategies to promote UV protection throughout life, they said.

The study was supported in part by the National Institutes of Health, the Fred Hutchinson Cancer Research Center Integrated Immunotherapy Research Core, and a Society for Immunotherapy of Cancer–Merck fellowship. Dr. Paulson disclosed grants from the Society for Immunotherapy of Cancer–Merck, bluebird biosciences, EMD Serono; she also disclosed an issued and licensed patent for a Merkel cell carcinoma T cell receptor.

SOURCE: Paulson KG et al. JAMA Dermatol. 2019. Nov 13. doi: 10.1001/jamadermatol.2019.3353.

The incidence of melanoma in the United States dropped significantly among adolescents and young adults aged 10 to 29 years between 2006 and 2015, according to results of a population-based registry study of 988,103 cases of invasive melanoma.

These data are observational, “and thus cannot conclusively determine the cause of this statistically and clinically significant decrease,” wrote Kelly G. Paulson, MD, PhD, of the Fred Hutchinson Cancer Research Center, Seattle, and colleagues. However, they added, “a likely explanation for the reduced melanoma incidence in adolescents and young adults is success at increased UV exposure protection. These data provide an impetus to further improve multimodal efforts aimed at reducing the burden of melanoma and encourage ongoing UV exposure protection efforts throughout the lifetime of individuals.”

Public health measures to promote sun-protective behaviors including sunscreen use, protective clothing, and seeking shade were initiated in the United States in the late 1990s and early 2000s, but the public health impact remains unknown, they noted in the study, published in JAMA Dermatology.

For the study, they reviewed data from the National Program of Cancer Registries – Surveillance Epidemiology and End Results combined database for the years 2001-2015. Overall, the incidence of invasive melanoma among people of all ages in the United States increased from 50,272 cases in 2001 to 83,362 in 2015. However, in 2015 only 67 cases were reported in children younger than 10 years, 251 in adolescents aged 10-19 years, and 1,973 in young adults (aged 20-29 years).

Between 2006 and 2015, the annual percentage change in melanoma incidence decreased by 4.4% for male adolescents, 5.4% for female adolescents, 3.7% for male young adults, and 3.6% for female young adults; these changes were statistically significant. The trends in incidence was similar when the population was limited to non-Hispanic whites, considered a high-risk group for melanoma.

By contrast, melanoma incidence increased by an annual percentage change of 1.8% for both men and women aged 40 years and older during the same period of time. Young adult women had a greater incidence of melanoma compared with young adult men (about twofold greater), but older men had a greater incidence of melanoma compared with older women, the researchers said.

The findings were limited by a lack of data about potential confounders, such as skin pigmentation, UV light exposure, sunburn history, sunscreen use, sun avoidance, protective clothing, and tanning bed use; and the absence of information kept the researchers from estimating an association between increased sun-protective behaviors and decreased incidence of melanoma.

“However, this change in behavior remains a plausible explanation for decreased melanoma rates in adolescent and young adult populations,” and the data support continued strategies to promote UV protection throughout life, they said.

The study was supported in part by the National Institutes of Health, the Fred Hutchinson Cancer Research Center Integrated Immunotherapy Research Core, and a Society for Immunotherapy of Cancer–Merck fellowship. Dr. Paulson disclosed grants from the Society for Immunotherapy of Cancer–Merck, bluebird biosciences, EMD Serono; she also disclosed an issued and licensed patent for a Merkel cell carcinoma T cell receptor.

SOURCE: Paulson KG et al. JAMA Dermatol. 2019. Nov 13. doi: 10.1001/jamadermatol.2019.3353.

NEW ORLEANS – The incidence of acute otitis media has decreased by 25% to 35% in the past decade, thanks largely to the widespread and near universal use of the pneumococcal conjugate vaccine, according to Ellen R. Wald, MD.

Courtesy Wikimedia Commons/Mar10029/Creative Commons License

“To a smaller degree, it is also attributable to the use of influenza vaccine, and to the use of more stringent diagnostic criteria,” Dr. Wald, who chairs the department of pediatrics at the University of Wisconsin, Madison, said at the annual meeting of the American Academy of Pediatrics. “The fact that we are decreasing the number of episodes of otitis media in children in the first year of life means that we’re going to have fewer otitis-prone children and therefore less of a need for tympanostomy tubes, either as a solution to the problem of recurrence of acute otitis media (AOM) or for the problem of persistent effusion.”

The best way to limit antimicrobial use is for clinicians to increase their ability to differentiate AOM from otitis media with effusion (OME), said Dr. Wald, pediatrician-in-chief at the American Family Children’s Hospital in Madison. She noted that OME is a nonbacterial inflammatory state that usually resolves spontaneously. It tends to occur before or after AOM, and often without ever progressing to AOM. “Its principal importance is as a cause of hearing loss and as a confounder in the diagnosis AOM,” she explained. “Because it is a nonbacterial process, antibiotics are not indicated in the management of OME. In contrast, children with AOM have a bacterial infection that will benefit from the use of antimicrobials.”*

Middle ear effusion is common to both OME and AOM, she continued. To discriminate between the two conditions, clinicians must look for signs of acute inflammation of the tympanic membrane, “which we expect to see in AOM,” she said. “The most powerful sign of inflammation of the tympanic membrane is distinct fullness or bulging of the tympanic membrane on exam.”

Dr. Wald advises clinicians to be as systematic as possible when conducting the otoscopic exam, by looking at color and classifying it as pink, gray, white, yellow, red, amber, or blue, and by documenting the position as neutral, retracted, full, or bulging. “When we gauge how light passes through the tympanic membrane, we judge it as translucent, opaque, or partially opaque, and mobility as normal, decreased, or absent,” she added. “When we find decreased or absent mobility of the tympanic membrane, it tells us that we have fluid in the middle ear, but it does not discriminate between AOM and OME.”

Advances in digital otoscopy are helping pediatricians to improve their diagnostic skills. An early device, the iPhone otoscope by CellScope, uses an iOS smartphone to capture images and videos of the external ear canal and eardrum. “The image is pretty much the same as that seen through the eye of a hand-held otoscope,” Dr. Wald said. “The problem with this particular design is that the speculum is kind of large. It does still require the removal of cerumen, and the smartphone is kind of awkward to use as a handle during an otoscopic exam.”

A new digital otoscope called Wispr was unveiled at the AAP meeting. First developed at the University of Wisconsin and now marketed by WiscMed, Wispr delivers high-resolution views of the eardrum in even small or partially obstructed ear canals with one-button image and video capture. WiscMed was founded by Jim Berbee, MD, MBA, an engineer turned emergency medicine physician.

“One of the advantages of this particular model is that it handles a lot more like a usual otoscope and can be attached to the rechargeable handles that are commercially available,” Dr. Wald said. “It has an extremely tiny speculum. Within the head, there is even a smaller camera that allows the photographs to be taken. Because the speculum is so tiny, it allows the device to sometimes avoid the presence of cerumen, or sometimes go through it and still obtain an image.”

dbrunk@mdedge.com

*This article was updated 12/13/2019

NEW ORLEANS – The incidence of acute otitis media has decreased by 25% to 35% in the past decade, thanks largely to the widespread and near universal use of the pneumococcal conjugate vaccine, according to Ellen R. Wald, MD.

Courtesy Wikimedia Commons/Mar10029/Creative Commons License

“To a smaller degree, it is also attributable to the use of influenza vaccine, and to the use of more stringent diagnostic criteria,” Dr. Wald, who chairs the department of pediatrics at the University of Wisconsin, Madison, said at the annual meeting of the American Academy of Pediatrics. “The fact that we are decreasing the number of episodes of otitis media in children in the first year of life means that we’re going to have fewer otitis-prone children and therefore less of a need for tympanostomy tubes, either as a solution to the problem of recurrence of acute otitis media (AOM) or for the problem of persistent effusion.”

The best way to limit antimicrobial use is for clinicians to increase their ability to differentiate AOM from otitis media with effusion (OME), said Dr. Wald, pediatrician-in-chief at the American Family Children’s Hospital in Madison. She noted that OME is a nonbacterial inflammatory state that usually resolves spontaneously. It tends to occur before or after AOM, and often without ever progressing to AOM. “Its principal importance is as a cause of hearing loss and as a confounder in the diagnosis AOM,” she explained. “Because it is a nonbacterial process, antibiotics are not indicated in the management of OME. In contrast, children with AOM have a bacterial infection that will benefit from the use of antimicrobials.”*

Middle ear effusion is common to both OME and AOM, she continued. To discriminate between the two conditions, clinicians must look for signs of acute inflammation of the tympanic membrane, “which we expect to see in AOM,” she said. “The most powerful sign of inflammation of the tympanic membrane is distinct fullness or bulging of the tympanic membrane on exam.”

Dr. Wald advises clinicians to be as systematic as possible when conducting the otoscopic exam, by looking at color and classifying it as pink, gray, white, yellow, red, amber, or blue, and by documenting the position as neutral, retracted, full, or bulging. “When we gauge how light passes through the tympanic membrane, we judge it as translucent, opaque, or partially opaque, and mobility as normal, decreased, or absent,” she added. “When we find decreased or absent mobility of the tympanic membrane, it tells us that we have fluid in the middle ear, but it does not discriminate between AOM and OME.”

Advances in digital otoscopy are helping pediatricians to improve their diagnostic skills. An early device, the iPhone otoscope by CellScope, uses an iOS smartphone to capture images and videos of the external ear canal and eardrum. “The image is pretty much the same as that seen through the eye of a hand-held otoscope,” Dr. Wald said. “The problem with this particular design is that the speculum is kind of large. It does still require the removal of cerumen, and the smartphone is kind of awkward to use as a handle during an otoscopic exam.”

A new digital otoscope called Wispr was unveiled at the AAP meeting. First developed at the University of Wisconsin and now marketed by WiscMed, Wispr delivers high-resolution views of the eardrum in even small or partially obstructed ear canals with one-button image and video capture. WiscMed was founded by Jim Berbee, MD, MBA, an engineer turned emergency medicine physician.

“One of the advantages of this particular model is that it handles a lot more like a usual otoscope and can be attached to the rechargeable handles that are commercially available,” Dr. Wald said. “It has an extremely tiny speculum. Within the head, there is even a smaller camera that allows the photographs to be taken. Because the speculum is so tiny, it allows the device to sometimes avoid the presence of cerumen, or sometimes go through it and still obtain an image.”

dbrunk@mdedge.com

*This article was updated 12/13/2019

NEW ORLEANS – The incidence of acute otitis media has decreased by 25% to 35% in the past decade, thanks largely to the widespread and near universal use of the pneumococcal conjugate vaccine, according to Ellen R. Wald, MD.

Courtesy Wikimedia Commons/Mar10029/Creative Commons License

“To a smaller degree, it is also attributable to the use of influenza vaccine, and to the use of more stringent diagnostic criteria,” Dr. Wald, who chairs the department of pediatrics at the University of Wisconsin, Madison, said at the annual meeting of the American Academy of Pediatrics. “The fact that we are decreasing the number of episodes of otitis media in children in the first year of life means that we’re going to have fewer otitis-prone children and therefore less of a need for tympanostomy tubes, either as a solution to the problem of recurrence of acute otitis media (AOM) or for the problem of persistent effusion.”

The best way to limit antimicrobial use is for clinicians to increase their ability to differentiate AOM from otitis media with effusion (OME), said Dr. Wald, pediatrician-in-chief at the American Family Children’s Hospital in Madison. She noted that OME is a nonbacterial inflammatory state that usually resolves spontaneously. It tends to occur before or after AOM, and often without ever progressing to AOM. “Its principal importance is as a cause of hearing loss and as a confounder in the diagnosis AOM,” she explained. “Because it is a nonbacterial process, antibiotics are not indicated in the management of OME. In contrast, children with AOM have a bacterial infection that will benefit from the use of antimicrobials.”*

Middle ear effusion is common to both OME and AOM, she continued. To discriminate between the two conditions, clinicians must look for signs of acute inflammation of the tympanic membrane, “which we expect to see in AOM,” she said. “The most powerful sign of inflammation of the tympanic membrane is distinct fullness or bulging of the tympanic membrane on exam.”

Dr. Wald advises clinicians to be as systematic as possible when conducting the otoscopic exam, by looking at color and classifying it as pink, gray, white, yellow, red, amber, or blue, and by documenting the position as neutral, retracted, full, or bulging. “When we gauge how light passes through the tympanic membrane, we judge it as translucent, opaque, or partially opaque, and mobility as normal, decreased, or absent,” she added. “When we find decreased or absent mobility of the tympanic membrane, it tells us that we have fluid in the middle ear, but it does not discriminate between AOM and OME.”

Advances in digital otoscopy are helping pediatricians to improve their diagnostic skills. An early device, the iPhone otoscope by CellScope, uses an iOS smartphone to capture images and videos of the external ear canal and eardrum. “The image is pretty much the same as that seen through the eye of a hand-held otoscope,” Dr. Wald said. “The problem with this particular design is that the speculum is kind of large. It does still require the removal of cerumen, and the smartphone is kind of awkward to use as a handle during an otoscopic exam.”

A new digital otoscope called Wispr was unveiled at the AAP meeting. First developed at the University of Wisconsin and now marketed by WiscMed, Wispr delivers high-resolution views of the eardrum in even small or partially obstructed ear canals with one-button image and video capture. WiscMed was founded by Jim Berbee, MD, MBA, an engineer turned emergency medicine physician.

“One of the advantages of this particular model is that it handles a lot more like a usual otoscope and can be attached to the rechargeable handles that are commercially available,” Dr. Wald said. “It has an extremely tiny speculum. Within the head, there is even a smaller camera that allows the photographs to be taken. Because the speculum is so tiny, it allows the device to sometimes avoid the presence of cerumen, or sometimes go through it and still obtain an image.”

dbrunk@mdedge.com

*This article was updated 12/13/2019

BOSTON – ED-based screening is a feasible method of detecting hepatitis C virus (HCV) in high-risk populations, but linkage to care remains low, according to investigators.

Will Pass/MDedge News

An HCV screening program involving three Seattle hospitals and more than 4,000 patients showed that linkage to care was lowest among patients who were younger, homeless, or used injection drugs, reported lead author Charles S. Landis, MD, PhD, of the University of Washington, Seattle.

“In the U.S., rates of acute HCV infections are increasing in younger patients and in areas disproportionally affected by the opiate epidemic,” Dr. Landis said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In order to achieve a goal of elimination, HCV screening, appropriate linkage to care, and treatment will need to be directed toward younger, marginalized, and underserved populations.”

Dr. Landis explained that EDs are suitable for HCV screening because users of emergency services are disproportionately affected by HCV, compared with patients in primary and specialty care settings. Despite this, linkage to care remains historically higher in primary and specialty care settings at approximately 70%, compared with 30% via the ED, Dr. Landis said.

Historically, EDs have been resistant to HCV screening programs, Dr. Landis said, but with the model used in the present study, which relied upon a full-time staff member in each ED who was employed by the infectious disease or hepatology department, no ED resources were needed.

Participants were willing adults who had reliable contact information. Patients were excluded if they were non–English speaking, incarcerated, enrolled or expected to enroll in another clinical study which excludes coenrollment, planned to move out of the region in the next 6 months, admitted to the ED with an acute life-threatening illness, or admitted to the ED for sexual assault. The program had three objectives: Screening, linkage to care, and treatment, all of which were coordinated by the aforementioned case manager.

To date, 4,182 patients have been screened, 936 have been enrolled, 95 have tested positive for HCV RNA, 32 have been linked with care, and 19 have been treated.

“So you can see, a lot of squeeze for a just a little bit of juice here,” Dr. Landis said, referring to the relatively low number of treated patients, compared with how many were screened.

The prevalence of HCV infection based on RNA testing was 2%, though one hospital had a rate of 5%. “This [prevalence] compares to, but is maybe slightly less than, the prevalence seen in others studies based in the emergency department,” Dr. Landis said. “The thought is, not all emergency departments are equal in terms of the patient population that they serve.”

Data analysis showed that the overall linkage to care was 36%. “This is still suboptimal, from my perspective,” Dr. Landis said, “but it does compare with several other ED-based studies.”

A closer look at the data showed that linkage was not uniform across the population. Among patients with homes, linkage to care was 59%, compared with 20% for patients who were homeless (P = .02).

“Ultimately, we need to tailor our approaches for linking homeless patients differently than patients who are not homeless,” Dr. Landis said.

Patients who reported no injection-drug use had a linkage to care of 50%, which was numerically higher than the rate of 20% among users of injection drugs; this difference was not statistically significant, which Dr. Landis attributed to insufficient population size. Similarly, younger patients showed numerical trends toward lower linkage to care.

“Future work will attempt to optimize linkage to care strategies based on patient demographic factors, such as active injection drug use or homelessness,” Dr. Landis said.

During discussion, a conference attendee from the United States expressed skepticism of the program’s merits.

“I may be a glass-half-empty person, but is it worth all this effort?” the attendee asked. “In all honesty, you treated a few dozen [patients] for 180,000 visits [per year]. I’m really not sure it’s worth those efforts, and I’m wondering if those efforts could be placed in different areas, especially for a higher yield.”

“Point well taken,” Dr. Landis said. “I think that was the purpose of the study, to see if the emergency department is a place to screen and link patients to care, and we’re trying to optimize that. Remember, there were 4,000 patients, but for many of those, it took literally a minute to screen them.”

An attendee from Australia offered a slightly more positive take on the findings, followed by a suggestion to improve linkage in marginalized populations.

“I’m not sure I’d be pessimistic,” the attendee said. “I think you ought to be commended for getting that number of people to link, because it is very difficult when we are looking at linking people from a hospital-based setting who actually live in the community and suffer from homelessness and mental health issues and incarceration and a whole range of other things. ... Maybe we need to change our idea of having these centralized silos where people are referred, and go out into the community, much like [tuberculosis] clinics used to do, and track people down.”

The study was funded by Gilead. The investigators disclosed additional relationships with HighTide Therapeutics, Intercept, AbbVie, and others.

SOURCE: Landis CS et al. The Liver Meeting 2019, Abstract 168.

BOSTON – ED-based screening is a feasible method of detecting hepatitis C virus (HCV) in high-risk populations, but linkage to care remains low, according to investigators.

Will Pass/MDedge News

An HCV screening program involving three Seattle hospitals and more than 4,000 patients showed that linkage to care was lowest among patients who were younger, homeless, or used injection drugs, reported lead author Charles S. Landis, MD, PhD, of the University of Washington, Seattle.

“In the U.S., rates of acute HCV infections are increasing in younger patients and in areas disproportionally affected by the opiate epidemic,” Dr. Landis said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In order to achieve a goal of elimination, HCV screening, appropriate linkage to care, and treatment will need to be directed toward younger, marginalized, and underserved populations.”

Dr. Landis explained that EDs are suitable for HCV screening because users of emergency services are disproportionately affected by HCV, compared with patients in primary and specialty care settings. Despite this, linkage to care remains historically higher in primary and specialty care settings at approximately 70%, compared with 30% via the ED, Dr. Landis said.

Historically, EDs have been resistant to HCV screening programs, Dr. Landis said, but with the model used in the present study, which relied upon a full-time staff member in each ED who was employed by the infectious disease or hepatology department, no ED resources were needed.

Participants were willing adults who had reliable contact information. Patients were excluded if they were non–English speaking, incarcerated, enrolled or expected to enroll in another clinical study which excludes coenrollment, planned to move out of the region in the next 6 months, admitted to the ED with an acute life-threatening illness, or admitted to the ED for sexual assault. The program had three objectives: Screening, linkage to care, and treatment, all of which were coordinated by the aforementioned case manager.

To date, 4,182 patients have been screened, 936 have been enrolled, 95 have tested positive for HCV RNA, 32 have been linked with care, and 19 have been treated.

“So you can see, a lot of squeeze for a just a little bit of juice here,” Dr. Landis said, referring to the relatively low number of treated patients, compared with how many were screened.

The prevalence of HCV infection based on RNA testing was 2%, though one hospital had a rate of 5%. “This [prevalence] compares to, but is maybe slightly less than, the prevalence seen in others studies based in the emergency department,” Dr. Landis said. “The thought is, not all emergency departments are equal in terms of the patient population that they serve.”

Data analysis showed that the overall linkage to care was 36%. “This is still suboptimal, from my perspective,” Dr. Landis said, “but it does compare with several other ED-based studies.”

A closer look at the data showed that linkage was not uniform across the population. Among patients with homes, linkage to care was 59%, compared with 20% for patients who were homeless (P = .02).

“Ultimately, we need to tailor our approaches for linking homeless patients differently than patients who are not homeless,” Dr. Landis said.

Patients who reported no injection-drug use had a linkage to care of 50%, which was numerically higher than the rate of 20% among users of injection drugs; this difference was not statistically significant, which Dr. Landis attributed to insufficient population size. Similarly, younger patients showed numerical trends toward lower linkage to care.

“Future work will attempt to optimize linkage to care strategies based on patient demographic factors, such as active injection drug use or homelessness,” Dr. Landis said.

During discussion, a conference attendee from the United States expressed skepticism of the program’s merits.

“I may be a glass-half-empty person, but is it worth all this effort?” the attendee asked. “In all honesty, you treated a few dozen [patients] for 180,000 visits [per year]. I’m really not sure it’s worth those efforts, and I’m wondering if those efforts could be placed in different areas, especially for a higher yield.”

“Point well taken,” Dr. Landis said. “I think that was the purpose of the study, to see if the emergency department is a place to screen and link patients to care, and we’re trying to optimize that. Remember, there were 4,000 patients, but for many of those, it took literally a minute to screen them.”

An attendee from Australia offered a slightly more positive take on the findings, followed by a suggestion to improve linkage in marginalized populations.

“I’m not sure I’d be pessimistic,” the attendee said. “I think you ought to be commended for getting that number of people to link, because it is very difficult when we are looking at linking people from a hospital-based setting who actually live in the community and suffer from homelessness and mental health issues and incarceration and a whole range of other things. ... Maybe we need to change our idea of having these centralized silos where people are referred, and go out into the community, much like [tuberculosis] clinics used to do, and track people down.”

The study was funded by Gilead. The investigators disclosed additional relationships with HighTide Therapeutics, Intercept, AbbVie, and others.

SOURCE: Landis CS et al. The Liver Meeting 2019, Abstract 168.

BOSTON – ED-based screening is a feasible method of detecting hepatitis C virus (HCV) in high-risk populations, but linkage to care remains low, according to investigators.

Will Pass/MDedge News

An HCV screening program involving three Seattle hospitals and more than 4,000 patients showed that linkage to care was lowest among patients who were younger, homeless, or used injection drugs, reported lead author Charles S. Landis, MD, PhD, of the University of Washington, Seattle.

“In the U.S., rates of acute HCV infections are increasing in younger patients and in areas disproportionally affected by the opiate epidemic,” Dr. Landis said in a presentation at the annual meeting of the American Association for the Study of Liver Diseases. “In order to achieve a goal of elimination, HCV screening, appropriate linkage to care, and treatment will need to be directed toward younger, marginalized, and underserved populations.”

Dr. Landis explained that EDs are suitable for HCV screening because users of emergency services are disproportionately affected by HCV, compared with patients in primary and specialty care settings. Despite this, linkage to care remains historically higher in primary and specialty care settings at approximately 70%, compared with 30% via the ED, Dr. Landis said.

Historically, EDs have been resistant to HCV screening programs, Dr. Landis said, but with the model used in the present study, which relied upon a full-time staff member in each ED who was employed by the infectious disease or hepatology department, no ED resources were needed.

Participants were willing adults who had reliable contact information. Patients were excluded if they were non–English speaking, incarcerated, enrolled or expected to enroll in another clinical study which excludes coenrollment, planned to move out of the region in the next 6 months, admitted to the ED with an acute life-threatening illness, or admitted to the ED for sexual assault. The program had three objectives: Screening, linkage to care, and treatment, all of which were coordinated by the aforementioned case manager.

To date, 4,182 patients have been screened, 936 have been enrolled, 95 have tested positive for HCV RNA, 32 have been linked with care, and 19 have been treated.

“So you can see, a lot of squeeze for a just a little bit of juice here,” Dr. Landis said, referring to the relatively low number of treated patients, compared with how many were screened.

The prevalence of HCV infection based on RNA testing was 2%, though one hospital had a rate of 5%. “This [prevalence] compares to, but is maybe slightly less than, the prevalence seen in others studies based in the emergency department,” Dr. Landis said. “The thought is, not all emergency departments are equal in terms of the patient population that they serve.”

Data analysis showed that the overall linkage to care was 36%. “This is still suboptimal, from my perspective,” Dr. Landis said, “but it does compare with several other ED-based studies.”

A closer look at the data showed that linkage was not uniform across the population. Among patients with homes, linkage to care was 59%, compared with 20% for patients who were homeless (P = .02).

“Ultimately, we need to tailor our approaches for linking homeless patients differently than patients who are not homeless,” Dr. Landis said.

Patients who reported no injection-drug use had a linkage to care of 50%, which was numerically higher than the rate of 20% among users of injection drugs; this difference was not statistically significant, which Dr. Landis attributed to insufficient population size. Similarly, younger patients showed numerical trends toward lower linkage to care.

“Future work will attempt to optimize linkage to care strategies based on patient demographic factors, such as active injection drug use or homelessness,” Dr. Landis said.

During discussion, a conference attendee from the United States expressed skepticism of the program’s merits.

“I may be a glass-half-empty person, but is it worth all this effort?” the attendee asked. “In all honesty, you treated a few dozen [patients] for 180,000 visits [per year]. I’m really not sure it’s worth those efforts, and I’m wondering if those efforts could be placed in different areas, especially for a higher yield.”

“Point well taken,” Dr. Landis said. “I think that was the purpose of the study, to see if the emergency department is a place to screen and link patients to care, and we’re trying to optimize that. Remember, there were 4,000 patients, but for many of those, it took literally a minute to screen them.”

An attendee from Australia offered a slightly more positive take on the findings, followed by a suggestion to improve linkage in marginalized populations.

“I’m not sure I’d be pessimistic,” the attendee said. “I think you ought to be commended for getting that number of people to link, because it is very difficult when we are looking at linking people from a hospital-based setting who actually live in the community and suffer from homelessness and mental health issues and incarceration and a whole range of other things. ... Maybe we need to change our idea of having these centralized silos where people are referred, and go out into the community, much like [tuberculosis] clinics used to do, and track people down.”

The study was funded by Gilead. The investigators disclosed additional relationships with HighTide Therapeutics, Intercept, AbbVie, and others.

SOURCE: Landis CS et al. The Liver Meeting 2019, Abstract 168.

Ibrutinib monotherapy was associated with lower total health care costs compared with chemoimmunotherapy in the frontline treatment of patients with chronic lymphocytic leukemia (CLL), according to a retrospective study.

©Mathier/thinkstockphotos.com

“This study compared time to next treatment, health care resource utilization, and total direct costs among patients with CLL initiating front-line ibrutinib single agent or chemoimmunotherapy,” wrote Bruno Emond, of Analysis Group, Montreal, and colleagues. Their report is in Clinical Lymphoma, Myeloma & Leukemia.

The researchers retrospectively analyzed data from 1,161 patients with CLL who were started on ibrutinib monotherapy or chemoimmunotherapy from 2014 to 2017. Data were collected from the Optum Clinformatics Extended DataMart De-Identified Databases.

Between the two groups, differences in baseline characteristics were controlled for by way of inverse probability of treatment weighting. Two treatment periods were included in the study: the initial 6 months of treatment and entire duration of frontline therapy.

The team also conducted a subgroup analysis of patients treated with bendamustine and rituximab. This cohort was analyzed independently since the regimen is commonly used in clinical practice.

After analysis, the researchers found that ibrutinib monotherapy was associated with net monthly cost savings of $3,766 (P less than .0001), compared with chemoimmunotherapy and bendamustine/rituximab over the frontline therapy period.

Ibrutinib patients had fewer monthly days with outpatient services (rate ratio, 0.75; 95% confidence interval, 0.60-0.94; P = .0200), compared with those on chemoimmunotherapy; and were less likely to initiate a next line of treatment, compared with chemoimmunotherapy patients (hazard ratio, 0.54; 95% CI, 0.33-0.90; P = .0163).

“Cost savings and reductions in health care resource utilization were even more pronounced when considering only the first 6 months of front-line treatment,” the researchers wrote.

The researchers acknowledged that two key limitations of the study were the potential influence of unobserved confounding factors and the use of claims data, which could include errors and omissions.

“These results suggest that ibrutinib single-agent is associated with lower total costs driven by lower medical costs, despite higher pharmacy costs, compared with chemoimmunotherapy and bendamustine/rituximab,” they concluded.

The authors reported financial affiliations with Janssen Scientific Affairs, which funded the study, and other companies.

SOURCE: Emond B et al. Clin Lymphoma Myeloma Leuk. 2019 Aug 26. doi: 10.1016/j.clml.2019.08.004.

Ibrutinib monotherapy was associated with lower total health care costs compared with chemoimmunotherapy in the frontline treatment of patients with chronic lymphocytic leukemia (CLL), according to a retrospective study.

©Mathier/thinkstockphotos.com

“This study compared time to next treatment, health care resource utilization, and total direct costs among patients with CLL initiating front-line ibrutinib single agent or chemoimmunotherapy,” wrote Bruno Emond, of Analysis Group, Montreal, and colleagues. Their report is in Clinical Lymphoma, Myeloma & Leukemia.

The researchers retrospectively analyzed data from 1,161 patients with CLL who were started on ibrutinib monotherapy or chemoimmunotherapy from 2014 to 2017. Data were collected from the Optum Clinformatics Extended DataMart De-Identified Databases.

Between the two groups, differences in baseline characteristics were controlled for by way of inverse probability of treatment weighting. Two treatment periods were included in the study: the initial 6 months of treatment and entire duration of frontline therapy.

The team also conducted a subgroup analysis of patients treated with bendamustine and rituximab. This cohort was analyzed independently since the regimen is commonly used in clinical practice.

After analysis, the researchers found that ibrutinib monotherapy was associated with net monthly cost savings of $3,766 (P less than .0001), compared with chemoimmunotherapy and bendamustine/rituximab over the frontline therapy period.

Ibrutinib patients had fewer monthly days with outpatient services (rate ratio, 0.75; 95% confidence interval, 0.60-0.94; P = .0200), compared with those on chemoimmunotherapy; and were less likely to initiate a next line of treatment, compared with chemoimmunotherapy patients (hazard ratio, 0.54; 95% CI, 0.33-0.90; P = .0163).

“Cost savings and reductions in health care resource utilization were even more pronounced when considering only the first 6 months of front-line treatment,” the researchers wrote.

The researchers acknowledged that two key limitations of the study were the potential influence of unobserved confounding factors and the use of claims data, which could include errors and omissions.

“These results suggest that ibrutinib single-agent is associated with lower total costs driven by lower medical costs, despite higher pharmacy costs, compared with chemoimmunotherapy and bendamustine/rituximab,” they concluded.

The authors reported financial affiliations with Janssen Scientific Affairs, which funded the study, and other companies.

SOURCE: Emond B et al. Clin Lymphoma Myeloma Leuk. 2019 Aug 26. doi: 10.1016/j.clml.2019.08.004.

Ibrutinib monotherapy was associated with lower total health care costs compared with chemoimmunotherapy in the frontline treatment of patients with chronic lymphocytic leukemia (CLL), according to a retrospective study.

©Mathier/thinkstockphotos.com

“This study compared time to next treatment, health care resource utilization, and total direct costs among patients with CLL initiating front-line ibrutinib single agent or chemoimmunotherapy,” wrote Bruno Emond, of Analysis Group, Montreal, and colleagues. Their report is in Clinical Lymphoma, Myeloma & Leukemia.

The researchers retrospectively analyzed data from 1,161 patients with CLL who were started on ibrutinib monotherapy or chemoimmunotherapy from 2014 to 2017. Data were collected from the Optum Clinformatics Extended DataMart De-Identified Databases.

Between the two groups, differences in baseline characteristics were controlled for by way of inverse probability of treatment weighting. Two treatment periods were included in the study: the initial 6 months of treatment and entire duration of frontline therapy.

The team also conducted a subgroup analysis of patients treated with bendamustine and rituximab. This cohort was analyzed independently since the regimen is commonly used in clinical practice.

After analysis, the researchers found that ibrutinib monotherapy was associated with net monthly cost savings of $3,766 (P less than .0001), compared with chemoimmunotherapy and bendamustine/rituximab over the frontline therapy period.

Ibrutinib patients had fewer monthly days with outpatient services (rate ratio, 0.75; 95% confidence interval, 0.60-0.94; P = .0200), compared with those on chemoimmunotherapy; and were less likely to initiate a next line of treatment, compared with chemoimmunotherapy patients (hazard ratio, 0.54; 95% CI, 0.33-0.90; P = .0163).

“Cost savings and reductions in health care resource utilization were even more pronounced when considering only the first 6 months of front-line treatment,” the researchers wrote.

The researchers acknowledged that two key limitations of the study were the potential influence of unobserved confounding factors and the use of claims data, which could include errors and omissions.

“These results suggest that ibrutinib single-agent is associated with lower total costs driven by lower medical costs, despite higher pharmacy costs, compared with chemoimmunotherapy and bendamustine/rituximab,” they concluded.

The authors reported financial affiliations with Janssen Scientific Affairs, which funded the study, and other companies.

SOURCE: Emond B et al. Clin Lymphoma Myeloma Leuk. 2019 Aug 26. doi: 10.1016/j.clml.2019.08.004.

NEW YORK – Seven years after the formation of the first pulmonary embolism response team (PERT), more than 100 institutions have joined the PERT Consortium, which was created to guide care and research for this thrombotic complication, according to a status report at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.

Ted Bosworth/MDedge News

“Why are PERTs needed? Pulmonary embolism patients are like snowflakes. No two are the same,” explained Richard Channick, MD, director of the pulmonary vascular disease program, University of California, Los Angeles.

Patient variability is an issue because algorithms for pulmonary embolism (PE) often differ at the point of diagnosis, such as the emergency department or intensive are unit, according to Dr. Channick, who was present when the first PERT was created in 2012 at Massachusetts General Hospital (MGH) in Boston. In addition, treatment algorithms can seem complex at a time when patients are deteriorating quickly.

“The treatment algorithms always say consider this or consider that, and then you get a recommendation with a 2B grade of evidence. So what do you do?” Dr. Channick asked, “This has really been crying for an organized approach.”

PERTs were created to fill this need. In most centers, PERTs are organized to respond to a diagnosis of PE wherever it occurs in the hospital. The goal is rapid activation of a team of experts who can reach a single consensus recommendation.

At MGH and UCLA, a similar relatively simple scheme has been created to guide physicians on how to activate the PERT and which situations make this appropriate.

“A big part of the PERT value has been our ability to conduct a real-time virtual consultation where we leverage online technology to look at images together in order to agree on a strategy,” Dr. Channick explained.

Although frequently asked what specialists are needed for an effective PERT, Dr. Channick said it depends on institutional structures, the types of specialists available, and, in some cases, the specific characteristics of the patient. In many situations, a pulmonary vascular specialist and an interventional radiologist might be sufficient. In others, team members might include some combination of an interventional cardiologist, a cardiac surgeon, and a hematologist.

It is also appropriate to include clinicians likely to participate in care following acute treatment of the PE. “One of the most critical values to PERT is the ability to systematically follow patients” after the PE is treated, Dr. Channick said.

So far, there are no data to confirm patients managed with PERT achieve better outcomes than those who are not. Reductions in mortality, length of stay, and costs are reasonably anticipated and might eventually be demonstrated, but Dr. Channick said that PERTs already have value.

“I think the efficiency of care is important,”he said. He called PERT a “one-stop shopping” approach to ensuring that multiple strategies are considered systematically.

There are many anecdotal examples of the benefits of shared decision-making for PE treatment. In one, a pulmonary specialist in a PERT team narrowly averted a planned thrombolysis in a patient diagnosed with PE who was actually found to have severe pulmonary fibrosis, according to Dr. Channick.

Not least important, the shared decision-making of a PERT could relieve the burden of difficult choices in complex situations. Bad outcomes in PE can be unavoidable even with optimal therapy.

“To me personally, a very important benefit of being part of a PERT is the feeling that we are all in it together,” Dr. Channick said. “Patients can go from being pretty stable to being dead very quickly.”

The PERT Consortium has sponsored an annual meeting on PE since 2015. It also maintains an ongoing registry for PE data from member institutions. These data are expected to have increasing value for comparing the impact of patient characteristics, treatment strategies, and other variables on outcomes.

For clinicians who are uncertain whether the PE incidence at their institution justifies a PERT, Dr. Channick had some advice. “If you build it, they will clot,” he said, meaning that due to the frequency of PE, a PERT will generally have plenty of work once created.

SOURCE: VEITHSYMPOSIUM

NEW YORK – Seven years after the formation of the first pulmonary embolism response team (PERT), more than 100 institutions have joined the PERT Consortium, which was created to guide care and research for this thrombotic complication, according to a status report at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.

Ted Bosworth/MDedge News

“Why are PERTs needed? Pulmonary embolism patients are like snowflakes. No two are the same,” explained Richard Channick, MD, director of the pulmonary vascular disease program, University of California, Los Angeles.

Patient variability is an issue because algorithms for pulmonary embolism (PE) often differ at the point of diagnosis, such as the emergency department or intensive are unit, according to Dr. Channick, who was present when the first PERT was created in 2012 at Massachusetts General Hospital (MGH) in Boston. In addition, treatment algorithms can seem complex at a time when patients are deteriorating quickly.

“The treatment algorithms always say consider this or consider that, and then you get a recommendation with a 2B grade of evidence. So what do you do?” Dr. Channick asked, “This has really been crying for an organized approach.”

PERTs were created to fill this need. In most centers, PERTs are organized to respond to a diagnosis of PE wherever it occurs in the hospital. The goal is rapid activation of a team of experts who can reach a single consensus recommendation.

At MGH and UCLA, a similar relatively simple scheme has been created to guide physicians on how to activate the PERT and which situations make this appropriate.

“A big part of the PERT value has been our ability to conduct a real-time virtual consultation where we leverage online technology to look at images together in order to agree on a strategy,” Dr. Channick explained.

Although frequently asked what specialists are needed for an effective PERT, Dr. Channick said it depends on institutional structures, the types of specialists available, and, in some cases, the specific characteristics of the patient. In many situations, a pulmonary vascular specialist and an interventional radiologist might be sufficient. In others, team members might include some combination of an interventional cardiologist, a cardiac surgeon, and a hematologist.

It is also appropriate to include clinicians likely to participate in care following acute treatment of the PE. “One of the most critical values to PERT is the ability to systematically follow patients” after the PE is treated, Dr. Channick said.

So far, there are no data to confirm patients managed with PERT achieve better outcomes than those who are not. Reductions in mortality, length of stay, and costs are reasonably anticipated and might eventually be demonstrated, but Dr. Channick said that PERTs already have value.

“I think the efficiency of care is important,”he said. He called PERT a “one-stop shopping” approach to ensuring that multiple strategies are considered systematically.

There are many anecdotal examples of the benefits of shared decision-making for PE treatment. In one, a pulmonary specialist in a PERT team narrowly averted a planned thrombolysis in a patient diagnosed with PE who was actually found to have severe pulmonary fibrosis, according to Dr. Channick.

Not least important, the shared decision-making of a PERT could relieve the burden of difficult choices in complex situations. Bad outcomes in PE can be unavoidable even with optimal therapy.

“To me personally, a very important benefit of being part of a PERT is the feeling that we are all in it together,” Dr. Channick said. “Patients can go from being pretty stable to being dead very quickly.”

The PERT Consortium has sponsored an annual meeting on PE since 2015. It also maintains an ongoing registry for PE data from member institutions. These data are expected to have increasing value for comparing the impact of patient characteristics, treatment strategies, and other variables on outcomes.

For clinicians who are uncertain whether the PE incidence at their institution justifies a PERT, Dr. Channick had some advice. “If you build it, they will clot,” he said, meaning that due to the frequency of PE, a PERT will generally have plenty of work once created.

SOURCE: VEITHSYMPOSIUM

NEW YORK – Seven years after the formation of the first pulmonary embolism response team (PERT), more than 100 institutions have joined the PERT Consortium, which was created to guide care and research for this thrombotic complication, according to a status report at a symposium on vascular and endovascular issues sponsored by the Cleveland Clinic Foundation.

Ted Bosworth/MDedge News

“Why are PERTs needed? Pulmonary embolism patients are like snowflakes. No two are the same,” explained Richard Channick, MD, director of the pulmonary vascular disease program, University of California, Los Angeles.

Patient variability is an issue because algorithms for pulmonary embolism (PE) often differ at the point of diagnosis, such as the emergency department or intensive are unit, according to Dr. Channick, who was present when the first PERT was created in 2012 at Massachusetts General Hospital (MGH) in Boston. In addition, treatment algorithms can seem complex at a time when patients are deteriorating quickly.

“The treatment algorithms always say consider this or consider that, and then you get a recommendation with a 2B grade of evidence. So what do you do?” Dr. Channick asked, “This has really been crying for an organized approach.”

PERTs were created to fill this need. In most centers, PERTs are organized to respond to a diagnosis of PE wherever it occurs in the hospital. The goal is rapid activation of a team of experts who can reach a single consensus recommendation.

At MGH and UCLA, a similar relatively simple scheme has been created to guide physicians on how to activate the PERT and which situations make this appropriate.

“A big part of the PERT value has been our ability to conduct a real-time virtual consultation where we leverage online technology to look at images together in order to agree on a strategy,” Dr. Channick explained.

Although frequently asked what specialists are needed for an effective PERT, Dr. Channick said it depends on institutional structures, the types of specialists available, and, in some cases, the specific characteristics of the patient. In many situations, a pulmonary vascular specialist and an interventional radiologist might be sufficient. In others, team members might include some combination of an interventional cardiologist, a cardiac surgeon, and a hematologist.

It is also appropriate to include clinicians likely to participate in care following acute treatment of the PE. “One of the most critical values to PERT is the ability to systematically follow patients” after the PE is treated, Dr. Channick said.

So far, there are no data to confirm patients managed with PERT achieve better outcomes than those who are not. Reductions in mortality, length of stay, and costs are reasonably anticipated and might eventually be demonstrated, but Dr. Channick said that PERTs already have value.

“I think the efficiency of care is important,”he said. He called PERT a “one-stop shopping” approach to ensuring that multiple strategies are considered systematically.

There are many anecdotal examples of the benefits of shared decision-making for PE treatment. In one, a pulmonary specialist in a PERT team narrowly averted a planned thrombolysis in a patient diagnosed with PE who was actually found to have severe pulmonary fibrosis, according to Dr. Channick.

Not least important, the shared decision-making of a PERT could relieve the burden of difficult choices in complex situations. Bad outcomes in PE can be unavoidable even with optimal therapy.

“To me personally, a very important benefit of being part of a PERT is the feeling that we are all in it together,” Dr. Channick said. “Patients can go from being pretty stable to being dead very quickly.”

The PERT Consortium has sponsored an annual meeting on PE since 2015. It also maintains an ongoing registry for PE data from member institutions. These data are expected to have increasing value for comparing the impact of patient characteristics, treatment strategies, and other variables on outcomes.

For clinicians who are uncertain whether the PE incidence at their institution justifies a PERT, Dr. Channick had some advice. “If you build it, they will clot,” he said, meaning that due to the frequency of PE, a PERT will generally have plenty of work once created.

SOURCE: VEITHSYMPOSIUM

Viral bronchiolitis is the most common indication for infant hospitalization in the United States.¹ The treatment mainstay remains supportive care, including supplemental oxygen when indicated.¹ High flow nasal cannula (HFNC) therapy delivers humidified, heated air blended with oxygen, allowing much higher flow rates than standard nasal cannula therapy and is being used more frequently in inpatient settings.

Infants and toddlers with bronchiolitis develop increased work of breathing to preserve oxygenation and ventilation in the setting of altered airway resistance and lung compliance.^2,3 In addition to oxygen supplementation, HFNC is used to reduce work of breathing through several mechanisms:^2-6 (1) Nasopharyngeal dead space washout clears oxygen-depleted gas at the end of expiration, facilitating alveolar ventilation (ie, carbon dioxide retention improves); (2) High flow rates match increased inspiratory flow demands of acutely ill patients, reducing nasopharyngeal inspiratory resistance and optimizing dead space washout, thus decreasing work of breathing; (3) Adequate flow rates generate distending pressure, which prevents pharyngeal collapse, supports lung recruitment, and reduces respiratory effort (demonstrated in younger infants); and (4) HFNC systems heat and humidify the breathing gas, reducing the metabolic work required to condition cool, dry gas and improving conductance and pulmonary compliance.^2-5

HFNC therapy is used more commonly in acute care units despite limited literature on its effectiveness outside the intensive care unit (ICU).^7,8 We asked the question, “Does use of HFNC therapy for infants with bronchiolitis hospitalized in acute care units result in improved outcomes when compared with standard nasal cannula oxygen therapy, including length of stay (LOS), oxygen therapy duration, and preventing escalations of care such as ICU transfer, positive pressure ventilation, and intubation?” Also, do published studies provide guidance for the initiation and management of HFNC? We focused our search on studies published in the last five years that included patients with bronchiolitis treated with HFNC outside the ICU; here, we review those studies most relevant to pediatric hospitalists.

No guideline exists for initiating flow or fraction of inspired oxygen (FiO₂). HFNC may be initiated for hypoxia, increased work of breathing, or both in patients with bronchiolitis. To achieve optimal dead space washout, inspiratory flow, and distending pressure, initial flow rates should be 1.5 to 2 L/kg/min, particularly for infants and young children.^2-5 Weiler et al.³ evaluated the breathing effort of ICU patients at 0.5, 1, 1.5, and 2 L/kg/min and found optimal flow rates for improved work of breathing were 1.5-2 L/kg/min. The smallest patients, ≤8 kg, saw the greatest benefit, a finding likely explained by larger anatomic dead space in infants/small children compared with older children.³ For older/larger children (>20 kg), an initial flow closer to 1 L/kg/min is often appropriate.⁵ When used for hypoxia, initiating flow without supplemental FiO₂ may improve oxygenation by flushing nasopharyngeal dead space. FiO₂ should be titrated to achieve the goal set by the treatment team, often ≥90%. Improvement in heart rate and peripheral oxygen saturation (SpO₂) can be observed within 60 minutes of initiating HFNC in patients responsive to therapy.⁶

HFNC therapy is safe when used correctly.^6,9,10Potential adverse effects include pneumothorax, pressure injury, mucosal injury/bleeding, and delayed escalation to invasive ventilation. While difficult to quantify, recent studies report low rates or no serious HFNC complications. For example, only 2 of 1,127 patients supported with HFNC developed a pneumothorax and neither required evacuation.^2,9-12

Inclusion criteria and HFNC protocols vary among published studies. Most HFNC protocols reviewed may not have optimally supported all of the patients in their HFNC groups, often by limiting flow to <2 L/kg/min.^6-9,11,12 These variables may explain the disparate results, with some studies demonstrating apparent benefits and others no difference.^7,9,10,12

Two studies of infants with bronchiolitis showed HFNC therapy may prevent ICU transfer, but this benefit may be limited to rescue when standard oxygen therapy fails, rather than as a superior initial support modality.^7,9 Kepreotes et al.⁹ reported a single-center, randomized controlled trial comparing HFNC with standard oxygen therapy with 101 patients in each treatment arm. The primary outcome, median time to wean off oxygen, was not significantly different between the two groups: 24 hours (95% CI: 18-28) in the HFNC group versus 20 hours in the standard therapy group (95% CI: 17-34). The HFNC group had fewer treatment failures (abnormal heart rate, respiratory rate, SpO₂ <90%, or severe respiratory distress score while on maximum therapy) than the standard therapy group, and 20 (63%) of the 33 patients who failed standard therapy were rescued with HFNC, avoiding transfer to the ICU. Fourteen patients from the HFNC group and 12 from the standard oxygen group required transfer to the ICU for support escalation. Although this study did not show a significant difference in oxygen weaning time between groups, it appears to support HFNC use as a rescue modality to reduce or prevent ICU transfer.⁹ Franklin et al.¹⁰ conducted a multicenter, randomized, controlled trial to compare standard nasal cannula oxygen therapy with HFNC (2 L/kg/min) in 1,472 patients. Patients receiving HFNC had lower care escalation rates due to treatment failure, defined as the presence of at least three of four clinical criteria and the clinician determining escalation was indicated. Oxygen therapy duration, ICU admission rates, and LOS were not significantly different between groups. Similar to the previous study, a large portion of the standard therapy patients who failed treatment (102 of 167) crossed over to the HFNC arm in an attempt to avoid ICU transfer. Twelve patients required intubation: 8 (1%) receiving HFNC and 4 (0.5%) receiving the standard therapy.¹⁰

Two additional studies, both with study design limitations, did not demonstrate differences in ICU transfer rates and had variable differences in outcomes. Riese et al.⁷ retrospectively assessed HFNC use outside the ICU at one institution and included 936 patients admitted before and 1,001 patients admitted after HFNC guideline implementation on the wards. Flow rates were based on age and not weight. They found no difference in LOS, ICU transfer rate, ICU LOS, intubation rates, or 30-day readmission rates, though HFNC use increased over time. The HFNC guideline is a potentially significant limitation as it may not have provided optimal flow rates to all subjects given it was based on age rather than weight. Milani et al.¹² performed a single-center observational study of 36 infants aged <12 months, treated for bronchiolitis on the ward, who were informally assigned to HFNC or standard therapy based upon HFNC device availability. HFNC flow rate was determined by the equation: L/min = 8 mL/kg × respiratory rate × 0.3. Using mean weight and respiratory rate for patients in this group, it appears patients in the HFNC group were treated with flow rates less than the 1.5-2 L/kg/min recommended to be effective.^2,3,12 Despite this, clinical improvement was faster in the HFNC group, including respiratory rate and effort, ability to feed, days on oxygen supplementation, and hospital LOS. ICU admission was not different between the two groups.¹² The Table compares the four studies discussed above.

Many children’s hospitals have extended the use of HFNC outside the ICU for children with bronchiolitis despite the paucity of evidence demonstrating its benefit over standard flow oxygen. Given variation in protocols, study designs, outcomes, and number of patients studied, it is difficult to assess its efficacy outside the ICU. However, based on the studies reviewed herein, HFNC therapy does not appear to decrease LOS, time on oxygen, or escalations of care, such as ICU transfers, positive pressure ventilation, or intubation, when used as a primary therapy.^7,9,11,12 Future research will ideally use optimal flow rates to determine the effectiveness of HFNC on acute care units. Although not addressed in the above studies, additional benefits to be considered in future studies include: (1) increased critical care capacity by allowing patients to be supported on the floor and (2) the ability for patients to remain closer to home when HFNC is used in the community hospital setting.

In each of the large, randomized studies reviewed, most (66%-75%) patients treated with standard low flow oxygen were supported successfully and did not require escalation to HFNC.^9,10 Hospitalists should continue to use standard low flow oxygen as first-line respiratory support for patients with bronchiolitis.¹ No evidence supports the use of HFNC therapy early in a child’s inpatient course; rather, it should be used when standard oxygen therapy fails. Future research should focus on better elucidating which patients will benefit most from HFNC to prevent overuse.

Viral bronchiolitis is the most common indication for infant hospitalization in the United States.¹ The treatment mainstay remains supportive care, including supplemental oxygen when indicated.¹ High flow nasal cannula (HFNC) therapy delivers humidified, heated air blended with oxygen, allowing much higher flow rates than standard nasal cannula therapy and is being used more frequently in inpatient settings.

Infants and toddlers with bronchiolitis develop increased work of breathing to preserve oxygenation and ventilation in the setting of altered airway resistance and lung compliance.^2,3 In addition to oxygen supplementation, HFNC is used to reduce work of breathing through several mechanisms:^2-6 (1) Nasopharyngeal dead space washout clears oxygen-depleted gas at the end of expiration, facilitating alveolar ventilation (ie, carbon dioxide retention improves); (2) High flow rates match increased inspiratory flow demands of acutely ill patients, reducing nasopharyngeal inspiratory resistance and optimizing dead space washout, thus decreasing work of breathing; (3) Adequate flow rates generate distending pressure, which prevents pharyngeal collapse, supports lung recruitment, and reduces respiratory effort (demonstrated in younger infants); and (4) HFNC systems heat and humidify the breathing gas, reducing the metabolic work required to condition cool, dry gas and improving conductance and pulmonary compliance.^2-5

HFNC therapy is used more commonly in acute care units despite limited literature on its effectiveness outside the intensive care unit (ICU).^7,8 We asked the question, “Does use of HFNC therapy for infants with bronchiolitis hospitalized in acute care units result in improved outcomes when compared with standard nasal cannula oxygen therapy, including length of stay (LOS), oxygen therapy duration, and preventing escalations of care such as ICU transfer, positive pressure ventilation, and intubation?” Also, do published studies provide guidance for the initiation and management of HFNC? We focused our search on studies published in the last five years that included patients with bronchiolitis treated with HFNC outside the ICU; here, we review those studies most relevant to pediatric hospitalists.

No guideline exists for initiating flow or fraction of inspired oxygen (FiO₂). HFNC may be initiated for hypoxia, increased work of breathing, or both in patients with bronchiolitis. To achieve optimal dead space washout, inspiratory flow, and distending pressure, initial flow rates should be 1.5 to 2 L/kg/min, particularly for infants and young children.^2-5 Weiler et al.³ evaluated the breathing effort of ICU patients at 0.5, 1, 1.5, and 2 L/kg/min and found optimal flow rates for improved work of breathing were 1.5-2 L/kg/min. The smallest patients, ≤8 kg, saw the greatest benefit, a finding likely explained by larger anatomic dead space in infants/small children compared with older children.³ For older/larger children (>20 kg), an initial flow closer to 1 L/kg/min is often appropriate.⁵ When used for hypoxia, initiating flow without supplemental FiO₂ may improve oxygenation by flushing nasopharyngeal dead space. FiO₂ should be titrated to achieve the goal set by the treatment team, often ≥90%. Improvement in heart rate and peripheral oxygen saturation (SpO₂) can be observed within 60 minutes of initiating HFNC in patients responsive to therapy.⁶

HFNC therapy is safe when used correctly.^6,9,10Potential adverse effects include pneumothorax, pressure injury, mucosal injury/bleeding, and delayed escalation to invasive ventilation. While difficult to quantify, recent studies report low rates or no serious HFNC complications. For example, only 2 of 1,127 patients supported with HFNC developed a pneumothorax and neither required evacuation.^2,9-12

Inclusion criteria and HFNC protocols vary among published studies. Most HFNC protocols reviewed may not have optimally supported all of the patients in their HFNC groups, often by limiting flow to <2 L/kg/min.^6-9,11,12 These variables may explain the disparate results, with some studies demonstrating apparent benefits and others no difference.^7,9,10,12

Two studies of infants with bronchiolitis showed HFNC therapy may prevent ICU transfer, but this benefit may be limited to rescue when standard oxygen therapy fails, rather than as a superior initial support modality.^7,9 Kepreotes et al.⁹ reported a single-center, randomized controlled trial comparing HFNC with standard oxygen therapy with 101 patients in each treatment arm. The primary outcome, median time to wean off oxygen, was not significantly different between the two groups: 24 hours (95% CI: 18-28) in the HFNC group versus 20 hours in the standard therapy group (95% CI: 17-34). The HFNC group had fewer treatment failures (abnormal heart rate, respiratory rate, SpO₂ <90%, or severe respiratory distress score while on maximum therapy) than the standard therapy group, and 20 (63%) of the 33 patients who failed standard therapy were rescued with HFNC, avoiding transfer to the ICU. Fourteen patients from the HFNC group and 12 from the standard oxygen group required transfer to the ICU for support escalation. Although this study did not show a significant difference in oxygen weaning time between groups, it appears to support HFNC use as a rescue modality to reduce or prevent ICU transfer.⁹ Franklin et al.¹⁰ conducted a multicenter, randomized, controlled trial to compare standard nasal cannula oxygen therapy with HFNC (2 L/kg/min) in 1,472 patients. Patients receiving HFNC had lower care escalation rates due to treatment failure, defined as the presence of at least three of four clinical criteria and the clinician determining escalation was indicated. Oxygen therapy duration, ICU admission rates, and LOS were not significantly different between groups. Similar to the previous study, a large portion of the standard therapy patients who failed treatment (102 of 167) crossed over to the HFNC arm in an attempt to avoid ICU transfer. Twelve patients required intubation: 8 (1%) receiving HFNC and 4 (0.5%) receiving the standard therapy.¹⁰

Two additional studies, both with study design limitations, did not demonstrate differences in ICU transfer rates and had variable differences in outcomes. Riese et al.⁷ retrospectively assessed HFNC use outside the ICU at one institution and included 936 patients admitted before and 1,001 patients admitted after HFNC guideline implementation on the wards. Flow rates were based on age and not weight. They found no difference in LOS, ICU transfer rate, ICU LOS, intubation rates, or 30-day readmission rates, though HFNC use increased over time. The HFNC guideline is a potentially significant limitation as it may not have provided optimal flow rates to all subjects given it was based on age rather than weight. Milani et al.¹² performed a single-center observational study of 36 infants aged <12 months, treated for bronchiolitis on the ward, who were informally assigned to HFNC or standard therapy based upon HFNC device availability. HFNC flow rate was determined by the equation: L/min = 8 mL/kg × respiratory rate × 0.3. Using mean weight and respiratory rate for patients in this group, it appears patients in the HFNC group were treated with flow rates less than the 1.5-2 L/kg/min recommended to be effective.^2,3,12 Despite this, clinical improvement was faster in the HFNC group, including respiratory rate and effort, ability to feed, days on oxygen supplementation, and hospital LOS. ICU admission was not different between the two groups.¹² The Table compares the four studies discussed above.

Many children’s hospitals have extended the use of HFNC outside the ICU for children with bronchiolitis despite the paucity of evidence demonstrating its benefit over standard flow oxygen. Given variation in protocols, study designs, outcomes, and number of patients studied, it is difficult to assess its efficacy outside the ICU. However, based on the studies reviewed herein, HFNC therapy does not appear to decrease LOS, time on oxygen, or escalations of care, such as ICU transfers, positive pressure ventilation, or intubation, when used as a primary therapy.^7,9,11,12 Future research will ideally use optimal flow rates to determine the effectiveness of HFNC on acute care units. Although not addressed in the above studies, additional benefits to be considered in future studies include: (1) increased critical care capacity by allowing patients to be supported on the floor and (2) the ability for patients to remain closer to home when HFNC is used in the community hospital setting.

In each of the large, randomized studies reviewed, most (66%-75%) patients treated with standard low flow oxygen were supported successfully and did not require escalation to HFNC.^9,10 Hospitalists should continue to use standard low flow oxygen as first-line respiratory support for patients with bronchiolitis.¹ No evidence supports the use of HFNC therapy early in a child’s inpatient course; rather, it should be used when standard oxygen therapy fails. Future research should focus on better elucidating which patients will benefit most from HFNC to prevent overuse.

Viral bronchiolitis is the most common indication for infant hospitalization in the United States.¹ The treatment mainstay remains supportive care, including supplemental oxygen when indicated.¹ High flow nasal cannula (HFNC) therapy delivers humidified, heated air blended with oxygen, allowing much higher flow rates than standard nasal cannula therapy and is being used more frequently in inpatient settings.

Infants and toddlers with bronchiolitis develop increased work of breathing to preserve oxygenation and ventilation in the setting of altered airway resistance and lung compliance.^2,3 In addition to oxygen supplementation, HFNC is used to reduce work of breathing through several mechanisms:^2-6 (1) Nasopharyngeal dead space washout clears oxygen-depleted gas at the end of expiration, facilitating alveolar ventilation (ie, carbon dioxide retention improves); (2) High flow rates match increased inspiratory flow demands of acutely ill patients, reducing nasopharyngeal inspiratory resistance and optimizing dead space washout, thus decreasing work of breathing; (3) Adequate flow rates generate distending pressure, which prevents pharyngeal collapse, supports lung recruitment, and reduces respiratory effort (demonstrated in younger infants); and (4) HFNC systems heat and humidify the breathing gas, reducing the metabolic work required to condition cool, dry gas and improving conductance and pulmonary compliance.^2-5

HFNC therapy is used more commonly in acute care units despite limited literature on its effectiveness outside the intensive care unit (ICU).^7,8 We asked the question, “Does use of HFNC therapy for infants with bronchiolitis hospitalized in acute care units result in improved outcomes when compared with standard nasal cannula oxygen therapy, including length of stay (LOS), oxygen therapy duration, and preventing escalations of care such as ICU transfer, positive pressure ventilation, and intubation?” Also, do published studies provide guidance for the initiation and management of HFNC? We focused our search on studies published in the last five years that included patients with bronchiolitis treated with HFNC outside the ICU; here, we review those studies most relevant to pediatric hospitalists.

No guideline exists for initiating flow or fraction of inspired oxygen (FiO₂). HFNC may be initiated for hypoxia, increased work of breathing, or both in patients with bronchiolitis. To achieve optimal dead space washout, inspiratory flow, and distending pressure, initial flow rates should be 1.5 to 2 L/kg/min, particularly for infants and young children.^2-5 Weiler et al.³ evaluated the breathing effort of ICU patients at 0.5, 1, 1.5, and 2 L/kg/min and found optimal flow rates for improved work of breathing were 1.5-2 L/kg/min. The smallest patients, ≤8 kg, saw the greatest benefit, a finding likely explained by larger anatomic dead space in infants/small children compared with older children.³ For older/larger children (>20 kg), an initial flow closer to 1 L/kg/min is often appropriate.⁵ When used for hypoxia, initiating flow without supplemental FiO₂ may improve oxygenation by flushing nasopharyngeal dead space. FiO₂ should be titrated to achieve the goal set by the treatment team, often ≥90%. Improvement in heart rate and peripheral oxygen saturation (SpO₂) can be observed within 60 minutes of initiating HFNC in patients responsive to therapy.⁶

HFNC therapy is safe when used correctly.^6,9,10Potential adverse effects include pneumothorax, pressure injury, mucosal injury/bleeding, and delayed escalation to invasive ventilation. While difficult to quantify, recent studies report low rates or no serious HFNC complications. For example, only 2 of 1,127 patients supported with HFNC developed a pneumothorax and neither required evacuation.^2,9-12

Inclusion criteria and HFNC protocols vary among published studies. Most HFNC protocols reviewed may not have optimally supported all of the patients in their HFNC groups, often by limiting flow to <2 L/kg/min.^6-9,11,12 These variables may explain the disparate results, with some studies demonstrating apparent benefits and others no difference.^7,9,10,12

Two studies of infants with bronchiolitis showed HFNC therapy may prevent ICU transfer, but this benefit may be limited to rescue when standard oxygen therapy fails, rather than as a superior initial support modality.^7,9 Kepreotes et al.⁹ reported a single-center, randomized controlled trial comparing HFNC with standard oxygen therapy with 101 patients in each treatment arm. The primary outcome, median time to wean off oxygen, was not significantly different between the two groups: 24 hours (95% CI: 18-28) in the HFNC group versus 20 hours in the standard therapy group (95% CI: 17-34). The HFNC group had fewer treatment failures (abnormal heart rate, respiratory rate, SpO₂ <90%, or severe respiratory distress score while on maximum therapy) than the standard therapy group, and 20 (63%) of the 33 patients who failed standard therapy were rescued with HFNC, avoiding transfer to the ICU. Fourteen patients from the HFNC group and 12 from the standard oxygen group required transfer to the ICU for support escalation. Although this study did not show a significant difference in oxygen weaning time between groups, it appears to support HFNC use as a rescue modality to reduce or prevent ICU transfer.⁹ Franklin et al.¹⁰ conducted a multicenter, randomized, controlled trial to compare standard nasal cannula oxygen therapy with HFNC (2 L/kg/min) in 1,472 patients. Patients receiving HFNC had lower care escalation rates due to treatment failure, defined as the presence of at least three of four clinical criteria and the clinician determining escalation was indicated. Oxygen therapy duration, ICU admission rates, and LOS were not significantly different between groups. Similar to the previous study, a large portion of the standard therapy patients who failed treatment (102 of 167) crossed over to the HFNC arm in an attempt to avoid ICU transfer. Twelve patients required intubation: 8 (1%) receiving HFNC and 4 (0.5%) receiving the standard therapy.¹⁰

Two additional studies, both with study design limitations, did not demonstrate differences in ICU transfer rates and had variable differences in outcomes. Riese et al.⁷ retrospectively assessed HFNC use outside the ICU at one institution and included 936 patients admitted before and 1,001 patients admitted after HFNC guideline implementation on the wards. Flow rates were based on age and not weight. They found no difference in LOS, ICU transfer rate, ICU LOS, intubation rates, or 30-day readmission rates, though HFNC use increased over time. The HFNC guideline is a potentially significant limitation as it may not have provided optimal flow rates to all subjects given it was based on age rather than weight. Milani et al.¹² performed a single-center observational study of 36 infants aged <12 months, treated for bronchiolitis on the ward, who were informally assigned to HFNC or standard therapy based upon HFNC device availability. HFNC flow rate was determined by the equation: L/min = 8 mL/kg × respiratory rate × 0.3. Using mean weight and respiratory rate for patients in this group, it appears patients in the HFNC group were treated with flow rates less than the 1.5-2 L/kg/min recommended to be effective.^2,3,12 Despite this, clinical improvement was faster in the HFNC group, including respiratory rate and effort, ability to feed, days on oxygen supplementation, and hospital LOS. ICU admission was not different between the two groups.¹² The Table compares the four studies discussed above.

Many children’s hospitals have extended the use of HFNC outside the ICU for children with bronchiolitis despite the paucity of evidence demonstrating its benefit over standard flow oxygen. Given variation in protocols, study designs, outcomes, and number of patients studied, it is difficult to assess its efficacy outside the ICU. However, based on the studies reviewed herein, HFNC therapy does not appear to decrease LOS, time on oxygen, or escalations of care, such as ICU transfers, positive pressure ventilation, or intubation, when used as a primary therapy.^7,9,11,12 Future research will ideally use optimal flow rates to determine the effectiveness of HFNC on acute care units. Although not addressed in the above studies, additional benefits to be considered in future studies include: (1) increased critical care capacity by allowing patients to be supported on the floor and (2) the ability for patients to remain closer to home when HFNC is used in the community hospital setting.

In each of the large, randomized studies reviewed, most (66%-75%) patients treated with standard low flow oxygen were supported successfully and did not require escalation to HFNC.^9,10 Hospitalists should continue to use standard low flow oxygen as first-line respiratory support for patients with bronchiolitis.¹ No evidence supports the use of HFNC therapy early in a child’s inpatient course; rather, it should be used when standard oxygen therapy fails. Future research should focus on better elucidating which patients will benefit most from HFNC to prevent overuse.

High-flow nasal cannula (HFNC) oxygen therapy is effective in treating adults with acute hypoxemic respiratory failure, and to a lesser extent acute hypercapnic respiratory failure.^1-3 HFNC oxygen is capable of delivering oxygen with flows of 30-60 liters/minute, and can provide a high fraction of inspired oxygen, flush anatomic dead space, augment respiratory efforts, and provide mild continuous positive airway pressure effects. Several systematic reviews and meta-analyses have evaluated the effectiveness of HFNC oxygen and have shown modestly lower rates of intubation compared with conventional oxygen^4,5 and similar intubation rates compared with noninvasive positive pressure ventilation.^4-9 Although one randomized trial showed a lower risk of 90-day mortality for HFNC oxygen compared with either conventional oxygen or noninvasive positive pressure ventilation, several meta-analyses have shown no difference in intensive care unit (ICU) mortality.^4,6,8,10 The majority of studies have shown improvements in oxygenation, comfort, dyspnea scores, and breathing pattern with the initiation of HFNC oxygen.⁶

While the evidence to support the use of HFNC oxygen in patients with nonhypercapnic acute hypoxemic respiratory failure is growing, this evidence is based on patients enrolled in clinical trials who have no treatment limitations and consent to intubation if necessary. Indeed, several, if not all, randomized trials evaluating HFNC oxygen excluded patients who had do-not-intubate (DNI) or do-not-resuscitate (DNR) orders.^1,2,11 For patients with acute respiratory failure whose primary goal is not to extend life or utilize life support interventions such as invasive mechanical ventilation, HFNC oxygen may offer several benefits compared with other treatment options such as noninvasive positive pressure ventilation, conventional oxygen therapy, or palliative opioid therapy (Appendix Table 1). Determining which treatment options to use depends on the goals of care of the individual patient and the reasonable ability of a particular treatment to help the patient achieve those goals.

While a recent systematic review evaluated the existing evidence regarding the utility and outcomes of noninvasive positive pressure ventilation in adult patients with DNI orders,¹² a systematic review evaluating the evidence and rationale for HFNC oxygen in patients with DNI and/or DNR orders is lacking. Assessing such evidence is necessary to help clinicians and patients determine appropriate treatment choices and establish research priorities. Therefore, our primary objective was to determine what were the following outcomes: mortality, dyspnea, work of breathing, opioid doses, and quality of life in patients who received HFNC oxygen for acute respiratory failure and had a DNI and/or DNR order.

We conducted a systematic review of studies that evaluated patients who used HFNC oxygen for acute respiratory failure and had a DNI and/or DNR order. We reported the results using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements.¹³ This review was registered with the PROSPERO registry, CRD42017059914.

We included studies that enrolled patients who were (1) hospitalized, (2) >18 years old, (3) had an acute respiratory failure of any cause, (4) received HFNC oxygen, and (5) had a DNI or DNR or comfort measures only order. We included publications of all study designs (interventional, observational, and posthoc analyses) and all languages. We excluded studies that enrolled <5 patients. If necessary, we contacted the authors of the included studies for additional information.

Our search strategy included the following databases from inception to October 14, 2018: PubMed, MEDLINE, CINAHL, MICROMEDEX, EMBASE, Web of Science, and Scopus. The database-specific search strategy was developed using an experienced librarian (Appendix Table 2). In addition, we screened the reference lists of systematic reviews as well as the included studies to find additional relevant articles. Two authors (AM, MEW) independently assessed the inclusion criteria of the titles and abstracts that were identified in the search. In addition, these two authors abstracted relevant data of the included studies.

Using the search strategy, we identified 2,757 citations and included 301 of these in the full-text review (Figure). We included six studies, which enrolled 293 patients in the final systematic review. Table 1 summarizes the characteristics of the included investigations, all of which were observational studies.^15-20 The studies were conducted in the United States of America (n = 3), Europe (n = 2), and Asia (n = 1). Two studies were conducted in the general ICU populations and included patients with hypoxemic respiratory failure only. Four studies were conducted in cancer populations in the hospital wards or ICU and did not specify the type of respiratory failure (hypoxemic versus hypercapnic). Two studies included patients with DNI orders only.^15,20 One study included patients with DNR orders only (DNI orders were excluded).¹⁷ Three studies included patients with both DNR and DNI orders.^16,18,19 The numbers of enrolled patients with treatment limitations were generally low, with the two largest studies including 101 patients each on HFNC oxygen.^18,19

Risk of Bias

All included studies had a high risk of bias (Table 2). A high risk of bias was suggested because the investigations were single-center studies with unclear patient selection methods, did not explicitly report how decisions to limit treatments were made, and did not explicitly differentiate and separately analyze patients with “comfort measures only” goals of care.

Mortality

The hospital mortality rates of patients with DNI and/or DNR orders receiving HFNC were variable and ranged from 40% to 87%. In the two studies enrolling general ICU patient populations, the hospital mortality rates ranged from 40% to 60%. In the four studies enrolling patients with active malignancy, the hospital mortality rates ranged from 75% to 87%. No studies compared mortality rates with and without DNI and/or DNR orders.

Dyspnea, Work of Breathing, and Reduction in Opioid Doses

The impact of HFNC oxygen on symptom relief was reported in one retrospective observational study (published as a conference abstract only to date), which compared the effect of HFNC oxygen (n = 101) with conventional oxygen (n = 110).¹⁸ At first evaluation after hospital admission to a palliative care unit (after the patients had previously been started on either conventional oxygen or high-flow oxygen), patients in the HFNC oxygen group had worse (higher) dyspnea scores compared with patients who used conventional oxygen (Edmonton Symptom Assessment Scale score of 7.5 versus 5, P < .001). At follow-up, approximately 24 hours after admission to the hospital palliative care unit, there was no difference in the change of dyspnea between the HFNC oxygen group (dyspnea score change of 0) and the conventional oxygen group (dyspnea score change of −1, P = .18. In the same study, there was also no significant difference in the morphine dose requirement in each group, and exact doses were not reported.

Two studies reported improvement in oxygen saturation and respiratory rate after HFNC oxygen initiation (compared with before HFNC initiation).^16,20 Oxygen saturation increased from 89% to 95%, P < .01, in one study and 92% to 97%, P < .01, in a second study. The respiratory rate decreased from 31 to 25 breaths/minute in one study, and from 28 to 25 breaths/minute in a second study (both P < .01).

Quality of Life

No studies evaluated the quality of life of survivors.

Secondary Outcomes

Transition to Noninvasive Positive Pressure Ventilation

The proportion of patients who transitioned from HFNC oxygen to NPPV was relatively low in the two studies that reported this outcome, ranging from 0%²⁰ to 18%.¹⁶ In one observational study of a general ICU population, 9/50 (18%) of patients transitioned from HFNC oxygen to NPPV. There was no statistically significant difference in hospital mortality rates among those who progressed to NPPV (67%) versus those who did not progress to NPPV (58%), P = .72.

Tolerance of HFNC and Adverse Events

HFNC oxygen was generally well tolerated based on the assessment of three studies (Table 1). One study reported no adverse events,¹⁶ one study reported that HFNC oxygen had to be discontinued because of nasal discomfort in 1% of patients,¹⁹ and a second study reported that HFNC oxygen had to be discontinued because of agitation in 4% of patients.²⁰

Quality of Death in Nonsurvivors

No studies evaluated the quality of death in those patients who died.

In this systematic review of six studies, all with a high risk of bias, a significant proportion of patients with a DNI and/or DNR order who used HFNC oxygen survived to hospital discharge. Oxygen saturation and respiratory rate consistently improved in the three studies that reported these outcomes. Only one study (published as a conference abstract only to date),¹⁸ however, measured patient-important outcomes related to symptom management and found no significant difference in dyspnea or morphine dose requirements in patients on HFNC oxygen compared with patients on conventional oxygen. HFNC oxygen was generally well tolerated and only had to be stopped in <5% of patients due to intolerance. We found no studies that assessed the quality of life in survivors or the quality of death in nonsurvivors.

Based on the limited evidence in the included studies, HFNC may be a viable treatment option for patients with preset treatment limitations who have acute respiratory failure—with potential benefits of improved oxygenation, decreased respiratory rates, and hospital survival in a proportion of patients. Nevertheless, this systematic review highlights the vast paucity of data available to guide the use of HFNC oxygen in patients with treatment limitations and acute respiratory failure. Only a few studies, which were at high risk of bias, have been conducted on this topic to date. There is an inadequate evidence base to evaluate the comparative effectiveness of HFNC oxygen (versus NPPV versus conventional oxygen versus palliative opioids) in patients with DNI orders or comfort measures only orders.

Our review included two studies that evaluated the comparative effectiveness of HFNC oxygen in patients with DNI and/or DNR orders. The first retrospective observational study compared HFNC oxygen with conventional oxygen in patients with DNR and DNI orders and malignancy—and found no change in dyspnea—but did note an increase in mortality with HFNC oxygen (76% versus 51%).¹⁸ The second observational study compared HFNC oxygen with NPPV in patients with DNR orders with malignancy noted no difference in mortality.¹⁷ In patients with full-code orders, systematic reviews have shown that HFNC oxygen (compared with conventional oxygen) was associated with possible reductions in intubation rates, respiratory rates, and improvements in oxygenation—with no difference in mortality, dyspnea, patient comfort, or ICU/hospital length of stay. Compared with NPPV, HFNC oxygen was associated with similar rates of intubation and mortality.^4-6,21

Future studies in patients with acute respiratory failure and DNI and/or DNR orders should identify which treatment modality (HFNC oxygen compared with other modalities, such as NPPV, conventional oxygen, with or without palliative opioids) impacts outcomes, such as dyspnea reduction while maintaining an alert mental status, short- and long-term quality of life in survivors, and quality of death in nonsurvivors. Future studies should also identify the optimal treatment pathway to utilize when patients using HFNC oxygen fail this therapy (eg, transition to NPPV versus intensifying palliative opioids) as well as the optimal process to withdraw palliative HFNC oxygen.²² Identifying which patient populations may benefit from different treatment pathways should also be considered as different treatment strategies may be more beneficial in different patient populations (eg, based on cause and severity of acute respiratory failure). In addition, it should be noted that the primary goal of care might affect which outcomes are the most important to measure. While patients with comfort measures only, orders usually have a primary goal to prepare for a high-quality death, patients with DNI and/or DNR orders (but without comfort measures only orders) may have a primary goal to survive—but with the desire not to endure the high burden of intubation and mechanical ventilation if it became necessary. Finally, future studies should utilize high-quality study designs (eg, randomized controlled trials) that enable robust evaluation of comparative effectiveness of clinically relevant treatment strategies.

While several previous systematic reviews have evaluated the efficacy of HFNC in patients with acute respiratory failure without preset limitations on life support; to our knowledge, this is the first systematic review to assess outcomes in patients rigorously with preset treatment limitations. Our review is, however, limited by the high risk of bias of the studies that were included (single-center nature, retrospective observational study designs, small sample sizes, and lack of a description of how DNI and/or DNR statuses were determined) as well as the small number of studies available to be included.

This systematic review points to a significant evidence gap in our understanding of the role for HFNC oxygen (compared with other acceptable alternative treatment strategies) in adult patients with acute respiratory failure who have DNI and/or DNR orders. Further high-quality research is needed to explore these unanswered questions in an effort to best treat, guide, and engage in optimal end-of-life decision making among patients with acute respiratory failure.

High-flow nasal cannula (HFNC) oxygen therapy is effective in treating adults with acute hypoxemic respiratory failure, and to a lesser extent acute hypercapnic respiratory failure.^1-3 HFNC oxygen is capable of delivering oxygen with flows of 30-60 liters/minute, and can provide a high fraction of inspired oxygen, flush anatomic dead space, augment respiratory efforts, and provide mild continuous positive airway pressure effects. Several systematic reviews and meta-analyses have evaluated the effectiveness of HFNC oxygen and have shown modestly lower rates of intubation compared with conventional oxygen^4,5 and similar intubation rates compared with noninvasive positive pressure ventilation.^4-9 Although one randomized trial showed a lower risk of 90-day mortality for HFNC oxygen compared with either conventional oxygen or noninvasive positive pressure ventilation, several meta-analyses have shown no difference in intensive care unit (ICU) mortality.^4,6,8,10 The majority of studies have shown improvements in oxygenation, comfort, dyspnea scores, and breathing pattern with the initiation of HFNC oxygen.⁶

While the evidence to support the use of HFNC oxygen in patients with nonhypercapnic acute hypoxemic respiratory failure is growing, this evidence is based on patients enrolled in clinical trials who have no treatment limitations and consent to intubation if necessary. Indeed, several, if not all, randomized trials evaluating HFNC oxygen excluded patients who had do-not-intubate (DNI) or do-not-resuscitate (DNR) orders.^1,2,11 For patients with acute respiratory failure whose primary goal is not to extend life or utilize life support interventions such as invasive mechanical ventilation, HFNC oxygen may offer several benefits compared with other treatment options such as noninvasive positive pressure ventilation, conventional oxygen therapy, or palliative opioid therapy (Appendix Table 1). Determining which treatment options to use depends on the goals of care of the individual patient and the reasonable ability of a particular treatment to help the patient achieve those goals.

While a recent systematic review evaluated the existing evidence regarding the utility and outcomes of noninvasive positive pressure ventilation in adult patients with DNI orders,¹² a systematic review evaluating the evidence and rationale for HFNC oxygen in patients with DNI and/or DNR orders is lacking. Assessing such evidence is necessary to help clinicians and patients determine appropriate treatment choices and establish research priorities. Therefore, our primary objective was to determine what were the following outcomes: mortality, dyspnea, work of breathing, opioid doses, and quality of life in patients who received HFNC oxygen for acute respiratory failure and had a DNI and/or DNR order.

We conducted a systematic review of studies that evaluated patients who used HFNC oxygen for acute respiratory failure and had a DNI and/or DNR order. We reported the results using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements.¹³ This review was registered with the PROSPERO registry, CRD42017059914.

We included studies that enrolled patients who were (1) hospitalized, (2) >18 years old, (3) had an acute respiratory failure of any cause, (4) received HFNC oxygen, and (5) had a DNI or DNR or comfort measures only order. We included publications of all study designs (interventional, observational, and posthoc analyses) and all languages. We excluded studies that enrolled <5 patients. If necessary, we contacted the authors of the included studies for additional information.

Our search strategy included the following databases from inception to October 14, 2018: PubMed, MEDLINE, CINAHL, MICROMEDEX, EMBASE, Web of Science, and Scopus. The database-specific search strategy was developed using an experienced librarian (Appendix Table 2). In addition, we screened the reference lists of systematic reviews as well as the included studies to find additional relevant articles. Two authors (AM, MEW) independently assessed the inclusion criteria of the titles and abstracts that were identified in the search. In addition, these two authors abstracted relevant data of the included studies.

Using the search strategy, we identified 2,757 citations and included 301 of these in the full-text review (Figure). We included six studies, which enrolled 293 patients in the final systematic review. Table 1 summarizes the characteristics of the included investigations, all of which were observational studies.^15-20 The studies were conducted in the United States of America (n = 3), Europe (n = 2), and Asia (n = 1). Two studies were conducted in the general ICU populations and included patients with hypoxemic respiratory failure only. Four studies were conducted in cancer populations in the hospital wards or ICU and did not specify the type of respiratory failure (hypoxemic versus hypercapnic). Two studies included patients with DNI orders only.^15,20 One study included patients with DNR orders only (DNI orders were excluded).¹⁷ Three studies included patients with both DNR and DNI orders.^16,18,19 The numbers of enrolled patients with treatment limitations were generally low, with the two largest studies including 101 patients each on HFNC oxygen.^18,19

Risk of Bias

All included studies had a high risk of bias (Table 2). A high risk of bias was suggested because the investigations were single-center studies with unclear patient selection methods, did not explicitly report how decisions to limit treatments were made, and did not explicitly differentiate and separately analyze patients with “comfort measures only” goals of care.

Mortality

The hospital mortality rates of patients with DNI and/or DNR orders receiving HFNC were variable and ranged from 40% to 87%. In the two studies enrolling general ICU patient populations, the hospital mortality rates ranged from 40% to 60%. In the four studies enrolling patients with active malignancy, the hospital mortality rates ranged from 75% to 87%. No studies compared mortality rates with and without DNI and/or DNR orders.

Dyspnea, Work of Breathing, and Reduction in Opioid Doses

The impact of HFNC oxygen on symptom relief was reported in one retrospective observational study (published as a conference abstract only to date), which compared the effect of HFNC oxygen (n = 101) with conventional oxygen (n = 110).¹⁸ At first evaluation after hospital admission to a palliative care unit (after the patients had previously been started on either conventional oxygen or high-flow oxygen), patients in the HFNC oxygen group had worse (higher) dyspnea scores compared with patients who used conventional oxygen (Edmonton Symptom Assessment Scale score of 7.5 versus 5, P < .001). At follow-up, approximately 24 hours after admission to the hospital palliative care unit, there was no difference in the change of dyspnea between the HFNC oxygen group (dyspnea score change of 0) and the conventional oxygen group (dyspnea score change of −1, P = .18. In the same study, there was also no significant difference in the morphine dose requirement in each group, and exact doses were not reported.

Two studies reported improvement in oxygen saturation and respiratory rate after HFNC oxygen initiation (compared with before HFNC initiation).^16,20 Oxygen saturation increased from 89% to 95%, P < .01, in one study and 92% to 97%, P < .01, in a second study. The respiratory rate decreased from 31 to 25 breaths/minute in one study, and from 28 to 25 breaths/minute in a second study (both P < .01).

Quality of Life

No studies evaluated the quality of life of survivors.

Secondary Outcomes

Transition to Noninvasive Positive Pressure Ventilation

The proportion of patients who transitioned from HFNC oxygen to NPPV was relatively low in the two studies that reported this outcome, ranging from 0%²⁰ to 18%.¹⁶ In one observational study of a general ICU population, 9/50 (18%) of patients transitioned from HFNC oxygen to NPPV. There was no statistically significant difference in hospital mortality rates among those who progressed to NPPV (67%) versus those who did not progress to NPPV (58%), P = .72.

Tolerance of HFNC and Adverse Events

HFNC oxygen was generally well tolerated based on the assessment of three studies (Table 1). One study reported no adverse events,¹⁶ one study reported that HFNC oxygen had to be discontinued because of nasal discomfort in 1% of patients,¹⁹ and a second study reported that HFNC oxygen had to be discontinued because of agitation in 4% of patients.²⁰

Quality of Death in Nonsurvivors

No studies evaluated the quality of death in those patients who died.

In this systematic review of six studies, all with a high risk of bias, a significant proportion of patients with a DNI and/or DNR order who used HFNC oxygen survived to hospital discharge. Oxygen saturation and respiratory rate consistently improved in the three studies that reported these outcomes. Only one study (published as a conference abstract only to date),¹⁸ however, measured patient-important outcomes related to symptom management and found no significant difference in dyspnea or morphine dose requirements in patients on HFNC oxygen compared with patients on conventional oxygen. HFNC oxygen was generally well tolerated and only had to be stopped in <5% of patients due to intolerance. We found no studies that assessed the quality of life in survivors or the quality of death in nonsurvivors.

Based on the limited evidence in the included studies, HFNC may be a viable treatment option for patients with preset treatment limitations who have acute respiratory failure—with potential benefits of improved oxygenation, decreased respiratory rates, and hospital survival in a proportion of patients. Nevertheless, this systematic review highlights the vast paucity of data available to guide the use of HFNC oxygen in patients with treatment limitations and acute respiratory failure. Only a few studies, which were at high risk of bias, have been conducted on this topic to date. There is an inadequate evidence base to evaluate the comparative effectiveness of HFNC oxygen (versus NPPV versus conventional oxygen versus palliative opioids) in patients with DNI orders or comfort measures only orders.

Our review included two studies that evaluated the comparative effectiveness of HFNC oxygen in patients with DNI and/or DNR orders. The first retrospective observational study compared HFNC oxygen with conventional oxygen in patients with DNR and DNI orders and malignancy—and found no change in dyspnea—but did note an increase in mortality with HFNC oxygen (76% versus 51%).¹⁸ The second observational study compared HFNC oxygen with NPPV in patients with DNR orders with malignancy noted no difference in mortality.¹⁷ In patients with full-code orders, systematic reviews have shown that HFNC oxygen (compared with conventional oxygen) was associated with possible reductions in intubation rates, respiratory rates, and improvements in oxygenation—with no difference in mortality, dyspnea, patient comfort, or ICU/hospital length of stay. Compared with NPPV, HFNC oxygen was associated with similar rates of intubation and mortality.^4-6,21

Future studies in patients with acute respiratory failure and DNI and/or DNR orders should identify which treatment modality (HFNC oxygen compared with other modalities, such as NPPV, conventional oxygen, with or without palliative opioids) impacts outcomes, such as dyspnea reduction while maintaining an alert mental status, short- and long-term quality of life in survivors, and quality of death in nonsurvivors. Future studies should also identify the optimal treatment pathway to utilize when patients using HFNC oxygen fail this therapy (eg, transition to NPPV versus intensifying palliative opioids) as well as the optimal process to withdraw palliative HFNC oxygen.²² Identifying which patient populations may benefit from different treatment pathways should also be considered as different treatment strategies may be more beneficial in different patient populations (eg, based on cause and severity of acute respiratory failure). In addition, it should be noted that the primary goal of care might affect which outcomes are the most important to measure. While patients with comfort measures only, orders usually have a primary goal to prepare for a high-quality death, patients with DNI and/or DNR orders (but without comfort measures only orders) may have a primary goal to survive—but with the desire not to endure the high burden of intubation and mechanical ventilation if it became necessary. Finally, future studies should utilize high-quality study designs (eg, randomized controlled trials) that enable robust evaluation of comparative effectiveness of clinically relevant treatment strategies.

While several previous systematic reviews have evaluated the efficacy of HFNC in patients with acute respiratory failure without preset limitations on life support; to our knowledge, this is the first systematic review to assess outcomes in patients rigorously with preset treatment limitations. Our review is, however, limited by the high risk of bias of the studies that were included (single-center nature, retrospective observational study designs, small sample sizes, and lack of a description of how DNI and/or DNR statuses were determined) as well as the small number of studies available to be included.

This systematic review points to a significant evidence gap in our understanding of the role for HFNC oxygen (compared with other acceptable alternative treatment strategies) in adult patients with acute respiratory failure who have DNI and/or DNR orders. Further high-quality research is needed to explore these unanswered questions in an effort to best treat, guide, and engage in optimal end-of-life decision making among patients with acute respiratory failure.

High-flow nasal cannula (HFNC) oxygen therapy is effective in treating adults with acute hypoxemic respiratory failure, and to a lesser extent acute hypercapnic respiratory failure.^1-3 HFNC oxygen is capable of delivering oxygen with flows of 30-60 liters/minute, and can provide a high fraction of inspired oxygen, flush anatomic dead space, augment respiratory efforts, and provide mild continuous positive airway pressure effects. Several systematic reviews and meta-analyses have evaluated the effectiveness of HFNC oxygen and have shown modestly lower rates of intubation compared with conventional oxygen^4,5 and similar intubation rates compared with noninvasive positive pressure ventilation.^4-9 Although one randomized trial showed a lower risk of 90-day mortality for HFNC oxygen compared with either conventional oxygen or noninvasive positive pressure ventilation, several meta-analyses have shown no difference in intensive care unit (ICU) mortality.^4,6,8,10 The majority of studies have shown improvements in oxygenation, comfort, dyspnea scores, and breathing pattern with the initiation of HFNC oxygen.⁶

While the evidence to support the use of HFNC oxygen in patients with nonhypercapnic acute hypoxemic respiratory failure is growing, this evidence is based on patients enrolled in clinical trials who have no treatment limitations and consent to intubation if necessary. Indeed, several, if not all, randomized trials evaluating HFNC oxygen excluded patients who had do-not-intubate (DNI) or do-not-resuscitate (DNR) orders.^1,2,11 For patients with acute respiratory failure whose primary goal is not to extend life or utilize life support interventions such as invasive mechanical ventilation, HFNC oxygen may offer several benefits compared with other treatment options such as noninvasive positive pressure ventilation, conventional oxygen therapy, or palliative opioid therapy (Appendix Table 1). Determining which treatment options to use depends on the goals of care of the individual patient and the reasonable ability of a particular treatment to help the patient achieve those goals.

While a recent systematic review evaluated the existing evidence regarding the utility and outcomes of noninvasive positive pressure ventilation in adult patients with DNI orders,¹² a systematic review evaluating the evidence and rationale for HFNC oxygen in patients with DNI and/or DNR orders is lacking. Assessing such evidence is necessary to help clinicians and patients determine appropriate treatment choices and establish research priorities. Therefore, our primary objective was to determine what were the following outcomes: mortality, dyspnea, work of breathing, opioid doses, and quality of life in patients who received HFNC oxygen for acute respiratory failure and had a DNI and/or DNR order.

We conducted a systematic review of studies that evaluated patients who used HFNC oxygen for acute respiratory failure and had a DNI and/or DNR order. We reported the results using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements.¹³ This review was registered with the PROSPERO registry, CRD42017059914.

We included studies that enrolled patients who were (1) hospitalized, (2) >18 years old, (3) had an acute respiratory failure of any cause, (4) received HFNC oxygen, and (5) had a DNI or DNR or comfort measures only order. We included publications of all study designs (interventional, observational, and posthoc analyses) and all languages. We excluded studies that enrolled <5 patients. If necessary, we contacted the authors of the included studies for additional information.

Our search strategy included the following databases from inception to October 14, 2018: PubMed, MEDLINE, CINAHL, MICROMEDEX, EMBASE, Web of Science, and Scopus. The database-specific search strategy was developed using an experienced librarian (Appendix Table 2). In addition, we screened the reference lists of systematic reviews as well as the included studies to find additional relevant articles. Two authors (AM, MEW) independently assessed the inclusion criteria of the titles and abstracts that were identified in the search. In addition, these two authors abstracted relevant data of the included studies.

Using the search strategy, we identified 2,757 citations and included 301 of these in the full-text review (Figure). We included six studies, which enrolled 293 patients in the final systematic review. Table 1 summarizes the characteristics of the included investigations, all of which were observational studies.^15-20 The studies were conducted in the United States of America (n = 3), Europe (n = 2), and Asia (n = 1). Two studies were conducted in the general ICU populations and included patients with hypoxemic respiratory failure only. Four studies were conducted in cancer populations in the hospital wards or ICU and did not specify the type of respiratory failure (hypoxemic versus hypercapnic). Two studies included patients with DNI orders only.^15,20 One study included patients with DNR orders only (DNI orders were excluded).¹⁷ Three studies included patients with both DNR and DNI orders.^16,18,19 The numbers of enrolled patients with treatment limitations were generally low, with the two largest studies including 101 patients each on HFNC oxygen.^18,19

Risk of Bias

All included studies had a high risk of bias (Table 2). A high risk of bias was suggested because the investigations were single-center studies with unclear patient selection methods, did not explicitly report how decisions to limit treatments were made, and did not explicitly differentiate and separately analyze patients with “comfort measures only” goals of care.

Mortality

The hospital mortality rates of patients with DNI and/or DNR orders receiving HFNC were variable and ranged from 40% to 87%. In the two studies enrolling general ICU patient populations, the hospital mortality rates ranged from 40% to 60%. In the four studies enrolling patients with active malignancy, the hospital mortality rates ranged from 75% to 87%. No studies compared mortality rates with and without DNI and/or DNR orders.

Dyspnea, Work of Breathing, and Reduction in Opioid Doses

The impact of HFNC oxygen on symptom relief was reported in one retrospective observational study (published as a conference abstract only to date), which compared the effect of HFNC oxygen (n = 101) with conventional oxygen (n = 110).¹⁸ At first evaluation after hospital admission to a palliative care unit (after the patients had previously been started on either conventional oxygen or high-flow oxygen), patients in the HFNC oxygen group had worse (higher) dyspnea scores compared with patients who used conventional oxygen (Edmonton Symptom Assessment Scale score of 7.5 versus 5, P < .001). At follow-up, approximately 24 hours after admission to the hospital palliative care unit, there was no difference in the change of dyspnea between the HFNC oxygen group (dyspnea score change of 0) and the conventional oxygen group (dyspnea score change of −1, P = .18. In the same study, there was also no significant difference in the morphine dose requirement in each group, and exact doses were not reported.

Two studies reported improvement in oxygen saturation and respiratory rate after HFNC oxygen initiation (compared with before HFNC initiation).^16,20 Oxygen saturation increased from 89% to 95%, P < .01, in one study and 92% to 97%, P < .01, in a second study. The respiratory rate decreased from 31 to 25 breaths/minute in one study, and from 28 to 25 breaths/minute in a second study (both P < .01).

Quality of Life

No studies evaluated the quality of life of survivors.

Secondary Outcomes

Transition to Noninvasive Positive Pressure Ventilation

The proportion of patients who transitioned from HFNC oxygen to NPPV was relatively low in the two studies that reported this outcome, ranging from 0%²⁰ to 18%.¹⁶ In one observational study of a general ICU population, 9/50 (18%) of patients transitioned from HFNC oxygen to NPPV. There was no statistically significant difference in hospital mortality rates among those who progressed to NPPV (67%) versus those who did not progress to NPPV (58%), P = .72.

Tolerance of HFNC and Adverse Events

HFNC oxygen was generally well tolerated based on the assessment of three studies (Table 1). One study reported no adverse events,¹⁶ one study reported that HFNC oxygen had to be discontinued because of nasal discomfort in 1% of patients,¹⁹ and a second study reported that HFNC oxygen had to be discontinued because of agitation in 4% of patients.²⁰

Quality of Death in Nonsurvivors

No studies evaluated the quality of death in those patients who died.

In this systematic review of six studies, all with a high risk of bias, a significant proportion of patients with a DNI and/or DNR order who used HFNC oxygen survived to hospital discharge. Oxygen saturation and respiratory rate consistently improved in the three studies that reported these outcomes. Only one study (published as a conference abstract only to date),¹⁸ however, measured patient-important outcomes related to symptom management and found no significant difference in dyspnea or morphine dose requirements in patients on HFNC oxygen compared with patients on conventional oxygen. HFNC oxygen was generally well tolerated and only had to be stopped in <5% of patients due to intolerance. We found no studies that assessed the quality of life in survivors or the quality of death in nonsurvivors.

Based on the limited evidence in the included studies, HFNC may be a viable treatment option for patients with preset treatment limitations who have acute respiratory failure—with potential benefits of improved oxygenation, decreased respiratory rates, and hospital survival in a proportion of patients. Nevertheless, this systematic review highlights the vast paucity of data available to guide the use of HFNC oxygen in patients with treatment limitations and acute respiratory failure. Only a few studies, which were at high risk of bias, have been conducted on this topic to date. There is an inadequate evidence base to evaluate the comparative effectiveness of HFNC oxygen (versus NPPV versus conventional oxygen versus palliative opioids) in patients with DNI orders or comfort measures only orders.

Our review included two studies that evaluated the comparative effectiveness of HFNC oxygen in patients with DNI and/or DNR orders. The first retrospective observational study compared HFNC oxygen with conventional oxygen in patients with DNR and DNI orders and malignancy—and found no change in dyspnea—but did note an increase in mortality with HFNC oxygen (76% versus 51%).¹⁸ The second observational study compared HFNC oxygen with NPPV in patients with DNR orders with malignancy noted no difference in mortality.¹⁷ In patients with full-code orders, systematic reviews have shown that HFNC oxygen (compared with conventional oxygen) was associated with possible reductions in intubation rates, respiratory rates, and improvements in oxygenation—with no difference in mortality, dyspnea, patient comfort, or ICU/hospital length of stay. Compared with NPPV, HFNC oxygen was associated with similar rates of intubation and mortality.^4-6,21

Future studies in patients with acute respiratory failure and DNI and/or DNR orders should identify which treatment modality (HFNC oxygen compared with other modalities, such as NPPV, conventional oxygen, with or without palliative opioids) impacts outcomes, such as dyspnea reduction while maintaining an alert mental status, short- and long-term quality of life in survivors, and quality of death in nonsurvivors. Future studies should also identify the optimal treatment pathway to utilize when patients using HFNC oxygen fail this therapy (eg, transition to NPPV versus intensifying palliative opioids) as well as the optimal process to withdraw palliative HFNC oxygen.²² Identifying which patient populations may benefit from different treatment pathways should also be considered as different treatment strategies may be more beneficial in different patient populations (eg, based on cause and severity of acute respiratory failure). In addition, it should be noted that the primary goal of care might affect which outcomes are the most important to measure. While patients with comfort measures only, orders usually have a primary goal to prepare for a high-quality death, patients with DNI and/or DNR orders (but without comfort measures only orders) may have a primary goal to survive—but with the desire not to endure the high burden of intubation and mechanical ventilation if it became necessary. Finally, future studies should utilize high-quality study designs (eg, randomized controlled trials) that enable robust evaluation of comparative effectiveness of clinically relevant treatment strategies.

While several previous systematic reviews have evaluated the efficacy of HFNC in patients with acute respiratory failure without preset limitations on life support; to our knowledge, this is the first systematic review to assess outcomes in patients rigorously with preset treatment limitations. Our review is, however, limited by the high risk of bias of the studies that were included (single-center nature, retrospective observational study designs, small sample sizes, and lack of a description of how DNI and/or DNR statuses were determined) as well as the small number of studies available to be included.

This systematic review points to a significant evidence gap in our understanding of the role for HFNC oxygen (compared with other acceptable alternative treatment strategies) in adult patients with acute respiratory failure who have DNI and/or DNR orders. Further high-quality research is needed to explore these unanswered questions in an effort to best treat, guide, and engage in optimal end-of-life decision making among patients with acute respiratory failure.