Ph-like ALL is highly prevalent in adults

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Philadelphia chromosome–like acute lymphoblastic leukemia, a high-risk subtype of childhood ALL, accounts for more than 24% of ALL in adults and is associated with poor outcome, according to gene-expression profiling in nearly 800 adults with B-cell ALL.

In the 798 subjects aged 21-86 years, Philadelphia chromosome–like (Ph-like) ALL accounted for 27.9% of ALL cases in those aged 21-39 years, 20.4% of cases in those aged 40-59 years, and 24% of cases in those aged 60-86 years. The overall 5-year event-free survival rate was inferior in those with Ph-like ALL vs. non–Ph-like ALL (22.5% vs. 49.3%), as was the 5-year overall survival (23.8% vs. 52.4%). Increasing age also was associated with inferior outcomes: 5-year event-free survival was 40.4%, 29.8%, and 18.9% in the age groups, respectively, and 5-year overall survival was 45.2%, 35.1%, and 28.4% in the groups, respectively, Kathryn G. Roberts, Ph.D., of St. Jude Children’s Research Hospital in Memphis and her colleagues reported online ahead of print (J Clin Oncol. 2016 Nov 21. doi: 10.1200/JCO.2016.69.0073).

Dr. Kathryn G. Roberts
The investigators identified kinase-activating alterations in 88% of patients with Ph-like ALL. These included CRLF2 rearrangements in 51% of patients, ABL class fusions in 9.8%, JAK2 or EPOR rearrangements in 12.4%, other JAK-STAT sequence mutations in 7.2%, other kinase alterations in 4.1%, and Ras pathway mutations in 3.6%. Additionally, 11 new kinase rearrangements were identified, they said, noting that the diverse range of kinase-activating alterations – four of the newly identified rearrangements involved new kinase or cytokine receptor genes and seven involved new partner for previously identified genes – has important therapeutic implications.

Ph-like ALL in children is characterized by kinase-activating alterations amenable to treatment with tyrosine kinase inhibitors, but the prevalence in adults was unclear.

“These findings warrant the development of clinical trials in adults that assess the efficacy of TKIs, similar to those that are being established for pediatric ALL,” Dr. Roberts and her associates wrote.

This study was supported by grants and other awards, some to individual authors, from the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital; Stand Up to Cancer, St. Baldrick’s Foundation, the American Society of Hematology, the Lady Tata Memorial Trust, the Leukemia Research Foundation, the National Cancer Institute, and the National Institutes of Health. Dr. Roberts reported that she is the inventor on a pending patent application related to gene-expression signatures for detection of underlying Philadelphia chromosome-live events and therapeutic targeting in leukemia.

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Philadelphia chromosome–like acute lymphoblastic leukemia, a high-risk subtype of childhood ALL, accounts for more than 24% of ALL in adults and is associated with poor outcome, according to gene-expression profiling in nearly 800 adults with B-cell ALL.

In the 798 subjects aged 21-86 years, Philadelphia chromosome–like (Ph-like) ALL accounted for 27.9% of ALL cases in those aged 21-39 years, 20.4% of cases in those aged 40-59 years, and 24% of cases in those aged 60-86 years. The overall 5-year event-free survival rate was inferior in those with Ph-like ALL vs. non–Ph-like ALL (22.5% vs. 49.3%), as was the 5-year overall survival (23.8% vs. 52.4%). Increasing age also was associated with inferior outcomes: 5-year event-free survival was 40.4%, 29.8%, and 18.9% in the age groups, respectively, and 5-year overall survival was 45.2%, 35.1%, and 28.4% in the groups, respectively, Kathryn G. Roberts, Ph.D., of St. Jude Children’s Research Hospital in Memphis and her colleagues reported online ahead of print (J Clin Oncol. 2016 Nov 21. doi: 10.1200/JCO.2016.69.0073).

Dr. Kathryn G. Roberts
The investigators identified kinase-activating alterations in 88% of patients with Ph-like ALL. These included CRLF2 rearrangements in 51% of patients, ABL class fusions in 9.8%, JAK2 or EPOR rearrangements in 12.4%, other JAK-STAT sequence mutations in 7.2%, other kinase alterations in 4.1%, and Ras pathway mutations in 3.6%. Additionally, 11 new kinase rearrangements were identified, they said, noting that the diverse range of kinase-activating alterations – four of the newly identified rearrangements involved new kinase or cytokine receptor genes and seven involved new partner for previously identified genes – has important therapeutic implications.

Ph-like ALL in children is characterized by kinase-activating alterations amenable to treatment with tyrosine kinase inhibitors, but the prevalence in adults was unclear.

“These findings warrant the development of clinical trials in adults that assess the efficacy of TKIs, similar to those that are being established for pediatric ALL,” Dr. Roberts and her associates wrote.

This study was supported by grants and other awards, some to individual authors, from the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital; Stand Up to Cancer, St. Baldrick’s Foundation, the American Society of Hematology, the Lady Tata Memorial Trust, the Leukemia Research Foundation, the National Cancer Institute, and the National Institutes of Health. Dr. Roberts reported that she is the inventor on a pending patent application related to gene-expression signatures for detection of underlying Philadelphia chromosome-live events and therapeutic targeting in leukemia.

 

Philadelphia chromosome–like acute lymphoblastic leukemia, a high-risk subtype of childhood ALL, accounts for more than 24% of ALL in adults and is associated with poor outcome, according to gene-expression profiling in nearly 800 adults with B-cell ALL.

In the 798 subjects aged 21-86 years, Philadelphia chromosome–like (Ph-like) ALL accounted for 27.9% of ALL cases in those aged 21-39 years, 20.4% of cases in those aged 40-59 years, and 24% of cases in those aged 60-86 years. The overall 5-year event-free survival rate was inferior in those with Ph-like ALL vs. non–Ph-like ALL (22.5% vs. 49.3%), as was the 5-year overall survival (23.8% vs. 52.4%). Increasing age also was associated with inferior outcomes: 5-year event-free survival was 40.4%, 29.8%, and 18.9% in the age groups, respectively, and 5-year overall survival was 45.2%, 35.1%, and 28.4% in the groups, respectively, Kathryn G. Roberts, Ph.D., of St. Jude Children’s Research Hospital in Memphis and her colleagues reported online ahead of print (J Clin Oncol. 2016 Nov 21. doi: 10.1200/JCO.2016.69.0073).

Dr. Kathryn G. Roberts
The investigators identified kinase-activating alterations in 88% of patients with Ph-like ALL. These included CRLF2 rearrangements in 51% of patients, ABL class fusions in 9.8%, JAK2 or EPOR rearrangements in 12.4%, other JAK-STAT sequence mutations in 7.2%, other kinase alterations in 4.1%, and Ras pathway mutations in 3.6%. Additionally, 11 new kinase rearrangements were identified, they said, noting that the diverse range of kinase-activating alterations – four of the newly identified rearrangements involved new kinase or cytokine receptor genes and seven involved new partner for previously identified genes – has important therapeutic implications.

Ph-like ALL in children is characterized by kinase-activating alterations amenable to treatment with tyrosine kinase inhibitors, but the prevalence in adults was unclear.

“These findings warrant the development of clinical trials in adults that assess the efficacy of TKIs, similar to those that are being established for pediatric ALL,” Dr. Roberts and her associates wrote.

This study was supported by grants and other awards, some to individual authors, from the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital; Stand Up to Cancer, St. Baldrick’s Foundation, the American Society of Hematology, the Lady Tata Memorial Trust, the Leukemia Research Foundation, the National Cancer Institute, and the National Institutes of Health. Dr. Roberts reported that she is the inventor on a pending patent application related to gene-expression signatures for detection of underlying Philadelphia chromosome-live events and therapeutic targeting in leukemia.

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FROM THE JOURNAL OF CLINICAL ONCOLOGY

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Key clinical point: Ph-like ALL accounts for more than 24% of ALL in adults and is associated with poor outcomes.

Major finding: Ph-like ALL accounted for 27.9% of ALL cases in adults aged 21-39 years, 20.4% of cases in those aged 40-59 years, and 24% of cases in those aged 60-86 years.

Data source: Gene-expression profiling of 798 patients.

Disclosures: This study was supported by grants and other awards, some to individual authors, from the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital; Stand Up to Cancer, St. Baldrick’s Foundation, the American Society of Hematology, the Lady Tata Memorial Trust, the Leukemia Research Foundation, the National Cancer Institute, and the National Institutes of Health. Dr. Roberts reported that she is the inventor on a pending patent application related to gene-expression signatures for detection of underlying Philadelphia chromosome–like events and therapeutic targeting in leukemia.

Blood Pressure Changes and Persistent Hypertension Increase Dementia Risk

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BALTIMORE—The impact of blood pressure on the risk of dementia in late life follows a U-shaped curve in which elevated mid-life and late-life blood pressure, as well as late-life decline in blood pressure, all independently increase the risk of dementia, according to findings from a longitudinal study of the Framingham Offspring cohort of the Framingham Heart Study.

The findings highlight the benefits of establishing and maintaining lower blood pressure in mid-life for preventing or decreasing the risk of dementia, said Emer McGrath, MD, a neurology resident at Massachusetts General Hospital in Boston, at the 141st Annual Meeting of the American Neurological Association.

Emer McGrath, MD

Hypertension has been linked to stroke and dementia and is the most important modifiable risk factor for both outcomes. Likewise, elevated blood pressure in mid-life (ie, ages 40 to 64) and late life (ie, age 65 or older) has been linked with a heightened risk of cognitive decline, as has low blood pressure in late life, but “the relationship between blood pressure in mid and late life and dementia [is] less clear, and the relationship of blood pressure changes from mid to late life is unknown,” said Dr. McGrath.

The researchers explored the issue using data from the Framingham Offspring cohort of the Framingham Heart Study. The cohort comprises 5,124 children and spouses of children of the original Framingham cohort. They have been examined clinically at regular intervals since 1971. The present study focused on 1,440 individuals who had five consecutive examinations during a 15-year period anytime between 1983 and 2001 and who had not been diagnosed with dementia at the time of the final blood pressure determination.

The 1,440 participants had a mean age of 69 at their fifth examination. Slightly more than half were female, 20% had been diagnosed with cardiovascular disease, and slightly less than 20% had been diagnosed with diabetes. Half were using antihypertensive medications.

During a mean eight-year follow-up period, 107 individuals developed dementia. Dementia was independently associated with mid-life hypertension (ie, blood pressure of 140/90 mm Hg or higher), with a stronger association for systolic hypertension (hazard ratio [HR], 1.57). Persistence of hypertension into late life, particularly systolic hypertension (HR, 1.96), was another independent risk factor for dementia.

Among individuals who did not have hypertension at mid-life, a decline in systolic blood pressure to less than 100/70 mm Hg in the ensuing years increased the risk of dementia (HR, 1.63).

The findings support the hypothesis of the U-shaped relationship between blood pressure and dementia, according to the researchers. “Our data also highlight the potential sustained cognitive benefits of lower mid-life blood pressure,” said Dr. McGrath.

The study was funded by the Framingham Heart Study, the National Institute on Aging, and the National Institute for Neurological Diseases and Stroke.

Brian Hoyle

Suggested Reading

McDonald C, Pearce MS, Kerr SR, Newton JL. Blood pressure variability and cognitive decline in older people: a 5-year longitudinal study. J Hypertens. 2016 Sep 17 [Epub ahead of print].

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BALTIMORE—The impact of blood pressure on the risk of dementia in late life follows a U-shaped curve in which elevated mid-life and late-life blood pressure, as well as late-life decline in blood pressure, all independently increase the risk of dementia, according to findings from a longitudinal study of the Framingham Offspring cohort of the Framingham Heart Study.

The findings highlight the benefits of establishing and maintaining lower blood pressure in mid-life for preventing or decreasing the risk of dementia, said Emer McGrath, MD, a neurology resident at Massachusetts General Hospital in Boston, at the 141st Annual Meeting of the American Neurological Association.

Emer McGrath, MD

Hypertension has been linked to stroke and dementia and is the most important modifiable risk factor for both outcomes. Likewise, elevated blood pressure in mid-life (ie, ages 40 to 64) and late life (ie, age 65 or older) has been linked with a heightened risk of cognitive decline, as has low blood pressure in late life, but “the relationship between blood pressure in mid and late life and dementia [is] less clear, and the relationship of blood pressure changes from mid to late life is unknown,” said Dr. McGrath.

The researchers explored the issue using data from the Framingham Offspring cohort of the Framingham Heart Study. The cohort comprises 5,124 children and spouses of children of the original Framingham cohort. They have been examined clinically at regular intervals since 1971. The present study focused on 1,440 individuals who had five consecutive examinations during a 15-year period anytime between 1983 and 2001 and who had not been diagnosed with dementia at the time of the final blood pressure determination.

The 1,440 participants had a mean age of 69 at their fifth examination. Slightly more than half were female, 20% had been diagnosed with cardiovascular disease, and slightly less than 20% had been diagnosed with diabetes. Half were using antihypertensive medications.

During a mean eight-year follow-up period, 107 individuals developed dementia. Dementia was independently associated with mid-life hypertension (ie, blood pressure of 140/90 mm Hg or higher), with a stronger association for systolic hypertension (hazard ratio [HR], 1.57). Persistence of hypertension into late life, particularly systolic hypertension (HR, 1.96), was another independent risk factor for dementia.

Among individuals who did not have hypertension at mid-life, a decline in systolic blood pressure to less than 100/70 mm Hg in the ensuing years increased the risk of dementia (HR, 1.63).

The findings support the hypothesis of the U-shaped relationship between blood pressure and dementia, according to the researchers. “Our data also highlight the potential sustained cognitive benefits of lower mid-life blood pressure,” said Dr. McGrath.

The study was funded by the Framingham Heart Study, the National Institute on Aging, and the National Institute for Neurological Diseases and Stroke.

Brian Hoyle

Suggested Reading

McDonald C, Pearce MS, Kerr SR, Newton JL. Blood pressure variability and cognitive decline in older people: a 5-year longitudinal study. J Hypertens. 2016 Sep 17 [Epub ahead of print].

BALTIMORE—The impact of blood pressure on the risk of dementia in late life follows a U-shaped curve in which elevated mid-life and late-life blood pressure, as well as late-life decline in blood pressure, all independently increase the risk of dementia, according to findings from a longitudinal study of the Framingham Offspring cohort of the Framingham Heart Study.

The findings highlight the benefits of establishing and maintaining lower blood pressure in mid-life for preventing or decreasing the risk of dementia, said Emer McGrath, MD, a neurology resident at Massachusetts General Hospital in Boston, at the 141st Annual Meeting of the American Neurological Association.

Emer McGrath, MD

Hypertension has been linked to stroke and dementia and is the most important modifiable risk factor for both outcomes. Likewise, elevated blood pressure in mid-life (ie, ages 40 to 64) and late life (ie, age 65 or older) has been linked with a heightened risk of cognitive decline, as has low blood pressure in late life, but “the relationship between blood pressure in mid and late life and dementia [is] less clear, and the relationship of blood pressure changes from mid to late life is unknown,” said Dr. McGrath.

The researchers explored the issue using data from the Framingham Offspring cohort of the Framingham Heart Study. The cohort comprises 5,124 children and spouses of children of the original Framingham cohort. They have been examined clinically at regular intervals since 1971. The present study focused on 1,440 individuals who had five consecutive examinations during a 15-year period anytime between 1983 and 2001 and who had not been diagnosed with dementia at the time of the final blood pressure determination.

The 1,440 participants had a mean age of 69 at their fifth examination. Slightly more than half were female, 20% had been diagnosed with cardiovascular disease, and slightly less than 20% had been diagnosed with diabetes. Half were using antihypertensive medications.

During a mean eight-year follow-up period, 107 individuals developed dementia. Dementia was independently associated with mid-life hypertension (ie, blood pressure of 140/90 mm Hg or higher), with a stronger association for systolic hypertension (hazard ratio [HR], 1.57). Persistence of hypertension into late life, particularly systolic hypertension (HR, 1.96), was another independent risk factor for dementia.

Among individuals who did not have hypertension at mid-life, a decline in systolic blood pressure to less than 100/70 mm Hg in the ensuing years increased the risk of dementia (HR, 1.63).

The findings support the hypothesis of the U-shaped relationship between blood pressure and dementia, according to the researchers. “Our data also highlight the potential sustained cognitive benefits of lower mid-life blood pressure,” said Dr. McGrath.

The study was funded by the Framingham Heart Study, the National Institute on Aging, and the National Institute for Neurological Diseases and Stroke.

Brian Hoyle

Suggested Reading

McDonald C, Pearce MS, Kerr SR, Newton JL. Blood pressure variability and cognitive decline in older people: a 5-year longitudinal study. J Hypertens. 2016 Sep 17 [Epub ahead of print].

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Fear and hope: Helping LGBT youth cope with the 2016 election results

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The day after the election, Time magazine reported an increased call volume to the Trevor Project, an organization that provides suicide counseling for LGBT youth.1 A colleague of mine who works closely with the Trevor Project told me that this was the second-highest call volume the organization has received since its inception.

Regardless of your political affiliation, we all can agree that this year’s election was divisive. Many minority groups, including the LGBT community, felt singled out. Although many of us have seen contentious elections in our lifetimes, teenagers, especially LGBT youth, are sensitive to this divisiveness.

Dr. Gerald Montano
I will not debate whether the President-elect’s agenda will be beneficial or harmful to the LGBT community. I will not speculate what the Trump administration will actually do for the LGBT community. I will, however, highlight the fears many LGBT youth are feeling right now. I will attempt to explain why they are feeling this way, and what medical providers – or even parents who read this column – can do to address these fears.

Many LGBT youth who called the Trevor Project had expressed fear about the future. Whenever someone becomes suicidal, they have an overwhelming sense of hopelessness.2 Many perceive that the upcoming administration may be hostile to the LGBT community, and because many fear that this new administration may undo all the progress made in LGBT rights in the last 8 years, they have little hope for the future. Numerous reports of increased hate-crime incidents since the start of the election season last year may have exacerbated this feeling of hopelessness.3 This hopelessness may cause many to feel that the best way out is through suicide. Others feel that their sexual orientation or gender identity may be an additional burden to their family during this new era, and so to relieve them of this burden, they consider ending their own lives.4

For adults who have seen many administrations come and go, this may seem like hyperbole. But we have the advantage of living through various elections and administrations, knowing that they were not as catastrophic as others claimed. However, for many LGBT teens or young adults, this is probably their first election after reaching adolescence since Obama was elected in 2008. The Obama administration has been friendly to the LGBT community,5 and for LGBT youth, the upcoming Trump administration may be a substantial departure from this friendliness. In addition, people across the political spectrum have stoked fears among LGBT youth that the new administration will be devastating for the LGBT community. Adolescents, compared with adults, respond more strongly to the limbic system of the brain – the part of the brain involved in emotional processing, which includes fear.6 This fear will override any attempt by the prefrontal cortex – the part of the brain involved in cognitive processing6 – to put the results of this election within context and within perspective. In other words, it is easier for the adolescent brain to become much more despondent over a disappointing outcome.

What can providers do for LGBT youth who feel distressed over the outcome of the election? The approach is twofold. First, address the emotions emanating from the limbic system. Once this influence is dampened, engage the prefrontal cortex to process the emotions and address these fears in a more constructive way.

For LGBT youth who are actively suicidal, providers should first determine the risk for suicide (for example, determine the level of family support, access to lethal means of suicide, etc.) Then, depending on the risk, create a suicide safety plan that will help the teen or young adult cope with the distress. For more information on how to address suicidality among LGBT youth, please see my previous column (“It does get better... with your help: Preventing suicide,” October 2016, page 30).

Recognize and validate the fears of LGBT youth. Do not dismiss their fears as an overreaction. Because of the adolescent brain’s responsiveness to the limbic system, their fears and emotions are much more intense than are those of adults. Allow them to express how worried they are about the future. Remind them that you are their advocate and that your goal is to keep them safe. Remind your LGBT patients that people who have advocated for them did not disappear overnight because of the election. Some parents of my LGBT patients have pointed out that many LGBT youth feel safer when a nonfamily member advocates for them; therefore, it is essential to remind your LGBT patients about your role as their physician and their advocate.

Another way to support your LGBT patients during this stressful time is to help create a safe environment for them, especially at school. There are some concerns about an increase in antigay and antitrans harassment and bullying since the election.7 Schools are doing their best to respond appropriately to these incidents.8 Fortunately, many schools are responsive to physicians’ recommendations for preventing and addressing school bullying.9 For more information on how providers can address bullying of LGBT youth in school, please refer to my column on bullying (“Bullying,” May 2016, p.1).

Once you reduce the responsiveness of the adolescent brain to the limbic system, you then can focus on the prefrontal cortex to help adolescents engage and cope with their distress. Have them recall from their civics classes that the United States government has checks and balances and that one person does not have unilateral power. Remind the adolescent that administrations and governments do not last forever and that there is an opportunity to change administrations every 4 years.

One of the most powerful ways to engage the prefrontal cortex of the distressed adolescent is to provide the individual with opportunities to be an active member of the community. They can volunteer in many organizations that share their values and beliefs. These organizations do not need to be political, but they should provide some service to the community. This will remind the adolescents that they can have an impact on their own lives and in the lives of others. Volunteering in these organizations will give them a sense of purpose and create a stronger connection to their communities10 – both are antidotes to the intense feeling of despair and hopelessness.

The fear and concerns that LGBT youth have over the election results are intense and deserve attention. Their neurobiology and lack of experience make these fears much more powerful. Providers, parents, and advocates have the responsibility to address these fears, remind LGBT youth that they are their advocates, and remind LGBT youth of the ability to influence the outcomes of their own lives. Providing skills to cope with disappointing outcomes also will prepare LGBT youth for the challenges of adulthood and for the many elections to come.

Resources

The Trevor Project

AAP: Talking to your children about the election

HealthyChildren.org: How to support your child’s resilience in a time of crisis

Suicide Prevention Lifeline: Patient safety plan template

References

1. “Donald Trump Win Causes Spike in Crisis Support Line Calls,” Time magazine, Nov. 9, 2016.

2. Int Rev Psychiatry. 1992;4(2):177-84.

3. “U.S. Hate Crimes Surge 6%, Fueled by Attacks on Muslims,” the New York Times, Nov. 14, 2016.

4. Arch Suicide Res. 2015;19(3):385-400.

5. “The president of the United States shifted the mainstream in one interview,” Newsweek, May 13, 2012.

6. Neuropsychiatric Disease and Treatment. 2013;9:449-61.

7. “This is Trump’s America: LGBT community fears surge in hate crimes following reports of homophobic attacks,” Salon magazine, Nov. 13, 2016.

8. “School officials grapple with bullying, harassment after election,” Lansing State Journal, Nov. 13, 2016.

9. “Roles for pediatricians in bullying prevention and intervention,” StopBullying.gov, 2016.

10. Adv Psych Treatment. 2014;20(3):217-24.

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center and a postdoctoral fellow in the department of pediatrics the University of Pittsburgh. Email him at [email protected].

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The day after the election, Time magazine reported an increased call volume to the Trevor Project, an organization that provides suicide counseling for LGBT youth.1 A colleague of mine who works closely with the Trevor Project told me that this was the second-highest call volume the organization has received since its inception.

Regardless of your political affiliation, we all can agree that this year’s election was divisive. Many minority groups, including the LGBT community, felt singled out. Although many of us have seen contentious elections in our lifetimes, teenagers, especially LGBT youth, are sensitive to this divisiveness.

Dr. Gerald Montano
I will not debate whether the President-elect’s agenda will be beneficial or harmful to the LGBT community. I will not speculate what the Trump administration will actually do for the LGBT community. I will, however, highlight the fears many LGBT youth are feeling right now. I will attempt to explain why they are feeling this way, and what medical providers – or even parents who read this column – can do to address these fears.

Many LGBT youth who called the Trevor Project had expressed fear about the future. Whenever someone becomes suicidal, they have an overwhelming sense of hopelessness.2 Many perceive that the upcoming administration may be hostile to the LGBT community, and because many fear that this new administration may undo all the progress made in LGBT rights in the last 8 years, they have little hope for the future. Numerous reports of increased hate-crime incidents since the start of the election season last year may have exacerbated this feeling of hopelessness.3 This hopelessness may cause many to feel that the best way out is through suicide. Others feel that their sexual orientation or gender identity may be an additional burden to their family during this new era, and so to relieve them of this burden, they consider ending their own lives.4

For adults who have seen many administrations come and go, this may seem like hyperbole. But we have the advantage of living through various elections and administrations, knowing that they were not as catastrophic as others claimed. However, for many LGBT teens or young adults, this is probably their first election after reaching adolescence since Obama was elected in 2008. The Obama administration has been friendly to the LGBT community,5 and for LGBT youth, the upcoming Trump administration may be a substantial departure from this friendliness. In addition, people across the political spectrum have stoked fears among LGBT youth that the new administration will be devastating for the LGBT community. Adolescents, compared with adults, respond more strongly to the limbic system of the brain – the part of the brain involved in emotional processing, which includes fear.6 This fear will override any attempt by the prefrontal cortex – the part of the brain involved in cognitive processing6 – to put the results of this election within context and within perspective. In other words, it is easier for the adolescent brain to become much more despondent over a disappointing outcome.

What can providers do for LGBT youth who feel distressed over the outcome of the election? The approach is twofold. First, address the emotions emanating from the limbic system. Once this influence is dampened, engage the prefrontal cortex to process the emotions and address these fears in a more constructive way.

For LGBT youth who are actively suicidal, providers should first determine the risk for suicide (for example, determine the level of family support, access to lethal means of suicide, etc.) Then, depending on the risk, create a suicide safety plan that will help the teen or young adult cope with the distress. For more information on how to address suicidality among LGBT youth, please see my previous column (“It does get better... with your help: Preventing suicide,” October 2016, page 30).

Recognize and validate the fears of LGBT youth. Do not dismiss their fears as an overreaction. Because of the adolescent brain’s responsiveness to the limbic system, their fears and emotions are much more intense than are those of adults. Allow them to express how worried they are about the future. Remind them that you are their advocate and that your goal is to keep them safe. Remind your LGBT patients that people who have advocated for them did not disappear overnight because of the election. Some parents of my LGBT patients have pointed out that many LGBT youth feel safer when a nonfamily member advocates for them; therefore, it is essential to remind your LGBT patients about your role as their physician and their advocate.

Another way to support your LGBT patients during this stressful time is to help create a safe environment for them, especially at school. There are some concerns about an increase in antigay and antitrans harassment and bullying since the election.7 Schools are doing their best to respond appropriately to these incidents.8 Fortunately, many schools are responsive to physicians’ recommendations for preventing and addressing school bullying.9 For more information on how providers can address bullying of LGBT youth in school, please refer to my column on bullying (“Bullying,” May 2016, p.1).

Once you reduce the responsiveness of the adolescent brain to the limbic system, you then can focus on the prefrontal cortex to help adolescents engage and cope with their distress. Have them recall from their civics classes that the United States government has checks and balances and that one person does not have unilateral power. Remind the adolescent that administrations and governments do not last forever and that there is an opportunity to change administrations every 4 years.

One of the most powerful ways to engage the prefrontal cortex of the distressed adolescent is to provide the individual with opportunities to be an active member of the community. They can volunteer in many organizations that share their values and beliefs. These organizations do not need to be political, but they should provide some service to the community. This will remind the adolescents that they can have an impact on their own lives and in the lives of others. Volunteering in these organizations will give them a sense of purpose and create a stronger connection to their communities10 – both are antidotes to the intense feeling of despair and hopelessness.

The fear and concerns that LGBT youth have over the election results are intense and deserve attention. Their neurobiology and lack of experience make these fears much more powerful. Providers, parents, and advocates have the responsibility to address these fears, remind LGBT youth that they are their advocates, and remind LGBT youth of the ability to influence the outcomes of their own lives. Providing skills to cope with disappointing outcomes also will prepare LGBT youth for the challenges of adulthood and for the many elections to come.

Resources

The Trevor Project

AAP: Talking to your children about the election

HealthyChildren.org: How to support your child’s resilience in a time of crisis

Suicide Prevention Lifeline: Patient safety plan template

References

1. “Donald Trump Win Causes Spike in Crisis Support Line Calls,” Time magazine, Nov. 9, 2016.

2. Int Rev Psychiatry. 1992;4(2):177-84.

3. “U.S. Hate Crimes Surge 6%, Fueled by Attacks on Muslims,” the New York Times, Nov. 14, 2016.

4. Arch Suicide Res. 2015;19(3):385-400.

5. “The president of the United States shifted the mainstream in one interview,” Newsweek, May 13, 2012.

6. Neuropsychiatric Disease and Treatment. 2013;9:449-61.

7. “This is Trump’s America: LGBT community fears surge in hate crimes following reports of homophobic attacks,” Salon magazine, Nov. 13, 2016.

8. “School officials grapple with bullying, harassment after election,” Lansing State Journal, Nov. 13, 2016.

9. “Roles for pediatricians in bullying prevention and intervention,” StopBullying.gov, 2016.

10. Adv Psych Treatment. 2014;20(3):217-24.

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center and a postdoctoral fellow in the department of pediatrics the University of Pittsburgh. Email him at [email protected].

 

The day after the election, Time magazine reported an increased call volume to the Trevor Project, an organization that provides suicide counseling for LGBT youth.1 A colleague of mine who works closely with the Trevor Project told me that this was the second-highest call volume the organization has received since its inception.

Regardless of your political affiliation, we all can agree that this year’s election was divisive. Many minority groups, including the LGBT community, felt singled out. Although many of us have seen contentious elections in our lifetimes, teenagers, especially LGBT youth, are sensitive to this divisiveness.

Dr. Gerald Montano
I will not debate whether the President-elect’s agenda will be beneficial or harmful to the LGBT community. I will not speculate what the Trump administration will actually do for the LGBT community. I will, however, highlight the fears many LGBT youth are feeling right now. I will attempt to explain why they are feeling this way, and what medical providers – or even parents who read this column – can do to address these fears.

Many LGBT youth who called the Trevor Project had expressed fear about the future. Whenever someone becomes suicidal, they have an overwhelming sense of hopelessness.2 Many perceive that the upcoming administration may be hostile to the LGBT community, and because many fear that this new administration may undo all the progress made in LGBT rights in the last 8 years, they have little hope for the future. Numerous reports of increased hate-crime incidents since the start of the election season last year may have exacerbated this feeling of hopelessness.3 This hopelessness may cause many to feel that the best way out is through suicide. Others feel that their sexual orientation or gender identity may be an additional burden to their family during this new era, and so to relieve them of this burden, they consider ending their own lives.4

For adults who have seen many administrations come and go, this may seem like hyperbole. But we have the advantage of living through various elections and administrations, knowing that they were not as catastrophic as others claimed. However, for many LGBT teens or young adults, this is probably their first election after reaching adolescence since Obama was elected in 2008. The Obama administration has been friendly to the LGBT community,5 and for LGBT youth, the upcoming Trump administration may be a substantial departure from this friendliness. In addition, people across the political spectrum have stoked fears among LGBT youth that the new administration will be devastating for the LGBT community. Adolescents, compared with adults, respond more strongly to the limbic system of the brain – the part of the brain involved in emotional processing, which includes fear.6 This fear will override any attempt by the prefrontal cortex – the part of the brain involved in cognitive processing6 – to put the results of this election within context and within perspective. In other words, it is easier for the adolescent brain to become much more despondent over a disappointing outcome.

What can providers do for LGBT youth who feel distressed over the outcome of the election? The approach is twofold. First, address the emotions emanating from the limbic system. Once this influence is dampened, engage the prefrontal cortex to process the emotions and address these fears in a more constructive way.

For LGBT youth who are actively suicidal, providers should first determine the risk for suicide (for example, determine the level of family support, access to lethal means of suicide, etc.) Then, depending on the risk, create a suicide safety plan that will help the teen or young adult cope with the distress. For more information on how to address suicidality among LGBT youth, please see my previous column (“It does get better... with your help: Preventing suicide,” October 2016, page 30).

Recognize and validate the fears of LGBT youth. Do not dismiss their fears as an overreaction. Because of the adolescent brain’s responsiveness to the limbic system, their fears and emotions are much more intense than are those of adults. Allow them to express how worried they are about the future. Remind them that you are their advocate and that your goal is to keep them safe. Remind your LGBT patients that people who have advocated for them did not disappear overnight because of the election. Some parents of my LGBT patients have pointed out that many LGBT youth feel safer when a nonfamily member advocates for them; therefore, it is essential to remind your LGBT patients about your role as their physician and their advocate.

Another way to support your LGBT patients during this stressful time is to help create a safe environment for them, especially at school. There are some concerns about an increase in antigay and antitrans harassment and bullying since the election.7 Schools are doing their best to respond appropriately to these incidents.8 Fortunately, many schools are responsive to physicians’ recommendations for preventing and addressing school bullying.9 For more information on how providers can address bullying of LGBT youth in school, please refer to my column on bullying (“Bullying,” May 2016, p.1).

Once you reduce the responsiveness of the adolescent brain to the limbic system, you then can focus on the prefrontal cortex to help adolescents engage and cope with their distress. Have them recall from their civics classes that the United States government has checks and balances and that one person does not have unilateral power. Remind the adolescent that administrations and governments do not last forever and that there is an opportunity to change administrations every 4 years.

One of the most powerful ways to engage the prefrontal cortex of the distressed adolescent is to provide the individual with opportunities to be an active member of the community. They can volunteer in many organizations that share their values and beliefs. These organizations do not need to be political, but they should provide some service to the community. This will remind the adolescents that they can have an impact on their own lives and in the lives of others. Volunteering in these organizations will give them a sense of purpose and create a stronger connection to their communities10 – both are antidotes to the intense feeling of despair and hopelessness.

The fear and concerns that LGBT youth have over the election results are intense and deserve attention. Their neurobiology and lack of experience make these fears much more powerful. Providers, parents, and advocates have the responsibility to address these fears, remind LGBT youth that they are their advocates, and remind LGBT youth of the ability to influence the outcomes of their own lives. Providing skills to cope with disappointing outcomes also will prepare LGBT youth for the challenges of adulthood and for the many elections to come.

Resources

The Trevor Project

AAP: Talking to your children about the election

HealthyChildren.org: How to support your child’s resilience in a time of crisis

Suicide Prevention Lifeline: Patient safety plan template

References

1. “Donald Trump Win Causes Spike in Crisis Support Line Calls,” Time magazine, Nov. 9, 2016.

2. Int Rev Psychiatry. 1992;4(2):177-84.

3. “U.S. Hate Crimes Surge 6%, Fueled by Attacks on Muslims,” the New York Times, Nov. 14, 2016.

4. Arch Suicide Res. 2015;19(3):385-400.

5. “The president of the United States shifted the mainstream in one interview,” Newsweek, May 13, 2012.

6. Neuropsychiatric Disease and Treatment. 2013;9:449-61.

7. “This is Trump’s America: LGBT community fears surge in hate crimes following reports of homophobic attacks,” Salon magazine, Nov. 13, 2016.

8. “School officials grapple with bullying, harassment after election,” Lansing State Journal, Nov. 13, 2016.

9. “Roles for pediatricians in bullying prevention and intervention,” StopBullying.gov, 2016.

10. Adv Psych Treatment. 2014;20(3):217-24.

Dr. Montano is an adolescent medicine fellow at Children’s Hospital of Pittsburgh of the University of Pittsburgh Medical Center and a postdoctoral fellow in the department of pediatrics the University of Pittsburgh. Email him at [email protected].

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Opicinumab May Benefit Patients With Relapsing-Remitting MS

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LONDON—Opicinumab, an investigational remyelinating agent, may promote clinical improvement in patients with multiple sclerosis (MS) who are receiving interferon beta-1a, according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS. The monoclonal antibody appears not to have a linear dose response; the high and low doses are associated with less improvement than the moderate doses.

In a phase IIb study, patients with relapsing-remitting MS, shorter disease duration, and less severe damage to the brain had a stronger response to opicinumab. “These biological markers are, we believe, valuable to inform all future steps,” said Diego Cadavid, MD, Senior Director at Biogen in Cambridge, Massachusetts. Opicinumab was generally well tolerated. The main adverse events were hypersensitivity reactions that occurred at a dose of 100 mg/kg.

Diego Cadavid, MD

Testing Effects on Pre-Existing Disability

Dr. Cadavid and colleagues conducted the SYNERGY trial to assess the efficacy of four doses of opicinumab versus placebo in patients with MS, pre-existing disability, and recent active relapse. Of the 418 patients enrolled, 80% had relapsing-remitting MS and 20% had secondary progressive MS. All participants were receiving intramuscular interferon beta-1a.

The investigators randomized patients to placebo or one of four doses of opicinumab (ie, 3 mg/kg, 10 mg/kg, 30 mg/kg, and 100 mg/kg). A total of 418 participants were randomized and dosed; 334 completed the study. The treatment period was 72 weeks, and a final safety and efficacy analysis occurred at 84 weeks. The primary end point was confirmed improvement on Expanded Disability Status Scale (EDSS) score, Timed 25-Foot Walk (T25FW), Nine-Hole Peg Test (9HPT), or 3-second Paced Auditory Serial Addition Test (PASAT-3).

The majority of participants were female, and mean age at baseline was approximately 40. Average disease duration was approximately 10 years. The median EDSS score was 3.5. Mean T25FW score was approximately 8 seconds. Mean 9HPT score was 25 seconds. Mean PASAT-3 score was 49. Randomization resulted in well-balanced treatment groups.

Moderate Doses Brought Most Benefit

Increasing doses of opicinumab did not lead to increases in the percentage of patients experiencing improvement of pre-existing disability. The estimated percentage of improvement responders was 52% for placebo, 51% for the 3-mg/kg dose, 66% for the 10-mg/kg dose, 69% for the 30-mg/kg dose, and 41% for the 100-mg/kg dose.

“We have observed an inverted-U dose response for the improvement of pre-existing disability with opicinumab,” said Dr. Cadavid. The odds ratios for improvement on the EDSS and the 9HPT were greatest for the 10-mg/kg dose. The odds ratio for improvement on the T25FW was greatest for the 3-mg dose. The odds ratio for improvement on PASAT-3 was greatest for the 30-mg/kg dose. The study, however, was not powered for any individual component.

Participants with better whole brain multispectral thermal imaging, greater whole brain radial diffusivity on diffusion tensor imaging (DTI RD), and greater normalized whole brain volume responded better to opicinumab. The strongest odds ratios in this univariable analysis were observed on the DTI RD at 10 mg/kg.

“Further work is clearly needed to understand what explains the behavior of opicinumab at the highest dose,” said Dr. Cadavid. “We have identified an appropriate patient population, a dose and exposure, and end points to inform the next study, and [we] are in the process of evaluating the optimized study design.”

Erik Greb

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LONDON—Opicinumab, an investigational remyelinating agent, may promote clinical improvement in patients with multiple sclerosis (MS) who are receiving interferon beta-1a, according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS. The monoclonal antibody appears not to have a linear dose response; the high and low doses are associated with less improvement than the moderate doses.

In a phase IIb study, patients with relapsing-remitting MS, shorter disease duration, and less severe damage to the brain had a stronger response to opicinumab. “These biological markers are, we believe, valuable to inform all future steps,” said Diego Cadavid, MD, Senior Director at Biogen in Cambridge, Massachusetts. Opicinumab was generally well tolerated. The main adverse events were hypersensitivity reactions that occurred at a dose of 100 mg/kg.

Diego Cadavid, MD

Testing Effects on Pre-Existing Disability

Dr. Cadavid and colleagues conducted the SYNERGY trial to assess the efficacy of four doses of opicinumab versus placebo in patients with MS, pre-existing disability, and recent active relapse. Of the 418 patients enrolled, 80% had relapsing-remitting MS and 20% had secondary progressive MS. All participants were receiving intramuscular interferon beta-1a.

The investigators randomized patients to placebo or one of four doses of opicinumab (ie, 3 mg/kg, 10 mg/kg, 30 mg/kg, and 100 mg/kg). A total of 418 participants were randomized and dosed; 334 completed the study. The treatment period was 72 weeks, and a final safety and efficacy analysis occurred at 84 weeks. The primary end point was confirmed improvement on Expanded Disability Status Scale (EDSS) score, Timed 25-Foot Walk (T25FW), Nine-Hole Peg Test (9HPT), or 3-second Paced Auditory Serial Addition Test (PASAT-3).

The majority of participants were female, and mean age at baseline was approximately 40. Average disease duration was approximately 10 years. The median EDSS score was 3.5. Mean T25FW score was approximately 8 seconds. Mean 9HPT score was 25 seconds. Mean PASAT-3 score was 49. Randomization resulted in well-balanced treatment groups.

Moderate Doses Brought Most Benefit

Increasing doses of opicinumab did not lead to increases in the percentage of patients experiencing improvement of pre-existing disability. The estimated percentage of improvement responders was 52% for placebo, 51% for the 3-mg/kg dose, 66% for the 10-mg/kg dose, 69% for the 30-mg/kg dose, and 41% for the 100-mg/kg dose.

“We have observed an inverted-U dose response for the improvement of pre-existing disability with opicinumab,” said Dr. Cadavid. The odds ratios for improvement on the EDSS and the 9HPT were greatest for the 10-mg/kg dose. The odds ratio for improvement on the T25FW was greatest for the 3-mg dose. The odds ratio for improvement on PASAT-3 was greatest for the 30-mg/kg dose. The study, however, was not powered for any individual component.

Participants with better whole brain multispectral thermal imaging, greater whole brain radial diffusivity on diffusion tensor imaging (DTI RD), and greater normalized whole brain volume responded better to opicinumab. The strongest odds ratios in this univariable analysis were observed on the DTI RD at 10 mg/kg.

“Further work is clearly needed to understand what explains the behavior of opicinumab at the highest dose,” said Dr. Cadavid. “We have identified an appropriate patient population, a dose and exposure, and end points to inform the next study, and [we] are in the process of evaluating the optimized study design.”

Erik Greb

LONDON—Opicinumab, an investigational remyelinating agent, may promote clinical improvement in patients with multiple sclerosis (MS) who are receiving interferon beta-1a, according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS. The monoclonal antibody appears not to have a linear dose response; the high and low doses are associated with less improvement than the moderate doses.

In a phase IIb study, patients with relapsing-remitting MS, shorter disease duration, and less severe damage to the brain had a stronger response to opicinumab. “These biological markers are, we believe, valuable to inform all future steps,” said Diego Cadavid, MD, Senior Director at Biogen in Cambridge, Massachusetts. Opicinumab was generally well tolerated. The main adverse events were hypersensitivity reactions that occurred at a dose of 100 mg/kg.

Diego Cadavid, MD

Testing Effects on Pre-Existing Disability

Dr. Cadavid and colleagues conducted the SYNERGY trial to assess the efficacy of four doses of opicinumab versus placebo in patients with MS, pre-existing disability, and recent active relapse. Of the 418 patients enrolled, 80% had relapsing-remitting MS and 20% had secondary progressive MS. All participants were receiving intramuscular interferon beta-1a.

The investigators randomized patients to placebo or one of four doses of opicinumab (ie, 3 mg/kg, 10 mg/kg, 30 mg/kg, and 100 mg/kg). A total of 418 participants were randomized and dosed; 334 completed the study. The treatment period was 72 weeks, and a final safety and efficacy analysis occurred at 84 weeks. The primary end point was confirmed improvement on Expanded Disability Status Scale (EDSS) score, Timed 25-Foot Walk (T25FW), Nine-Hole Peg Test (9HPT), or 3-second Paced Auditory Serial Addition Test (PASAT-3).

The majority of participants were female, and mean age at baseline was approximately 40. Average disease duration was approximately 10 years. The median EDSS score was 3.5. Mean T25FW score was approximately 8 seconds. Mean 9HPT score was 25 seconds. Mean PASAT-3 score was 49. Randomization resulted in well-balanced treatment groups.

Moderate Doses Brought Most Benefit

Increasing doses of opicinumab did not lead to increases in the percentage of patients experiencing improvement of pre-existing disability. The estimated percentage of improvement responders was 52% for placebo, 51% for the 3-mg/kg dose, 66% for the 10-mg/kg dose, 69% for the 30-mg/kg dose, and 41% for the 100-mg/kg dose.

“We have observed an inverted-U dose response for the improvement of pre-existing disability with opicinumab,” said Dr. Cadavid. The odds ratios for improvement on the EDSS and the 9HPT were greatest for the 10-mg/kg dose. The odds ratio for improvement on the T25FW was greatest for the 3-mg dose. The odds ratio for improvement on PASAT-3 was greatest for the 30-mg/kg dose. The study, however, was not powered for any individual component.

Participants with better whole brain multispectral thermal imaging, greater whole brain radial diffusivity on diffusion tensor imaging (DTI RD), and greater normalized whole brain volume responded better to opicinumab. The strongest odds ratios in this univariable analysis were observed on the DTI RD at 10 mg/kg.

“Further work is clearly needed to understand what explains the behavior of opicinumab at the highest dose,” said Dr. Cadavid. “We have identified an appropriate patient population, a dose and exposure, and end points to inform the next study, and [we] are in the process of evaluating the optimized study design.”

Erik Greb

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Postelection anxiety

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Introduction

Since the election, many of the psychiatrists and psychologists in our office have reported a wave of anxiety among our patients. These fears have sometimes come from watching television commercials that highlight the faults of the other party or from watching the debates themselves. Children have reported fears of a nuclear war, of being taken away from family, or of being harmed or killed because of racial, religious, immigration, disability, gender, or sexual orientation status. In addition, some children are reporting remarks by peers.

Case summary

Dr. Allison Y. Hall
Jane is a 10-year-old girl in a family with two mothers who has been very interested in politics. She had been seeing one of our psychologists for mild separation anxiety. After the election, she was crushed and angry but also extremely anxious that her family would be forced to leave the country. She had difficulty sleeping and was preoccupied with numerous worries about her own family and the state of the world.

Discussion

How can we support our patients and their parents in responding to this surge in anxiety? First, we can reiterate the central importance of family. What the family models in values, behavior, and coping is central to how children respond to stress and winning and losing. Parents who manage their own emotions model how to cope with both victory and defeat, demonstrating appropriate celebration as well as grief and anger. Coping strategies for parents can include reaching out to supports from family and friends, using relaxation strategies, and then planning practical next steps to take.

Parents should reassure their children that they are there to keep their children safe. Modeling self-care and keeping the family routine as stable as possible is a powerful source of this sense of safety. As always, parents should think about what their children are consuming in the way of electronics.

In talking to children, listening is a first step. Help children find the words for what they are feeling. Consider your own words and the rhetoric of the election. Withering scorn of the other side has become increasingly common and not only damages our ability to understand other points of view and resolve conflicts but is also leading to intense anxiety in our children. The extreme nature of some of these words has led some children to believe that complete disaster is imminent should the other side win. Try to avoid using words that intensify fear. Acknowledge the feelings that children have, but provide reassurance of safety and hope.

Using the principles of cognitive-behavioral therapy, a therapist or parent can help a child think through how their thoughts are connected with feelings and behavior. When we are fearful, we often think that the absolute worst is going to happen, or we imagine that we definitely know the future. Sometimes an extreme thought can magnify feelings to the point that constructive behavior is blocked. A therapist might acknowledge feelings, but also help enlarge the child’s perspective. There are many reasons why people voted for or against candidates, and we don’t know everything about them just because of how they chose to vote. Discussing the three branches of government and the system of checks and balances that bring many people together to think over a problem can help a child see that the government is more than just one person. Parents or therapists can talk about protections in the Constitution such as freedom of the press, which allows us to be informed of what is going on. Parents might want to talk about the reality that we are one country, and that the vast majority of people on both sides share many, if not all, values.

Helping a child consider other perspectives isn’t saying that there are no reasons at all for anxiety, but that there are many possibilities for the future, and that a family can think together about what behaviors they want to engage in. There may be specific actions a child or family might want to take to have a voice in how the country moves forward.

Treatment plan for Jane

• Psychotherapy. Continue cognitive-behavioral therapy with a focus on identifying thoughts tied to anxiety that are overgeneralizations or exaggerations. Discuss alternative thoughts with greater perspective.

• Parents. Discuss supporting the child through listening, reassurance of safety, reestablishment of family routine, and family discussion about what actions to take to promote values.

• Health promotion. Discuss using exercise, pleasant activities, mindfulness, and minimizing of screen time as ways to cope with stress.

• Medications. There is no need to use medications for the child’s acute stress response.

Resources

1. Psychological First Aid: Field Operations Manual , 2nd ed. (National Child Traumatic Stress Network, National Center for PTSD, 2006).

2. Cognitive Behavioral Therapy for Anxious Children: Therapist Manual, 3rd edition. (Ardmore, Pa.: Workbook Publishing, 2006).

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures.

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Introduction

Since the election, many of the psychiatrists and psychologists in our office have reported a wave of anxiety among our patients. These fears have sometimes come from watching television commercials that highlight the faults of the other party or from watching the debates themselves. Children have reported fears of a nuclear war, of being taken away from family, or of being harmed or killed because of racial, religious, immigration, disability, gender, or sexual orientation status. In addition, some children are reporting remarks by peers.

Case summary

Dr. Allison Y. Hall
Jane is a 10-year-old girl in a family with two mothers who has been very interested in politics. She had been seeing one of our psychologists for mild separation anxiety. After the election, she was crushed and angry but also extremely anxious that her family would be forced to leave the country. She had difficulty sleeping and was preoccupied with numerous worries about her own family and the state of the world.

Discussion

How can we support our patients and their parents in responding to this surge in anxiety? First, we can reiterate the central importance of family. What the family models in values, behavior, and coping is central to how children respond to stress and winning and losing. Parents who manage their own emotions model how to cope with both victory and defeat, demonstrating appropriate celebration as well as grief and anger. Coping strategies for parents can include reaching out to supports from family and friends, using relaxation strategies, and then planning practical next steps to take.

Parents should reassure their children that they are there to keep their children safe. Modeling self-care and keeping the family routine as stable as possible is a powerful source of this sense of safety. As always, parents should think about what their children are consuming in the way of electronics.

In talking to children, listening is a first step. Help children find the words for what they are feeling. Consider your own words and the rhetoric of the election. Withering scorn of the other side has become increasingly common and not only damages our ability to understand other points of view and resolve conflicts but is also leading to intense anxiety in our children. The extreme nature of some of these words has led some children to believe that complete disaster is imminent should the other side win. Try to avoid using words that intensify fear. Acknowledge the feelings that children have, but provide reassurance of safety and hope.

Using the principles of cognitive-behavioral therapy, a therapist or parent can help a child think through how their thoughts are connected with feelings and behavior. When we are fearful, we often think that the absolute worst is going to happen, or we imagine that we definitely know the future. Sometimes an extreme thought can magnify feelings to the point that constructive behavior is blocked. A therapist might acknowledge feelings, but also help enlarge the child’s perspective. There are many reasons why people voted for or against candidates, and we don’t know everything about them just because of how they chose to vote. Discussing the three branches of government and the system of checks and balances that bring many people together to think over a problem can help a child see that the government is more than just one person. Parents or therapists can talk about protections in the Constitution such as freedom of the press, which allows us to be informed of what is going on. Parents might want to talk about the reality that we are one country, and that the vast majority of people on both sides share many, if not all, values.

Helping a child consider other perspectives isn’t saying that there are no reasons at all for anxiety, but that there are many possibilities for the future, and that a family can think together about what behaviors they want to engage in. There may be specific actions a child or family might want to take to have a voice in how the country moves forward.

Treatment plan for Jane

• Psychotherapy. Continue cognitive-behavioral therapy with a focus on identifying thoughts tied to anxiety that are overgeneralizations or exaggerations. Discuss alternative thoughts with greater perspective.

• Parents. Discuss supporting the child through listening, reassurance of safety, reestablishment of family routine, and family discussion about what actions to take to promote values.

• Health promotion. Discuss using exercise, pleasant activities, mindfulness, and minimizing of screen time as ways to cope with stress.

• Medications. There is no need to use medications for the child’s acute stress response.

Resources

1. Psychological First Aid: Field Operations Manual , 2nd ed. (National Child Traumatic Stress Network, National Center for PTSD, 2006).

2. Cognitive Behavioral Therapy for Anxious Children: Therapist Manual, 3rd edition. (Ardmore, Pa.: Workbook Publishing, 2006).

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures.

Introduction

Since the election, many of the psychiatrists and psychologists in our office have reported a wave of anxiety among our patients. These fears have sometimes come from watching television commercials that highlight the faults of the other party or from watching the debates themselves. Children have reported fears of a nuclear war, of being taken away from family, or of being harmed or killed because of racial, religious, immigration, disability, gender, or sexual orientation status. In addition, some children are reporting remarks by peers.

Case summary

Dr. Allison Y. Hall
Jane is a 10-year-old girl in a family with two mothers who has been very interested in politics. She had been seeing one of our psychologists for mild separation anxiety. After the election, she was crushed and angry but also extremely anxious that her family would be forced to leave the country. She had difficulty sleeping and was preoccupied with numerous worries about her own family and the state of the world.

Discussion

How can we support our patients and their parents in responding to this surge in anxiety? First, we can reiterate the central importance of family. What the family models in values, behavior, and coping is central to how children respond to stress and winning and losing. Parents who manage their own emotions model how to cope with both victory and defeat, demonstrating appropriate celebration as well as grief and anger. Coping strategies for parents can include reaching out to supports from family and friends, using relaxation strategies, and then planning practical next steps to take.

Parents should reassure their children that they are there to keep their children safe. Modeling self-care and keeping the family routine as stable as possible is a powerful source of this sense of safety. As always, parents should think about what their children are consuming in the way of electronics.

In talking to children, listening is a first step. Help children find the words for what they are feeling. Consider your own words and the rhetoric of the election. Withering scorn of the other side has become increasingly common and not only damages our ability to understand other points of view and resolve conflicts but is also leading to intense anxiety in our children. The extreme nature of some of these words has led some children to believe that complete disaster is imminent should the other side win. Try to avoid using words that intensify fear. Acknowledge the feelings that children have, but provide reassurance of safety and hope.

Using the principles of cognitive-behavioral therapy, a therapist or parent can help a child think through how their thoughts are connected with feelings and behavior. When we are fearful, we often think that the absolute worst is going to happen, or we imagine that we definitely know the future. Sometimes an extreme thought can magnify feelings to the point that constructive behavior is blocked. A therapist might acknowledge feelings, but also help enlarge the child’s perspective. There are many reasons why people voted for or against candidates, and we don’t know everything about them just because of how they chose to vote. Discussing the three branches of government and the system of checks and balances that bring many people together to think over a problem can help a child see that the government is more than just one person. Parents or therapists can talk about protections in the Constitution such as freedom of the press, which allows us to be informed of what is going on. Parents might want to talk about the reality that we are one country, and that the vast majority of people on both sides share many, if not all, values.

Helping a child consider other perspectives isn’t saying that there are no reasons at all for anxiety, but that there are many possibilities for the future, and that a family can think together about what behaviors they want to engage in. There may be specific actions a child or family might want to take to have a voice in how the country moves forward.

Treatment plan for Jane

• Psychotherapy. Continue cognitive-behavioral therapy with a focus on identifying thoughts tied to anxiety that are overgeneralizations or exaggerations. Discuss alternative thoughts with greater perspective.

• Parents. Discuss supporting the child through listening, reassurance of safety, reestablishment of family routine, and family discussion about what actions to take to promote values.

• Health promotion. Discuss using exercise, pleasant activities, mindfulness, and minimizing of screen time as ways to cope with stress.

• Medications. There is no need to use medications for the child’s acute stress response.

Resources

1. Psychological First Aid: Field Operations Manual , 2nd ed. (National Child Traumatic Stress Network, National Center for PTSD, 2006).

2. Cognitive Behavioral Therapy for Anxious Children: Therapist Manual, 3rd edition. (Ardmore, Pa.: Workbook Publishing, 2006).

Dr. Hall is assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. She said she had no relevant financial disclosures.

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An Overview of the History of Orthopedic Surgery

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An Overview of the History of Orthopedic Surgery

The modern term orthopedics stems from the older word orthopedia, which was the title of a book published in 1741 by Nicholas Andry, a professor of medicine at the University of Paris.1 The term orthopedia is a composite of 2 Greek words: orthos, meaning “straight and free from deformity,” and paidios, meaning “child.” Together, orthopedics literally means straight child, suggesting the importance of pediatric injuries and deformities in the development of this field. Interestingly, Andry’s book also depicted a crooked young tree attached to a straight and strong staff, which has become the universal symbol of orthopedic surgery and underscores the focus on correcting deformities in the young (Figure).1

Figure.
While the history of the term is relatively recent, the practice of orthopedics is an ancient art.

Orthopedic surgery is a rapidly advancing medical field with several recent advances noted within orthopedic subspecialties,2-4 basic science,5 and clinical research.6 It is important to recognize the role of history with regards to innovation and research, especially for young trainees and medical students interested in a particular medical specialty. More specifically, it is important to understand the successes and failures of the past in order to advance research and practice, and ultimately improve patient care and outcomes.

In the recent literature, there is no concise yet comprehensive article focusing on the history of orthopedic surgery. The goal of this review is to provide an overview of the history and development of orthopedic surgery from ancient practices to the modern era.

Ancient Orthopedics

While the evidence is limited, the practice of orthopedics dates back to the primitive man.7 Fossil evidence suggests that the orthopedic pathology of today, such as fractures and traumatic amputations, existed in primitive times.8 The union of fractures in fair alignment has also been observed, which emphasizes the efficacy of nonoperative orthopedics and suggests the early use of splints and rehabilitation practices.8,9 Since procedures such as trepanation and crude amputations occurred during the New Stone Age, it is feasible that sophisticated techniques had also been developed for the treatment of injuries.7-9 However, evidence continues to remain limited.7

Later civilizations also developed creative ways to manage orthopedic injuries. For example, the Shoshone Indians, who were known to exist around 700-2000 BCE, made a splint of fresh rawhide that had been soaked in water.9,10 Similarly, some South Australian tribes made splints of clay, which when dried were as good as plaster of Paris.9 Furthermore, bone-setting or reductions was practiced as a profession in many tribes, underscoring the importance of orthopedic injuries in early civilizations.8,9

Ancient Egypt

The ancient Egyptians seemed to have carried on the practices of splinting. For example, 2 splinted specimens were discovered during the Hearst Egyptian Expedition in 1903.7 More specifically, these specimens included a femur and forearm and dated to approximately 300 BCE.7 Other examples of splints made of bamboo and reed padded with linen have been found on mummies as well.8 Similarly, crutches were also used by this civilization, as depicted on a carving made on an Egyptian tomb in 2830 BCE.8

One of the earliest and most significant documents on medicine was discovered in 1862, known as the Edwin Smith papyrus. This document is thought to have been composed by Imhotep, a prominent Egyptian physician, astrologer, architect, and politician, and it specifically categorizes diseases and treatments. Many scholars recognize this medical document as the oldest surgical textbook.11,12 With regards to orthopedic conditions, this document describes the reduction of a dislocated mandible, signs of spinal or vertebral injuries, description of torticollis, and the treatment of fractures such as clavicle fractures.8 This document also discusses ryt, which refers to the purulent discharge from osteomyelitis.8 The following is an excerpt from this ancient document:9

“Instructions on erring a break in his upper arm…Thou shouldst spread out with his two shoulders in order to stretch apart his upper arm until that break falls into its place. Thou shouldst make for him two splints of linen, and thou shouldst apply for him one of them both on the inside of his arm, and the other of them both on the underside of his arm.”

This account illustrates the methodical and meticulous nature of this textbook, and it highlights some of the essentials of medical practice from diagnosis to medical decision-making to treatment.

There are various other contributions to the field of medicine from the Far East; however, many of these pertain to the fields of plastic surgery and general surgery.9

Greeks and Romans

The Greeks are considered to be the first to systematically employ the scientific approach to medicine.8 In the period between 430 BCE to 330 BCE, the Corpus Hippocrates was compiled, which is a Greek text on medicine. It is named for Hippocrates (460 BCE-370 BCE), the father of medicine, and it contains text that applies specifically to the field of orthopedic surgery. For example, this text discuses shoulder dislocations and describes various reduction maneuvers. Hippocrates had a keen understanding of the principles of traction and countertraction, especially as it pertains to the musculoskeletal system.8 In fact, the Hippocratic method is still used for reducing anterior shoulder dislocations, and its description can be found in several modern orthopedic texts, including recent articles.13 The Corpus Hippocrates also describes the correction of clubfoot deformity, and the treatment of infected open fractures with pitch cerate and wine compresses.8

 

 

Hippocrates also described the treatment of fractures, the principles of traction, and the implications of malunions. For example, Hippocrates wrote, “For the arm, when shortened, might be concealed and the mistake will not be great, but a shortened thigh bone will leave a man maimed.”1 In addition, spinal deformities were recognized by the Greeks, and Hippocrates devised an extension bench for the correction of such deformities.1 From their contributions to anatomy and surgical practice, the Greeks have made significant contributions to the field of surgery.9

During the Roman period, another Greek surgeon by the name of Galen described the musculoskeletal and nervous systems. He served as a gladiatorial surgeon in Rome, and today, he is considered to be the father of sports medicine.8 He is also credited with coining the terms scoliosis, kyphosis, and lordosis to denote the spinal deformities that were first described by Hippocrates.1 In the Roman period, amputations were also performed, and primitive prostheses were developed.9

The Middle Ages

There was relatively little progress in the study of medicine for a thousand years after the fall of the Roman Empire.9 This stagnation was predominantly due to the early Christian Church inhibiting freedom of thought and observation, as well as prohibiting human dissection and the study of anatomy. The first medical school in Europe was established in Salerno, Italy, during the ninth century. This school provided primarily pedantic teaching to its students and perpetuated the theories of the elements and humors. Later on, the University of Bologna became one of the first academic institutions to offer hands-on surgical training.9 One of the most famous surgeons of the Middle Ages was Guy de Chuauliac, who studied at Montpellier and Bologna. He was a leader in the ethical principles of surgery as well as the practice of surgery, and wrote the following with regards to femur fractures:9

“After the application of splints, I attach to the foot a mass of lead as a weight, taking care to pass the cord which supports the weight over a small pulley in such a manner that it shall pull on the leg in a horizontal direction.”

This description is strikingly similar to the modern-day nonoperative management of femur fractures, and underscores the importance of traction, which as mentioned above, was first described by Hippocrates.

Eventually, medicine began to separate from the Church, most likely due to an increase in the complexity of medical theories, the rise of secular universities, and an increase in medical knowledge from Eastern and Middle-Eastern groups.9

The Renaissance and the Foundations of Modern Orthopedics

Until the 16th century, the majority of medical theories were heavily influenced by the work of Hippocrates.8 The scientific study of anatomy gained prominence during this time, especially due to the work done by great artists, such as Leonardo Di Vinci.9 The Table

Table.
provides a list of some of the most prominent figures in the field of orthopedic surgery from across the world, as well as their contributions to the field. Collectively, these scholar and surgeons provided a strong foundation for the field of modern orthopedics.8 Additional discoveries by Joseph Lister, Louis Pasteur, Robert Koch, and Ignaz Semmelweis relating to antisepsis appeared to revolutionize the surgical management of orthopedic injuries.7

After a period of rapid expansion of the field of orthopedics, and following the Renaissance, many hospitals were built focusing on the sick and disabled, which solidified orthopedics’ position as a major medical specialty.1 For example, in 1863, James Knight founded the Hospital for the Ruptured and Crippled in New York City. This hospital became the oldest orthopedic hospital in the United States, and it later became known as the Hospital for Special Surgery.14,15 Several additional orthopedic institutions were formed, including the New York Orthopedic Dispensary in 1886 and Hospital for Deformities and Joint Diseases in 1917. Orthopedic surgery residency programs also began to be developed in the late 1800s.14 More specifically, Virgil Gibney at Hospital for the Ruptured and Crippled began the first orthopedic training program in the United States in 1888. Young doctors in this program trained for 1 year as junior assistant, senior assistant, and house surgeon, and began to be known as resident doctors.14

The Modern Era

In the 20th century, rapid development continued to better control infections as well as develop and introduce novel technology. For example, the invention of x-ray in 1895 by Wilhelm Conrad Röntgen improved our ability to diagnose and manage orthopedic conditions ranging from fractures to avascular necrosis of the femoral head to osteoarthritis.8,14 Spinal surgery also developed rapidly with Russell Hibbs describing a technique for spinal fusion at the New York Orthopedic Hospital.8 Similarly, the World Wars served as a catalyst in the development of the subspecialty of orthopedic trauma, with increasing attention placed on open wounds and proficiency with amputations, internal fixation, and wound care. In 1942, Austin Moore performed the first metal hip arthroplasty, and the field of joint replacement was subsequently advanced by the work of Sir John Charnley in the 1960s.8

 

 

Conclusion

Despite its relatively recent specialization, orthopedic surgery has a rich history rooted in ancient practices dating back to the primitive man. Over time, there has been significant development in the field in terms of surgical and nonsurgical treatment of orthopedic pathology and disease. Various cultures have played an instrumental role in developing this field, and it is remarkable to see that several practices have persisted since the time of these ancient civilizations. During the Renaissance, there was a considerable emphasis placed on pediatric deformity, but orthopedic surgeons have now branched out to subspecialty practice ranging from orthopedic trauma to joint replacement to oncology.1 For students of medicine and orthopedics, it is important to learn about the origins of this field and to appreciate its gradual development. Orthopedic surgery is a diverse and fascinating field that will most likely continue to develop with increased subspecialization and improved research at the molecular and population level. With a growing emphasis placed on outcomes and healthcare cost by today’s society, it will be fascinating to see how this field continues to evolve in the future.

Am J Orthop. 2016;45(7):E434-E438. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

References

1. Ponseti IV. History of orthopedic surgery. Iowa Orthop J. 1991;11:59-64.

2. Ninomiya JT, Dean JC, Incavo SJ. What’s new in hip replacement. J Bone Joint Surg Am. 2015;97(18):1543-1551.

3. Sabharwal S, Nelson SC, Sontich JK. What’s new in limb lengthening and deformity correction. J Bone Joint Surg Am. 2015;97(16):1375-1384.

4. Ricci WM, Black JC, McAndrew CM, Gardner MJ. What’s new in orthopedic trauma. J Bone Joint Surg Am. 2015;97(14):1200-1207.

5. Rodeo SA, Sugiguchi F, Fortier LA, Cunningham ME, Maher S. What’s new in orthopedic research. J Bone Joint Surg Am. 2014;96(23):2015-2019.

6. Pugley AJ, Martin CT, Harwood J, Ong KL, Bozic KJ, Callaghan JJ. Database and registry research in orthopedic surgery. Part 1: Claims-based data. J Bone Joint Surg Am. 2015;97(15):1278-1287.

7. Colton CL. The history of fracture treatment. In: Browner BD, Jupiter JB, Levine AM, Trafton PG, Krettek C, eds. Skeletal Trauma: Basic Science, Management, and Reconstruction. 4th ed. Philadelphia, PA: Saunders Elsevier; 2009:3-32.

8. Brakoulias,V. History of orthopaedics. WorldOrtho Web site. http://pioa.net/documents/Historyoforthopaedics.pdf. Accessed October 6, 2016.

9. Bishop WJ. The Early History of Surgery. New York, NY: Barnes & Noble Books; 1995.

10. Watson T. Wyoming site reveals more prehistoric mountain villages. USA Today. October 20, 2013. http://www.usatoday.com/story/news/nation/2013/10/20/wyoming-prehistoric-villages/2965263. Accessed October 6, 2016.

11. Minagar A, Ragheb J, Kelley RE. The Edwin Smith surgical papyrus: description and analysis of the earliest case of aphasia. J Med Biogr. 2003;11(2):114-117.

12. Atta HM. Edwin Smith Surgical Papyrus: the oldest known surgical treatise. Am Surg. 1999;65(12):1190-1192.

13. Sayegh FE, Kenanidis EI, Papavasiliou KA, Potoupnis ME, Kirkos JM, Kapetanos GA. Reduction of acute anterior dislocations: a prospective randomized study comparing a new technique with the Hippocratic and Kocher methods. J Bone Joint Surg Am. 2009;91(12):2775-2782.

14. Levine DB. Anatomy of a Hospital: Hospital for Special Surgery 1863-2013. New York, NY: Print Mattes; 2013.

15. Wilson PD, Levine DB. Hospital for special surgery. A brief review of its development and current position. Clin Orthop Relat Res. 2000;(374):90-106.

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The modern term orthopedics stems from the older word orthopedia, which was the title of a book published in 1741 by Nicholas Andry, a professor of medicine at the University of Paris.1 The term orthopedia is a composite of 2 Greek words: orthos, meaning “straight and free from deformity,” and paidios, meaning “child.” Together, orthopedics literally means straight child, suggesting the importance of pediatric injuries and deformities in the development of this field. Interestingly, Andry’s book also depicted a crooked young tree attached to a straight and strong staff, which has become the universal symbol of orthopedic surgery and underscores the focus on correcting deformities in the young (Figure).1

Figure.
While the history of the term is relatively recent, the practice of orthopedics is an ancient art.

Orthopedic surgery is a rapidly advancing medical field with several recent advances noted within orthopedic subspecialties,2-4 basic science,5 and clinical research.6 It is important to recognize the role of history with regards to innovation and research, especially for young trainees and medical students interested in a particular medical specialty. More specifically, it is important to understand the successes and failures of the past in order to advance research and practice, and ultimately improve patient care and outcomes.

In the recent literature, there is no concise yet comprehensive article focusing on the history of orthopedic surgery. The goal of this review is to provide an overview of the history and development of orthopedic surgery from ancient practices to the modern era.

Ancient Orthopedics

While the evidence is limited, the practice of orthopedics dates back to the primitive man.7 Fossil evidence suggests that the orthopedic pathology of today, such as fractures and traumatic amputations, existed in primitive times.8 The union of fractures in fair alignment has also been observed, which emphasizes the efficacy of nonoperative orthopedics and suggests the early use of splints and rehabilitation practices.8,9 Since procedures such as trepanation and crude amputations occurred during the New Stone Age, it is feasible that sophisticated techniques had also been developed for the treatment of injuries.7-9 However, evidence continues to remain limited.7

Later civilizations also developed creative ways to manage orthopedic injuries. For example, the Shoshone Indians, who were known to exist around 700-2000 BCE, made a splint of fresh rawhide that had been soaked in water.9,10 Similarly, some South Australian tribes made splints of clay, which when dried were as good as plaster of Paris.9 Furthermore, bone-setting or reductions was practiced as a profession in many tribes, underscoring the importance of orthopedic injuries in early civilizations.8,9

Ancient Egypt

The ancient Egyptians seemed to have carried on the practices of splinting. For example, 2 splinted specimens were discovered during the Hearst Egyptian Expedition in 1903.7 More specifically, these specimens included a femur and forearm and dated to approximately 300 BCE.7 Other examples of splints made of bamboo and reed padded with linen have been found on mummies as well.8 Similarly, crutches were also used by this civilization, as depicted on a carving made on an Egyptian tomb in 2830 BCE.8

One of the earliest and most significant documents on medicine was discovered in 1862, known as the Edwin Smith papyrus. This document is thought to have been composed by Imhotep, a prominent Egyptian physician, astrologer, architect, and politician, and it specifically categorizes diseases and treatments. Many scholars recognize this medical document as the oldest surgical textbook.11,12 With regards to orthopedic conditions, this document describes the reduction of a dislocated mandible, signs of spinal or vertebral injuries, description of torticollis, and the treatment of fractures such as clavicle fractures.8 This document also discusses ryt, which refers to the purulent discharge from osteomyelitis.8 The following is an excerpt from this ancient document:9

“Instructions on erring a break in his upper arm…Thou shouldst spread out with his two shoulders in order to stretch apart his upper arm until that break falls into its place. Thou shouldst make for him two splints of linen, and thou shouldst apply for him one of them both on the inside of his arm, and the other of them both on the underside of his arm.”

This account illustrates the methodical and meticulous nature of this textbook, and it highlights some of the essentials of medical practice from diagnosis to medical decision-making to treatment.

There are various other contributions to the field of medicine from the Far East; however, many of these pertain to the fields of plastic surgery and general surgery.9

Greeks and Romans

The Greeks are considered to be the first to systematically employ the scientific approach to medicine.8 In the period between 430 BCE to 330 BCE, the Corpus Hippocrates was compiled, which is a Greek text on medicine. It is named for Hippocrates (460 BCE-370 BCE), the father of medicine, and it contains text that applies specifically to the field of orthopedic surgery. For example, this text discuses shoulder dislocations and describes various reduction maneuvers. Hippocrates had a keen understanding of the principles of traction and countertraction, especially as it pertains to the musculoskeletal system.8 In fact, the Hippocratic method is still used for reducing anterior shoulder dislocations, and its description can be found in several modern orthopedic texts, including recent articles.13 The Corpus Hippocrates also describes the correction of clubfoot deformity, and the treatment of infected open fractures with pitch cerate and wine compresses.8

 

 

Hippocrates also described the treatment of fractures, the principles of traction, and the implications of malunions. For example, Hippocrates wrote, “For the arm, when shortened, might be concealed and the mistake will not be great, but a shortened thigh bone will leave a man maimed.”1 In addition, spinal deformities were recognized by the Greeks, and Hippocrates devised an extension bench for the correction of such deformities.1 From their contributions to anatomy and surgical practice, the Greeks have made significant contributions to the field of surgery.9

During the Roman period, another Greek surgeon by the name of Galen described the musculoskeletal and nervous systems. He served as a gladiatorial surgeon in Rome, and today, he is considered to be the father of sports medicine.8 He is also credited with coining the terms scoliosis, kyphosis, and lordosis to denote the spinal deformities that were first described by Hippocrates.1 In the Roman period, amputations were also performed, and primitive prostheses were developed.9

The Middle Ages

There was relatively little progress in the study of medicine for a thousand years after the fall of the Roman Empire.9 This stagnation was predominantly due to the early Christian Church inhibiting freedom of thought and observation, as well as prohibiting human dissection and the study of anatomy. The first medical school in Europe was established in Salerno, Italy, during the ninth century. This school provided primarily pedantic teaching to its students and perpetuated the theories of the elements and humors. Later on, the University of Bologna became one of the first academic institutions to offer hands-on surgical training.9 One of the most famous surgeons of the Middle Ages was Guy de Chuauliac, who studied at Montpellier and Bologna. He was a leader in the ethical principles of surgery as well as the practice of surgery, and wrote the following with regards to femur fractures:9

“After the application of splints, I attach to the foot a mass of lead as a weight, taking care to pass the cord which supports the weight over a small pulley in such a manner that it shall pull on the leg in a horizontal direction.”

This description is strikingly similar to the modern-day nonoperative management of femur fractures, and underscores the importance of traction, which as mentioned above, was first described by Hippocrates.

Eventually, medicine began to separate from the Church, most likely due to an increase in the complexity of medical theories, the rise of secular universities, and an increase in medical knowledge from Eastern and Middle-Eastern groups.9

The Renaissance and the Foundations of Modern Orthopedics

Until the 16th century, the majority of medical theories were heavily influenced by the work of Hippocrates.8 The scientific study of anatomy gained prominence during this time, especially due to the work done by great artists, such as Leonardo Di Vinci.9 The Table

Table.
provides a list of some of the most prominent figures in the field of orthopedic surgery from across the world, as well as their contributions to the field. Collectively, these scholar and surgeons provided a strong foundation for the field of modern orthopedics.8 Additional discoveries by Joseph Lister, Louis Pasteur, Robert Koch, and Ignaz Semmelweis relating to antisepsis appeared to revolutionize the surgical management of orthopedic injuries.7

After a period of rapid expansion of the field of orthopedics, and following the Renaissance, many hospitals were built focusing on the sick and disabled, which solidified orthopedics’ position as a major medical specialty.1 For example, in 1863, James Knight founded the Hospital for the Ruptured and Crippled in New York City. This hospital became the oldest orthopedic hospital in the United States, and it later became known as the Hospital for Special Surgery.14,15 Several additional orthopedic institutions were formed, including the New York Orthopedic Dispensary in 1886 and Hospital for Deformities and Joint Diseases in 1917. Orthopedic surgery residency programs also began to be developed in the late 1800s.14 More specifically, Virgil Gibney at Hospital for the Ruptured and Crippled began the first orthopedic training program in the United States in 1888. Young doctors in this program trained for 1 year as junior assistant, senior assistant, and house surgeon, and began to be known as resident doctors.14

The Modern Era

In the 20th century, rapid development continued to better control infections as well as develop and introduce novel technology. For example, the invention of x-ray in 1895 by Wilhelm Conrad Röntgen improved our ability to diagnose and manage orthopedic conditions ranging from fractures to avascular necrosis of the femoral head to osteoarthritis.8,14 Spinal surgery also developed rapidly with Russell Hibbs describing a technique for spinal fusion at the New York Orthopedic Hospital.8 Similarly, the World Wars served as a catalyst in the development of the subspecialty of orthopedic trauma, with increasing attention placed on open wounds and proficiency with amputations, internal fixation, and wound care. In 1942, Austin Moore performed the first metal hip arthroplasty, and the field of joint replacement was subsequently advanced by the work of Sir John Charnley in the 1960s.8

 

 

Conclusion

Despite its relatively recent specialization, orthopedic surgery has a rich history rooted in ancient practices dating back to the primitive man. Over time, there has been significant development in the field in terms of surgical and nonsurgical treatment of orthopedic pathology and disease. Various cultures have played an instrumental role in developing this field, and it is remarkable to see that several practices have persisted since the time of these ancient civilizations. During the Renaissance, there was a considerable emphasis placed on pediatric deformity, but orthopedic surgeons have now branched out to subspecialty practice ranging from orthopedic trauma to joint replacement to oncology.1 For students of medicine and orthopedics, it is important to learn about the origins of this field and to appreciate its gradual development. Orthopedic surgery is a diverse and fascinating field that will most likely continue to develop with increased subspecialization and improved research at the molecular and population level. With a growing emphasis placed on outcomes and healthcare cost by today’s society, it will be fascinating to see how this field continues to evolve in the future.

Am J Orthop. 2016;45(7):E434-E438. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

The modern term orthopedics stems from the older word orthopedia, which was the title of a book published in 1741 by Nicholas Andry, a professor of medicine at the University of Paris.1 The term orthopedia is a composite of 2 Greek words: orthos, meaning “straight and free from deformity,” and paidios, meaning “child.” Together, orthopedics literally means straight child, suggesting the importance of pediatric injuries and deformities in the development of this field. Interestingly, Andry’s book also depicted a crooked young tree attached to a straight and strong staff, which has become the universal symbol of orthopedic surgery and underscores the focus on correcting deformities in the young (Figure).1

Figure.
While the history of the term is relatively recent, the practice of orthopedics is an ancient art.

Orthopedic surgery is a rapidly advancing medical field with several recent advances noted within orthopedic subspecialties,2-4 basic science,5 and clinical research.6 It is important to recognize the role of history with regards to innovation and research, especially for young trainees and medical students interested in a particular medical specialty. More specifically, it is important to understand the successes and failures of the past in order to advance research and practice, and ultimately improve patient care and outcomes.

In the recent literature, there is no concise yet comprehensive article focusing on the history of orthopedic surgery. The goal of this review is to provide an overview of the history and development of orthopedic surgery from ancient practices to the modern era.

Ancient Orthopedics

While the evidence is limited, the practice of orthopedics dates back to the primitive man.7 Fossil evidence suggests that the orthopedic pathology of today, such as fractures and traumatic amputations, existed in primitive times.8 The union of fractures in fair alignment has also been observed, which emphasizes the efficacy of nonoperative orthopedics and suggests the early use of splints and rehabilitation practices.8,9 Since procedures such as trepanation and crude amputations occurred during the New Stone Age, it is feasible that sophisticated techniques had also been developed for the treatment of injuries.7-9 However, evidence continues to remain limited.7

Later civilizations also developed creative ways to manage orthopedic injuries. For example, the Shoshone Indians, who were known to exist around 700-2000 BCE, made a splint of fresh rawhide that had been soaked in water.9,10 Similarly, some South Australian tribes made splints of clay, which when dried were as good as plaster of Paris.9 Furthermore, bone-setting or reductions was practiced as a profession in many tribes, underscoring the importance of orthopedic injuries in early civilizations.8,9

Ancient Egypt

The ancient Egyptians seemed to have carried on the practices of splinting. For example, 2 splinted specimens were discovered during the Hearst Egyptian Expedition in 1903.7 More specifically, these specimens included a femur and forearm and dated to approximately 300 BCE.7 Other examples of splints made of bamboo and reed padded with linen have been found on mummies as well.8 Similarly, crutches were also used by this civilization, as depicted on a carving made on an Egyptian tomb in 2830 BCE.8

One of the earliest and most significant documents on medicine was discovered in 1862, known as the Edwin Smith papyrus. This document is thought to have been composed by Imhotep, a prominent Egyptian physician, astrologer, architect, and politician, and it specifically categorizes diseases and treatments. Many scholars recognize this medical document as the oldest surgical textbook.11,12 With regards to orthopedic conditions, this document describes the reduction of a dislocated mandible, signs of spinal or vertebral injuries, description of torticollis, and the treatment of fractures such as clavicle fractures.8 This document also discusses ryt, which refers to the purulent discharge from osteomyelitis.8 The following is an excerpt from this ancient document:9

“Instructions on erring a break in his upper arm…Thou shouldst spread out with his two shoulders in order to stretch apart his upper arm until that break falls into its place. Thou shouldst make for him two splints of linen, and thou shouldst apply for him one of them both on the inside of his arm, and the other of them both on the underside of his arm.”

This account illustrates the methodical and meticulous nature of this textbook, and it highlights some of the essentials of medical practice from diagnosis to medical decision-making to treatment.

There are various other contributions to the field of medicine from the Far East; however, many of these pertain to the fields of plastic surgery and general surgery.9

Greeks and Romans

The Greeks are considered to be the first to systematically employ the scientific approach to medicine.8 In the period between 430 BCE to 330 BCE, the Corpus Hippocrates was compiled, which is a Greek text on medicine. It is named for Hippocrates (460 BCE-370 BCE), the father of medicine, and it contains text that applies specifically to the field of orthopedic surgery. For example, this text discuses shoulder dislocations and describes various reduction maneuvers. Hippocrates had a keen understanding of the principles of traction and countertraction, especially as it pertains to the musculoskeletal system.8 In fact, the Hippocratic method is still used for reducing anterior shoulder dislocations, and its description can be found in several modern orthopedic texts, including recent articles.13 The Corpus Hippocrates also describes the correction of clubfoot deformity, and the treatment of infected open fractures with pitch cerate and wine compresses.8

 

 

Hippocrates also described the treatment of fractures, the principles of traction, and the implications of malunions. For example, Hippocrates wrote, “For the arm, when shortened, might be concealed and the mistake will not be great, but a shortened thigh bone will leave a man maimed.”1 In addition, spinal deformities were recognized by the Greeks, and Hippocrates devised an extension bench for the correction of such deformities.1 From their contributions to anatomy and surgical practice, the Greeks have made significant contributions to the field of surgery.9

During the Roman period, another Greek surgeon by the name of Galen described the musculoskeletal and nervous systems. He served as a gladiatorial surgeon in Rome, and today, he is considered to be the father of sports medicine.8 He is also credited with coining the terms scoliosis, kyphosis, and lordosis to denote the spinal deformities that were first described by Hippocrates.1 In the Roman period, amputations were also performed, and primitive prostheses were developed.9

The Middle Ages

There was relatively little progress in the study of medicine for a thousand years after the fall of the Roman Empire.9 This stagnation was predominantly due to the early Christian Church inhibiting freedom of thought and observation, as well as prohibiting human dissection and the study of anatomy. The first medical school in Europe was established in Salerno, Italy, during the ninth century. This school provided primarily pedantic teaching to its students and perpetuated the theories of the elements and humors. Later on, the University of Bologna became one of the first academic institutions to offer hands-on surgical training.9 One of the most famous surgeons of the Middle Ages was Guy de Chuauliac, who studied at Montpellier and Bologna. He was a leader in the ethical principles of surgery as well as the practice of surgery, and wrote the following with regards to femur fractures:9

“After the application of splints, I attach to the foot a mass of lead as a weight, taking care to pass the cord which supports the weight over a small pulley in such a manner that it shall pull on the leg in a horizontal direction.”

This description is strikingly similar to the modern-day nonoperative management of femur fractures, and underscores the importance of traction, which as mentioned above, was first described by Hippocrates.

Eventually, medicine began to separate from the Church, most likely due to an increase in the complexity of medical theories, the rise of secular universities, and an increase in medical knowledge from Eastern and Middle-Eastern groups.9

The Renaissance and the Foundations of Modern Orthopedics

Until the 16th century, the majority of medical theories were heavily influenced by the work of Hippocrates.8 The scientific study of anatomy gained prominence during this time, especially due to the work done by great artists, such as Leonardo Di Vinci.9 The Table

Table.
provides a list of some of the most prominent figures in the field of orthopedic surgery from across the world, as well as their contributions to the field. Collectively, these scholar and surgeons provided a strong foundation for the field of modern orthopedics.8 Additional discoveries by Joseph Lister, Louis Pasteur, Robert Koch, and Ignaz Semmelweis relating to antisepsis appeared to revolutionize the surgical management of orthopedic injuries.7

After a period of rapid expansion of the field of orthopedics, and following the Renaissance, many hospitals were built focusing on the sick and disabled, which solidified orthopedics’ position as a major medical specialty.1 For example, in 1863, James Knight founded the Hospital for the Ruptured and Crippled in New York City. This hospital became the oldest orthopedic hospital in the United States, and it later became known as the Hospital for Special Surgery.14,15 Several additional orthopedic institutions were formed, including the New York Orthopedic Dispensary in 1886 and Hospital for Deformities and Joint Diseases in 1917. Orthopedic surgery residency programs also began to be developed in the late 1800s.14 More specifically, Virgil Gibney at Hospital for the Ruptured and Crippled began the first orthopedic training program in the United States in 1888. Young doctors in this program trained for 1 year as junior assistant, senior assistant, and house surgeon, and began to be known as resident doctors.14

The Modern Era

In the 20th century, rapid development continued to better control infections as well as develop and introduce novel technology. For example, the invention of x-ray in 1895 by Wilhelm Conrad Röntgen improved our ability to diagnose and manage orthopedic conditions ranging from fractures to avascular necrosis of the femoral head to osteoarthritis.8,14 Spinal surgery also developed rapidly with Russell Hibbs describing a technique for spinal fusion at the New York Orthopedic Hospital.8 Similarly, the World Wars served as a catalyst in the development of the subspecialty of orthopedic trauma, with increasing attention placed on open wounds and proficiency with amputations, internal fixation, and wound care. In 1942, Austin Moore performed the first metal hip arthroplasty, and the field of joint replacement was subsequently advanced by the work of Sir John Charnley in the 1960s.8

 

 

Conclusion

Despite its relatively recent specialization, orthopedic surgery has a rich history rooted in ancient practices dating back to the primitive man. Over time, there has been significant development in the field in terms of surgical and nonsurgical treatment of orthopedic pathology and disease. Various cultures have played an instrumental role in developing this field, and it is remarkable to see that several practices have persisted since the time of these ancient civilizations. During the Renaissance, there was a considerable emphasis placed on pediatric deformity, but orthopedic surgeons have now branched out to subspecialty practice ranging from orthopedic trauma to joint replacement to oncology.1 For students of medicine and orthopedics, it is important to learn about the origins of this field and to appreciate its gradual development. Orthopedic surgery is a diverse and fascinating field that will most likely continue to develop with increased subspecialization and improved research at the molecular and population level. With a growing emphasis placed on outcomes and healthcare cost by today’s society, it will be fascinating to see how this field continues to evolve in the future.

Am J Orthop. 2016;45(7):E434-E438. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

References

1. Ponseti IV. History of orthopedic surgery. Iowa Orthop J. 1991;11:59-64.

2. Ninomiya JT, Dean JC, Incavo SJ. What’s new in hip replacement. J Bone Joint Surg Am. 2015;97(18):1543-1551.

3. Sabharwal S, Nelson SC, Sontich JK. What’s new in limb lengthening and deformity correction. J Bone Joint Surg Am. 2015;97(16):1375-1384.

4. Ricci WM, Black JC, McAndrew CM, Gardner MJ. What’s new in orthopedic trauma. J Bone Joint Surg Am. 2015;97(14):1200-1207.

5. Rodeo SA, Sugiguchi F, Fortier LA, Cunningham ME, Maher S. What’s new in orthopedic research. J Bone Joint Surg Am. 2014;96(23):2015-2019.

6. Pugley AJ, Martin CT, Harwood J, Ong KL, Bozic KJ, Callaghan JJ. Database and registry research in orthopedic surgery. Part 1: Claims-based data. J Bone Joint Surg Am. 2015;97(15):1278-1287.

7. Colton CL. The history of fracture treatment. In: Browner BD, Jupiter JB, Levine AM, Trafton PG, Krettek C, eds. Skeletal Trauma: Basic Science, Management, and Reconstruction. 4th ed. Philadelphia, PA: Saunders Elsevier; 2009:3-32.

8. Brakoulias,V. History of orthopaedics. WorldOrtho Web site. http://pioa.net/documents/Historyoforthopaedics.pdf. Accessed October 6, 2016.

9. Bishop WJ. The Early History of Surgery. New York, NY: Barnes & Noble Books; 1995.

10. Watson T. Wyoming site reveals more prehistoric mountain villages. USA Today. October 20, 2013. http://www.usatoday.com/story/news/nation/2013/10/20/wyoming-prehistoric-villages/2965263. Accessed October 6, 2016.

11. Minagar A, Ragheb J, Kelley RE. The Edwin Smith surgical papyrus: description and analysis of the earliest case of aphasia. J Med Biogr. 2003;11(2):114-117.

12. Atta HM. Edwin Smith Surgical Papyrus: the oldest known surgical treatise. Am Surg. 1999;65(12):1190-1192.

13. Sayegh FE, Kenanidis EI, Papavasiliou KA, Potoupnis ME, Kirkos JM, Kapetanos GA. Reduction of acute anterior dislocations: a prospective randomized study comparing a new technique with the Hippocratic and Kocher methods. J Bone Joint Surg Am. 2009;91(12):2775-2782.

14. Levine DB. Anatomy of a Hospital: Hospital for Special Surgery 1863-2013. New York, NY: Print Mattes; 2013.

15. Wilson PD, Levine DB. Hospital for special surgery. A brief review of its development and current position. Clin Orthop Relat Res. 2000;(374):90-106.

References

1. Ponseti IV. History of orthopedic surgery. Iowa Orthop J. 1991;11:59-64.

2. Ninomiya JT, Dean JC, Incavo SJ. What’s new in hip replacement. J Bone Joint Surg Am. 2015;97(18):1543-1551.

3. Sabharwal S, Nelson SC, Sontich JK. What’s new in limb lengthening and deformity correction. J Bone Joint Surg Am. 2015;97(16):1375-1384.

4. Ricci WM, Black JC, McAndrew CM, Gardner MJ. What’s new in orthopedic trauma. J Bone Joint Surg Am. 2015;97(14):1200-1207.

5. Rodeo SA, Sugiguchi F, Fortier LA, Cunningham ME, Maher S. What’s new in orthopedic research. J Bone Joint Surg Am. 2014;96(23):2015-2019.

6. Pugley AJ, Martin CT, Harwood J, Ong KL, Bozic KJ, Callaghan JJ. Database and registry research in orthopedic surgery. Part 1: Claims-based data. J Bone Joint Surg Am. 2015;97(15):1278-1287.

7. Colton CL. The history of fracture treatment. In: Browner BD, Jupiter JB, Levine AM, Trafton PG, Krettek C, eds. Skeletal Trauma: Basic Science, Management, and Reconstruction. 4th ed. Philadelphia, PA: Saunders Elsevier; 2009:3-32.

8. Brakoulias,V. History of orthopaedics. WorldOrtho Web site. http://pioa.net/documents/Historyoforthopaedics.pdf. Accessed October 6, 2016.

9. Bishop WJ. The Early History of Surgery. New York, NY: Barnes & Noble Books; 1995.

10. Watson T. Wyoming site reveals more prehistoric mountain villages. USA Today. October 20, 2013. http://www.usatoday.com/story/news/nation/2013/10/20/wyoming-prehistoric-villages/2965263. Accessed October 6, 2016.

11. Minagar A, Ragheb J, Kelley RE. The Edwin Smith surgical papyrus: description and analysis of the earliest case of aphasia. J Med Biogr. 2003;11(2):114-117.

12. Atta HM. Edwin Smith Surgical Papyrus: the oldest known surgical treatise. Am Surg. 1999;65(12):1190-1192.

13. Sayegh FE, Kenanidis EI, Papavasiliou KA, Potoupnis ME, Kirkos JM, Kapetanos GA. Reduction of acute anterior dislocations: a prospective randomized study comparing a new technique with the Hippocratic and Kocher methods. J Bone Joint Surg Am. 2009;91(12):2775-2782.

14. Levine DB. Anatomy of a Hospital: Hospital for Special Surgery 1863-2013. New York, NY: Print Mattes; 2013.

15. Wilson PD, Levine DB. Hospital for special surgery. A brief review of its development and current position. Clin Orthop Relat Res. 2000;(374):90-106.

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The $400 generic

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Oren is 11. I often see him around the neighborhood.

The other day I gave his father a lift. “Oren had a rash on his face,” said Ben, slipping into the passenger seat. “The pediatrician said she thought it was eczema, but she gave him an acne medicine.”

I raised my eyebrows, but said nothing.

Dr. Alan Rockoff
“She warned me that the cream was going to be expensive,” Ben said, “and it was, but she says she gets good results with it. And it did help. The rash went away in 2 days.”

“How much did it cost?” I asked.

“$400.”

“$400!” I couldn’t quite stifle my shock. “What was in the cream?” I asked.

“Here it is,” he said. “I took a picture of the tube on my phone.”

He showed me a snapshot of a tube of clindamycin/benzoyl peroxide.

Although I try not to meddle in the medical issues of friends, I decided to make a small exception in this case. “Next time someone prescribes an expensive skin cream,” I said, “let me know. Maybe I can help you find a more affordable alternative.”

What skin problem did Oren have? I have no idea. I see his face enough to know that he has no acne at all. Nor would acne go away in 2 days.

On the other hand, if he did have a flare of eczema – I’ve never noticed that on him either – acne medicine would aggravate it, if anything.

Besides those questions, I have another one: Regardless of what she thought the diagnosis was, why on earth did Oren’s pediatrician feel compelled to prescribe a $400 generic? I say “compelled” because she told Ben straight out that the cream was going to cost a lot. But she just had to prescribe it because her experience told her it worked.

What experience did she have, exactly? What else had she tried that didn’t work? And what did she mean by “work”?

Ben’s and Oren’s experience is just a small, unnoticed incident of no general interest. It will spur no magazine exposés, incite no lawsuits, launch no professional or political inquiries.

• Oren’s pediatrician will go on prescribing a hideously priced cream intended to treat who-knows-what. Nobody will suggest to her that she might at least consider doing otherwise.

• Pharmacy benefit managers will not crack down on either pediatrician or cream. They have bigger fish to fry, like biologics that cost $50K per year.

• Health care administrators will take no notice. They will instead think up more creative and onerous disincentives to restrain providers from prescribing anything expensive. Whether they will also figure out how to keep monopolistic generic drug manufacturers from jacking up prices into the stratosphere is something else.

• Medical educators will strengthen their focus on sophisticated science (Genomics! Precision Medicine!), while doing a wholly inadequate job of passing on simple lessons that might help primary clinicians do a better job of managing everyday skin problems. Just yesterday, my colleague and I saw two patients who had been taking doxycycline for years with no clinical benefit, three kids with eczema who had used a succession of antifungal creams for over 4 months, one woman who had been dousing herself repeatedly with permethrin – to no avail – because her mites lived exclusively in her brain and those of her prescribers, and a partridge with alopecia in a pear tree. (OK, not the last one). All that in just 1 day!

• Simple common sense will stay elusive. Most rashes are really not rocket science.

I apologize, dear colleagues, for being so cranky. Much jollier to be upbeat and amusing. It’s just that, after 40 years in the business, observing the same skull-exploding clinical behaviors gets a little old, along with the observer.

Oren and Ben are fine, though. Oren’s face is as clear as ever. (It’s genetic – his mom has great skin). Even Ben isn’t disturbed. First of all, the rash went away. Second, he has an annual $2,000 drug cost deductible, “so I’d have to spend it anyway.”

“Look, Ben,” I told him, “if you need help exhausting your deductible, I’ll be happy to send you a couple of bills. No problem.”

He smiled. I guess he doesn’t really need my help on that.
 

Dr. Rockoff practices dermatology in Brookline, Mass, and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His new book “Act Like a Doctor, Think Like a Patient” is now available at amazon.com and barnesandnoble.com. This is his second book. Write to him at [email protected].

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Oren is 11. I often see him around the neighborhood.

The other day I gave his father a lift. “Oren had a rash on his face,” said Ben, slipping into the passenger seat. “The pediatrician said she thought it was eczema, but she gave him an acne medicine.”

I raised my eyebrows, but said nothing.

Dr. Alan Rockoff
“She warned me that the cream was going to be expensive,” Ben said, “and it was, but she says she gets good results with it. And it did help. The rash went away in 2 days.”

“How much did it cost?” I asked.

“$400.”

“$400!” I couldn’t quite stifle my shock. “What was in the cream?” I asked.

“Here it is,” he said. “I took a picture of the tube on my phone.”

He showed me a snapshot of a tube of clindamycin/benzoyl peroxide.

Although I try not to meddle in the medical issues of friends, I decided to make a small exception in this case. “Next time someone prescribes an expensive skin cream,” I said, “let me know. Maybe I can help you find a more affordable alternative.”

What skin problem did Oren have? I have no idea. I see his face enough to know that he has no acne at all. Nor would acne go away in 2 days.

On the other hand, if he did have a flare of eczema – I’ve never noticed that on him either – acne medicine would aggravate it, if anything.

Besides those questions, I have another one: Regardless of what she thought the diagnosis was, why on earth did Oren’s pediatrician feel compelled to prescribe a $400 generic? I say “compelled” because she told Ben straight out that the cream was going to cost a lot. But she just had to prescribe it because her experience told her it worked.

What experience did she have, exactly? What else had she tried that didn’t work? And what did she mean by “work”?

Ben’s and Oren’s experience is just a small, unnoticed incident of no general interest. It will spur no magazine exposés, incite no lawsuits, launch no professional or political inquiries.

• Oren’s pediatrician will go on prescribing a hideously priced cream intended to treat who-knows-what. Nobody will suggest to her that she might at least consider doing otherwise.

• Pharmacy benefit managers will not crack down on either pediatrician or cream. They have bigger fish to fry, like biologics that cost $50K per year.

• Health care administrators will take no notice. They will instead think up more creative and onerous disincentives to restrain providers from prescribing anything expensive. Whether they will also figure out how to keep monopolistic generic drug manufacturers from jacking up prices into the stratosphere is something else.

• Medical educators will strengthen their focus on sophisticated science (Genomics! Precision Medicine!), while doing a wholly inadequate job of passing on simple lessons that might help primary clinicians do a better job of managing everyday skin problems. Just yesterday, my colleague and I saw two patients who had been taking doxycycline for years with no clinical benefit, three kids with eczema who had used a succession of antifungal creams for over 4 months, one woman who had been dousing herself repeatedly with permethrin – to no avail – because her mites lived exclusively in her brain and those of her prescribers, and a partridge with alopecia in a pear tree. (OK, not the last one). All that in just 1 day!

• Simple common sense will stay elusive. Most rashes are really not rocket science.

I apologize, dear colleagues, for being so cranky. Much jollier to be upbeat and amusing. It’s just that, after 40 years in the business, observing the same skull-exploding clinical behaviors gets a little old, along with the observer.

Oren and Ben are fine, though. Oren’s face is as clear as ever. (It’s genetic – his mom has great skin). Even Ben isn’t disturbed. First of all, the rash went away. Second, he has an annual $2,000 drug cost deductible, “so I’d have to spend it anyway.”

“Look, Ben,” I told him, “if you need help exhausting your deductible, I’ll be happy to send you a couple of bills. No problem.”

He smiled. I guess he doesn’t really need my help on that.
 

Dr. Rockoff practices dermatology in Brookline, Mass, and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His new book “Act Like a Doctor, Think Like a Patient” is now available at amazon.com and barnesandnoble.com. This is his second book. Write to him at [email protected].

Oren is 11. I often see him around the neighborhood.

The other day I gave his father a lift. “Oren had a rash on his face,” said Ben, slipping into the passenger seat. “The pediatrician said she thought it was eczema, but she gave him an acne medicine.”

I raised my eyebrows, but said nothing.

Dr. Alan Rockoff
“She warned me that the cream was going to be expensive,” Ben said, “and it was, but she says she gets good results with it. And it did help. The rash went away in 2 days.”

“How much did it cost?” I asked.

“$400.”

“$400!” I couldn’t quite stifle my shock. “What was in the cream?” I asked.

“Here it is,” he said. “I took a picture of the tube on my phone.”

He showed me a snapshot of a tube of clindamycin/benzoyl peroxide.

Although I try not to meddle in the medical issues of friends, I decided to make a small exception in this case. “Next time someone prescribes an expensive skin cream,” I said, “let me know. Maybe I can help you find a more affordable alternative.”

What skin problem did Oren have? I have no idea. I see his face enough to know that he has no acne at all. Nor would acne go away in 2 days.

On the other hand, if he did have a flare of eczema – I’ve never noticed that on him either – acne medicine would aggravate it, if anything.

Besides those questions, I have another one: Regardless of what she thought the diagnosis was, why on earth did Oren’s pediatrician feel compelled to prescribe a $400 generic? I say “compelled” because she told Ben straight out that the cream was going to cost a lot. But she just had to prescribe it because her experience told her it worked.

What experience did she have, exactly? What else had she tried that didn’t work? And what did she mean by “work”?

Ben’s and Oren’s experience is just a small, unnoticed incident of no general interest. It will spur no magazine exposés, incite no lawsuits, launch no professional or political inquiries.

• Oren’s pediatrician will go on prescribing a hideously priced cream intended to treat who-knows-what. Nobody will suggest to her that she might at least consider doing otherwise.

• Pharmacy benefit managers will not crack down on either pediatrician or cream. They have bigger fish to fry, like biologics that cost $50K per year.

• Health care administrators will take no notice. They will instead think up more creative and onerous disincentives to restrain providers from prescribing anything expensive. Whether they will also figure out how to keep monopolistic generic drug manufacturers from jacking up prices into the stratosphere is something else.

• Medical educators will strengthen their focus on sophisticated science (Genomics! Precision Medicine!), while doing a wholly inadequate job of passing on simple lessons that might help primary clinicians do a better job of managing everyday skin problems. Just yesterday, my colleague and I saw two patients who had been taking doxycycline for years with no clinical benefit, three kids with eczema who had used a succession of antifungal creams for over 4 months, one woman who had been dousing herself repeatedly with permethrin – to no avail – because her mites lived exclusively in her brain and those of her prescribers, and a partridge with alopecia in a pear tree. (OK, not the last one). All that in just 1 day!

• Simple common sense will stay elusive. Most rashes are really not rocket science.

I apologize, dear colleagues, for being so cranky. Much jollier to be upbeat and amusing. It’s just that, after 40 years in the business, observing the same skull-exploding clinical behaviors gets a little old, along with the observer.

Oren and Ben are fine, though. Oren’s face is as clear as ever. (It’s genetic – his mom has great skin). Even Ben isn’t disturbed. First of all, the rash went away. Second, he has an annual $2,000 drug cost deductible, “so I’d have to spend it anyway.”

“Look, Ben,” I told him, “if you need help exhausting your deductible, I’ll be happy to send you a couple of bills. No problem.”

He smiled. I guess he doesn’t really need my help on that.
 

Dr. Rockoff practices dermatology in Brookline, Mass, and is a longtime contributor to Dermatology News. He serves on the clinical faculty at Tufts University, Boston, and has taught senior medical students and other trainees for 30 years. His new book “Act Like a Doctor, Think Like a Patient” is now available at amazon.com and barnesandnoble.com. This is his second book. Write to him at [email protected].

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Study supports palliative care in HSCT recipients

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Study supports palliative care in HSCT recipients

Preparing for HSCT

Photo by Chad McNeeley

Palliative care can be beneficial for patients undergoing hematopoietic stem cell transplant (HSCT) to treat hematologic malignancies, according to research published in JAMA.

The single-center study suggested that palliative care can improve HSCT recipients’ quality of life, relieve symptoms associated with the procedure, and reduce depression and anxiety.

Researchers observed such benefits during hospitalization for HSCT and a few months later.

In addition, caregivers of patients receiving palliative care experienced less depression and were better at coping with the stress associated with the illness of their loved one.

“Palliative care clinicians are increasingly asked to help care for patients with solid tumors but are rarely consulted for patients with hematologic malignancies, especially those receiving therapy designed to cure their disease,” said study author Areej El-Jawahri, MD, of Massachusette General Hospital in Boston.

“The physical and psychological symptoms associated with HSCT are sometimes regarded as expected and unavoidable, which, combined with the persistent misperception that equates palliative care with end-of-life care, has contributed to a lack of involvement of palliative care clinicians in the care of these patients.”

Intervention

Dr El-Jawahri and her colleagues studied 160 patients who underwent autologous or allogeneic HSCT to treat a variety of hematologic malignancies from August 2014 into January 2016.

Participants were randomized to receive either standard care (n=79) or the palliative care intervention (n=81).

Within 3 days of their admission to the hospital, patients in the intervention group had an initial meeting with a palliative care clinician—a physician or advance practice nurse—who continued to meet with them at least twice a week during their hospitalization.

At the meetings, which could be attended by a family member or friend of the patient, clinicians first focused on establishing a rapport with patients and their caregivers.

Clinicians addressed ways of managing the physical and psychological symptoms patients were experiencing and provided support and strategies for coping with distress. Patients received an average of 8 palliative care visits during their hospitalizations, which lasted on average 20 days.

At the outset of the study and 2 weeks into the process, a time when symptoms tend to be at their worst, patients in both groups and participating caregivers completed questionnaires assessing their mood and quality of life.

Patients also completed questionnaires asking about symptoms of their illness and those associated with the procedure. Patients completed additional assessments 3 months after HSCT as well.

Results

The study’s primary endpoint was change in quality of life from baseline to week 2. Patients receiving the palliative care intervention had significantly better quality of life scores at week 2 than patients in the control group.

Also at the 2-week mark, patients receiving the palliative care intervention reported lower levels of depression, anxiety, and symptoms than the control group, but there was no significant difference between the groups with regard to fatigue.

At 3 months, patients receiving the palliative care intervention still had higher quality of life scores and less depression than controls, but there were no significant between-group differences in anxiety, fatigue, or symptom burden.

Caregivers attended 42% of the palliative care sessions. At the 2-week assessment, caregivers in the intervention group were found to have fewer depressive symptoms and improved coping skills, compared with caregivers in the control group.

“Caregivers play a crucial role in supporting patients during the transplant process, and they are substantially impacted as they watch their loved ones struggle with side effects that can be emotionally challenging,” Dr El-Jawahri said.

She and her colleagues noted that additional, larger studies are needed to assess caregiver impacts more completely, to replicate patient results at centers with more diverse patient populations, to assess the inclusion of more complete palliative care teams, to collect cost data, and to adapt the palliative care intervention to assist patients receiving other potentially curative treatment for hematologic or other cancers.

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Preparing for HSCT

Photo by Chad McNeeley

Palliative care can be beneficial for patients undergoing hematopoietic stem cell transplant (HSCT) to treat hematologic malignancies, according to research published in JAMA.

The single-center study suggested that palliative care can improve HSCT recipients’ quality of life, relieve symptoms associated with the procedure, and reduce depression and anxiety.

Researchers observed such benefits during hospitalization for HSCT and a few months later.

In addition, caregivers of patients receiving palliative care experienced less depression and were better at coping with the stress associated with the illness of their loved one.

“Palliative care clinicians are increasingly asked to help care for patients with solid tumors but are rarely consulted for patients with hematologic malignancies, especially those receiving therapy designed to cure their disease,” said study author Areej El-Jawahri, MD, of Massachusette General Hospital in Boston.

“The physical and psychological symptoms associated with HSCT are sometimes regarded as expected and unavoidable, which, combined with the persistent misperception that equates palliative care with end-of-life care, has contributed to a lack of involvement of palliative care clinicians in the care of these patients.”

Intervention

Dr El-Jawahri and her colleagues studied 160 patients who underwent autologous or allogeneic HSCT to treat a variety of hematologic malignancies from August 2014 into January 2016.

Participants were randomized to receive either standard care (n=79) or the palliative care intervention (n=81).

Within 3 days of their admission to the hospital, patients in the intervention group had an initial meeting with a palliative care clinician—a physician or advance practice nurse—who continued to meet with them at least twice a week during their hospitalization.

At the meetings, which could be attended by a family member or friend of the patient, clinicians first focused on establishing a rapport with patients and their caregivers.

Clinicians addressed ways of managing the physical and psychological symptoms patients were experiencing and provided support and strategies for coping with distress. Patients received an average of 8 palliative care visits during their hospitalizations, which lasted on average 20 days.

At the outset of the study and 2 weeks into the process, a time when symptoms tend to be at their worst, patients in both groups and participating caregivers completed questionnaires assessing their mood and quality of life.

Patients also completed questionnaires asking about symptoms of their illness and those associated with the procedure. Patients completed additional assessments 3 months after HSCT as well.

Results

The study’s primary endpoint was change in quality of life from baseline to week 2. Patients receiving the palliative care intervention had significantly better quality of life scores at week 2 than patients in the control group.

Also at the 2-week mark, patients receiving the palliative care intervention reported lower levels of depression, anxiety, and symptoms than the control group, but there was no significant difference between the groups with regard to fatigue.

At 3 months, patients receiving the palliative care intervention still had higher quality of life scores and less depression than controls, but there were no significant between-group differences in anxiety, fatigue, or symptom burden.

Caregivers attended 42% of the palliative care sessions. At the 2-week assessment, caregivers in the intervention group were found to have fewer depressive symptoms and improved coping skills, compared with caregivers in the control group.

“Caregivers play a crucial role in supporting patients during the transplant process, and they are substantially impacted as they watch their loved ones struggle with side effects that can be emotionally challenging,” Dr El-Jawahri said.

She and her colleagues noted that additional, larger studies are needed to assess caregiver impacts more completely, to replicate patient results at centers with more diverse patient populations, to assess the inclusion of more complete palliative care teams, to collect cost data, and to adapt the palliative care intervention to assist patients receiving other potentially curative treatment for hematologic or other cancers.

Preparing for HSCT

Photo by Chad McNeeley

Palliative care can be beneficial for patients undergoing hematopoietic stem cell transplant (HSCT) to treat hematologic malignancies, according to research published in JAMA.

The single-center study suggested that palliative care can improve HSCT recipients’ quality of life, relieve symptoms associated with the procedure, and reduce depression and anxiety.

Researchers observed such benefits during hospitalization for HSCT and a few months later.

In addition, caregivers of patients receiving palliative care experienced less depression and were better at coping with the stress associated with the illness of their loved one.

“Palliative care clinicians are increasingly asked to help care for patients with solid tumors but are rarely consulted for patients with hematologic malignancies, especially those receiving therapy designed to cure their disease,” said study author Areej El-Jawahri, MD, of Massachusette General Hospital in Boston.

“The physical and psychological symptoms associated with HSCT are sometimes regarded as expected and unavoidable, which, combined with the persistent misperception that equates palliative care with end-of-life care, has contributed to a lack of involvement of palliative care clinicians in the care of these patients.”

Intervention

Dr El-Jawahri and her colleagues studied 160 patients who underwent autologous or allogeneic HSCT to treat a variety of hematologic malignancies from August 2014 into January 2016.

Participants were randomized to receive either standard care (n=79) or the palliative care intervention (n=81).

Within 3 days of their admission to the hospital, patients in the intervention group had an initial meeting with a palliative care clinician—a physician or advance practice nurse—who continued to meet with them at least twice a week during their hospitalization.

At the meetings, which could be attended by a family member or friend of the patient, clinicians first focused on establishing a rapport with patients and their caregivers.

Clinicians addressed ways of managing the physical and psychological symptoms patients were experiencing and provided support and strategies for coping with distress. Patients received an average of 8 palliative care visits during their hospitalizations, which lasted on average 20 days.

At the outset of the study and 2 weeks into the process, a time when symptoms tend to be at their worst, patients in both groups and participating caregivers completed questionnaires assessing their mood and quality of life.

Patients also completed questionnaires asking about symptoms of their illness and those associated with the procedure. Patients completed additional assessments 3 months after HSCT as well.

Results

The study’s primary endpoint was change in quality of life from baseline to week 2. Patients receiving the palliative care intervention had significantly better quality of life scores at week 2 than patients in the control group.

Also at the 2-week mark, patients receiving the palliative care intervention reported lower levels of depression, anxiety, and symptoms than the control group, but there was no significant difference between the groups with regard to fatigue.

At 3 months, patients receiving the palliative care intervention still had higher quality of life scores and less depression than controls, but there were no significant between-group differences in anxiety, fatigue, or symptom burden.

Caregivers attended 42% of the palliative care sessions. At the 2-week assessment, caregivers in the intervention group were found to have fewer depressive symptoms and improved coping skills, compared with caregivers in the control group.

“Caregivers play a crucial role in supporting patients during the transplant process, and they are substantially impacted as they watch their loved ones struggle with side effects that can be emotionally challenging,” Dr El-Jawahri said.

She and her colleagues noted that additional, larger studies are needed to assess caregiver impacts more completely, to replicate patient results at centers with more diverse patient populations, to assess the inclusion of more complete palliative care teams, to collect cost data, and to adapt the palliative care intervention to assist patients receiving other potentially curative treatment for hematologic or other cancers.

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EC approves nivolumab for relapsed/refractory cHL

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Nivolumab (Opdivo)

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The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of adults with relapsed or refractory classical Hodgkin lymphoma (cHL) who have already received an autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV).

Nivolumab is the first PD-1 inhibitor approved in the European Economic Area as a treatment for a hematologic malignancy.

The EC previously approved nivolumab to treat advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. In Europe, nivolumab is marketed by Bristol-Myers Squibb.

Trials in cHL

The EC’s approval of nivolumab in cHL is based on an integrated analysis of data from 2 trials—the phase 1 CheckMate -039 trial and the phase 2 CheckMate -205 trial.

In CheckMate -039, researchers evaluated nivolumab in patients with cHL, non-Hodgkin lymphoma, and multiple myeloma. Results from this trial were presented at the 13th International Congress on Malignant Lymphoma in June 2015.

In CheckMate -205, researchers are evaluating nivolumab in 4 cohorts of cHL patients. Cohort A includes patients who previously received auto-HSCT and were BV-naïve at enrollment (n=63). Cohort B includes patients who previously received auto-HSCT followed by BV (n=80).

Cohort C includes patients who previously received BV before and/or after auto-HSCT (n=100). And cohort D, which is currently enrolling, is an evaluation of nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Results from cohort B were presented at the 21st Congress of the European Hematology Association in June 2016. Results from cohort C were presented at the 10th International Symposium on Hodgkin Lymphoma last month.

Integrated analysis

The analysis included cHL patients from CheckMate -205 and -039 who had received auto-HSCT and BV.

In the efficacy population (n=95), the objective response rate was 66%. The percentage of patients with a complete response was 6%. Twenty-three percent of patients had stable disease.

The median time to response was 2.0 months (range, 0.7-11.1), and the median duration of response was 13.1 months (range, 0.0+, 23.1+). At 12 months, the progression-free survival rate was 57%.

The safety of nivolumab in cHL was evaluated in 263 patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Serious adverse events (AEs) occurred in 21% of these patients.

The most common serious AEs (reported in at least 1% of patients) were infusion-related reactions, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis.

The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%).

Twenty-three percent of patients had a dose delay resulting from an AE, and 4.2% of patients discontinued treatment due to AEs.

Forty patients went on to allogeneic HSCT after nivolumab, and 6 of these patients died from complications of the transplant. The 40 patients had a median follow-up from allogeneic HSCT of 2.9 months (range, 0-22).

Because of these deaths, the US Food and Drug Administration asked Bristol-Myers Squibb to study the safety of allogeneic HSCT after nivolumab.

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Nivolumab (Opdivo)

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The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of adults with relapsed or refractory classical Hodgkin lymphoma (cHL) who have already received an autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV).

Nivolumab is the first PD-1 inhibitor approved in the European Economic Area as a treatment for a hematologic malignancy.

The EC previously approved nivolumab to treat advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. In Europe, nivolumab is marketed by Bristol-Myers Squibb.

Trials in cHL

The EC’s approval of nivolumab in cHL is based on an integrated analysis of data from 2 trials—the phase 1 CheckMate -039 trial and the phase 2 CheckMate -205 trial.

In CheckMate -039, researchers evaluated nivolumab in patients with cHL, non-Hodgkin lymphoma, and multiple myeloma. Results from this trial were presented at the 13th International Congress on Malignant Lymphoma in June 2015.

In CheckMate -205, researchers are evaluating nivolumab in 4 cohorts of cHL patients. Cohort A includes patients who previously received auto-HSCT and were BV-naïve at enrollment (n=63). Cohort B includes patients who previously received auto-HSCT followed by BV (n=80).

Cohort C includes patients who previously received BV before and/or after auto-HSCT (n=100). And cohort D, which is currently enrolling, is an evaluation of nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Results from cohort B were presented at the 21st Congress of the European Hematology Association in June 2016. Results from cohort C were presented at the 10th International Symposium on Hodgkin Lymphoma last month.

Integrated analysis

The analysis included cHL patients from CheckMate -205 and -039 who had received auto-HSCT and BV.

In the efficacy population (n=95), the objective response rate was 66%. The percentage of patients with a complete response was 6%. Twenty-three percent of patients had stable disease.

The median time to response was 2.0 months (range, 0.7-11.1), and the median duration of response was 13.1 months (range, 0.0+, 23.1+). At 12 months, the progression-free survival rate was 57%.

The safety of nivolumab in cHL was evaluated in 263 patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Serious adverse events (AEs) occurred in 21% of these patients.

The most common serious AEs (reported in at least 1% of patients) were infusion-related reactions, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis.

The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%).

Twenty-three percent of patients had a dose delay resulting from an AE, and 4.2% of patients discontinued treatment due to AEs.

Forty patients went on to allogeneic HSCT after nivolumab, and 6 of these patients died from complications of the transplant. The 40 patients had a median follow-up from allogeneic HSCT of 2.9 months (range, 0-22).

Because of these deaths, the US Food and Drug Administration asked Bristol-Myers Squibb to study the safety of allogeneic HSCT after nivolumab.

Nivolumab (Opdivo)

Photo from Business Wire

The European Commission (EC) has approved nivolumab (Opdivo) for the treatment of adults with relapsed or refractory classical Hodgkin lymphoma (cHL) who have already received an autologous hematopoietic stem cell transplant (auto-HSCT) and treatment with brentuximab vedotin (BV).

Nivolumab is the first PD-1 inhibitor approved in the European Economic Area as a treatment for a hematologic malignancy.

The EC previously approved nivolumab to treat advanced melanoma, non-small cell lung cancer, and renal cell carcinoma. In Europe, nivolumab is marketed by Bristol-Myers Squibb.

Trials in cHL

The EC’s approval of nivolumab in cHL is based on an integrated analysis of data from 2 trials—the phase 1 CheckMate -039 trial and the phase 2 CheckMate -205 trial.

In CheckMate -039, researchers evaluated nivolumab in patients with cHL, non-Hodgkin lymphoma, and multiple myeloma. Results from this trial were presented at the 13th International Congress on Malignant Lymphoma in June 2015.

In CheckMate -205, researchers are evaluating nivolumab in 4 cohorts of cHL patients. Cohort A includes patients who previously received auto-HSCT and were BV-naïve at enrollment (n=63). Cohort B includes patients who previously received auto-HSCT followed by BV (n=80).

Cohort C includes patients who previously received BV before and/or after auto-HSCT (n=100). And cohort D, which is currently enrolling, is an evaluation of nivolumab in combination with chemotherapy in newly diagnosed, advanced-stage cHL patients who are treatment-naïve (n=50).

Results from cohort B were presented at the 21st Congress of the European Hematology Association in June 2016. Results from cohort C were presented at the 10th International Symposium on Hodgkin Lymphoma last month.

Integrated analysis

The analysis included cHL patients from CheckMate -205 and -039 who had received auto-HSCT and BV.

In the efficacy population (n=95), the objective response rate was 66%. The percentage of patients with a complete response was 6%. Twenty-three percent of patients had stable disease.

The median time to response was 2.0 months (range, 0.7-11.1), and the median duration of response was 13.1 months (range, 0.0+, 23.1+). At 12 months, the progression-free survival rate was 57%.

The safety of nivolumab in cHL was evaluated in 263 patients from CheckMate -205 (n=240) and CheckMate -039 (n=23). Serious adverse events (AEs) occurred in 21% of these patients.

The most common serious AEs (reported in at least 1% of patients) were infusion-related reactions, pneumonia, pleural effusion, pyrexia, rash, and pneumonitis.

The most common AEs (reported in at least 20% of patients) were fatigue (32%), upper respiratory tract infection (28%), pyrexia (24%), diarrhea (23%), and cough (22%).

Twenty-three percent of patients had a dose delay resulting from an AE, and 4.2% of patients discontinued treatment due to AEs.

Forty patients went on to allogeneic HSCT after nivolumab, and 6 of these patients died from complications of the transplant. The 40 patients had a median follow-up from allogeneic HSCT of 2.9 months (range, 0-22).

Because of these deaths, the US Food and Drug Administration asked Bristol-Myers Squibb to study the safety of allogeneic HSCT after nivolumab.

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The very nature of America’s hospitals is changing. At one time in the not too distant past, hospitals could charge “cost-plus,” tacking on a profit above their actual expenses. Hospitals generated most of their revenue from procedures on horizontal patients with long stays in house. Physicians viewed the hospital as a swap meet, with each physician having an autonomous booth and not caring much what went on elsewhere in the facility.

Larry Wellikson, MD, MHM

Today, hospitals are under tough cost pressures, with changes in payments from Medicare, Medicaid, and private insurers. Many hospitals now get more than 50% of their revenue from vertical patients from what was previously considered the outpatient segment of healthcare. Physicians have moved from being revenue providers to being potential competitors or, in the best-case scenario, active partners and teammates with their hospital.

And hospitalists are right in the middle of this changing dynamic.

Because the hospital and the healthcare system are rapidly evolving, it should not surprise anyone that the very nature of hospital medicine is changing rapidly. Some would say too rapidly.

At a strategic planning session I led almost 20 years when the National Association of Inpatient Physicians (NAIP), the precursor to SHM, was just starting out, the prevailing consensus was that hospitalists might take over inpatient services for 50% of family physicians and 25% of internists. Obviously, the penetrance of hospital medicine into almost every hospital in the U.S. and the transfer of the acute-care management of most of the inpatients previously handled by family physicians and internists are just part of the growth in hospital medicine.

Even more innovative and disruptive has been the almost relentless scope creep as hospitalists now actively comanage many surgical and subspecialty patients. As the neurologists have given up most of their acute-care duties, hospitalists are now the de facto inpatient neurologists. Hospitalists also now manage the majority of inpatient senior citizens and have become the inpatient geriatricians without the formal training. In-hospital procedures (e.g., central line, ultrasound, intubation, etc.) previously done by surgeons or critical-care or primary-care physicians now are done by default by hospitalists.

But these expansions of hospitalist scope pale in comparison with the continued broadening of responsibilities that continues to stretch even the most well-trained hospitalists beyond their training or capacity.

Palliative Care

There are not enough trained and certified palliative-care physicians to allocate one of them to each hospital. Yet treatment and survival of cancer and other serious diseases as well as the aging of the population demand that hospitals be prepared to provide the most compassionate and up-to-date palliative approach possible. Palliative care is more than just end-of-life care. It involves hospice as well as pain and symptom management. It is aimed at improvement in quality of life and is used in the presence or absence of curative strategies.

Hospitalists have been thrust into the breach and are being asked more and more to provide palliative-care services. SHM has recognized the gap between the increasing demand on hospitalists and the inadequate training we all receive in residency. That’s why we’re working with palliative-care societies and experts to develop educational and training initiatives to close these gaps.

Critical Care

Our hospitals are becoming increasingly critical care intensive as simpler cases are treated as outpatients and only the very ill come to be admitted to hospital. This has created an increasing demand for more physicians trained in critical care at a time when older intensivists are retiring or going into sleep medicine and younger physicians, who might have chosen a career in critical care, are becoming hospitalists. The shortage of trained critical-care providers is reaching a crisis point in many American hospitals, with hospitalists being asked to be the critical-care extender.

 

 

Over the years, SHM has partnered with the Society of Critical Care Medicine (SCCM) to propose innovative training options (e.g., one-year critical-care fellowship obtained midcareer), but the boards and others in the critical-care establishment have not been supportive. SHM plans to continue to work with open-minded critical-care thought leaders to develop and promote additional training in critical-care skills for hospitalists, who continue to be thrust into this role at their local hospitals.

Post-Acute Care

For many of hospital medicine’s larger national and regional companies, the management of the care in the post-acute-care space of skilled nursing facilities, long-term acute-care facilities, and the like has been the fastest-growing part of their business in the last few years. Skills and process improvement that have helped improve effectiveness and efficiency in our nation’s hospitals are being applied to post-acute-care facilities. Once again, hospitalists are finding themselves being asked to perform at a high level in environments that are new to them.

In this arena, the hospitalist’s ability to impact care is evident in managing transfers and information as well as providing leadership in patient safety. Determining the correct postdischarge disposition is the largest driver of costs in the acute-care and post-acute-care setting. Hospitalists and the hospital medicine organizations are providing key direction.

Preoperative Care

Many may not know that bundled into the anesthesia fee is the funding to cover pre-op assessment and post-op management as well as the intraoperative oversight of anesthesia and vital signs for the surgical patient. In reality, the role of perioperative management has fallen for many years initially to internists and more recently to hospitalists.

Hospitalists have been active in optimizing the patient for surgery and medically clearing the patient. Hospitalists work with surgeons to manage comorbidities; prevent complications, such as infections, DVTs, and pulmonary emboli; and help with pain management and transitions to discharge from the hospital. Hospitalists have worked with surgeons to create efficiencies like reduced length of stay and prevention of readmission as well as to help the patient return to function postoperatively.

SHM’s Perioperative Care Work Group is publishing a set of Perioperative Care Guidelines in the Journal of Hospital Medicine. SHM is actively working with the American College of Surgeons on a teamwork approach to the surgical patient as well as innovative alternative payment models with bundling at the level of the individual surgical patients, which the Centers for Medicare & Medicaid Services is currently evaluating.

Working through a Dilemma

The one thing all these expansions of scope have in common is that there is an unfilled need and hospitalists are being thrust onto the front lines, thrown into the deep water without the benefit of thorough training that should be requisite with the responsibilities. This is not a turf battle where we have stolen someone’s cheese. This is pure and simple where need is trumping training, and if not done properly, the patient may suffer, and hospitalists will bear the uncomfortable feeling of being asked to do more than we should.

SHM and our national hospitalist thought leaders see this dilemma. We are working diligently with other professional medical societies and key specialty educators and thought leaders to create training pathways to support the expansion of the hospitalist’s scope. This is building the boat while you are going down a rapidly moving river. It is not easy stuff. But our patients and our hospitalists demand this, and SHM will step up. Help is on the way.


Larry Wellikson, MD, MHM, is CEO of the Society of Hospital Medicine.

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The Hospitalist - 2016(11)
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The very nature of America’s hospitals is changing. At one time in the not too distant past, hospitals could charge “cost-plus,” tacking on a profit above their actual expenses. Hospitals generated most of their revenue from procedures on horizontal patients with long stays in house. Physicians viewed the hospital as a swap meet, with each physician having an autonomous booth and not caring much what went on elsewhere in the facility.

Larry Wellikson, MD, MHM

Today, hospitals are under tough cost pressures, with changes in payments from Medicare, Medicaid, and private insurers. Many hospitals now get more than 50% of their revenue from vertical patients from what was previously considered the outpatient segment of healthcare. Physicians have moved from being revenue providers to being potential competitors or, in the best-case scenario, active partners and teammates with their hospital.

And hospitalists are right in the middle of this changing dynamic.

Because the hospital and the healthcare system are rapidly evolving, it should not surprise anyone that the very nature of hospital medicine is changing rapidly. Some would say too rapidly.

At a strategic planning session I led almost 20 years when the National Association of Inpatient Physicians (NAIP), the precursor to SHM, was just starting out, the prevailing consensus was that hospitalists might take over inpatient services for 50% of family physicians and 25% of internists. Obviously, the penetrance of hospital medicine into almost every hospital in the U.S. and the transfer of the acute-care management of most of the inpatients previously handled by family physicians and internists are just part of the growth in hospital medicine.

Even more innovative and disruptive has been the almost relentless scope creep as hospitalists now actively comanage many surgical and subspecialty patients. As the neurologists have given up most of their acute-care duties, hospitalists are now the de facto inpatient neurologists. Hospitalists also now manage the majority of inpatient senior citizens and have become the inpatient geriatricians without the formal training. In-hospital procedures (e.g., central line, ultrasound, intubation, etc.) previously done by surgeons or critical-care or primary-care physicians now are done by default by hospitalists.

But these expansions of hospitalist scope pale in comparison with the continued broadening of responsibilities that continues to stretch even the most well-trained hospitalists beyond their training or capacity.

Palliative Care

There are not enough trained and certified palliative-care physicians to allocate one of them to each hospital. Yet treatment and survival of cancer and other serious diseases as well as the aging of the population demand that hospitals be prepared to provide the most compassionate and up-to-date palliative approach possible. Palliative care is more than just end-of-life care. It involves hospice as well as pain and symptom management. It is aimed at improvement in quality of life and is used in the presence or absence of curative strategies.

Hospitalists have been thrust into the breach and are being asked more and more to provide palliative-care services. SHM has recognized the gap between the increasing demand on hospitalists and the inadequate training we all receive in residency. That’s why we’re working with palliative-care societies and experts to develop educational and training initiatives to close these gaps.

Critical Care

Our hospitals are becoming increasingly critical care intensive as simpler cases are treated as outpatients and only the very ill come to be admitted to hospital. This has created an increasing demand for more physicians trained in critical care at a time when older intensivists are retiring or going into sleep medicine and younger physicians, who might have chosen a career in critical care, are becoming hospitalists. The shortage of trained critical-care providers is reaching a crisis point in many American hospitals, with hospitalists being asked to be the critical-care extender.

 

 

Over the years, SHM has partnered with the Society of Critical Care Medicine (SCCM) to propose innovative training options (e.g., one-year critical-care fellowship obtained midcareer), but the boards and others in the critical-care establishment have not been supportive. SHM plans to continue to work with open-minded critical-care thought leaders to develop and promote additional training in critical-care skills for hospitalists, who continue to be thrust into this role at their local hospitals.

Post-Acute Care

For many of hospital medicine’s larger national and regional companies, the management of the care in the post-acute-care space of skilled nursing facilities, long-term acute-care facilities, and the like has been the fastest-growing part of their business in the last few years. Skills and process improvement that have helped improve effectiveness and efficiency in our nation’s hospitals are being applied to post-acute-care facilities. Once again, hospitalists are finding themselves being asked to perform at a high level in environments that are new to them.

In this arena, the hospitalist’s ability to impact care is evident in managing transfers and information as well as providing leadership in patient safety. Determining the correct postdischarge disposition is the largest driver of costs in the acute-care and post-acute-care setting. Hospitalists and the hospital medicine organizations are providing key direction.

Preoperative Care

Many may not know that bundled into the anesthesia fee is the funding to cover pre-op assessment and post-op management as well as the intraoperative oversight of anesthesia and vital signs for the surgical patient. In reality, the role of perioperative management has fallen for many years initially to internists and more recently to hospitalists.

Hospitalists have been active in optimizing the patient for surgery and medically clearing the patient. Hospitalists work with surgeons to manage comorbidities; prevent complications, such as infections, DVTs, and pulmonary emboli; and help with pain management and transitions to discharge from the hospital. Hospitalists have worked with surgeons to create efficiencies like reduced length of stay and prevention of readmission as well as to help the patient return to function postoperatively.

SHM’s Perioperative Care Work Group is publishing a set of Perioperative Care Guidelines in the Journal of Hospital Medicine. SHM is actively working with the American College of Surgeons on a teamwork approach to the surgical patient as well as innovative alternative payment models with bundling at the level of the individual surgical patients, which the Centers for Medicare & Medicaid Services is currently evaluating.

Working through a Dilemma

The one thing all these expansions of scope have in common is that there is an unfilled need and hospitalists are being thrust onto the front lines, thrown into the deep water without the benefit of thorough training that should be requisite with the responsibilities. This is not a turf battle where we have stolen someone’s cheese. This is pure and simple where need is trumping training, and if not done properly, the patient may suffer, and hospitalists will bear the uncomfortable feeling of being asked to do more than we should.

SHM and our national hospitalist thought leaders see this dilemma. We are working diligently with other professional medical societies and key specialty educators and thought leaders to create training pathways to support the expansion of the hospitalist’s scope. This is building the boat while you are going down a rapidly moving river. It is not easy stuff. But our patients and our hospitalists demand this, and SHM will step up. Help is on the way.


Larry Wellikson, MD, MHM, is CEO of the Society of Hospital Medicine.

The very nature of America’s hospitals is changing. At one time in the not too distant past, hospitals could charge “cost-plus,” tacking on a profit above their actual expenses. Hospitals generated most of their revenue from procedures on horizontal patients with long stays in house. Physicians viewed the hospital as a swap meet, with each physician having an autonomous booth and not caring much what went on elsewhere in the facility.

Larry Wellikson, MD, MHM

Today, hospitals are under tough cost pressures, with changes in payments from Medicare, Medicaid, and private insurers. Many hospitals now get more than 50% of their revenue from vertical patients from what was previously considered the outpatient segment of healthcare. Physicians have moved from being revenue providers to being potential competitors or, in the best-case scenario, active partners and teammates with their hospital.

And hospitalists are right in the middle of this changing dynamic.

Because the hospital and the healthcare system are rapidly evolving, it should not surprise anyone that the very nature of hospital medicine is changing rapidly. Some would say too rapidly.

At a strategic planning session I led almost 20 years when the National Association of Inpatient Physicians (NAIP), the precursor to SHM, was just starting out, the prevailing consensus was that hospitalists might take over inpatient services for 50% of family physicians and 25% of internists. Obviously, the penetrance of hospital medicine into almost every hospital in the U.S. and the transfer of the acute-care management of most of the inpatients previously handled by family physicians and internists are just part of the growth in hospital medicine.

Even more innovative and disruptive has been the almost relentless scope creep as hospitalists now actively comanage many surgical and subspecialty patients. As the neurologists have given up most of their acute-care duties, hospitalists are now the de facto inpatient neurologists. Hospitalists also now manage the majority of inpatient senior citizens and have become the inpatient geriatricians without the formal training. In-hospital procedures (e.g., central line, ultrasound, intubation, etc.) previously done by surgeons or critical-care or primary-care physicians now are done by default by hospitalists.

But these expansions of hospitalist scope pale in comparison with the continued broadening of responsibilities that continues to stretch even the most well-trained hospitalists beyond their training or capacity.

Palliative Care

There are not enough trained and certified palliative-care physicians to allocate one of them to each hospital. Yet treatment and survival of cancer and other serious diseases as well as the aging of the population demand that hospitals be prepared to provide the most compassionate and up-to-date palliative approach possible. Palliative care is more than just end-of-life care. It involves hospice as well as pain and symptom management. It is aimed at improvement in quality of life and is used in the presence or absence of curative strategies.

Hospitalists have been thrust into the breach and are being asked more and more to provide palliative-care services. SHM has recognized the gap between the increasing demand on hospitalists and the inadequate training we all receive in residency. That’s why we’re working with palliative-care societies and experts to develop educational and training initiatives to close these gaps.

Critical Care

Our hospitals are becoming increasingly critical care intensive as simpler cases are treated as outpatients and only the very ill come to be admitted to hospital. This has created an increasing demand for more physicians trained in critical care at a time when older intensivists are retiring or going into sleep medicine and younger physicians, who might have chosen a career in critical care, are becoming hospitalists. The shortage of trained critical-care providers is reaching a crisis point in many American hospitals, with hospitalists being asked to be the critical-care extender.

 

 

Over the years, SHM has partnered with the Society of Critical Care Medicine (SCCM) to propose innovative training options (e.g., one-year critical-care fellowship obtained midcareer), but the boards and others in the critical-care establishment have not been supportive. SHM plans to continue to work with open-minded critical-care thought leaders to develop and promote additional training in critical-care skills for hospitalists, who continue to be thrust into this role at their local hospitals.

Post-Acute Care

For many of hospital medicine’s larger national and regional companies, the management of the care in the post-acute-care space of skilled nursing facilities, long-term acute-care facilities, and the like has been the fastest-growing part of their business in the last few years. Skills and process improvement that have helped improve effectiveness and efficiency in our nation’s hospitals are being applied to post-acute-care facilities. Once again, hospitalists are finding themselves being asked to perform at a high level in environments that are new to them.

In this arena, the hospitalist’s ability to impact care is evident in managing transfers and information as well as providing leadership in patient safety. Determining the correct postdischarge disposition is the largest driver of costs in the acute-care and post-acute-care setting. Hospitalists and the hospital medicine organizations are providing key direction.

Preoperative Care

Many may not know that bundled into the anesthesia fee is the funding to cover pre-op assessment and post-op management as well as the intraoperative oversight of anesthesia and vital signs for the surgical patient. In reality, the role of perioperative management has fallen for many years initially to internists and more recently to hospitalists.

Hospitalists have been active in optimizing the patient for surgery and medically clearing the patient. Hospitalists work with surgeons to manage comorbidities; prevent complications, such as infections, DVTs, and pulmonary emboli; and help with pain management and transitions to discharge from the hospital. Hospitalists have worked with surgeons to create efficiencies like reduced length of stay and prevention of readmission as well as to help the patient return to function postoperatively.

SHM’s Perioperative Care Work Group is publishing a set of Perioperative Care Guidelines in the Journal of Hospital Medicine. SHM is actively working with the American College of Surgeons on a teamwork approach to the surgical patient as well as innovative alternative payment models with bundling at the level of the individual surgical patients, which the Centers for Medicare & Medicaid Services is currently evaluating.

Working through a Dilemma

The one thing all these expansions of scope have in common is that there is an unfilled need and hospitalists are being thrust onto the front lines, thrown into the deep water without the benefit of thorough training that should be requisite with the responsibilities. This is not a turf battle where we have stolen someone’s cheese. This is pure and simple where need is trumping training, and if not done properly, the patient may suffer, and hospitalists will bear the uncomfortable feeling of being asked to do more than we should.

SHM and our national hospitalist thought leaders see this dilemma. We are working diligently with other professional medical societies and key specialty educators and thought leaders to create training pathways to support the expansion of the hospitalist’s scope. This is building the boat while you are going down a rapidly moving river. It is not easy stuff. But our patients and our hospitalists demand this, and SHM will step up. Help is on the way.


Larry Wellikson, MD, MHM, is CEO of the Society of Hospital Medicine.

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