Cardiovascular health should be routinely assessed and addressed in LGBTQ adults, the American Heart Association concluded in a new scientific statement.

“Among the most important takeaways from this scientific statement is the need for health care providers in clinical settings to routinely assess sexual orientation and gender identity,” Billy A. Caceres, PhD, RN, chair of the statement writing group, said in an interview.

“This will help health care providers engage LGBTQ patients in discussions about their heart health that account for the unique experiences of this population,” said Dr. Caceres, assistant professor at Columbia University, New York.

The statement was published online Oct. 8 in Circulation.
 

‘Invisible’ population

There are roughly 11 million LGBTQ adults in the United States, yet they are often “invisible in health care settings and cardiovascular research,” Dr. Caceres noted. The AHA scientific statement is the first from a national organization in the United States to comprehensively summarize the evidence on cardiovascular (CV) research in LGBTQ adults.

There is mounting evidence that LGBTQ adults experience worse CV health relative to their cisgender heterosexual peers. Disparities in CV health may be driven by unique psychosocial stressors in the LGBTQ individuals such as family rejection and anxiety of concealment of their sexual orientation or gender identity.

While there is limited information on the CV health of LGBTQ people, the writing group said providers should be aware of the following:

• LGBTQ adults are more likely to use tobacco than their cisgender heterosexual peers.
• Transgender adults may be less physically active than their cisgender counterparts. Gender-affirming care might play a role in promoting physical activity among transgender people.
• Transgender women may be at increased risk for heart disease because of behavioral and clinical factors (such as the use of gender-affirming hormones like estrogen).
• Transgender women and nonbinary persons are more likely to binge drink.
• Lesbian and bisexual women have a higher prevalence of obesity than heterosexual women do.

“We need to better understand how to support LGBTQ adults in optimizing their CV health. To do this, we will need rigorous research that examines potential explanations for the CV health disparities that have been observed in LGBTQ adults,” Dr. Caceres said.

He noted that research is also needed within the LGBTQ population among groups that might be at greater risk for heart disease, including racial- and ethnic-minority and low-income LGBTQ adults.

“Researchers should also design and test evidence-based interventions to promote the heart health of LGBTQ adults. This is an area that is greatly lacking within CV health research,” said Dr. Caceres.
 

Discrimination in health care

Discrimination against LGBTQ adults in health care settings also remains a problem, the authors noted.

The writing group cites data showing that nearly 56% of sexual-minority and 70% of gender-minority adults report having experienced some form of discrimination from clinicians, including the use of harsh/abusive language.

“Perhaps most alarming,” roughly 8% of sexual-minority and 25% of transgender individuals have been denied health care by clinicians, they noted.

“LGBTQ individuals are delaying primary care and preventative visits because there is a great fear of being treated differently. Being treated differently often means receiving inadequate or inferior care because of sexual orientation or gender identity,” Dr. Caceres said in a news release.

The writing group calls for greater emphasis on LGBTQ health issues in the education of all health care providers. Dr. Caceres said it’s “paramount to include content about LGBTQ health in clinical training and licensure requirements in order to address these cardiovascular health disparities.”

Traditionally, there has been very little LGBTQ-related content in health care professional education training. A 2018 online survey of students at 10 medical schools found that approximately 80% of students did not feel competent to provide care for transgender patients.

But that may soon change. In September 2020, the Accreditation Review Commission on Education for the Physician Assistant began requiring LGBTQ curricular content, the writing group notes.

The AHA scientific statement on LGBTQ was developed by the writing group on behalf of the AHA Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, the Council on Lifestyle and Cardiometabolic Health, the Council on Peripheral Vascular Disease, and the Stroke Council.

A version of this article originally appeared on Medscape.com.

Cardiovascular health should be routinely assessed and addressed in LGBTQ adults, the American Heart Association concluded in a new scientific statement.

“Among the most important takeaways from this scientific statement is the need for health care providers in clinical settings to routinely assess sexual orientation and gender identity,” Billy A. Caceres, PhD, RN, chair of the statement writing group, said in an interview.

“This will help health care providers engage LGBTQ patients in discussions about their heart health that account for the unique experiences of this population,” said Dr. Caceres, assistant professor at Columbia University, New York.

The statement was published online Oct. 8 in Circulation.
 

‘Invisible’ population

There are roughly 11 million LGBTQ adults in the United States, yet they are often “invisible in health care settings and cardiovascular research,” Dr. Caceres noted. The AHA scientific statement is the first from a national organization in the United States to comprehensively summarize the evidence on cardiovascular (CV) research in LGBTQ adults.

There is mounting evidence that LGBTQ adults experience worse CV health relative to their cisgender heterosexual peers. Disparities in CV health may be driven by unique psychosocial stressors in the LGBTQ individuals such as family rejection and anxiety of concealment of their sexual orientation or gender identity.

While there is limited information on the CV health of LGBTQ people, the writing group said providers should be aware of the following:

• LGBTQ adults are more likely to use tobacco than their cisgender heterosexual peers.
• Transgender adults may be less physically active than their cisgender counterparts. Gender-affirming care might play a role in promoting physical activity among transgender people.
• Transgender women may be at increased risk for heart disease because of behavioral and clinical factors (such as the use of gender-affirming hormones like estrogen).
• Transgender women and nonbinary persons are more likely to binge drink.
• Lesbian and bisexual women have a higher prevalence of obesity than heterosexual women do.

“We need to better understand how to support LGBTQ adults in optimizing their CV health. To do this, we will need rigorous research that examines potential explanations for the CV health disparities that have been observed in LGBTQ adults,” Dr. Caceres said.

He noted that research is also needed within the LGBTQ population among groups that might be at greater risk for heart disease, including racial- and ethnic-minority and low-income LGBTQ adults.

“Researchers should also design and test evidence-based interventions to promote the heart health of LGBTQ adults. This is an area that is greatly lacking within CV health research,” said Dr. Caceres.
 

Discrimination in health care

Discrimination against LGBTQ adults in health care settings also remains a problem, the authors noted.

The writing group cites data showing that nearly 56% of sexual-minority and 70% of gender-minority adults report having experienced some form of discrimination from clinicians, including the use of harsh/abusive language.

“Perhaps most alarming,” roughly 8% of sexual-minority and 25% of transgender individuals have been denied health care by clinicians, they noted.

“LGBTQ individuals are delaying primary care and preventative visits because there is a great fear of being treated differently. Being treated differently often means receiving inadequate or inferior care because of sexual orientation or gender identity,” Dr. Caceres said in a news release.

The writing group calls for greater emphasis on LGBTQ health issues in the education of all health care providers. Dr. Caceres said it’s “paramount to include content about LGBTQ health in clinical training and licensure requirements in order to address these cardiovascular health disparities.”

Traditionally, there has been very little LGBTQ-related content in health care professional education training. A 2018 online survey of students at 10 medical schools found that approximately 80% of students did not feel competent to provide care for transgender patients.

But that may soon change. In September 2020, the Accreditation Review Commission on Education for the Physician Assistant began requiring LGBTQ curricular content, the writing group notes.

The AHA scientific statement on LGBTQ was developed by the writing group on behalf of the AHA Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, the Council on Lifestyle and Cardiometabolic Health, the Council on Peripheral Vascular Disease, and the Stroke Council.

A version of this article originally appeared on Medscape.com.

Cardiovascular health should be routinely assessed and addressed in LGBTQ adults, the American Heart Association concluded in a new scientific statement.

“Among the most important takeaways from this scientific statement is the need for health care providers in clinical settings to routinely assess sexual orientation and gender identity,” Billy A. Caceres, PhD, RN, chair of the statement writing group, said in an interview.

“This will help health care providers engage LGBTQ patients in discussions about their heart health that account for the unique experiences of this population,” said Dr. Caceres, assistant professor at Columbia University, New York.

The statement was published online Oct. 8 in Circulation.
 

‘Invisible’ population

There are roughly 11 million LGBTQ adults in the United States, yet they are often “invisible in health care settings and cardiovascular research,” Dr. Caceres noted. The AHA scientific statement is the first from a national organization in the United States to comprehensively summarize the evidence on cardiovascular (CV) research in LGBTQ adults.

There is mounting evidence that LGBTQ adults experience worse CV health relative to their cisgender heterosexual peers. Disparities in CV health may be driven by unique psychosocial stressors in the LGBTQ individuals such as family rejection and anxiety of concealment of their sexual orientation or gender identity.

While there is limited information on the CV health of LGBTQ people, the writing group said providers should be aware of the following:

• LGBTQ adults are more likely to use tobacco than their cisgender heterosexual peers.
• Transgender adults may be less physically active than their cisgender counterparts. Gender-affirming care might play a role in promoting physical activity among transgender people.
• Transgender women may be at increased risk for heart disease because of behavioral and clinical factors (such as the use of gender-affirming hormones like estrogen).
• Transgender women and nonbinary persons are more likely to binge drink.
• Lesbian and bisexual women have a higher prevalence of obesity than heterosexual women do.

“We need to better understand how to support LGBTQ adults in optimizing their CV health. To do this, we will need rigorous research that examines potential explanations for the CV health disparities that have been observed in LGBTQ adults,” Dr. Caceres said.

He noted that research is also needed within the LGBTQ population among groups that might be at greater risk for heart disease, including racial- and ethnic-minority and low-income LGBTQ adults.

“Researchers should also design and test evidence-based interventions to promote the heart health of LGBTQ adults. This is an area that is greatly lacking within CV health research,” said Dr. Caceres.
 

Discrimination in health care

Discrimination against LGBTQ adults in health care settings also remains a problem, the authors noted.

The writing group cites data showing that nearly 56% of sexual-minority and 70% of gender-minority adults report having experienced some form of discrimination from clinicians, including the use of harsh/abusive language.

“Perhaps most alarming,” roughly 8% of sexual-minority and 25% of transgender individuals have been denied health care by clinicians, they noted.

“LGBTQ individuals are delaying primary care and preventative visits because there is a great fear of being treated differently. Being treated differently often means receiving inadequate or inferior care because of sexual orientation or gender identity,” Dr. Caceres said in a news release.

The writing group calls for greater emphasis on LGBTQ health issues in the education of all health care providers. Dr. Caceres said it’s “paramount to include content about LGBTQ health in clinical training and licensure requirements in order to address these cardiovascular health disparities.”

Traditionally, there has been very little LGBTQ-related content in health care professional education training. A 2018 online survey of students at 10 medical schools found that approximately 80% of students did not feel competent to provide care for transgender patients.

But that may soon change. In September 2020, the Accreditation Review Commission on Education for the Physician Assistant began requiring LGBTQ curricular content, the writing group notes.

The AHA scientific statement on LGBTQ was developed by the writing group on behalf of the AHA Council on Cardiovascular and Stroke Nursing, the Council on Hypertension, the Council on Lifestyle and Cardiometabolic Health, the Council on Peripheral Vascular Disease, and the Stroke Council.

A version of this article originally appeared on Medscape.com.

One of the hottest topics now in psychiatry is the possibility of repurposing long-established cardiovascular medications for treatment of patients with serious mental illness, Livia De Picker, MD, PhD, said at the virtual congress of the European College of Neuropsychopharmacology.

Courtesy Dr. Livia De Picker

The appeal is multifold. A huge unmet need exists in psychiatry for new and better treatments with novel mechanisms of action. Many guideline-recommended cardiovascular medications have a long track record, including a well-established safety profile with no surprises, and are available in generic versions. They can be developed for a new indication at minimal cost, noted Dr. De Picker, a psychiatrist at the University of Antwerp (Belgium).

The idea of psychiatric repurposing of drugs originally developed for nonpsychiatric indications is nothing new, she added. Examples include lithium for gout, valproate for epilepsy, and ketamine for anesthesiology.

One hitch in efforts to repurpose cardiovascular medications is that, when psychiatric patients have been included in randomized trials of the drugs’ cardiovascular effects, the psychiatric outcomes often went untallied.

Indeed, the only high-quality randomized trial evidence of psychiatric benefits for any class of cardiovascular medications is for statins, where a modest-sized meta-analysis of six placebo-controlled trials in 339 patients with schizophrenia showed the lipid-lowering agents had benefit for both positive and negative symptoms (Psychiatry Res. 2018 Apr;262:84-93). But that’s not a body of data of sufficient size to be definitive, in Dr. De Picker’s view.

Much of the recent enthusiasm for exploring the potential of cardiovascular drugs for psychiatric conditions comes from hypothesis-generating big data analyses drawn from Scandinavian national patient registries. Danish investigators scrutinized all 1.6 million Danes exposed to six classes of drugs of interest during 2005-2015 and determined that those on long-term statins, low-dose aspirin, ACE inhibitors, angiotensin receptor blockers, or allopurinol were associated with a decreased rate of new-onset depression, while high-dose aspirin and non-aspirin NSAIDs were associated with an increased rate, compared with a 30% random sample of the country’s population (Acta Psychiatr Scand. 2019 Jan;1391:68-77).

Similarly, the Danish group found that continued use of statins, angiotensin agents, or low-dose aspirin was associated with a decreased rate of new-onset bipolar disorder, while high-dose aspirin and other NSAIDs were linked to increased risk (Bipolar Disord. 2019 Aug;[15]:410-8). What these agents have in common, the investigators observed, is that they act on inflammation and potentially on the stress response system.

Meanwhile, Swedish investigators examined the course of 142,691 Swedes with a diagnosis of bipolar disorder, schizophrenia, or nonaffective psychosis during 2005-2016. They determined that, during periods when those individuals were on a statin, calcium channel blocker, or metformin, they had reduced rates of psychiatric hospitalization and self-harm (JAMA Psychiatry. 2019 Apr 1;76[4]:382-90).

Scottish researchers analyzed the health records of 144,066 patients placed on monotherapy for hypertension and determined that the lowest risk for hospitalization for a mood disorder during follow-up was in those prescribed an ACE inhibitor or angiotensin receptor blocker. The risk was significantly higher in patients on a beta-blocker or calcium channel blocker, and intermediate in those on a thiazide diuretic (Hypertension. 2016 Nov;68[5:1132-8).

“Obviously, this is all at a very macro scale and we have no idea whatsoever what this means for individual patients, number needed to treat, or which type of patients would benefit, but it does provide us with some guidance for future research,” according to Dr. De Picker.

In the meantime, while physicians await definitive evidence of any impact of cardiovascular drugs might have on psychiatric outcomes, abundant data exist underscoring what she called “shockingly high levels” of inadequate management of cardiovascular risk factors in patients with serious mental illness. That problem needs to be addressed, and Dr. De Picker offered her personal recommendations for doing so in a manner consistent with the evidence to date suggestive of potential mental health benefits of some cardiovascular medications.

She advised that, for treatment of hypertension in patients with bipolar disorder or major depression, an ACE inhibitor or angiotensin-converting enzyme inhibitor is preferred as first-line. There is some evidence to suggest lipophilic beta-blockers, which cross the blood-brain barrier, improve anxiety symptoms and panic attacks, and prevent memory consolidation in patients with posttraumatic stress disorder. But the Scottish data suggest that they may worsen mood disorders.

“I would be careful in using beta-blockers as first-line treatment for hypertension. They’re not in the guidelines for anxiety disorders. British guidelines recommend them to prevent memory consolidation in PTSD, but do not use them as first-line in patients with major depressive disorder or bipolar disorder,” she said. As for calcium channel blockers, the jury is still out, with mixed and inconsistent evidence to date as to the impact of this drug class on mental illness outcomes.

She recommended a very low threshold for prescribing statin therapy in patients with serious mental illness in light of the superb risk/benefit ratio for this drug class. She makes sure a statin is onboard in her patients with schizophrenia, major depressive disorder, or bipolar disorder who are over age 60. In her younger patients, she turns for guidance to an online calculator of an individual’s 10-year risk of a first acute MI or stroke.

Metformin has been shown to be beneficial for addressing the weight gain and other adverse metabolic effects caused by antipsychotic agents, and there is some preliminary evidence of improved psychiatric outcomes in patients with serious mental illness.

Christian Otte, MD, who also spoke at the session, noted that not only do emerging data point to the possibility that cardiovascular drugs might have benefit in terms of psychiatric outcomes, there is also some evidence, albeit mixed, that the converse is true: that is, psychiatric drugs may have cardiovascular benefits. He pointed to a South Korean trial in which 300 patients with a recent acute coronary syndrome and major depression were randomized to 24 weeks of escitalopram or placebo. At median 8.1 years of follow-up, the group that received the SSRI had a 31% relative risk reduction in the primary composite endpoint of all-cause mortality, acute MI, or percutaneous coronary intervention (JAMA. 2018 Jul 24; 320[4]:350–7).

“Potentially independent of their antidepressant effects, some SSRIs’ antiplatelet effects could be beneficial for patients with coronary heart disease, although the jury is still open regarding this question, with evidence in both directions,” said Dr. Otte, professor of psychiatry at Charite University Medical Center in Berlin.

Dr. De Picker offered an example as well: Finnish psychiatrists recently reported that cardiovascular mortality was reduced by an adjusted 38% during periods when 62,250 Finnish schizophrenia patients were on antipsychotic agents, compared with periods of nonuse of the drugs in a national study with a median 14.1 years of follow-up (World Psychiatry. 2020 Feb;19[1]:61-8).

“What they discovered – and this is quite contrary to what we are used to hearing about antipsychotic medication and cardiovascular risk – is that while the number of cardiovascular hospitalizations was not different in periods with or without antipsychotic use, the cardiovascular mortality was quite strikingly reduced when patients were on antipsychotic medication,” she said.

Asked by an audience member whether she personally prescribes metformin, Dr. De Picker replied: “Well, yes, why not? One of the very nice things about metformin is that it is actually a very safe drug, even in the hands of nonspecialists.

“I understand that maybe psychiatrists may not feel very comfortable in starting patients on metformin due to a lack of experience. But there are really only two things you need to take into account. About one-quarter of patients will experience GI side effects – nausea, vomiting, abdominal discomfort – and this can be reduced by gradually uptitrating the dose, dosing at mealtime, and using an extended-release formulation. And the second thing is that metformin can impair vitamin B₁₂ absorption, so I think, especially in psychiatric patients, it would be good to do an annual measurement of vitamin B₁₂ level and, if necessary, administer intramuscular supplements,” Dr. De Picker said.

She reported having no financial conflicts regarding her presentation.

[email protected]

SOURCE: De Picker L. ECNP 2020. Session EDU.05.

One of the hottest topics now in psychiatry is the possibility of repurposing long-established cardiovascular medications for treatment of patients with serious mental illness, Livia De Picker, MD, PhD, said at the virtual congress of the European College of Neuropsychopharmacology.

Courtesy Dr. Livia De Picker

The appeal is multifold. A huge unmet need exists in psychiatry for new and better treatments with novel mechanisms of action. Many guideline-recommended cardiovascular medications have a long track record, including a well-established safety profile with no surprises, and are available in generic versions. They can be developed for a new indication at minimal cost, noted Dr. De Picker, a psychiatrist at the University of Antwerp (Belgium).

The idea of psychiatric repurposing of drugs originally developed for nonpsychiatric indications is nothing new, she added. Examples include lithium for gout, valproate for epilepsy, and ketamine for anesthesiology.

One hitch in efforts to repurpose cardiovascular medications is that, when psychiatric patients have been included in randomized trials of the drugs’ cardiovascular effects, the psychiatric outcomes often went untallied.

Indeed, the only high-quality randomized trial evidence of psychiatric benefits for any class of cardiovascular medications is for statins, where a modest-sized meta-analysis of six placebo-controlled trials in 339 patients with schizophrenia showed the lipid-lowering agents had benefit for both positive and negative symptoms (Psychiatry Res. 2018 Apr;262:84-93). But that’s not a body of data of sufficient size to be definitive, in Dr. De Picker’s view.

Much of the recent enthusiasm for exploring the potential of cardiovascular drugs for psychiatric conditions comes from hypothesis-generating big data analyses drawn from Scandinavian national patient registries. Danish investigators scrutinized all 1.6 million Danes exposed to six classes of drugs of interest during 2005-2015 and determined that those on long-term statins, low-dose aspirin, ACE inhibitors, angiotensin receptor blockers, or allopurinol were associated with a decreased rate of new-onset depression, while high-dose aspirin and non-aspirin NSAIDs were associated with an increased rate, compared with a 30% random sample of the country’s population (Acta Psychiatr Scand. 2019 Jan;1391:68-77).

Similarly, the Danish group found that continued use of statins, angiotensin agents, or low-dose aspirin was associated with a decreased rate of new-onset bipolar disorder, while high-dose aspirin and other NSAIDs were linked to increased risk (Bipolar Disord. 2019 Aug;[15]:410-8). What these agents have in common, the investigators observed, is that they act on inflammation and potentially on the stress response system.

Meanwhile, Swedish investigators examined the course of 142,691 Swedes with a diagnosis of bipolar disorder, schizophrenia, or nonaffective psychosis during 2005-2016. They determined that, during periods when those individuals were on a statin, calcium channel blocker, or metformin, they had reduced rates of psychiatric hospitalization and self-harm (JAMA Psychiatry. 2019 Apr 1;76[4]:382-90).

Scottish researchers analyzed the health records of 144,066 patients placed on monotherapy for hypertension and determined that the lowest risk for hospitalization for a mood disorder during follow-up was in those prescribed an ACE inhibitor or angiotensin receptor blocker. The risk was significantly higher in patients on a beta-blocker or calcium channel blocker, and intermediate in those on a thiazide diuretic (Hypertension. 2016 Nov;68[5:1132-8).

“Obviously, this is all at a very macro scale and we have no idea whatsoever what this means for individual patients, number needed to treat, or which type of patients would benefit, but it does provide us with some guidance for future research,” according to Dr. De Picker.

In the meantime, while physicians await definitive evidence of any impact of cardiovascular drugs might have on psychiatric outcomes, abundant data exist underscoring what she called “shockingly high levels” of inadequate management of cardiovascular risk factors in patients with serious mental illness. That problem needs to be addressed, and Dr. De Picker offered her personal recommendations for doing so in a manner consistent with the evidence to date suggestive of potential mental health benefits of some cardiovascular medications.

She advised that, for treatment of hypertension in patients with bipolar disorder or major depression, an ACE inhibitor or angiotensin-converting enzyme inhibitor is preferred as first-line. There is some evidence to suggest lipophilic beta-blockers, which cross the blood-brain barrier, improve anxiety symptoms and panic attacks, and prevent memory consolidation in patients with posttraumatic stress disorder. But the Scottish data suggest that they may worsen mood disorders.

“I would be careful in using beta-blockers as first-line treatment for hypertension. They’re not in the guidelines for anxiety disorders. British guidelines recommend them to prevent memory consolidation in PTSD, but do not use them as first-line in patients with major depressive disorder or bipolar disorder,” she said. As for calcium channel blockers, the jury is still out, with mixed and inconsistent evidence to date as to the impact of this drug class on mental illness outcomes.

She recommended a very low threshold for prescribing statin therapy in patients with serious mental illness in light of the superb risk/benefit ratio for this drug class. She makes sure a statin is onboard in her patients with schizophrenia, major depressive disorder, or bipolar disorder who are over age 60. In her younger patients, she turns for guidance to an online calculator of an individual’s 10-year risk of a first acute MI or stroke.

Metformin has been shown to be beneficial for addressing the weight gain and other adverse metabolic effects caused by antipsychotic agents, and there is some preliminary evidence of improved psychiatric outcomes in patients with serious mental illness.

Christian Otte, MD, who also spoke at the session, noted that not only do emerging data point to the possibility that cardiovascular drugs might have benefit in terms of psychiatric outcomes, there is also some evidence, albeit mixed, that the converse is true: that is, psychiatric drugs may have cardiovascular benefits. He pointed to a South Korean trial in which 300 patients with a recent acute coronary syndrome and major depression were randomized to 24 weeks of escitalopram or placebo. At median 8.1 years of follow-up, the group that received the SSRI had a 31% relative risk reduction in the primary composite endpoint of all-cause mortality, acute MI, or percutaneous coronary intervention (JAMA. 2018 Jul 24; 320[4]:350–7).

“Potentially independent of their antidepressant effects, some SSRIs’ antiplatelet effects could be beneficial for patients with coronary heart disease, although the jury is still open regarding this question, with evidence in both directions,” said Dr. Otte, professor of psychiatry at Charite University Medical Center in Berlin.

Dr. De Picker offered an example as well: Finnish psychiatrists recently reported that cardiovascular mortality was reduced by an adjusted 38% during periods when 62,250 Finnish schizophrenia patients were on antipsychotic agents, compared with periods of nonuse of the drugs in a national study with a median 14.1 years of follow-up (World Psychiatry. 2020 Feb;19[1]:61-8).

“What they discovered – and this is quite contrary to what we are used to hearing about antipsychotic medication and cardiovascular risk – is that while the number of cardiovascular hospitalizations was not different in periods with or without antipsychotic use, the cardiovascular mortality was quite strikingly reduced when patients were on antipsychotic medication,” she said.

Asked by an audience member whether she personally prescribes metformin, Dr. De Picker replied: “Well, yes, why not? One of the very nice things about metformin is that it is actually a very safe drug, even in the hands of nonspecialists.

“I understand that maybe psychiatrists may not feel very comfortable in starting patients on metformin due to a lack of experience. But there are really only two things you need to take into account. About one-quarter of patients will experience GI side effects – nausea, vomiting, abdominal discomfort – and this can be reduced by gradually uptitrating the dose, dosing at mealtime, and using an extended-release formulation. And the second thing is that metformin can impair vitamin B₁₂ absorption, so I think, especially in psychiatric patients, it would be good to do an annual measurement of vitamin B₁₂ level and, if necessary, administer intramuscular supplements,” Dr. De Picker said.

She reported having no financial conflicts regarding her presentation.

[email protected]

SOURCE: De Picker L. ECNP 2020. Session EDU.05.

One of the hottest topics now in psychiatry is the possibility of repurposing long-established cardiovascular medications for treatment of patients with serious mental illness, Livia De Picker, MD, PhD, said at the virtual congress of the European College of Neuropsychopharmacology.

Courtesy Dr. Livia De Picker

The appeal is multifold. A huge unmet need exists in psychiatry for new and better treatments with novel mechanisms of action. Many guideline-recommended cardiovascular medications have a long track record, including a well-established safety profile with no surprises, and are available in generic versions. They can be developed for a new indication at minimal cost, noted Dr. De Picker, a psychiatrist at the University of Antwerp (Belgium).

The idea of psychiatric repurposing of drugs originally developed for nonpsychiatric indications is nothing new, she added. Examples include lithium for gout, valproate for epilepsy, and ketamine for anesthesiology.

One hitch in efforts to repurpose cardiovascular medications is that, when psychiatric patients have been included in randomized trials of the drugs’ cardiovascular effects, the psychiatric outcomes often went untallied.

Indeed, the only high-quality randomized trial evidence of psychiatric benefits for any class of cardiovascular medications is for statins, where a modest-sized meta-analysis of six placebo-controlled trials in 339 patients with schizophrenia showed the lipid-lowering agents had benefit for both positive and negative symptoms (Psychiatry Res. 2018 Apr;262:84-93). But that’s not a body of data of sufficient size to be definitive, in Dr. De Picker’s view.

Much of the recent enthusiasm for exploring the potential of cardiovascular drugs for psychiatric conditions comes from hypothesis-generating big data analyses drawn from Scandinavian national patient registries. Danish investigators scrutinized all 1.6 million Danes exposed to six classes of drugs of interest during 2005-2015 and determined that those on long-term statins, low-dose aspirin, ACE inhibitors, angiotensin receptor blockers, or allopurinol were associated with a decreased rate of new-onset depression, while high-dose aspirin and non-aspirin NSAIDs were associated with an increased rate, compared with a 30% random sample of the country’s population (Acta Psychiatr Scand. 2019 Jan;1391:68-77).

Similarly, the Danish group found that continued use of statins, angiotensin agents, or low-dose aspirin was associated with a decreased rate of new-onset bipolar disorder, while high-dose aspirin and other NSAIDs were linked to increased risk (Bipolar Disord. 2019 Aug;[15]:410-8). What these agents have in common, the investigators observed, is that they act on inflammation and potentially on the stress response system.

Meanwhile, Swedish investigators examined the course of 142,691 Swedes with a diagnosis of bipolar disorder, schizophrenia, or nonaffective psychosis during 2005-2016. They determined that, during periods when those individuals were on a statin, calcium channel blocker, or metformin, they had reduced rates of psychiatric hospitalization and self-harm (JAMA Psychiatry. 2019 Apr 1;76[4]:382-90).

Scottish researchers analyzed the health records of 144,066 patients placed on monotherapy for hypertension and determined that the lowest risk for hospitalization for a mood disorder during follow-up was in those prescribed an ACE inhibitor or angiotensin receptor blocker. The risk was significantly higher in patients on a beta-blocker or calcium channel blocker, and intermediate in those on a thiazide diuretic (Hypertension. 2016 Nov;68[5:1132-8).

“Obviously, this is all at a very macro scale and we have no idea whatsoever what this means for individual patients, number needed to treat, or which type of patients would benefit, but it does provide us with some guidance for future research,” according to Dr. De Picker.

In the meantime, while physicians await definitive evidence of any impact of cardiovascular drugs might have on psychiatric outcomes, abundant data exist underscoring what she called “shockingly high levels” of inadequate management of cardiovascular risk factors in patients with serious mental illness. That problem needs to be addressed, and Dr. De Picker offered her personal recommendations for doing so in a manner consistent with the evidence to date suggestive of potential mental health benefits of some cardiovascular medications.

She advised that, for treatment of hypertension in patients with bipolar disorder or major depression, an ACE inhibitor or angiotensin-converting enzyme inhibitor is preferred as first-line. There is some evidence to suggest lipophilic beta-blockers, which cross the blood-brain barrier, improve anxiety symptoms and panic attacks, and prevent memory consolidation in patients with posttraumatic stress disorder. But the Scottish data suggest that they may worsen mood disorders.

“I would be careful in using beta-blockers as first-line treatment for hypertension. They’re not in the guidelines for anxiety disorders. British guidelines recommend them to prevent memory consolidation in PTSD, but do not use them as first-line in patients with major depressive disorder or bipolar disorder,” she said. As for calcium channel blockers, the jury is still out, with mixed and inconsistent evidence to date as to the impact of this drug class on mental illness outcomes.

She recommended a very low threshold for prescribing statin therapy in patients with serious mental illness in light of the superb risk/benefit ratio for this drug class. She makes sure a statin is onboard in her patients with schizophrenia, major depressive disorder, or bipolar disorder who are over age 60. In her younger patients, she turns for guidance to an online calculator of an individual’s 10-year risk of a first acute MI or stroke.

Metformin has been shown to be beneficial for addressing the weight gain and other adverse metabolic effects caused by antipsychotic agents, and there is some preliminary evidence of improved psychiatric outcomes in patients with serious mental illness.

Christian Otte, MD, who also spoke at the session, noted that not only do emerging data point to the possibility that cardiovascular drugs might have benefit in terms of psychiatric outcomes, there is also some evidence, albeit mixed, that the converse is true: that is, psychiatric drugs may have cardiovascular benefits. He pointed to a South Korean trial in which 300 patients with a recent acute coronary syndrome and major depression were randomized to 24 weeks of escitalopram or placebo. At median 8.1 years of follow-up, the group that received the SSRI had a 31% relative risk reduction in the primary composite endpoint of all-cause mortality, acute MI, or percutaneous coronary intervention (JAMA. 2018 Jul 24; 320[4]:350–7).

“Potentially independent of their antidepressant effects, some SSRIs’ antiplatelet effects could be beneficial for patients with coronary heart disease, although the jury is still open regarding this question, with evidence in both directions,” said Dr. Otte, professor of psychiatry at Charite University Medical Center in Berlin.

Dr. De Picker offered an example as well: Finnish psychiatrists recently reported that cardiovascular mortality was reduced by an adjusted 38% during periods when 62,250 Finnish schizophrenia patients were on antipsychotic agents, compared with periods of nonuse of the drugs in a national study with a median 14.1 years of follow-up (World Psychiatry. 2020 Feb;19[1]:61-8).

“What they discovered – and this is quite contrary to what we are used to hearing about antipsychotic medication and cardiovascular risk – is that while the number of cardiovascular hospitalizations was not different in periods with or without antipsychotic use, the cardiovascular mortality was quite strikingly reduced when patients were on antipsychotic medication,” she said.

Asked by an audience member whether she personally prescribes metformin, Dr. De Picker replied: “Well, yes, why not? One of the very nice things about metformin is that it is actually a very safe drug, even in the hands of nonspecialists.

“I understand that maybe psychiatrists may not feel very comfortable in starting patients on metformin due to a lack of experience. But there are really only two things you need to take into account. About one-quarter of patients will experience GI side effects – nausea, vomiting, abdominal discomfort – and this can be reduced by gradually uptitrating the dose, dosing at mealtime, and using an extended-release formulation. And the second thing is that metformin can impair vitamin B₁₂ absorption, so I think, especially in psychiatric patients, it would be good to do an annual measurement of vitamin B₁₂ level and, if necessary, administer intramuscular supplements,” Dr. De Picker said.

She reported having no financial conflicts regarding her presentation.

[email protected]

SOURCE: De Picker L. ECNP 2020. Session EDU.05.

The absolute benefit of adding low-dose rivaroxaban to low-dose aspirin following revascularization for symptomatic lower-extremity peripheral artery disease (PAD) is significantly greater in patients with comorbid coronary artery disease (CAD), according to a new secondary analysis of the VOYAGER PAD trial.

“These findings suggest heterogeneity of prognostic risk for ischemic events in lower-extremity PAD patients, and may support shared decision-making with these patients,” William R. Hiatt, MD, observed in presenting the study results at the virtual annual congress of the European Society of Cardiology.

VOYAGER PAD was a 3-year, 34-country clinical trial in which 6,564 patients with symptomatic PAD who had recently undergone lower-limb revascularization were randomized in double-blind fashion to rivaroxaban (Xarelto) at 2.5 mg twice daily or placebo on top of background standard therapy with low-dose aspirin.

Among the 2,067 participants with baseline comorbid CAD, the primary outcome – a composite comprised of cardiovascular death, acute MI, ischemic stroke, acute limb ischemia, and major amputation – occurred in 18.9% of the rivaroxaban group at 3 years and 24.3% on placebo, for a highly significant 22% relative risk reduction.

In contrast, in the 4,497 patients with PAD only, the primary outcome occurred in 16.1% of those on rivaroxaban and 17.9% of controls, an 11% relative risk reduction which failed to reach statistical significance. The absolute risk reduction achieved with rivaroxaban was 5.4% in patients with PAD plus CAD versus 1.8% in those with PAD alone. Thus, the significant clinical benefit with rivaroxaban plus aspirin previously reported in the overall study population, with a number needed to treat for 3 years of 39 in order to prevent one primary outcome event, was largely driven by the superior outcomes in the dual-diagnosis subgroup, reported Dr. Hiatt, professor of medicine at the University of Colorado at Denver, Aurora.

“A strategy of rivaroxaban at 2.5 mg twice daily plus low-dose aspirin versus low-dose aspirin alone reduces ischemic events of the limb, brain, and heart, but also increases bleeding, with an overall net benefit,” the cardiologist said. “In particular, the benefits of this strategy for MI and ischemic stroke are robust, especially in patients with PAD and CAD.”

Indeed, the MI rate at 3 years in the dual diagnosis subgroup was 7.3% with rivaroxaban and 8.8% with placebo, for a 23% relative risk reduction, compared with rates of 3.3% and 3.7%, respectively, in patients with PAD only. Similarly, ischemic stroke occurred in 2.9% of patients with PAD and CAD in the rivaroxaban group, compared with 3.9% with placebo, whereas the rate in the PAD only group was identical at 2.6% regardless of whether patients were on rivaroxaban or placebo.

In patients without CAD, the clinical benefit of rivaroxaban was driven by reductions in severe limb events. Their rate of acute limb ischemia was 5.2% with rivaroxaban, compared with 8.3% with placebo, for a 37% relative risk reduction. In contrast, the reduction in acute limb ischemia with rivaroxaban in patients with PAD and CAD wasn’t significantly different from placebo.

Thrombolysis in Myocardial Infarction major bleeding occurred in 2.4% of patients with PAD and CAD on rivaroxaban, compared with 1.1% on placebo, and in 1.7% and 1.5% of patients with PAD alone. Of note, rates of ischemic stroke or fatal hemorrhage were low and similar at less than 1% in all four groups, Dr. Hiatt noted.

VOYAGER PAD was sponsored by Bayer and Janssen. Dr. Hiatt reported receiving research grant support from those two companies as well as Amgen.

[email protected]

The absolute benefit of adding low-dose rivaroxaban to low-dose aspirin following revascularization for symptomatic lower-extremity peripheral artery disease (PAD) is significantly greater in patients with comorbid coronary artery disease (CAD), according to a new secondary analysis of the VOYAGER PAD trial.

“These findings suggest heterogeneity of prognostic risk for ischemic events in lower-extremity PAD patients, and may support shared decision-making with these patients,” William R. Hiatt, MD, observed in presenting the study results at the virtual annual congress of the European Society of Cardiology.

VOYAGER PAD was a 3-year, 34-country clinical trial in which 6,564 patients with symptomatic PAD who had recently undergone lower-limb revascularization were randomized in double-blind fashion to rivaroxaban (Xarelto) at 2.5 mg twice daily or placebo on top of background standard therapy with low-dose aspirin.

Among the 2,067 participants with baseline comorbid CAD, the primary outcome – a composite comprised of cardiovascular death, acute MI, ischemic stroke, acute limb ischemia, and major amputation – occurred in 18.9% of the rivaroxaban group at 3 years and 24.3% on placebo, for a highly significant 22% relative risk reduction.

In contrast, in the 4,497 patients with PAD only, the primary outcome occurred in 16.1% of those on rivaroxaban and 17.9% of controls, an 11% relative risk reduction which failed to reach statistical significance. The absolute risk reduction achieved with rivaroxaban was 5.4% in patients with PAD plus CAD versus 1.8% in those with PAD alone. Thus, the significant clinical benefit with rivaroxaban plus aspirin previously reported in the overall study population, with a number needed to treat for 3 years of 39 in order to prevent one primary outcome event, was largely driven by the superior outcomes in the dual-diagnosis subgroup, reported Dr. Hiatt, professor of medicine at the University of Colorado at Denver, Aurora.

“A strategy of rivaroxaban at 2.5 mg twice daily plus low-dose aspirin versus low-dose aspirin alone reduces ischemic events of the limb, brain, and heart, but also increases bleeding, with an overall net benefit,” the cardiologist said. “In particular, the benefits of this strategy for MI and ischemic stroke are robust, especially in patients with PAD and CAD.”

Indeed, the MI rate at 3 years in the dual diagnosis subgroup was 7.3% with rivaroxaban and 8.8% with placebo, for a 23% relative risk reduction, compared with rates of 3.3% and 3.7%, respectively, in patients with PAD only. Similarly, ischemic stroke occurred in 2.9% of patients with PAD and CAD in the rivaroxaban group, compared with 3.9% with placebo, whereas the rate in the PAD only group was identical at 2.6% regardless of whether patients were on rivaroxaban or placebo.

In patients without CAD, the clinical benefit of rivaroxaban was driven by reductions in severe limb events. Their rate of acute limb ischemia was 5.2% with rivaroxaban, compared with 8.3% with placebo, for a 37% relative risk reduction. In contrast, the reduction in acute limb ischemia with rivaroxaban in patients with PAD and CAD wasn’t significantly different from placebo.

Thrombolysis in Myocardial Infarction major bleeding occurred in 2.4% of patients with PAD and CAD on rivaroxaban, compared with 1.1% on placebo, and in 1.7% and 1.5% of patients with PAD alone. Of note, rates of ischemic stroke or fatal hemorrhage were low and similar at less than 1% in all four groups, Dr. Hiatt noted.

VOYAGER PAD was sponsored by Bayer and Janssen. Dr. Hiatt reported receiving research grant support from those two companies as well as Amgen.

[email protected]

The absolute benefit of adding low-dose rivaroxaban to low-dose aspirin following revascularization for symptomatic lower-extremity peripheral artery disease (PAD) is significantly greater in patients with comorbid coronary artery disease (CAD), according to a new secondary analysis of the VOYAGER PAD trial.

“These findings suggest heterogeneity of prognostic risk for ischemic events in lower-extremity PAD patients, and may support shared decision-making with these patients,” William R. Hiatt, MD, observed in presenting the study results at the virtual annual congress of the European Society of Cardiology.

VOYAGER PAD was a 3-year, 34-country clinical trial in which 6,564 patients with symptomatic PAD who had recently undergone lower-limb revascularization were randomized in double-blind fashion to rivaroxaban (Xarelto) at 2.5 mg twice daily or placebo on top of background standard therapy with low-dose aspirin.

Among the 2,067 participants with baseline comorbid CAD, the primary outcome – a composite comprised of cardiovascular death, acute MI, ischemic stroke, acute limb ischemia, and major amputation – occurred in 18.9% of the rivaroxaban group at 3 years and 24.3% on placebo, for a highly significant 22% relative risk reduction.

In contrast, in the 4,497 patients with PAD only, the primary outcome occurred in 16.1% of those on rivaroxaban and 17.9% of controls, an 11% relative risk reduction which failed to reach statistical significance. The absolute risk reduction achieved with rivaroxaban was 5.4% in patients with PAD plus CAD versus 1.8% in those with PAD alone. Thus, the significant clinical benefit with rivaroxaban plus aspirin previously reported in the overall study population, with a number needed to treat for 3 years of 39 in order to prevent one primary outcome event, was largely driven by the superior outcomes in the dual-diagnosis subgroup, reported Dr. Hiatt, professor of medicine at the University of Colorado at Denver, Aurora.

“A strategy of rivaroxaban at 2.5 mg twice daily plus low-dose aspirin versus low-dose aspirin alone reduces ischemic events of the limb, brain, and heart, but also increases bleeding, with an overall net benefit,” the cardiologist said. “In particular, the benefits of this strategy for MI and ischemic stroke are robust, especially in patients with PAD and CAD.”

Indeed, the MI rate at 3 years in the dual diagnosis subgroup was 7.3% with rivaroxaban and 8.8% with placebo, for a 23% relative risk reduction, compared with rates of 3.3% and 3.7%, respectively, in patients with PAD only. Similarly, ischemic stroke occurred in 2.9% of patients with PAD and CAD in the rivaroxaban group, compared with 3.9% with placebo, whereas the rate in the PAD only group was identical at 2.6% regardless of whether patients were on rivaroxaban or placebo.

In patients without CAD, the clinical benefit of rivaroxaban was driven by reductions in severe limb events. Their rate of acute limb ischemia was 5.2% with rivaroxaban, compared with 8.3% with placebo, for a 37% relative risk reduction. In contrast, the reduction in acute limb ischemia with rivaroxaban in patients with PAD and CAD wasn’t significantly different from placebo.

Thrombolysis in Myocardial Infarction major bleeding occurred in 2.4% of patients with PAD and CAD on rivaroxaban, compared with 1.1% on placebo, and in 1.7% and 1.5% of patients with PAD alone. Of note, rates of ischemic stroke or fatal hemorrhage were low and similar at less than 1% in all four groups, Dr. Hiatt noted.

VOYAGER PAD was sponsored by Bayer and Janssen. Dr. Hiatt reported receiving research grant support from those two companies as well as Amgen.

[email protected]

Elevated pulmonary artery diastolic pressure is “perhaps the best predictor of bad outcomes in patients with heart failure, including hospitalization and death,” and new evidence clearly showed that the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin cuts this metric in patients by a clinically significant amount, Mikhail Kosiborod, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America.

Doug Brunk/MDedge News

The evidence he collected from a total of 65 heart failure patients with either reduced or preserved ejection fraction is the first documentation from a randomized, controlled study to show a direct effect by a SGLT2 inhibitor on pulmonary artery (PA) pressures.

Other key findings were that the drop in PA diastolic pressure with empagliflozin treatment compared with placebo became discernible early (within the first 4 weeks on treatment), that the pressure-lowering effect steadily grew over time, and that it showed no link to the intensity of loop diuretic treatment, which held steady during 12 weeks on treatment and 13 weeks of overall monitoring.

The study’s primary endpoint was the change from baseline in PA diastolic pressure after 12 weeks on treatment. The 31 patients who completed the full 12-week course had an average drop in their PA diastolic pressure of about 1.5 mm Hg, compared with 28 patients who completed 12 weeks on placebo. Average PA diastolic pressure at baseline was about 21 mm Hg in both treatment arms, and on treatment this fell by more than 0.5 mm Hg among those who received empagliflozin and rose by close to 1 mm Hg among control patients.

“There appears to be a direct effect of empagliflozin on pulmonary artery pressure that’s not been previously demonstrated” by an SGLT2 inhibitor, Dr. Kosiborod said. “I think this is one mechanism of action” for this drug class. “If you control pulmonary artery filling pressures you can prevent hospitalizations and deaths.”
 

Small reductions matter

“Small pressure differences are particularly important for pulmonary hypertension,” commented Lynne W. Stevenson, MD, professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn., and the report’s designated discussant.

“In the Vanderbilt heart failure database, patients with a pulmonary artery mean pressure of 20-24 mm Hg had 30% higher mortality than patients with lower pressures,” Dr. Stevenson noted. “This has led to a new definition of pulmonary hypertension, a mean pulmonary artery pressure above at or above 20 mm Hg.”

In Dr. Kosiborod’s study, patients began with an average PA mean pressure of about 30 mm Hg, and empagliflozin treatment led to a reduction in this metric with about the same magnitude as its effect on PA diastolic pressure. Empagliflozin also produced a similar reduction in average PA systolic pressure.

Mitchel L. Zoler/MDedge News

A study built on ambulatory PA monitoring

The results “also provide more proof for the concept of ambulatory hemodynamic monitoring” in patients with heart failure to monitor their status, she added. The study enrolled only patients who had already received a CardioMEMS implant as part of their routine care. This device allows for frequent, noninvasive monitoring of PA pressures. Researchers collected PA pressure data from patients twice daily for the entire 13-week study.

The EMBRACE HF (Empagliflozin Impact on Hemodynamics in Patients With Heart Failure) study enrolled patients with established heart failure, a CardioMEMS implant, and New York Heart Association class II-IV symptoms at any of eight U.S. centers. Patients averaged about 65 years old, and slightly more than half had class III disease, which denotes marked limitation of physical activity.

Despite the brief treatment period, patients who received empagliflozin showed other evidence of benefit including a trend toward improved quality of life scores, reduced levels of two different forms of brain natriuretic peptide, and significant weight loss, compared with controls, that averaged 2.4 kg.

The mechanism by which empagliflozin and other drugs in its class might lower PA filling pressures is unclear, but Dr. Kosiborod stressed that the consistent level of loop diuretic use during the study seems to rule out a diuretic effect from the SGLT2 inhibitor as having a role. A pulmonary vasculature effect is “much more likely,” perhaps mediated through modified endothelial function and vasodilation, he suggested.

EMBRACE HF was funded by Boehringer Ingelheim, the company that markets empagliflozin (Jardiance) along with Eli Lilly. Dr. Kosiborod has received research support and honoraria from Boehringer Ingelheim, and he has received honoraria from several other companies. Dr. Stevenson had no disclosures.

[email protected]

Elevated pulmonary artery diastolic pressure is “perhaps the best predictor of bad outcomes in patients with heart failure, including hospitalization and death,” and new evidence clearly showed that the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin cuts this metric in patients by a clinically significant amount, Mikhail Kosiborod, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America.

Doug Brunk/MDedge News

The evidence he collected from a total of 65 heart failure patients with either reduced or preserved ejection fraction is the first documentation from a randomized, controlled study to show a direct effect by a SGLT2 inhibitor on pulmonary artery (PA) pressures.

Other key findings were that the drop in PA diastolic pressure with empagliflozin treatment compared with placebo became discernible early (within the first 4 weeks on treatment), that the pressure-lowering effect steadily grew over time, and that it showed no link to the intensity of loop diuretic treatment, which held steady during 12 weeks on treatment and 13 weeks of overall monitoring.

The study’s primary endpoint was the change from baseline in PA diastolic pressure after 12 weeks on treatment. The 31 patients who completed the full 12-week course had an average drop in their PA diastolic pressure of about 1.5 mm Hg, compared with 28 patients who completed 12 weeks on placebo. Average PA diastolic pressure at baseline was about 21 mm Hg in both treatment arms, and on treatment this fell by more than 0.5 mm Hg among those who received empagliflozin and rose by close to 1 mm Hg among control patients.

“There appears to be a direct effect of empagliflozin on pulmonary artery pressure that’s not been previously demonstrated” by an SGLT2 inhibitor, Dr. Kosiborod said. “I think this is one mechanism of action” for this drug class. “If you control pulmonary artery filling pressures you can prevent hospitalizations and deaths.”
 

Small reductions matter

“Small pressure differences are particularly important for pulmonary hypertension,” commented Lynne W. Stevenson, MD, professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn., and the report’s designated discussant.

“In the Vanderbilt heart failure database, patients with a pulmonary artery mean pressure of 20-24 mm Hg had 30% higher mortality than patients with lower pressures,” Dr. Stevenson noted. “This has led to a new definition of pulmonary hypertension, a mean pulmonary artery pressure above at or above 20 mm Hg.”

In Dr. Kosiborod’s study, patients began with an average PA mean pressure of about 30 mm Hg, and empagliflozin treatment led to a reduction in this metric with about the same magnitude as its effect on PA diastolic pressure. Empagliflozin also produced a similar reduction in average PA systolic pressure.

Mitchel L. Zoler/MDedge News

A study built on ambulatory PA monitoring

The results “also provide more proof for the concept of ambulatory hemodynamic monitoring” in patients with heart failure to monitor their status, she added. The study enrolled only patients who had already received a CardioMEMS implant as part of their routine care. This device allows for frequent, noninvasive monitoring of PA pressures. Researchers collected PA pressure data from patients twice daily for the entire 13-week study.

The EMBRACE HF (Empagliflozin Impact on Hemodynamics in Patients With Heart Failure) study enrolled patients with established heart failure, a CardioMEMS implant, and New York Heart Association class II-IV symptoms at any of eight U.S. centers. Patients averaged about 65 years old, and slightly more than half had class III disease, which denotes marked limitation of physical activity.

Despite the brief treatment period, patients who received empagliflozin showed other evidence of benefit including a trend toward improved quality of life scores, reduced levels of two different forms of brain natriuretic peptide, and significant weight loss, compared with controls, that averaged 2.4 kg.

The mechanism by which empagliflozin and other drugs in its class might lower PA filling pressures is unclear, but Dr. Kosiborod stressed that the consistent level of loop diuretic use during the study seems to rule out a diuretic effect from the SGLT2 inhibitor as having a role. A pulmonary vasculature effect is “much more likely,” perhaps mediated through modified endothelial function and vasodilation, he suggested.

EMBRACE HF was funded by Boehringer Ingelheim, the company that markets empagliflozin (Jardiance) along with Eli Lilly. Dr. Kosiborod has received research support and honoraria from Boehringer Ingelheim, and he has received honoraria from several other companies. Dr. Stevenson had no disclosures.

[email protected]

Elevated pulmonary artery diastolic pressure is “perhaps the best predictor of bad outcomes in patients with heart failure, including hospitalization and death,” and new evidence clearly showed that the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin cuts this metric in patients by a clinically significant amount, Mikhail Kosiborod, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America.

Doug Brunk/MDedge News

The evidence he collected from a total of 65 heart failure patients with either reduced or preserved ejection fraction is the first documentation from a randomized, controlled study to show a direct effect by a SGLT2 inhibitor on pulmonary artery (PA) pressures.

Other key findings were that the drop in PA diastolic pressure with empagliflozin treatment compared with placebo became discernible early (within the first 4 weeks on treatment), that the pressure-lowering effect steadily grew over time, and that it showed no link to the intensity of loop diuretic treatment, which held steady during 12 weeks on treatment and 13 weeks of overall monitoring.

The study’s primary endpoint was the change from baseline in PA diastolic pressure after 12 weeks on treatment. The 31 patients who completed the full 12-week course had an average drop in their PA diastolic pressure of about 1.5 mm Hg, compared with 28 patients who completed 12 weeks on placebo. Average PA diastolic pressure at baseline was about 21 mm Hg in both treatment arms, and on treatment this fell by more than 0.5 mm Hg among those who received empagliflozin and rose by close to 1 mm Hg among control patients.

“There appears to be a direct effect of empagliflozin on pulmonary artery pressure that’s not been previously demonstrated” by an SGLT2 inhibitor, Dr. Kosiborod said. “I think this is one mechanism of action” for this drug class. “If you control pulmonary artery filling pressures you can prevent hospitalizations and deaths.”
 

Small reductions matter

“Small pressure differences are particularly important for pulmonary hypertension,” commented Lynne W. Stevenson, MD, professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn., and the report’s designated discussant.

“In the Vanderbilt heart failure database, patients with a pulmonary artery mean pressure of 20-24 mm Hg had 30% higher mortality than patients with lower pressures,” Dr. Stevenson noted. “This has led to a new definition of pulmonary hypertension, a mean pulmonary artery pressure above at or above 20 mm Hg.”

In Dr. Kosiborod’s study, patients began with an average PA mean pressure of about 30 mm Hg, and empagliflozin treatment led to a reduction in this metric with about the same magnitude as its effect on PA diastolic pressure. Empagliflozin also produced a similar reduction in average PA systolic pressure.

Mitchel L. Zoler/MDedge News

A study built on ambulatory PA monitoring

The results “also provide more proof for the concept of ambulatory hemodynamic monitoring” in patients with heart failure to monitor their status, she added. The study enrolled only patients who had already received a CardioMEMS implant as part of their routine care. This device allows for frequent, noninvasive monitoring of PA pressures. Researchers collected PA pressure data from patients twice daily for the entire 13-week study.

The EMBRACE HF (Empagliflozin Impact on Hemodynamics in Patients With Heart Failure) study enrolled patients with established heart failure, a CardioMEMS implant, and New York Heart Association class II-IV symptoms at any of eight U.S. centers. Patients averaged about 65 years old, and slightly more than half had class III disease, which denotes marked limitation of physical activity.

Despite the brief treatment period, patients who received empagliflozin showed other evidence of benefit including a trend toward improved quality of life scores, reduced levels of two different forms of brain natriuretic peptide, and significant weight loss, compared with controls, that averaged 2.4 kg.

The mechanism by which empagliflozin and other drugs in its class might lower PA filling pressures is unclear, but Dr. Kosiborod stressed that the consistent level of loop diuretic use during the study seems to rule out a diuretic effect from the SGLT2 inhibitor as having a role. A pulmonary vasculature effect is “much more likely,” perhaps mediated through modified endothelial function and vasodilation, he suggested.

EMBRACE HF was funded by Boehringer Ingelheim, the company that markets empagliflozin (Jardiance) along with Eli Lilly. Dr. Kosiborod has received research support and honoraria from Boehringer Ingelheim, and he has received honoraria from several other companies. Dr. Stevenson had no disclosures.

[email protected]

Halloween is fast approaching and retail stores are fully stocked with costumes and candy. Physician dialog is beginning to shift from school access toward how to counsel patients and families on COVID-19 safety around Halloween. What steps families ultimately take about Halloween will hinge on where they live and what the COVID infection and death rates are in their area, advised pediatrician Shelly Vaziri Flais, MD.

Courtesy Andrew Beattie

Halloween “is going to look very different this year, especially in urban and rural settings, according to Dr. Flais, who is a spokesperson for the American Academy of Pediatrics and assistant professor of clinical pediatrics at Northwestern University, Chicago. The notion that trick-or-treating automatically involves physically distancing is a misconception. Urban celebrations frequently see many people gathering on the streets, and that will be even more likely in a pandemic year when people have been separated for long periods of time.

For pediatricians advising families on COVID-19 safety measures to follow while celebrating Halloween, it’s not going to be a one-size-fits-all approach, said Dr. Flais, who practices pediatrics at Pediatric Health Associates in Naperville, Ill.

The goal for physicians across the board should be “to ensure that we aren’t so cautious that we drive folks to do things that are higher risk,” she said in an interview. “We are now 6-7 months into the pandemic and the public is growing weary of laying low, so it is important for physicians to not recommend safety measures that are too restrictive.”

The balance pediatricians will need to strike in advising their patients is tricky at best. So in dispensing advice, it is important to make sure that it has a benefit to the overall population, cautioned Dr. Flais. Activities such as hosting independently organized, heavily packed indoor gatherings where people are eating, drinking, and not wearing masks is not going to be beneficial for the masses.

Courtesy Dr. Shelly V. Flais

“We’re all lucky that we have technology. We’ve gotten used to doing virtual hugs and activities on Zoom,” she said, adding that she has already seen some really creative ideas on social media for enjoying a COVID-conscious Halloween, including a festive candy chute created by an Ohio family that is perfect for distributing candy while minimizing physical contact.

In an AAP press release, Dr. Flais noted that “this is a good time to teach children the importance of protecting not just ourselves but each other.” How we choose to manage our safety and the safety of our children “can have a ripple effect on our family members.” It is possible to make safe, responsible choices when celebrating and still create magical memories for our children.

Francis E. Rushton Jr., MD, of the University of South Carolina, Columbia, said in an interview, “ I certainly support the AAP recommendations. Because of the way COVID-19 virus is spread, I would emphasize with my patients that the No. 1 thing to do is to enforce facial mask wearing while out trick-or-treating.

“I would also err on the side of safety if my child was showing any signs of illness and find an alternative method of celebrating Halloween that would not involve close contact with other individuals,” said Dr. Rushton, who is a member of the Pediatric News editorial advisory board.

AAP-recommended Do’s and Don’ts for celebrating Halloween

DO:

• Avoid large gatherings.
• Maintain 6 feet distance.
• Wear cloth masks and wash hands often.
• Use hand sanitizer before and after visiting pumpkin patches and apple orchards.

DON’T:

• Wear painted cloth masks since paints can contain toxins that should not be breathed.
• Use a costume mask unless it has layers of breathable fabric snugly covering mouth and nose.
• Wear cloth mask under costume mask.
• Attend indoor parties or haunted houses.

CDC safety considerations (supplemental to state and local safety laws)

• Assess current cases and overall spread in your community before making any plans.
• Choose outdoor venues or indoor facilities that are well ventilated.
• Consider the length of the event, how many are attending, where they are coming from, and how they behave before and during the event.
• If you are awaiting test results, have COVID-19 symptoms, or have been exposed to COVID-19, stay home.
• If you are at higher risk, avoid large gatherings and limit exposure to anyone you do not live with.
• Make available to others masks, 60% or greater alcohol-based hand sanitizer, and tissues.
• Avoid touching your nose, eyes, and mouth.
• For a complete set of Centers for Disease Control and Prevention COVID safety recommendations go here.

Suggested safe, fun activities

• Use Zoom and other chat programs to share costumes, play games, and watch festive movies.
• Participate in socially distanced outdoor community events at local parks, zoos, etc.
• Attend haunted forests and corn mazes. Maintain more than 6 feet of distance around screaming patrons.
• Decorate pumpkins.
• Cook a Halloween-themed meal.
• If trick-or-treating has been canceled, try a scavenger hunt in the house or yard.
• When handing out treats, wear gloves and mask. Consider prepackaging treat bags. Line up visitors 6 feet apart and discourage gatherings around entranceways.
• Wipe down all goodies received and consider quarantining them for a few days.
• Always wash hands before and after trick-or-treating and when handling treats.

Halloween is fast approaching and retail stores are fully stocked with costumes and candy. Physician dialog is beginning to shift from school access toward how to counsel patients and families on COVID-19 safety around Halloween. What steps families ultimately take about Halloween will hinge on where they live and what the COVID infection and death rates are in their area, advised pediatrician Shelly Vaziri Flais, MD.

Courtesy Andrew Beattie

Halloween “is going to look very different this year, especially in urban and rural settings, according to Dr. Flais, who is a spokesperson for the American Academy of Pediatrics and assistant professor of clinical pediatrics at Northwestern University, Chicago. The notion that trick-or-treating automatically involves physically distancing is a misconception. Urban celebrations frequently see many people gathering on the streets, and that will be even more likely in a pandemic year when people have been separated for long periods of time.

For pediatricians advising families on COVID-19 safety measures to follow while celebrating Halloween, it’s not going to be a one-size-fits-all approach, said Dr. Flais, who practices pediatrics at Pediatric Health Associates in Naperville, Ill.

The goal for physicians across the board should be “to ensure that we aren’t so cautious that we drive folks to do things that are higher risk,” she said in an interview. “We are now 6-7 months into the pandemic and the public is growing weary of laying low, so it is important for physicians to not recommend safety measures that are too restrictive.”

The balance pediatricians will need to strike in advising their patients is tricky at best. So in dispensing advice, it is important to make sure that it has a benefit to the overall population, cautioned Dr. Flais. Activities such as hosting independently organized, heavily packed indoor gatherings where people are eating, drinking, and not wearing masks is not going to be beneficial for the masses.

Courtesy Dr. Shelly V. Flais

“We’re all lucky that we have technology. We’ve gotten used to doing virtual hugs and activities on Zoom,” she said, adding that she has already seen some really creative ideas on social media for enjoying a COVID-conscious Halloween, including a festive candy chute created by an Ohio family that is perfect for distributing candy while minimizing physical contact.

In an AAP press release, Dr. Flais noted that “this is a good time to teach children the importance of protecting not just ourselves but each other.” How we choose to manage our safety and the safety of our children “can have a ripple effect on our family members.” It is possible to make safe, responsible choices when celebrating and still create magical memories for our children.

Francis E. Rushton Jr., MD, of the University of South Carolina, Columbia, said in an interview, “ I certainly support the AAP recommendations. Because of the way COVID-19 virus is spread, I would emphasize with my patients that the No. 1 thing to do is to enforce facial mask wearing while out trick-or-treating.

“I would also err on the side of safety if my child was showing any signs of illness and find an alternative method of celebrating Halloween that would not involve close contact with other individuals,” said Dr. Rushton, who is a member of the Pediatric News editorial advisory board.

AAP-recommended Do’s and Don’ts for celebrating Halloween

DO:

• Avoid large gatherings.
• Maintain 6 feet distance.
• Wear cloth masks and wash hands often.
• Use hand sanitizer before and after visiting pumpkin patches and apple orchards.

DON’T:

• Wear painted cloth masks since paints can contain toxins that should not be breathed.
• Use a costume mask unless it has layers of breathable fabric snugly covering mouth and nose.
• Wear cloth mask under costume mask.
• Attend indoor parties or haunted houses.

CDC safety considerations (supplemental to state and local safety laws)

• Assess current cases and overall spread in your community before making any plans.
• Choose outdoor venues or indoor facilities that are well ventilated.
• Consider the length of the event, how many are attending, where they are coming from, and how they behave before and during the event.
• If you are awaiting test results, have COVID-19 symptoms, or have been exposed to COVID-19, stay home.
• If you are at higher risk, avoid large gatherings and limit exposure to anyone you do not live with.
• Make available to others masks, 60% or greater alcohol-based hand sanitizer, and tissues.
• Avoid touching your nose, eyes, and mouth.
• For a complete set of Centers for Disease Control and Prevention COVID safety recommendations go here.

Suggested safe, fun activities

• Use Zoom and other chat programs to share costumes, play games, and watch festive movies.
• Participate in socially distanced outdoor community events at local parks, zoos, etc.
• Attend haunted forests and corn mazes. Maintain more than 6 feet of distance around screaming patrons.
• Decorate pumpkins.
• Cook a Halloween-themed meal.
• If trick-or-treating has been canceled, try a scavenger hunt in the house or yard.
• When handing out treats, wear gloves and mask. Consider prepackaging treat bags. Line up visitors 6 feet apart and discourage gatherings around entranceways.
• Wipe down all goodies received and consider quarantining them for a few days.
• Always wash hands before and after trick-or-treating and when handling treats.

Halloween is fast approaching and retail stores are fully stocked with costumes and candy. Physician dialog is beginning to shift from school access toward how to counsel patients and families on COVID-19 safety around Halloween. What steps families ultimately take about Halloween will hinge on where they live and what the COVID infection and death rates are in their area, advised pediatrician Shelly Vaziri Flais, MD.

Courtesy Andrew Beattie

Halloween “is going to look very different this year, especially in urban and rural settings, according to Dr. Flais, who is a spokesperson for the American Academy of Pediatrics and assistant professor of clinical pediatrics at Northwestern University, Chicago. The notion that trick-or-treating automatically involves physically distancing is a misconception. Urban celebrations frequently see many people gathering on the streets, and that will be even more likely in a pandemic year when people have been separated for long periods of time.

For pediatricians advising families on COVID-19 safety measures to follow while celebrating Halloween, it’s not going to be a one-size-fits-all approach, said Dr. Flais, who practices pediatrics at Pediatric Health Associates in Naperville, Ill.

The goal for physicians across the board should be “to ensure that we aren’t so cautious that we drive folks to do things that are higher risk,” she said in an interview. “We are now 6-7 months into the pandemic and the public is growing weary of laying low, so it is important for physicians to not recommend safety measures that are too restrictive.”

The balance pediatricians will need to strike in advising their patients is tricky at best. So in dispensing advice, it is important to make sure that it has a benefit to the overall population, cautioned Dr. Flais. Activities such as hosting independently organized, heavily packed indoor gatherings where people are eating, drinking, and not wearing masks is not going to be beneficial for the masses.

Courtesy Dr. Shelly V. Flais

“We’re all lucky that we have technology. We’ve gotten used to doing virtual hugs and activities on Zoom,” she said, adding that she has already seen some really creative ideas on social media for enjoying a COVID-conscious Halloween, including a festive candy chute created by an Ohio family that is perfect for distributing candy while minimizing physical contact.

In an AAP press release, Dr. Flais noted that “this is a good time to teach children the importance of protecting not just ourselves but each other.” How we choose to manage our safety and the safety of our children “can have a ripple effect on our family members.” It is possible to make safe, responsible choices when celebrating and still create magical memories for our children.

Francis E. Rushton Jr., MD, of the University of South Carolina, Columbia, said in an interview, “ I certainly support the AAP recommendations. Because of the way COVID-19 virus is spread, I would emphasize with my patients that the No. 1 thing to do is to enforce facial mask wearing while out trick-or-treating.

“I would also err on the side of safety if my child was showing any signs of illness and find an alternative method of celebrating Halloween that would not involve close contact with other individuals,” said Dr. Rushton, who is a member of the Pediatric News editorial advisory board.

AAP-recommended Do’s and Don’ts for celebrating Halloween

DO:

• Avoid large gatherings.
• Maintain 6 feet distance.
• Wear cloth masks and wash hands often.
• Use hand sanitizer before and after visiting pumpkin patches and apple orchards.

DON’T:

• Wear painted cloth masks since paints can contain toxins that should not be breathed.
• Use a costume mask unless it has layers of breathable fabric snugly covering mouth and nose.
• Wear cloth mask under costume mask.
• Attend indoor parties or haunted houses.

CDC safety considerations (supplemental to state and local safety laws)

• Assess current cases and overall spread in your community before making any plans.
• Choose outdoor venues or indoor facilities that are well ventilated.
• Consider the length of the event, how many are attending, where they are coming from, and how they behave before and during the event.
• If you are awaiting test results, have COVID-19 symptoms, or have been exposed to COVID-19, stay home.
• If you are at higher risk, avoid large gatherings and limit exposure to anyone you do not live with.
• Make available to others masks, 60% or greater alcohol-based hand sanitizer, and tissues.
• Avoid touching your nose, eyes, and mouth.
• For a complete set of Centers for Disease Control and Prevention COVID safety recommendations go here.

Suggested safe, fun activities

• Use Zoom and other chat programs to share costumes, play games, and watch festive movies.
• Participate in socially distanced outdoor community events at local parks, zoos, etc.
• Attend haunted forests and corn mazes. Maintain more than 6 feet of distance around screaming patrons.
• Decorate pumpkins.
• Cook a Halloween-themed meal.
• If trick-or-treating has been canceled, try a scavenger hunt in the house or yard.
• When handing out treats, wear gloves and mask. Consider prepackaging treat bags. Line up visitors 6 feet apart and discourage gatherings around entranceways.
• Wipe down all goodies received and consider quarantining them for a few days.
• Always wash hands before and after trick-or-treating and when handling treats.

The Diagnosis: Fusariosis 

A periodic acid-Schiff stain of the seropurulent drainage from a skin nodule revealed neutrophils and scarce branching hyaline hyphae. Skin and blood cultures grew a white cottony colony. Microscopic examination showed sickle-shaped macroconidia and septate hyaline hyphae with branching acute angles (Figure). Molecular analysis by polymerase chain reaction yielded Fusarium solani species complex. Histopathology as well as culture and molecular findings were consistent with a diagnosis of disseminated fusariosis. Amphotericin B was started with rapid clinical improvement. The patient was asymptomatic upon discharge with voriconazole 200 mg twice daily. 

Fusariosis is an emerging, opportunistic, and life-threatening mycosis. In immunocompetent patients it may cause onychomycosis and keratitis.¹ Invasive fusariosis predominantly is caused by the F solani species complex and affects immunocompromised patients, especially those with neutropenia or acute leukemia or hematopoietic stem cell transplant recipients.² 

Before invasion, the infection frequently may begin by affecting the nail apparatus as onychomycosis or paronychia of the skin. As in our case, trauma or manipulation of the nail favors dissemination.³ Skin manifestations include erythematous to violaceous papules, macules, and nodules with central necrosis or crust; some may exhibit target morphology. Other organs may be affected, including the sinuses, lungs, liver, spleen, and kidneys. A comprehensive clinical examination before hematopoietic cell transplant and during fever and neutropenia may opportunely identify these potential infective foci.^3,4 

The differential diagnosis of disseminated fusariosis includes bacterial infections, especially Staphylococcus aureus and Pseudomonas aeruginosa, and other invasive fungal infections, particularly aspergillosis, mucormycosis, and candidiasis.⁵ Symptom persistence after broad-spectrum antibiotic initiation should raise diagnostic suspicion of systemic mycosis or mycobacterial infection. Mucormycosis and candidiasis have histopathologic profiles that differ from fusariosis, presenting with broad ribbonlike hyphae with 90° angulation and pseudohyphae with budding yeast cells, respectively. Differentiation of disseminated fusariosis and aspergillosis in neutropenic patients is difficult. Hyphae cannot be differentiated from those of Aspergillus species on histology.⁶ Furthermore, serologic assays, such as galactomannan and (1,3)-β-D-glucan, cross-react with both genera. Clinically, Fusarium species exhibit metastatic skin lesions, cellulitis, and positive blood cultures due to adventitious sporulation more frequently than Aspergillus species. Patients with aspergillosis more commonly present with sinusitis, pneumonia, and pulmonary macronodules with the halo sign.⁶ Although nocardiosis presents with disseminated subcutaneous nodules with pulmonary affection in immunocompromised patients, its morphology is very different from fusariosis. Nocardia presents with a gram-positive bacillus with the microscopic appearance of branching filaments. Yeastlike microorganisms with morphology ranging from oval to sausagelike are found in talaromycosis, an uncommon fungal infection predominantly caused by Talaromyces marneffei. Fusarium species culture reveals white cottony colonies with characteristic hyaline, canoe-shaped or sickle-shaped (banana-shaped), multicellular macroconidia, and microconidia. Precise species identification requires molecular analyses such as polymerase chain reaction. 

Mortality is high, ranging from 50% to 70% of cases.⁵ Voriconazole or lipid-based amphotericin B are considered first-line treatments. Posaconazole may be employed as a second-line alternative. Surgical debridement of infected tissues and removal of colonized venous catheters is recommended. Secondary prophylaxis should be considered with agents such as voriconazole, posaconazole, or amphotericin B.⁵ Resolution of immunosuppression and neutropenia is an important factor to reduce the mortality rate. 

The Diagnosis: Fusariosis 

A periodic acid-Schiff stain of the seropurulent drainage from a skin nodule revealed neutrophils and scarce branching hyaline hyphae. Skin and blood cultures grew a white cottony colony. Microscopic examination showed sickle-shaped macroconidia and septate hyaline hyphae with branching acute angles (Figure). Molecular analysis by polymerase chain reaction yielded Fusarium solani species complex. Histopathology as well as culture and molecular findings were consistent with a diagnosis of disseminated fusariosis. Amphotericin B was started with rapid clinical improvement. The patient was asymptomatic upon discharge with voriconazole 200 mg twice daily. 

Fusariosis is an emerging, opportunistic, and life-threatening mycosis. In immunocompetent patients it may cause onychomycosis and keratitis.¹ Invasive fusariosis predominantly is caused by the F solani species complex and affects immunocompromised patients, especially those with neutropenia or acute leukemia or hematopoietic stem cell transplant recipients.² 

Before invasion, the infection frequently may begin by affecting the nail apparatus as onychomycosis or paronychia of the skin. As in our case, trauma or manipulation of the nail favors dissemination.³ Skin manifestations include erythematous to violaceous papules, macules, and nodules with central necrosis or crust; some may exhibit target morphology. Other organs may be affected, including the sinuses, lungs, liver, spleen, and kidneys. A comprehensive clinical examination before hematopoietic cell transplant and during fever and neutropenia may opportunely identify these potential infective foci.^3,4 

The differential diagnosis of disseminated fusariosis includes bacterial infections, especially Staphylococcus aureus and Pseudomonas aeruginosa, and other invasive fungal infections, particularly aspergillosis, mucormycosis, and candidiasis.⁵ Symptom persistence after broad-spectrum antibiotic initiation should raise diagnostic suspicion of systemic mycosis or mycobacterial infection. Mucormycosis and candidiasis have histopathologic profiles that differ from fusariosis, presenting with broad ribbonlike hyphae with 90° angulation and pseudohyphae with budding yeast cells, respectively. Differentiation of disseminated fusariosis and aspergillosis in neutropenic patients is difficult. Hyphae cannot be differentiated from those of Aspergillus species on histology.⁶ Furthermore, serologic assays, such as galactomannan and (1,3)-β-D-glucan, cross-react with both genera. Clinically, Fusarium species exhibit metastatic skin lesions, cellulitis, and positive blood cultures due to adventitious sporulation more frequently than Aspergillus species. Patients with aspergillosis more commonly present with sinusitis, pneumonia, and pulmonary macronodules with the halo sign.⁶ Although nocardiosis presents with disseminated subcutaneous nodules with pulmonary affection in immunocompromised patients, its morphology is very different from fusariosis. Nocardia presents with a gram-positive bacillus with the microscopic appearance of branching filaments. Yeastlike microorganisms with morphology ranging from oval to sausagelike are found in talaromycosis, an uncommon fungal infection predominantly caused by Talaromyces marneffei. Fusarium species culture reveals white cottony colonies with characteristic hyaline, canoe-shaped or sickle-shaped (banana-shaped), multicellular macroconidia, and microconidia. Precise species identification requires molecular analyses such as polymerase chain reaction. 

Mortality is high, ranging from 50% to 70% of cases.⁵ Voriconazole or lipid-based amphotericin B are considered first-line treatments. Posaconazole may be employed as a second-line alternative. Surgical debridement of infected tissues and removal of colonized venous catheters is recommended. Secondary prophylaxis should be considered with agents such as voriconazole, posaconazole, or amphotericin B.⁵ Resolution of immunosuppression and neutropenia is an important factor to reduce the mortality rate. 

The Diagnosis: Fusariosis 

A periodic acid-Schiff stain of the seropurulent drainage from a skin nodule revealed neutrophils and scarce branching hyaline hyphae. Skin and blood cultures grew a white cottony colony. Microscopic examination showed sickle-shaped macroconidia and septate hyaline hyphae with branching acute angles (Figure). Molecular analysis by polymerase chain reaction yielded Fusarium solani species complex. Histopathology as well as culture and molecular findings were consistent with a diagnosis of disseminated fusariosis. Amphotericin B was started with rapid clinical improvement. The patient was asymptomatic upon discharge with voriconazole 200 mg twice daily. 

Fusariosis is an emerging, opportunistic, and life-threatening mycosis. In immunocompetent patients it may cause onychomycosis and keratitis.¹ Invasive fusariosis predominantly is caused by the F solani species complex and affects immunocompromised patients, especially those with neutropenia or acute leukemia or hematopoietic stem cell transplant recipients.² 

Before invasion, the infection frequently may begin by affecting the nail apparatus as onychomycosis or paronychia of the skin. As in our case, trauma or manipulation of the nail favors dissemination.³ Skin manifestations include erythematous to violaceous papules, macules, and nodules with central necrosis or crust; some may exhibit target morphology. Other organs may be affected, including the sinuses, lungs, liver, spleen, and kidneys. A comprehensive clinical examination before hematopoietic cell transplant and during fever and neutropenia may opportunely identify these potential infective foci.^3,4 

The differential diagnosis of disseminated fusariosis includes bacterial infections, especially Staphylococcus aureus and Pseudomonas aeruginosa, and other invasive fungal infections, particularly aspergillosis, mucormycosis, and candidiasis.⁵ Symptom persistence after broad-spectrum antibiotic initiation should raise diagnostic suspicion of systemic mycosis or mycobacterial infection. Mucormycosis and candidiasis have histopathologic profiles that differ from fusariosis, presenting with broad ribbonlike hyphae with 90° angulation and pseudohyphae with budding yeast cells, respectively. Differentiation of disseminated fusariosis and aspergillosis in neutropenic patients is difficult. Hyphae cannot be differentiated from those of Aspergillus species on histology.⁶ Furthermore, serologic assays, such as galactomannan and (1,3)-β-D-glucan, cross-react with both genera. Clinically, Fusarium species exhibit metastatic skin lesions, cellulitis, and positive blood cultures due to adventitious sporulation more frequently than Aspergillus species. Patients with aspergillosis more commonly present with sinusitis, pneumonia, and pulmonary macronodules with the halo sign.⁶ Although nocardiosis presents with disseminated subcutaneous nodules with pulmonary affection in immunocompromised patients, its morphology is very different from fusariosis. Nocardia presents with a gram-positive bacillus with the microscopic appearance of branching filaments. Yeastlike microorganisms with morphology ranging from oval to sausagelike are found in talaromycosis, an uncommon fungal infection predominantly caused by Talaromyces marneffei. Fusarium species culture reveals white cottony colonies with characteristic hyaline, canoe-shaped or sickle-shaped (banana-shaped), multicellular macroconidia, and microconidia. Precise species identification requires molecular analyses such as polymerase chain reaction. 

Mortality is high, ranging from 50% to 70% of cases.⁵ Voriconazole or lipid-based amphotericin B are considered first-line treatments. Posaconazole may be employed as a second-line alternative. Surgical debridement of infected tissues and removal of colonized venous catheters is recommended. Secondary prophylaxis should be considered with agents such as voriconazole, posaconazole, or amphotericin B.⁵ Resolution of immunosuppression and neutropenia is an important factor to reduce the mortality rate. 

Gender-incongruent youth who present for gender-affirming medical care later in adolescence have higher rates of mental health problems than their younger counterparts, based on data from a review of 300 individuals.

Peerayot/Thinkstock.com

“Puberty is a vulnerable time for youth with gender dysphoria because distress may intensify with the development of secondary sex characteristics corresponding to the assigned rather than the experienced gender,” wrote Julia C. Sorbara, MD, of the University of Toronto and the Hospital for Sick Children, also in Toronto, and colleagues.

Although gender-affirming medical care (GAMC) in the form of hormone blockers and/or gender-affirming hormones early in puberty can decrease in emotional and behavioral problems, many teens present later in puberty, and the relationship between pubertal stage at presentation for treatment and mental health has not been examined, they wrote.

In a study published in Pediatrics, the researchers reviewed data from youth with gender incongruence who were seen at a single center; 116 were younger than 15 years at presentation for GAMC and were defined as younger-presenting youth (YPY), and 184 patients aged 15 years and older were defined as older-presenting youth (OPY).

Overall, 78% of the youth reported at least one mental health problem at their initial visit. Significantly more OPY than YPY reported diagnosed depression (46% vs. 30%), self-harm (40% vs. 28%), suicidal thoughts (52% vs. 40%), suicide attempts (17% vs. 9%), and use of psychoactive medications (36% vs. 23%), all with P < .05.

In a multivariate analysis, patients in Tanner stages 4 and 5 were five times more likely to experience depressive disorders (odds ratio, 5.49) and four times as likely to experience depressive disorders (OR, 4.18) as those in earlier Tanner stages. Older age remained significantly associated with use of psychoactive medications (OR, 1.31), but not with anxiety or depression, the researchers wrote.

The YPY group were significantly younger at the age of recognizing gender incongruence, compared with the OPY group, with median ages at recognition of 5.8 years and 9 years, respectively, and younger patients came out about their gender identity at an average of 12 years, compared with 15 years for older patients.

The quantitative data are among the first to relate pubertal stage to mental health in gender-incongruent youth, “supporting clinical observations that pubertal development, menses, and erections are distressing to these youth and consistent with the beneficial role of pubertal suppression, even when used as monotherapy without gender-affirming hormones,” Dr. Sorbara and associates wrote.

The study findings were limited by several factors including the cross-sectional design and the collection of mental health data at only one time point and by the use of self-reports. However, the results suggest that “[gender-incongruent] youth who present to GAMC later in life are a particularly high-risk subset of a vulnerable population,” they noted. “Further study is required to better describe the mental health trajectories of transgender youth and determine if mental health status or age at initiation of GAMC is correlated with psychological well-being in adulthood.”
 

Don’t rush to puberty suppression in younger teens

To reduce the stress of puberty on gender-nonconforming youth, puberty suppression as “a reversible medical intervention” was introduced by Dutch clinicians in the early 2000s, Annelou L.C. de Vries, MD, PhD, of Amsterdam University Medical Center, wrote in an accompanying editorial.

“The aim of puberty suppression was to prevent the psychological suffering stemming from undesired physical changes when puberty starts and allowing the adolescent time to make plans regarding further transition or not,” Dr. de Vries said. “Following this rationale, younger age at the time of starting medical-affirming treatment (puberty suppression or hormones) would be expected to correlate with fewer psychological difficulties related to physical changes than older individuals,” which was confirmed in the current study.

However, clinicians should be cautious in offering puberty suppression at a younger age, in part because “despite the increased availability of gender-affirming medical interventions for younger ages in recent years, there has not been a proportional decline in older presenting youth with gender incongruence,” she said.

More data are needed on youth with postpuberty adolescent-onset transgender histories. The original Dutch studies on gender-affirming medical interventions note case histories describing “the complexities that may be associated with later-presenting transgender adolescents and describe that some eventually detransition,” Dr. de Vries explained.

Ultimately, prospective studies with longer follow-up data are needed to better inform clinicians in developing an individualized treatment plan for youth with gender incongruence, Dr. de Vries concluded.
 

Care barriers can include parents, access, insurance

The study authors describe the situation of gender-affirming medical care in teens perfectly, M. Brett Cooper, MD, of the University of Texas Southwestern Medical Center/Children’s Health Dallas, said in an interview.

Given a variety of factors that need further exploration, “many youth often don’t end up seeking gender-affirming medical care until puberty has progressed to near full maturity,” he said. “The findings from this study provide preliminary evidence to show that if we can identify these youth earlier in their gender journey, we might be able to impact adverse mental health outcomes in a positive way.”

Dr. Cooper said he was not surprised by the study findings. “They are similar to what I see in my clinic.

“Many of our patients often don’t present for medical care until around age 15 or older, similar to the findings of the study,” he added. “The majority of our patients have had a diagnosis of anxiety or depression at some point in their lifetime, including inpatient hospitalizations for their mental health.”

One of the most important barriers to care often can be parents or guardians, said Dr. Cooper. “Young people usually know their gender identity by about age 4-5 but parents may think that a gender-diverse identity could simply be a ‘phase.’ Other times, young people may hide their identity out of fear of a negative reaction from their parents. The distress around identity may become more pronounced once pubertal changes, such as breast and testicle development, begin to worsen their dysphoria.”

“Another barrier to care can be the inability to find a competent, gender-affirming provider,” Dr. Cooper said. “Most large United States cities have at least one gender-affirming clinic, but for those youth who grow up in smaller towns, it may be difficult to access these clinics. In addition, some clinics require a letter from a therapist stating that the young person is transgender before they can be seen for medical care. This creates an access barrier, as it may be difficult not just to find a therapist but one who has experience working with gender-diverse youth.”

Insurance coverage, including lack thereof, is yet another barrier to care for transgender youth, said Dr. Cooper. “While many insurance companies have begun to cover medications such as testosterone and estrogen for gender-affirming care, many still have exclusions on things like puberty blockers and surgical interventions.” These interventions can be lifesaving, but financially prohibitive for many families if not covered by insurance.

As for the value of early timing of gender-affirming care, Dr. Cooper agreed with the study findings that the earlier that a young person can get into medical care for their gender identity, the better chance there is to reduce the prevalence of serious mental health outcomes. “This also prevents the potential development of secondary sexual characteristics, decreasing the need for or amount of surgery in the future if desired,” he said.

“More research is needed to better understand the reasons why many youth don’t present to care until later in puberty. In addition, we need better research on interventions that are effective at reducing serious mental health events in transgender and gender diverse youth,” Dr. Cooper stated. “Another area that I would like to see researched is looking at the mental health of non-Caucasian youth. As the authors noted in their study, many clinics have a high percentage of patients presenting for care who identify as White or Caucasian, and we need to better understand why these other youth are not presenting for care.”

The study received no outside funding. Dr. Sorbara disclosed salary support from the Canadian Pediatric Endocrine Group fellowship program. Dr. de Vries had no financial conflicts to disclose. Dr. Cooper had no financial conflicts to disclose, and serves as a contributor to LGBTQ Youth Consult in Pediatric News.

SOURCES: Sorbara JC et al. Pediatrics. 2020 Sep 21. doi: 10.1542/peds.2019-3600; de Vries ALC et al. Pediatrics. 2020 Sep 21. doi: 10.1542/peds.2020-010611.

Gender-incongruent youth who present for gender-affirming medical care later in adolescence have higher rates of mental health problems than their younger counterparts, based on data from a review of 300 individuals.

Peerayot/Thinkstock.com

“Puberty is a vulnerable time for youth with gender dysphoria because distress may intensify with the development of secondary sex characteristics corresponding to the assigned rather than the experienced gender,” wrote Julia C. Sorbara, MD, of the University of Toronto and the Hospital for Sick Children, also in Toronto, and colleagues.

Although gender-affirming medical care (GAMC) in the form of hormone blockers and/or gender-affirming hormones early in puberty can decrease in emotional and behavioral problems, many teens present later in puberty, and the relationship between pubertal stage at presentation for treatment and mental health has not been examined, they wrote.

In a study published in Pediatrics, the researchers reviewed data from youth with gender incongruence who were seen at a single center; 116 were younger than 15 years at presentation for GAMC and were defined as younger-presenting youth (YPY), and 184 patients aged 15 years and older were defined as older-presenting youth (OPY).

Overall, 78% of the youth reported at least one mental health problem at their initial visit. Significantly more OPY than YPY reported diagnosed depression (46% vs. 30%), self-harm (40% vs. 28%), suicidal thoughts (52% vs. 40%), suicide attempts (17% vs. 9%), and use of psychoactive medications (36% vs. 23%), all with P < .05.

In a multivariate analysis, patients in Tanner stages 4 and 5 were five times more likely to experience depressive disorders (odds ratio, 5.49) and four times as likely to experience depressive disorders (OR, 4.18) as those in earlier Tanner stages. Older age remained significantly associated with use of psychoactive medications (OR, 1.31), but not with anxiety or depression, the researchers wrote.

The YPY group were significantly younger at the age of recognizing gender incongruence, compared with the OPY group, with median ages at recognition of 5.8 years and 9 years, respectively, and younger patients came out about their gender identity at an average of 12 years, compared with 15 years for older patients.

The quantitative data are among the first to relate pubertal stage to mental health in gender-incongruent youth, “supporting clinical observations that pubertal development, menses, and erections are distressing to these youth and consistent with the beneficial role of pubertal suppression, even when used as monotherapy without gender-affirming hormones,” Dr. Sorbara and associates wrote.

The study findings were limited by several factors including the cross-sectional design and the collection of mental health data at only one time point and by the use of self-reports. However, the results suggest that “[gender-incongruent] youth who present to GAMC later in life are a particularly high-risk subset of a vulnerable population,” they noted. “Further study is required to better describe the mental health trajectories of transgender youth and determine if mental health status or age at initiation of GAMC is correlated with psychological well-being in adulthood.”
 

Don’t rush to puberty suppression in younger teens

To reduce the stress of puberty on gender-nonconforming youth, puberty suppression as “a reversible medical intervention” was introduced by Dutch clinicians in the early 2000s, Annelou L.C. de Vries, MD, PhD, of Amsterdam University Medical Center, wrote in an accompanying editorial.

“The aim of puberty suppression was to prevent the psychological suffering stemming from undesired physical changes when puberty starts and allowing the adolescent time to make plans regarding further transition or not,” Dr. de Vries said. “Following this rationale, younger age at the time of starting medical-affirming treatment (puberty suppression or hormones) would be expected to correlate with fewer psychological difficulties related to physical changes than older individuals,” which was confirmed in the current study.

However, clinicians should be cautious in offering puberty suppression at a younger age, in part because “despite the increased availability of gender-affirming medical interventions for younger ages in recent years, there has not been a proportional decline in older presenting youth with gender incongruence,” she said.

More data are needed on youth with postpuberty adolescent-onset transgender histories. The original Dutch studies on gender-affirming medical interventions note case histories describing “the complexities that may be associated with later-presenting transgender adolescents and describe that some eventually detransition,” Dr. de Vries explained.

Ultimately, prospective studies with longer follow-up data are needed to better inform clinicians in developing an individualized treatment plan for youth with gender incongruence, Dr. de Vries concluded.
 

Care barriers can include parents, access, insurance

The study authors describe the situation of gender-affirming medical care in teens perfectly, M. Brett Cooper, MD, of the University of Texas Southwestern Medical Center/Children’s Health Dallas, said in an interview.

Given a variety of factors that need further exploration, “many youth often don’t end up seeking gender-affirming medical care until puberty has progressed to near full maturity,” he said. “The findings from this study provide preliminary evidence to show that if we can identify these youth earlier in their gender journey, we might be able to impact adverse mental health outcomes in a positive way.”

Dr. Cooper said he was not surprised by the study findings. “They are similar to what I see in my clinic.

“Many of our patients often don’t present for medical care until around age 15 or older, similar to the findings of the study,” he added. “The majority of our patients have had a diagnosis of anxiety or depression at some point in their lifetime, including inpatient hospitalizations for their mental health.”

One of the most important barriers to care often can be parents or guardians, said Dr. Cooper. “Young people usually know their gender identity by about age 4-5 but parents may think that a gender-diverse identity could simply be a ‘phase.’ Other times, young people may hide their identity out of fear of a negative reaction from their parents. The distress around identity may become more pronounced once pubertal changes, such as breast and testicle development, begin to worsen their dysphoria.”

“Another barrier to care can be the inability to find a competent, gender-affirming provider,” Dr. Cooper said. “Most large United States cities have at least one gender-affirming clinic, but for those youth who grow up in smaller towns, it may be difficult to access these clinics. In addition, some clinics require a letter from a therapist stating that the young person is transgender before they can be seen for medical care. This creates an access barrier, as it may be difficult not just to find a therapist but one who has experience working with gender-diverse youth.”

Insurance coverage, including lack thereof, is yet another barrier to care for transgender youth, said Dr. Cooper. “While many insurance companies have begun to cover medications such as testosterone and estrogen for gender-affirming care, many still have exclusions on things like puberty blockers and surgical interventions.” These interventions can be lifesaving, but financially prohibitive for many families if not covered by insurance.

As for the value of early timing of gender-affirming care, Dr. Cooper agreed with the study findings that the earlier that a young person can get into medical care for their gender identity, the better chance there is to reduce the prevalence of serious mental health outcomes. “This also prevents the potential development of secondary sexual characteristics, decreasing the need for or amount of surgery in the future if desired,” he said.

“More research is needed to better understand the reasons why many youth don’t present to care until later in puberty. In addition, we need better research on interventions that are effective at reducing serious mental health events in transgender and gender diverse youth,” Dr. Cooper stated. “Another area that I would like to see researched is looking at the mental health of non-Caucasian youth. As the authors noted in their study, many clinics have a high percentage of patients presenting for care who identify as White or Caucasian, and we need to better understand why these other youth are not presenting for care.”

The study received no outside funding. Dr. Sorbara disclosed salary support from the Canadian Pediatric Endocrine Group fellowship program. Dr. de Vries had no financial conflicts to disclose. Dr. Cooper had no financial conflicts to disclose, and serves as a contributor to LGBTQ Youth Consult in Pediatric News.

SOURCES: Sorbara JC et al. Pediatrics. 2020 Sep 21. doi: 10.1542/peds.2019-3600; de Vries ALC et al. Pediatrics. 2020 Sep 21. doi: 10.1542/peds.2020-010611.

Gender-incongruent youth who present for gender-affirming medical care later in adolescence have higher rates of mental health problems than their younger counterparts, based on data from a review of 300 individuals.

Peerayot/Thinkstock.com

“Puberty is a vulnerable time for youth with gender dysphoria because distress may intensify with the development of secondary sex characteristics corresponding to the assigned rather than the experienced gender,” wrote Julia C. Sorbara, MD, of the University of Toronto and the Hospital for Sick Children, also in Toronto, and colleagues.

Although gender-affirming medical care (GAMC) in the form of hormone blockers and/or gender-affirming hormones early in puberty can decrease in emotional and behavioral problems, many teens present later in puberty, and the relationship between pubertal stage at presentation for treatment and mental health has not been examined, they wrote.

In a study published in Pediatrics, the researchers reviewed data from youth with gender incongruence who were seen at a single center; 116 were younger than 15 years at presentation for GAMC and were defined as younger-presenting youth (YPY), and 184 patients aged 15 years and older were defined as older-presenting youth (OPY).

Overall, 78% of the youth reported at least one mental health problem at their initial visit. Significantly more OPY than YPY reported diagnosed depression (46% vs. 30%), self-harm (40% vs. 28%), suicidal thoughts (52% vs. 40%), suicide attempts (17% vs. 9%), and use of psychoactive medications (36% vs. 23%), all with P < .05.

In a multivariate analysis, patients in Tanner stages 4 and 5 were five times more likely to experience depressive disorders (odds ratio, 5.49) and four times as likely to experience depressive disorders (OR, 4.18) as those in earlier Tanner stages. Older age remained significantly associated with use of psychoactive medications (OR, 1.31), but not with anxiety or depression, the researchers wrote.

The YPY group were significantly younger at the age of recognizing gender incongruence, compared with the OPY group, with median ages at recognition of 5.8 years and 9 years, respectively, and younger patients came out about their gender identity at an average of 12 years, compared with 15 years for older patients.

The quantitative data are among the first to relate pubertal stage to mental health in gender-incongruent youth, “supporting clinical observations that pubertal development, menses, and erections are distressing to these youth and consistent with the beneficial role of pubertal suppression, even when used as monotherapy without gender-affirming hormones,” Dr. Sorbara and associates wrote.

The study findings were limited by several factors including the cross-sectional design and the collection of mental health data at only one time point and by the use of self-reports. However, the results suggest that “[gender-incongruent] youth who present to GAMC later in life are a particularly high-risk subset of a vulnerable population,” they noted. “Further study is required to better describe the mental health trajectories of transgender youth and determine if mental health status or age at initiation of GAMC is correlated with psychological well-being in adulthood.”
 

Don’t rush to puberty suppression in younger teens

To reduce the stress of puberty on gender-nonconforming youth, puberty suppression as “a reversible medical intervention” was introduced by Dutch clinicians in the early 2000s, Annelou L.C. de Vries, MD, PhD, of Amsterdam University Medical Center, wrote in an accompanying editorial.

“The aim of puberty suppression was to prevent the psychological suffering stemming from undesired physical changes when puberty starts and allowing the adolescent time to make plans regarding further transition or not,” Dr. de Vries said. “Following this rationale, younger age at the time of starting medical-affirming treatment (puberty suppression or hormones) would be expected to correlate with fewer psychological difficulties related to physical changes than older individuals,” which was confirmed in the current study.

However, clinicians should be cautious in offering puberty suppression at a younger age, in part because “despite the increased availability of gender-affirming medical interventions for younger ages in recent years, there has not been a proportional decline in older presenting youth with gender incongruence,” she said.

More data are needed on youth with postpuberty adolescent-onset transgender histories. The original Dutch studies on gender-affirming medical interventions note case histories describing “the complexities that may be associated with later-presenting transgender adolescents and describe that some eventually detransition,” Dr. de Vries explained.

Ultimately, prospective studies with longer follow-up data are needed to better inform clinicians in developing an individualized treatment plan for youth with gender incongruence, Dr. de Vries concluded.
 

Care barriers can include parents, access, insurance

The study authors describe the situation of gender-affirming medical care in teens perfectly, M. Brett Cooper, MD, of the University of Texas Southwestern Medical Center/Children’s Health Dallas, said in an interview.

Given a variety of factors that need further exploration, “many youth often don’t end up seeking gender-affirming medical care until puberty has progressed to near full maturity,” he said. “The findings from this study provide preliminary evidence to show that if we can identify these youth earlier in their gender journey, we might be able to impact adverse mental health outcomes in a positive way.”

Dr. Cooper said he was not surprised by the study findings. “They are similar to what I see in my clinic.

“Many of our patients often don’t present for medical care until around age 15 or older, similar to the findings of the study,” he added. “The majority of our patients have had a diagnosis of anxiety or depression at some point in their lifetime, including inpatient hospitalizations for their mental health.”

One of the most important barriers to care often can be parents or guardians, said Dr. Cooper. “Young people usually know their gender identity by about age 4-5 but parents may think that a gender-diverse identity could simply be a ‘phase.’ Other times, young people may hide their identity out of fear of a negative reaction from their parents. The distress around identity may become more pronounced once pubertal changes, such as breast and testicle development, begin to worsen their dysphoria.”

“Another barrier to care can be the inability to find a competent, gender-affirming provider,” Dr. Cooper said. “Most large United States cities have at least one gender-affirming clinic, but for those youth who grow up in smaller towns, it may be difficult to access these clinics. In addition, some clinics require a letter from a therapist stating that the young person is transgender before they can be seen for medical care. This creates an access barrier, as it may be difficult not just to find a therapist but one who has experience working with gender-diverse youth.”

Insurance coverage, including lack thereof, is yet another barrier to care for transgender youth, said Dr. Cooper. “While many insurance companies have begun to cover medications such as testosterone and estrogen for gender-affirming care, many still have exclusions on things like puberty blockers and surgical interventions.” These interventions can be lifesaving, but financially prohibitive for many families if not covered by insurance.

As for the value of early timing of gender-affirming care, Dr. Cooper agreed with the study findings that the earlier that a young person can get into medical care for their gender identity, the better chance there is to reduce the prevalence of serious mental health outcomes. “This also prevents the potential development of secondary sexual characteristics, decreasing the need for or amount of surgery in the future if desired,” he said.

“More research is needed to better understand the reasons why many youth don’t present to care until later in puberty. In addition, we need better research on interventions that are effective at reducing serious mental health events in transgender and gender diverse youth,” Dr. Cooper stated. “Another area that I would like to see researched is looking at the mental health of non-Caucasian youth. As the authors noted in their study, many clinics have a high percentage of patients presenting for care who identify as White or Caucasian, and we need to better understand why these other youth are not presenting for care.”

The study received no outside funding. Dr. Sorbara disclosed salary support from the Canadian Pediatric Endocrine Group fellowship program. Dr. de Vries had no financial conflicts to disclose. Dr. Cooper had no financial conflicts to disclose, and serves as a contributor to LGBTQ Youth Consult in Pediatric News.

SOURCES: Sorbara JC et al. Pediatrics. 2020 Sep 21. doi: 10.1542/peds.2019-3600; de Vries ALC et al. Pediatrics. 2020 Sep 21. doi: 10.1542/peds.2020-010611.

An 80-year-old woman with a history of hypertension, hyperlipidemia, psoriasis vulgaris with associated pruritus, and well-controlled type 2 diabetes mellitus presented with a slowly enlarging ulceration on her left leg of 1 year’s duration. She noted that this lesion healed less rapidly than previous stasis leg ulcerations, despite using the same treatment approach that included dressings, elevation, and diuretics to decrease pedal edema.

Physical examination revealed plaques with white micaceous scaling over her extensor surfaces and scalp, as well as guttate lesions on the trunk, typical of psoriasis vulgaris. A 5.8 × 7.2-cm malodorous ulceration was superimposed on a large psoriatic plaque on her left anterior lower leg (FIGURE 1). A 4-mm punch biopsy was obtained from the peripheral margin.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Histopathological examination revealed elongated strands of closely packed basaloid cells embedded in a dense fibrous stroma with overlying ulceration and crusting (FIGURE 2). Immunohistochemical staining with cytokeratin (CK) 5/6 decorated the cytoplasm of the tumor cells, which confirmed that the tumor was a keratinocyte cancer. CK 20 was negative, excluding the possibility of a Merkel cell carcinoma. Scout biopsies from 3 additional areas of ulceration confirmed that the entire ulceration was infiltrated by basal cell carcinoma (BCC).

IMAGE COURTESY OF ROBERT BRODELL, MD

A surprise hidden in a chronic ulcer

More than 6 million Americans have chronic ulcers and most occur on the legs.¹ The majority of these chronic ulcerations are etiologically related to venous stasis, arterial insufficiency, or neuropathy.²

Bacterial pyoderma, chronic infection caused by atypical acid-fast bacilli or deep fungal infection, pyoderma gangrenosum, cutaneous vasculitis, calciphylaxis, and venous ulceration were all considered to explain this patient’s nonhealing wound. A biopsy was required to fully assess these possibilities.

Don’t overlook the possibility of malignancy. In a cross-sectional, multicenter study by Senet et al,³ 144 patients with 154 total chronic leg ulcers were evaluated in tertiary care centers for malignancy, which was found to occur at a rate of 10.4%. Similarly, Ghasemi et al⁴ demonstrated a malignancy rate of 16.1% in 124 patients who underwent biopsy; the anterior shin was determined to be the most frequent location for malignancy. The most common skin cancer identified within the setting of chronic ulcers is squamous cell carcinoma.³ Although rare, there are reports of BCC identified in chronic wounds.^3-7

Morphological signs suggestive of malignancy in chronic ulcerations include hyperkeratosis, granulation tissue surrounded by a raised border, unusual pain or bleeding, and increased tissue friability. Our patient had none of these signs and symptoms. However, it is possible that she had a tumor that ulcerated and would not heal.

Continue to: Which came first?

Which came first? It’s difficult to know in this case whether a persistent BCC ulcerated, forming this lesion, or if scarring associated with a chronic ulceration led to the development of the BCC.⁶ Based on biopsies taken at an earlier date, Schnirring-Judge and Belpedio⁷ concluded that a chronic leg ulcer could, indeed, transform into a BCC; however, pre-existing BCC more commonly ulcerates and then does not heal.

Treatment options

While smaller, superficial BCCs can be treated with topical imiquimod, photodynamic therapy, or electrodesiccation and curettage, larger lesions should be treated with Mohs micrographic surgery and excisional surgery with grafting. Inoperable tumors may be treated with radiation therapy and vismodegib.

Our patient. Once the diagnosis of BCC was established, treatment options were discussed, including excision, local radiation therapy, and oral hedgehog inhibitor drug therapy.⁸ Our patient opted to undergo a wide local excision of the lesion followed by negative-pressure wound therapy, which led to complete healing.

CORRESPONDENCE
David Crasto, DO, William Carey University College of Osteopathic Medicine, 498 Tuscan Avenue, Hattiesburg, MS 39401; [email protected]

An 80-year-old woman with a history of hypertension, hyperlipidemia, psoriasis vulgaris with associated pruritus, and well-controlled type 2 diabetes mellitus presented with a slowly enlarging ulceration on her left leg of 1 year’s duration. She noted that this lesion healed less rapidly than previous stasis leg ulcerations, despite using the same treatment approach that included dressings, elevation, and diuretics to decrease pedal edema.

Physical examination revealed plaques with white micaceous scaling over her extensor surfaces and scalp, as well as guttate lesions on the trunk, typical of psoriasis vulgaris. A 5.8 × 7.2-cm malodorous ulceration was superimposed on a large psoriatic plaque on her left anterior lower leg (FIGURE 1). A 4-mm punch biopsy was obtained from the peripheral margin.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Histopathological examination revealed elongated strands of closely packed basaloid cells embedded in a dense fibrous stroma with overlying ulceration and crusting (FIGURE 2). Immunohistochemical staining with cytokeratin (CK) 5/6 decorated the cytoplasm of the tumor cells, which confirmed that the tumor was a keratinocyte cancer. CK 20 was negative, excluding the possibility of a Merkel cell carcinoma. Scout biopsies from 3 additional areas of ulceration confirmed that the entire ulceration was infiltrated by basal cell carcinoma (BCC).

IMAGE COURTESY OF ROBERT BRODELL, MD

A surprise hidden in a chronic ulcer

More than 6 million Americans have chronic ulcers and most occur on the legs.¹ The majority of these chronic ulcerations are etiologically related to venous stasis, arterial insufficiency, or neuropathy.²

Bacterial pyoderma, chronic infection caused by atypical acid-fast bacilli or deep fungal infection, pyoderma gangrenosum, cutaneous vasculitis, calciphylaxis, and venous ulceration were all considered to explain this patient’s nonhealing wound. A biopsy was required to fully assess these possibilities.

Don’t overlook the possibility of malignancy. In a cross-sectional, multicenter study by Senet et al,³ 144 patients with 154 total chronic leg ulcers were evaluated in tertiary care centers for malignancy, which was found to occur at a rate of 10.4%. Similarly, Ghasemi et al⁴ demonstrated a malignancy rate of 16.1% in 124 patients who underwent biopsy; the anterior shin was determined to be the most frequent location for malignancy. The most common skin cancer identified within the setting of chronic ulcers is squamous cell carcinoma.³ Although rare, there are reports of BCC identified in chronic wounds.^3-7

Morphological signs suggestive of malignancy in chronic ulcerations include hyperkeratosis, granulation tissue surrounded by a raised border, unusual pain or bleeding, and increased tissue friability. Our patient had none of these signs and symptoms. However, it is possible that she had a tumor that ulcerated and would not heal.

Continue to: Which came first?

Which came first? It’s difficult to know in this case whether a persistent BCC ulcerated, forming this lesion, or if scarring associated with a chronic ulceration led to the development of the BCC.⁶ Based on biopsies taken at an earlier date, Schnirring-Judge and Belpedio⁷ concluded that a chronic leg ulcer could, indeed, transform into a BCC; however, pre-existing BCC more commonly ulcerates and then does not heal.

Treatment options

While smaller, superficial BCCs can be treated with topical imiquimod, photodynamic therapy, or electrodesiccation and curettage, larger lesions should be treated with Mohs micrographic surgery and excisional surgery with grafting. Inoperable tumors may be treated with radiation therapy and vismodegib.

Our patient. Once the diagnosis of BCC was established, treatment options were discussed, including excision, local radiation therapy, and oral hedgehog inhibitor drug therapy.⁸ Our patient opted to undergo a wide local excision of the lesion followed by negative-pressure wound therapy, which led to complete healing.

CORRESPONDENCE
David Crasto, DO, William Carey University College of Osteopathic Medicine, 498 Tuscan Avenue, Hattiesburg, MS 39401; [email protected]

An 80-year-old woman with a history of hypertension, hyperlipidemia, psoriasis vulgaris with associated pruritus, and well-controlled type 2 diabetes mellitus presented with a slowly enlarging ulceration on her left leg of 1 year’s duration. She noted that this lesion healed less rapidly than previous stasis leg ulcerations, despite using the same treatment approach that included dressings, elevation, and diuretics to decrease pedal edema.

Physical examination revealed plaques with white micaceous scaling over her extensor surfaces and scalp, as well as guttate lesions on the trunk, typical of psoriasis vulgaris. A 5.8 × 7.2-cm malodorous ulceration was superimposed on a large psoriatic plaque on her left anterior lower leg (FIGURE 1). A 4-mm punch biopsy was obtained from the peripheral margin.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Histopathological examination revealed elongated strands of closely packed basaloid cells embedded in a dense fibrous stroma with overlying ulceration and crusting (FIGURE 2). Immunohistochemical staining with cytokeratin (CK) 5/6 decorated the cytoplasm of the tumor cells, which confirmed that the tumor was a keratinocyte cancer. CK 20 was negative, excluding the possibility of a Merkel cell carcinoma. Scout biopsies from 3 additional areas of ulceration confirmed that the entire ulceration was infiltrated by basal cell carcinoma (BCC).

IMAGE COURTESY OF ROBERT BRODELL, MD

A surprise hidden in a chronic ulcer

More than 6 million Americans have chronic ulcers and most occur on the legs.¹ The majority of these chronic ulcerations are etiologically related to venous stasis, arterial insufficiency, or neuropathy.²

Bacterial pyoderma, chronic infection caused by atypical acid-fast bacilli or deep fungal infection, pyoderma gangrenosum, cutaneous vasculitis, calciphylaxis, and venous ulceration were all considered to explain this patient’s nonhealing wound. A biopsy was required to fully assess these possibilities.

Don’t overlook the possibility of malignancy. In a cross-sectional, multicenter study by Senet et al,³ 144 patients with 154 total chronic leg ulcers were evaluated in tertiary care centers for malignancy, which was found to occur at a rate of 10.4%. Similarly, Ghasemi et al⁴ demonstrated a malignancy rate of 16.1% in 124 patients who underwent biopsy; the anterior shin was determined to be the most frequent location for malignancy. The most common skin cancer identified within the setting of chronic ulcers is squamous cell carcinoma.³ Although rare, there are reports of BCC identified in chronic wounds.^3-7

Morphological signs suggestive of malignancy in chronic ulcerations include hyperkeratosis, granulation tissue surrounded by a raised border, unusual pain or bleeding, and increased tissue friability. Our patient had none of these signs and symptoms. However, it is possible that she had a tumor that ulcerated and would not heal.

Continue to: Which came first?

Which came first? It’s difficult to know in this case whether a persistent BCC ulcerated, forming this lesion, or if scarring associated with a chronic ulceration led to the development of the BCC.⁶ Based on biopsies taken at an earlier date, Schnirring-Judge and Belpedio⁷ concluded that a chronic leg ulcer could, indeed, transform into a BCC; however, pre-existing BCC more commonly ulcerates and then does not heal.

Treatment options

While smaller, superficial BCCs can be treated with topical imiquimod, photodynamic therapy, or electrodesiccation and curettage, larger lesions should be treated with Mohs micrographic surgery and excisional surgery with grafting. Inoperable tumors may be treated with radiation therapy and vismodegib.

Our patient. Once the diagnosis of BCC was established, treatment options were discussed, including excision, local radiation therapy, and oral hedgehog inhibitor drug therapy.⁸ Our patient opted to undergo a wide local excision of the lesion followed by negative-pressure wound therapy, which led to complete healing.

CORRESPONDENCE
David Crasto, DO, William Carey University College of Osteopathic Medicine, 498 Tuscan Avenue, Hattiesburg, MS 39401; [email protected]

Rates of human papillomavirus vaccination increased for both boys and girls in the United States over the past decade, but remain below target levels and vary widely across states based on data from a nested cohort study including more than 7 million children.

Dzurag/iStock/Getty Images

“Understanding regional and temporal variations in HPV vaccination coverage may help improve HPV vaccination uptake by informing public health policy,” Szu-Ta Chen, MD, of Harvard University, Boston, and colleagues wrote in Pediatrics.

To identify trends in one-dose and two-dose human papillomavirus (HPV) vaccination coverage, the researchers reviewed data from the MarketScan health care database between January 2003 and December 2017 that included 7,837,480 children and 19,843,737 person-years. The children were followed starting at age 9, when HPV vaccination could begin, and ending at one of the following: the first or second vaccination, insurance disenrollment, December 2017, or the end of the year in which they turned 17.

Overall, the proportion of 15-year-old girls and boys with at least a one-dose HPV vaccination increased from 38% and 5%, respectively, in 2011 to 57% and 51%, respectively, in 2017. The comparable proportions of girls and boys with at least a two-dose vaccination increased from 30% and 2%, respectively, in 2011 to 46% and 39%, respectively, in 2017.

Coverage lacks consistency across states

However, the vaccination coverage varied widely across states; two-dose HPV vaccination coverage ranged from 80% of girls in the District of Columbia to 15% of boys in Mississippi. In general, states with more HPV vaccine interventions had higher levels of vaccination, the researchers noted.

Legislation to improve vaccination education showed the strongest association with coverage; an 8.8% increase in coverage for girls and an 8.7% increase for boys. Pediatrician availability also was a factor associated with a 1.1% increase in coverage estimated for every pediatrician per 10,000 children.

Cumulative HPV vaccinations seen among children continuously enrolled in the study were similar to the primary analysis, the Dr. Chen and associates said. “After the initial HPV vaccination, 87% of girls and 82% of boys received a second dose by age 17 in the most recent cohorts.”

However, the HPV vaccination coverage remains below the Healthy People 2020 goal of 80% of children vaccinated by age 15 years, the researchers said. Barriers to vaccination may include a lack of routine clinical encounters in adolescents aged 11-17 years. HPV vaccination coverage was higher in urban populations, compared with rural, which may be related to a lack of providers in rural areas.

“Thus, measures beyond recommending routine vaccination at annual check-ups might be necessary to attain sufficient HPV vaccine coverage, and the optimal strategy may differ by state characteristics,” they wrote.

The study findings were limited by several factors including the use of data from only commercially-insured children and lack of data on vaccines received outside of insurance, the researchers noted.

However, the results were strengthened by the large, population-based sample, and support the need for increased efforts in HPV vaccination. “Most states will not achieve the Healthy People 2020 goal of 80% coverage with at least two HPV vaccine doses by 2020,” Dr. Chen and associates concluded.

Vaccination goals are possible with effort in the right places

The fact of below-target vaccination for HPV in the United States may be old news, but the current study offers new insights on HPV uptake, Amanda F. Dempsey, MD, PhD, of the University of Colorado at Denver, in Aurora, wrote in an accompanying editorial.

“A unique feature of this study is the ability of its researchers to study individuals over time, particularly at a national scope,” which yielded two key messages, she said.

The longitudinal examination of vaccination levels among birth cohorts showed that similar vaccination levels were achieved more quickly each year.

“For example, among the birth cohort from the year 2000, representing 17-year-olds at the time data were abstracted for the study, 40% vaccination coverage was achieved when this group was 14 years old. In contrast, among the birth cohort from the year 2005, representing 12-year-olds at the time of data abstraction, 40% vaccination coverage was reached at the age of 12,” Dr. Dempsey explained.

In addition, the study design allowed the researchers to model future vaccine coverage based on current trends, said Dr. Dempsey. “The authors estimate that, by the year 2022, the 2012 birth cohort will have reached 80% coverage for the first dose in the HPV vaccine series.”

Dr. Dempsey said she was surprised that the models did not support the hypothesis that school mandates for vaccination would increase coverage; however, there were few states in this category.

Although the findings were limited by the lack of data on uninsured children and those insured by Medicaid, the state-by-state results show that the achievement of national vaccination goals is possible, Dr. Dempsey said. In addition, the findings “warrant close consideration by policy makers and the medical community at large regarding vaccination policies and workforce,” she emphasized.The study received no outside funding. Dr. Chen had no financial conflicts to disclose. Several coauthors reported research grants to their institutions from pharmaceutical companies or being consultants to such companies. Dr. Dempsey disclosed serving on the advisory boards for Merck, Pfizer, and Sanofi Pasteur.

SOURCE: Chen S-T et al. Pediatrics. 2020 Sep 14. doi: 10.1542/peds.2019-3557.

Rates of human papillomavirus vaccination increased for both boys and girls in the United States over the past decade, but remain below target levels and vary widely across states based on data from a nested cohort study including more than 7 million children.

Dzurag/iStock/Getty Images

“Understanding regional and temporal variations in HPV vaccination coverage may help improve HPV vaccination uptake by informing public health policy,” Szu-Ta Chen, MD, of Harvard University, Boston, and colleagues wrote in Pediatrics.

To identify trends in one-dose and two-dose human papillomavirus (HPV) vaccination coverage, the researchers reviewed data from the MarketScan health care database between January 2003 and December 2017 that included 7,837,480 children and 19,843,737 person-years. The children were followed starting at age 9, when HPV vaccination could begin, and ending at one of the following: the first or second vaccination, insurance disenrollment, December 2017, or the end of the year in which they turned 17.

Overall, the proportion of 15-year-old girls and boys with at least a one-dose HPV vaccination increased from 38% and 5%, respectively, in 2011 to 57% and 51%, respectively, in 2017. The comparable proportions of girls and boys with at least a two-dose vaccination increased from 30% and 2%, respectively, in 2011 to 46% and 39%, respectively, in 2017.

Coverage lacks consistency across states

However, the vaccination coverage varied widely across states; two-dose HPV vaccination coverage ranged from 80% of girls in the District of Columbia to 15% of boys in Mississippi. In general, states with more HPV vaccine interventions had higher levels of vaccination, the researchers noted.

Legislation to improve vaccination education showed the strongest association with coverage; an 8.8% increase in coverage for girls and an 8.7% increase for boys. Pediatrician availability also was a factor associated with a 1.1% increase in coverage estimated for every pediatrician per 10,000 children.

Cumulative HPV vaccinations seen among children continuously enrolled in the study were similar to the primary analysis, the Dr. Chen and associates said. “After the initial HPV vaccination, 87% of girls and 82% of boys received a second dose by age 17 in the most recent cohorts.”

However, the HPV vaccination coverage remains below the Healthy People 2020 goal of 80% of children vaccinated by age 15 years, the researchers said. Barriers to vaccination may include a lack of routine clinical encounters in adolescents aged 11-17 years. HPV vaccination coverage was higher in urban populations, compared with rural, which may be related to a lack of providers in rural areas.

“Thus, measures beyond recommending routine vaccination at annual check-ups might be necessary to attain sufficient HPV vaccine coverage, and the optimal strategy may differ by state characteristics,” they wrote.

The study findings were limited by several factors including the use of data from only commercially-insured children and lack of data on vaccines received outside of insurance, the researchers noted.

However, the results were strengthened by the large, population-based sample, and support the need for increased efforts in HPV vaccination. “Most states will not achieve the Healthy People 2020 goal of 80% coverage with at least two HPV vaccine doses by 2020,” Dr. Chen and associates concluded.

Vaccination goals are possible with effort in the right places

The fact of below-target vaccination for HPV in the United States may be old news, but the current study offers new insights on HPV uptake, Amanda F. Dempsey, MD, PhD, of the University of Colorado at Denver, in Aurora, wrote in an accompanying editorial.

“A unique feature of this study is the ability of its researchers to study individuals over time, particularly at a national scope,” which yielded two key messages, she said.

The longitudinal examination of vaccination levels among birth cohorts showed that similar vaccination levels were achieved more quickly each year.

“For example, among the birth cohort from the year 2000, representing 17-year-olds at the time data were abstracted for the study, 40% vaccination coverage was achieved when this group was 14 years old. In contrast, among the birth cohort from the year 2005, representing 12-year-olds at the time of data abstraction, 40% vaccination coverage was reached at the age of 12,” Dr. Dempsey explained.

In addition, the study design allowed the researchers to model future vaccine coverage based on current trends, said Dr. Dempsey. “The authors estimate that, by the year 2022, the 2012 birth cohort will have reached 80% coverage for the first dose in the HPV vaccine series.”

Dr. Dempsey said she was surprised that the models did not support the hypothesis that school mandates for vaccination would increase coverage; however, there were few states in this category.

Although the findings were limited by the lack of data on uninsured children and those insured by Medicaid, the state-by-state results show that the achievement of national vaccination goals is possible, Dr. Dempsey said. In addition, the findings “warrant close consideration by policy makers and the medical community at large regarding vaccination policies and workforce,” she emphasized.The study received no outside funding. Dr. Chen had no financial conflicts to disclose. Several coauthors reported research grants to their institutions from pharmaceutical companies or being consultants to such companies. Dr. Dempsey disclosed serving on the advisory boards for Merck, Pfizer, and Sanofi Pasteur.

SOURCE: Chen S-T et al. Pediatrics. 2020 Sep 14. doi: 10.1542/peds.2019-3557.

Rates of human papillomavirus vaccination increased for both boys and girls in the United States over the past decade, but remain below target levels and vary widely across states based on data from a nested cohort study including more than 7 million children.

Dzurag/iStock/Getty Images

“Understanding regional and temporal variations in HPV vaccination coverage may help improve HPV vaccination uptake by informing public health policy,” Szu-Ta Chen, MD, of Harvard University, Boston, and colleagues wrote in Pediatrics.

To identify trends in one-dose and two-dose human papillomavirus (HPV) vaccination coverage, the researchers reviewed data from the MarketScan health care database between January 2003 and December 2017 that included 7,837,480 children and 19,843,737 person-years. The children were followed starting at age 9, when HPV vaccination could begin, and ending at one of the following: the first or second vaccination, insurance disenrollment, December 2017, or the end of the year in which they turned 17.

Overall, the proportion of 15-year-old girls and boys with at least a one-dose HPV vaccination increased from 38% and 5%, respectively, in 2011 to 57% and 51%, respectively, in 2017. The comparable proportions of girls and boys with at least a two-dose vaccination increased from 30% and 2%, respectively, in 2011 to 46% and 39%, respectively, in 2017.

Coverage lacks consistency across states

However, the vaccination coverage varied widely across states; two-dose HPV vaccination coverage ranged from 80% of girls in the District of Columbia to 15% of boys in Mississippi. In general, states with more HPV vaccine interventions had higher levels of vaccination, the researchers noted.

Legislation to improve vaccination education showed the strongest association with coverage; an 8.8% increase in coverage for girls and an 8.7% increase for boys. Pediatrician availability also was a factor associated with a 1.1% increase in coverage estimated for every pediatrician per 10,000 children.

Cumulative HPV vaccinations seen among children continuously enrolled in the study were similar to the primary analysis, the Dr. Chen and associates said. “After the initial HPV vaccination, 87% of girls and 82% of boys received a second dose by age 17 in the most recent cohorts.”

However, the HPV vaccination coverage remains below the Healthy People 2020 goal of 80% of children vaccinated by age 15 years, the researchers said. Barriers to vaccination may include a lack of routine clinical encounters in adolescents aged 11-17 years. HPV vaccination coverage was higher in urban populations, compared with rural, which may be related to a lack of providers in rural areas.

“Thus, measures beyond recommending routine vaccination at annual check-ups might be necessary to attain sufficient HPV vaccine coverage, and the optimal strategy may differ by state characteristics,” they wrote.

The study findings were limited by several factors including the use of data from only commercially-insured children and lack of data on vaccines received outside of insurance, the researchers noted.

However, the results were strengthened by the large, population-based sample, and support the need for increased efforts in HPV vaccination. “Most states will not achieve the Healthy People 2020 goal of 80% coverage with at least two HPV vaccine doses by 2020,” Dr. Chen and associates concluded.

Vaccination goals are possible with effort in the right places

The fact of below-target vaccination for HPV in the United States may be old news, but the current study offers new insights on HPV uptake, Amanda F. Dempsey, MD, PhD, of the University of Colorado at Denver, in Aurora, wrote in an accompanying editorial.

“A unique feature of this study is the ability of its researchers to study individuals over time, particularly at a national scope,” which yielded two key messages, she said.

The longitudinal examination of vaccination levels among birth cohorts showed that similar vaccination levels were achieved more quickly each year.

“For example, among the birth cohort from the year 2000, representing 17-year-olds at the time data were abstracted for the study, 40% vaccination coverage was achieved when this group was 14 years old. In contrast, among the birth cohort from the year 2005, representing 12-year-olds at the time of data abstraction, 40% vaccination coverage was reached at the age of 12,” Dr. Dempsey explained.

In addition, the study design allowed the researchers to model future vaccine coverage based on current trends, said Dr. Dempsey. “The authors estimate that, by the year 2022, the 2012 birth cohort will have reached 80% coverage for the first dose in the HPV vaccine series.”

Dr. Dempsey said she was surprised that the models did not support the hypothesis that school mandates for vaccination would increase coverage; however, there were few states in this category.

Although the findings were limited by the lack of data on uninsured children and those insured by Medicaid, the state-by-state results show that the achievement of national vaccination goals is possible, Dr. Dempsey said. In addition, the findings “warrant close consideration by policy makers and the medical community at large regarding vaccination policies and workforce,” she emphasized.The study received no outside funding. Dr. Chen had no financial conflicts to disclose. Several coauthors reported research grants to their institutions from pharmaceutical companies or being consultants to such companies. Dr. Dempsey disclosed serving on the advisory boards for Merck, Pfizer, and Sanofi Pasteur.

SOURCE: Chen S-T et al. Pediatrics. 2020 Sep 14. doi: 10.1542/peds.2019-3557.

THE CASE

A 28-year-old woman with an extensive psychiatric history—including generalized anxiety disorder, panic disorder, and recent postpartum depression—presented with a chief complaint of right leg weakness. She stated this weakness had begun 4 days earlier. It occurred episodically and was preceded by tingling and cramping sensations. Each episode lasted a couple of minutes and spontaneously resolved. Associated with it, she experienced slurred speech and altered mentation. There was no loss of consciousness and no pain. A panic attack usually followed, consisting of feelings of impending doom, rapid breathing, palpitations, and nausea.

She had 3 prior diagnostic evaluations for this same chief complaint, twice in an emergency department (ED) and once with her primary care physician. These evaluations included lab work and extensive head imaging, which demonstrated no acute intracranial pathology. At each previous presentation, the diagnosis was an exacerbation of her anxiety disorder, and she was treated with lorazepam.

At the current presentation, her vital signs were stable. Examination revealed a notably anxious patient. She repeatedly expressed concern that she might have a brain tumor or some other deadly disease, as she had a family history of brain cancer. Her physical exam was entirely normal, including normal strength, sensation, and reflexes in all extremities.

Further head imaging (computed tomography, CT angiography, and magnetic resonance imaging of the brain) failed to reveal an etiology of her symptoms. With no clear organic cause, her medical providers again suspected an anxiety or panic episode. She was given reassurance, and an outpatient neurology consult was arranged.

THE DIAGNOSIS

One week later, at her outpatient neurology appointment, an electroencephalogram (EEG) was performed. Following photic stimulation, the EEG showed multiple right- and left-hemisphere foci of cortical hyperexcitability including a subtle sharp component (see FIGURE). Immediately following the longest of these episodes, the patient expressed a sense of anxiety and an altered sensorium similar to her prior presentations.

The EEG findings, in addition to the postictal anxiety symptoms and clinical history, were all important components that led the treating neurologist to the diagnosis of localization-related (focal) epilepsy.¹ The patient was started on oxcarbazepine, a first-line anti-epileptic medication used in the treatment of focal epilepsy.² She is being followed by a neurologist regularly and after optimizing her anti-epileptic medication, is no longer having seizures.

DISCUSSION

The difficulty of this case stems from the atypical presentation of the patient’s seizures. The key step to the correct diagnosis was a neurological consultation and an ensuing EEG. However, the patient received a vast spectrum of care, including multiple work-ups, prior to a conclusive diagnosis—which highlights an important issue health care providers must address.

Continue to: The role of bias

The role of bias. From the patient’s initial visits to the ED to her hospital admission, there was a prominent affixation, known as the anchoring bias,³ by the clinicians providing her care: All were focused heavily on her psychiatric features. Conversely, the evaluation for patients with suspected psychiatric diagnoses should focus on successfully ruling out major organic etiology with a broad differential diagnosis. It is crucial for providers to take a step back and make a conscious attempt to avoid fixation on a particular diagnosis, especially when it is psychiatric in nature. This allows the provider to actively consider alternative explanations for a patient presentation and work through a more encompassing differential.

The distinguishing symptoms. There is a common association between comorbid mood disorders (eg, depression, anxiety) and epilepsy.⁴ Another clue is ictal anxiety or nervousness, which is commonly observed in patients with partial seizures (and occurred with our patient).

These ictal episodes can be difficult to identify within the context of an isolated psychiatric diagnosis.⁵ The distinction can be clarified by the presence of associated somatic symptoms, which in this case included unilateral cramping, paresthesia, and weakness. These symptoms should clue in a practitioner to the possibility of underlying neurologic pathology, which should prompt the ordering of either an EEG or, at minimum, a neurological consultation.

THE TAKEAWAY

This case report shows how anchoring bias can lead to a delay in diagnosis and treatment. Avoidance of this type of bias requires heightened cognitive awareness by medical providers. A more system-based approach is to have structured diagnostic assessments,⁶ such as conducting a thorough neurological exam for patients with somatic symptoms and exacerbating comorbid psychiatric conditions.

It may also help to review cases like this with colleagues from diverse disciplinary backgrounds, highlighting thought processes and sharing uncertainty.³ These processes may shed light on confounding diagnoses that might be playing a role in a patient’s presentation and ultimately aid in the decision-making process.

CORRESPONDENCE
Paimon Ameli, DO, Naval Medical Center San Diego, 34800 Bob Wilson Drive, San Diego, CA 92134; [email protected]

THE CASE

A 28-year-old woman with an extensive psychiatric history—including generalized anxiety disorder, panic disorder, and recent postpartum depression—presented with a chief complaint of right leg weakness. She stated this weakness had begun 4 days earlier. It occurred episodically and was preceded by tingling and cramping sensations. Each episode lasted a couple of minutes and spontaneously resolved. Associated with it, she experienced slurred speech and altered mentation. There was no loss of consciousness and no pain. A panic attack usually followed, consisting of feelings of impending doom, rapid breathing, palpitations, and nausea.

She had 3 prior diagnostic evaluations for this same chief complaint, twice in an emergency department (ED) and once with her primary care physician. These evaluations included lab work and extensive head imaging, which demonstrated no acute intracranial pathology. At each previous presentation, the diagnosis was an exacerbation of her anxiety disorder, and she was treated with lorazepam.

At the current presentation, her vital signs were stable. Examination revealed a notably anxious patient. She repeatedly expressed concern that she might have a brain tumor or some other deadly disease, as she had a family history of brain cancer. Her physical exam was entirely normal, including normal strength, sensation, and reflexes in all extremities.

Further head imaging (computed tomography, CT angiography, and magnetic resonance imaging of the brain) failed to reveal an etiology of her symptoms. With no clear organic cause, her medical providers again suspected an anxiety or panic episode. She was given reassurance, and an outpatient neurology consult was arranged.

THE DIAGNOSIS

One week later, at her outpatient neurology appointment, an electroencephalogram (EEG) was performed. Following photic stimulation, the EEG showed multiple right- and left-hemisphere foci of cortical hyperexcitability including a subtle sharp component (see FIGURE). Immediately following the longest of these episodes, the patient expressed a sense of anxiety and an altered sensorium similar to her prior presentations.

The EEG findings, in addition to the postictal anxiety symptoms and clinical history, were all important components that led the treating neurologist to the diagnosis of localization-related (focal) epilepsy.¹ The patient was started on oxcarbazepine, a first-line anti-epileptic medication used in the treatment of focal epilepsy.² She is being followed by a neurologist regularly and after optimizing her anti-epileptic medication, is no longer having seizures.

DISCUSSION

The difficulty of this case stems from the atypical presentation of the patient’s seizures. The key step to the correct diagnosis was a neurological consultation and an ensuing EEG. However, the patient received a vast spectrum of care, including multiple work-ups, prior to a conclusive diagnosis—which highlights an important issue health care providers must address.

Continue to: The role of bias

The role of bias. From the patient’s initial visits to the ED to her hospital admission, there was a prominent affixation, known as the anchoring bias,³ by the clinicians providing her care: All were focused heavily on her psychiatric features. Conversely, the evaluation for patients with suspected psychiatric diagnoses should focus on successfully ruling out major organic etiology with a broad differential diagnosis. It is crucial for providers to take a step back and make a conscious attempt to avoid fixation on a particular diagnosis, especially when it is psychiatric in nature. This allows the provider to actively consider alternative explanations for a patient presentation and work through a more encompassing differential.

The distinguishing symptoms. There is a common association between comorbid mood disorders (eg, depression, anxiety) and epilepsy.⁴ Another clue is ictal anxiety or nervousness, which is commonly observed in patients with partial seizures (and occurred with our patient).

These ictal episodes can be difficult to identify within the context of an isolated psychiatric diagnosis.⁵ The distinction can be clarified by the presence of associated somatic symptoms, which in this case included unilateral cramping, paresthesia, and weakness. These symptoms should clue in a practitioner to the possibility of underlying neurologic pathology, which should prompt the ordering of either an EEG or, at minimum, a neurological consultation.

THE TAKEAWAY

This case report shows how anchoring bias can lead to a delay in diagnosis and treatment. Avoidance of this type of bias requires heightened cognitive awareness by medical providers. A more system-based approach is to have structured diagnostic assessments,⁶ such as conducting a thorough neurological exam for patients with somatic symptoms and exacerbating comorbid psychiatric conditions.

It may also help to review cases like this with colleagues from diverse disciplinary backgrounds, highlighting thought processes and sharing uncertainty.³ These processes may shed light on confounding diagnoses that might be playing a role in a patient’s presentation and ultimately aid in the decision-making process.

CORRESPONDENCE
Paimon Ameli, DO, Naval Medical Center San Diego, 34800 Bob Wilson Drive, San Diego, CA 92134; [email protected]

THE CASE

A 28-year-old woman with an extensive psychiatric history—including generalized anxiety disorder, panic disorder, and recent postpartum depression—presented with a chief complaint of right leg weakness. She stated this weakness had begun 4 days earlier. It occurred episodically and was preceded by tingling and cramping sensations. Each episode lasted a couple of minutes and spontaneously resolved. Associated with it, she experienced slurred speech and altered mentation. There was no loss of consciousness and no pain. A panic attack usually followed, consisting of feelings of impending doom, rapid breathing, palpitations, and nausea.

She had 3 prior diagnostic evaluations for this same chief complaint, twice in an emergency department (ED) and once with her primary care physician. These evaluations included lab work and extensive head imaging, which demonstrated no acute intracranial pathology. At each previous presentation, the diagnosis was an exacerbation of her anxiety disorder, and she was treated with lorazepam.

At the current presentation, her vital signs were stable. Examination revealed a notably anxious patient. She repeatedly expressed concern that she might have a brain tumor or some other deadly disease, as she had a family history of brain cancer. Her physical exam was entirely normal, including normal strength, sensation, and reflexes in all extremities.

Further head imaging (computed tomography, CT angiography, and magnetic resonance imaging of the brain) failed to reveal an etiology of her symptoms. With no clear organic cause, her medical providers again suspected an anxiety or panic episode. She was given reassurance, and an outpatient neurology consult was arranged.

THE DIAGNOSIS

One week later, at her outpatient neurology appointment, an electroencephalogram (EEG) was performed. Following photic stimulation, the EEG showed multiple right- and left-hemisphere foci of cortical hyperexcitability including a subtle sharp component (see FIGURE). Immediately following the longest of these episodes, the patient expressed a sense of anxiety and an altered sensorium similar to her prior presentations.

The EEG findings, in addition to the postictal anxiety symptoms and clinical history, were all important components that led the treating neurologist to the diagnosis of localization-related (focal) epilepsy.¹ The patient was started on oxcarbazepine, a first-line anti-epileptic medication used in the treatment of focal epilepsy.² She is being followed by a neurologist regularly and after optimizing her anti-epileptic medication, is no longer having seizures.

DISCUSSION

The difficulty of this case stems from the atypical presentation of the patient’s seizures. The key step to the correct diagnosis was a neurological consultation and an ensuing EEG. However, the patient received a vast spectrum of care, including multiple work-ups, prior to a conclusive diagnosis—which highlights an important issue health care providers must address.

Continue to: The role of bias

The role of bias. From the patient’s initial visits to the ED to her hospital admission, there was a prominent affixation, known as the anchoring bias,³ by the clinicians providing her care: All were focused heavily on her psychiatric features. Conversely, the evaluation for patients with suspected psychiatric diagnoses should focus on successfully ruling out major organic etiology with a broad differential diagnosis. It is crucial for providers to take a step back and make a conscious attempt to avoid fixation on a particular diagnosis, especially when it is psychiatric in nature. This allows the provider to actively consider alternative explanations for a patient presentation and work through a more encompassing differential.

The distinguishing symptoms. There is a common association between comorbid mood disorders (eg, depression, anxiety) and epilepsy.⁴ Another clue is ictal anxiety or nervousness, which is commonly observed in patients with partial seizures (and occurred with our patient).

These ictal episodes can be difficult to identify within the context of an isolated psychiatric diagnosis.⁵ The distinction can be clarified by the presence of associated somatic symptoms, which in this case included unilateral cramping, paresthesia, and weakness. These symptoms should clue in a practitioner to the possibility of underlying neurologic pathology, which should prompt the ordering of either an EEG or, at minimum, a neurological consultation.

THE TAKEAWAY

This case report shows how anchoring bias can lead to a delay in diagnosis and treatment. Avoidance of this type of bias requires heightened cognitive awareness by medical providers. A more system-based approach is to have structured diagnostic assessments,⁶ such as conducting a thorough neurological exam for patients with somatic symptoms and exacerbating comorbid psychiatric conditions.

It may also help to review cases like this with colleagues from diverse disciplinary backgrounds, highlighting thought processes and sharing uncertainty.³ These processes may shed light on confounding diagnoses that might be playing a role in a patient’s presentation and ultimately aid in the decision-making process.

CORRESPONDENCE
Paimon Ameli, DO, Naval Medical Center San Diego, 34800 Bob Wilson Drive, San Diego, CA 92134; [email protected]