Mixed Topics

The new 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for blood pressure management for adults with chronic kidney disease (CKD) who are not receiving dialysis advises treating to a target systolic blood pressure of less than 120 mm Hg, provided measurements are “standardized” and that blood pressure is “measured properly.”

This blood pressure target – largely based on evidence from the Systolic Blood Pressure Intervention Trial (SPRINT) – represents “a major update” from the 2012 KDIGO guideline, which advised clinicians to treat to a target blood pressure of less than or equal to 130/80 mm Hg for patients with albuminuria or less than or equal to 140/90 mm Hg for patients without albuminuria.

The new goal is also lower than the less than 130/80 mm Hg target in the 2017 American College of Cardiology/American Heart Association guideline.

In a study of the public health implications of the guideline, Kathryn Foti, PhD, and colleagues determined that 70% of U.S. adults with CKD would now be eligible for treatment to lower blood pressure, as opposed to 50% under the previous KDIGO guideline and 56% under the ACC/AHA guideline.

“This is a major update of an influential set of guidelines for chronic kidney disease patients” at a time when blood pressure control is worsening in the United States, Dr. Foti, a postdoctoral researcher in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in a statement from her institution.

The 2021 KDIGO blood pressure guideline and executive summary and the public health implications study are published online in Kidney International.
 

First, ‘take blood pressure well’

The cochair of the new KDIGO guidelines, Alfred K. Cheung, MD, from the University of Utah, Salt Lake City, said in an interview that the guideline has “two important points.”

First, “take that blood pressure well,” he said. “That has a lot to do with patient preparation rather than any fancy instrument,” he emphasized.

Second, the guideline proposes a systolic blood pressure target of less than 120 mm Hg for most people with CKD not receiving dialysis, except for children and kidney transplant recipients. This target is “contingent on ‘standardized’ blood pressure measurement.”

The document provides a checklist for obtaining a standardized blood pressure measurement, adapted from the 2017 ACC/AHA blood pressure guidelines. It starts with the patient relaxed and sitting on a chair for more than 5 minutes.

In contrast to this measurement, a “routine” or “casual” office blood pressure measurement could be off by plus or minus 10 mm Hg, Dr. Cheung noted.

In a typical scenario, he continued, a patient cannot find a place to park, rushes into the clinic, and has his or her blood pressure checked right away, which would provide a “totally unreliable” reading. Adding a “fudge factor” (correction factor) would not provide an accurate reading.

Clinicians “would not settle for a potassium measurement that is 5.0 mmol/L plus or minus a few decimal points” to guide treatment, he pointed out.
 

Second, target 120, properly measured

“The very first chapter of the guidelines is devoted to blood pressure measurement, because we recognize if we’re going to do 120 [mm Hg] – the emphasis is on 120 measured properly – so we try to drive that point home,” Tara I. Chang, MD, guideline second author and a coauthor of the public health implications study, pointed out in an interview.

“There are a lot of other things that we base clinical decisions on where we really require some degree of precision, and blood pressure is important enough that to us it’s kind of in the same boat,” said Dr. Chang, from Stanford (Calif.) University.

“In SPRINT, people were randomized to less than less than 120 vs. less than 140 (they weren’t randomized to <130),” she noted.

“The recommendation should be widely adopted in clinical practice,” the guideline authors write, “since accurate measurements will ensure that proper guidance is being applied to the management of BP, as it is to the management of other risk factors.”
 

Still need individual treatment

Nevertheless, patients still need individualized treatment, the document stresses. “Not every patient with CKD will be appropriate to target to less than 120,” Dr. Chang said. However, “we want people to at least consider less than 120,” she added, to avoid therapeutic inertia.

“If you take the blood pressure in a standardized manner – such as in the ACCORD trial and in the SPRINT trial – even patients over 75 years old, or people over 80 years old, they have very little side effects,” Dr. Cheung noted.

“In the overall cohort,” he continued, “they do not have a significant increase in serious adverse events, do not have adverse events of postural hypotension, syncope, bradycardia, injurious falls – so people are worried about it, but it’s not borne out by the data.

“That said, I have two cautions,” Dr. Cheung noted. “One. If you drop somebody’s blood pressure rapidly over a week, you may be more likely to get in trouble. If you drop the blood pressure gradually over several weeks, several months, you’re much less likely to get into trouble.”

“Two. If the patient is old, you know the patient has carotid stenosis and already has postural dizziness, you may not want to try on that patient – but just because the patient is old is not the reason not to target 120.”
 

ACE inhibitors and ARBs beneficial in albuminuria, underused

“How do you get to less than 120? The short answer is, use whatever medications you need to – there is no necessarily right cocktail,” Dr. Chang said.

“We’ve known that angiotensin-converting enzyme (ACE) inhibitors and ARBs [angiotensin II receptor blockers] are beneficial in patients with CKD and in particular those with heavier albuminuria,” she continued. “We’ve known this for over 20 years.”

Yet, the study identified underutilization – “a persistent gap, just like blood pressure control and awareness,” she noted. “We’re just not making much headway.

“We are not recommending ACE inhibitors or ARBs for all the patients,” Dr. Cheung clarified. “If you are diabetic and have heavy proteinuria, that’s when the use of ACE inhibitors and ARBs are most indicated.”
 

Public health implications

SPRINT showed that treating to a systolic blood pressure of less than 120 mm Hg vs. less than 140 mm Hg reduced the risk for cardiovascular disease by 25% and all-cause mortality by 27% for participants with and those without CKD, Dr. Foti and colleagues stress.

They aimed to estimate how the new guideline would affect (1) the number of U.S. patients with CKD who would be eligible for blood pressure lowering treatment, and (2) the proportion of those with albuminuria who would be eligible for an ACE inhibitor or an ARB.

The researchers analyzed data from 1,699 adults with CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m² or a urinary albumin-to-creatinine ratio of ≥30 mg/g) who participated in the 2015-2018 National Health and Nutrition Examination Survey.

Both the 2021 and 2012 KDIGO guidelines recommend that patients with albuminuria and blood pressure higher than the target value who are not kidney transplant recipients should be treated with an ACE inhibitor or an ARB.

On the basis of the new target, 78% of patients with CKD and albuminuria were eligible for ACE inhibitor/ARB treatment by the 2021 KDIGO guideline, compared with 71% by the 2012 KDIGO guideline. However, only 39% were taking one of these drugs.

These findings show that “with the new guideline and with the lower blood pressure target, you potentially have an even larger pool of people who have blood pressure that’s not under control, and a potential larger group of people who may benefit from ACE inhibitors and ARBs,” Dr. Chang said.

“Our paper is not the only one to show that we haven’t made a whole lot of progress,” she said, “and now that the bar has been lowered, there [have] to be some renewed efforts on controlling blood pressure, because we know that blood pressure control is such an important risk factor for cardiovascular outcomes.”

Dr. Foti is supported by an NIH/National Heart, Lung, and Blood Institute grant. Dr. Cheung has received consultancy fees from Amgen, Bard, Boehringer Ingelheim, Calliditas, Tricida, and UpToDate, and grant/research support from the National Institutes of Health for SPRINT (monies paid to institution). Dr. Chang has received consultancy fees from Bayer, Gilead, Janssen Research and Development, Novo Nordisk, Tricida, and Vascular Dynamics; grant/research support from AstraZeneca and Satellite Healthcare (monies paid to institution), the NIH, and the American Heart Association; is on advisory boards for AstraZeneca and Fresenius Medical Care Renal Therapies Group; and has received workshop honoraria from Fresenius. Disclosures of relevant financial relationships of the other authors are listed in the original articles.

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

The new 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for blood pressure management for adults with chronic kidney disease (CKD) who are not receiving dialysis advises treating to a target systolic blood pressure of less than 120 mm Hg, provided measurements are “standardized” and that blood pressure is “measured properly.”

This blood pressure target – largely based on evidence from the Systolic Blood Pressure Intervention Trial (SPRINT) – represents “a major update” from the 2012 KDIGO guideline, which advised clinicians to treat to a target blood pressure of less than or equal to 130/80 mm Hg for patients with albuminuria or less than or equal to 140/90 mm Hg for patients without albuminuria.

The new goal is also lower than the less than 130/80 mm Hg target in the 2017 American College of Cardiology/American Heart Association guideline.

In a study of the public health implications of the guideline, Kathryn Foti, PhD, and colleagues determined that 70% of U.S. adults with CKD would now be eligible for treatment to lower blood pressure, as opposed to 50% under the previous KDIGO guideline and 56% under the ACC/AHA guideline.

“This is a major update of an influential set of guidelines for chronic kidney disease patients” at a time when blood pressure control is worsening in the United States, Dr. Foti, a postdoctoral researcher in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in a statement from her institution.

The 2021 KDIGO blood pressure guideline and executive summary and the public health implications study are published online in Kidney International.
 

First, ‘take blood pressure well’

The cochair of the new KDIGO guidelines, Alfred K. Cheung, MD, from the University of Utah, Salt Lake City, said in an interview that the guideline has “two important points.”

First, “take that blood pressure well,” he said. “That has a lot to do with patient preparation rather than any fancy instrument,” he emphasized.

Second, the guideline proposes a systolic blood pressure target of less than 120 mm Hg for most people with CKD not receiving dialysis, except for children and kidney transplant recipients. This target is “contingent on ‘standardized’ blood pressure measurement.”

The document provides a checklist for obtaining a standardized blood pressure measurement, adapted from the 2017 ACC/AHA blood pressure guidelines. It starts with the patient relaxed and sitting on a chair for more than 5 minutes.

In contrast to this measurement, a “routine” or “casual” office blood pressure measurement could be off by plus or minus 10 mm Hg, Dr. Cheung noted.

In a typical scenario, he continued, a patient cannot find a place to park, rushes into the clinic, and has his or her blood pressure checked right away, which would provide a “totally unreliable” reading. Adding a “fudge factor” (correction factor) would not provide an accurate reading.

Clinicians “would not settle for a potassium measurement that is 5.0 mmol/L plus or minus a few decimal points” to guide treatment, he pointed out.
 

Second, target 120, properly measured

“The very first chapter of the guidelines is devoted to blood pressure measurement, because we recognize if we’re going to do 120 [mm Hg] – the emphasis is on 120 measured properly – so we try to drive that point home,” Tara I. Chang, MD, guideline second author and a coauthor of the public health implications study, pointed out in an interview.

“There are a lot of other things that we base clinical decisions on where we really require some degree of precision, and blood pressure is important enough that to us it’s kind of in the same boat,” said Dr. Chang, from Stanford (Calif.) University.

“In SPRINT, people were randomized to less than less than 120 vs. less than 140 (they weren’t randomized to <130),” she noted.

“The recommendation should be widely adopted in clinical practice,” the guideline authors write, “since accurate measurements will ensure that proper guidance is being applied to the management of BP, as it is to the management of other risk factors.”
 

Still need individual treatment

Nevertheless, patients still need individualized treatment, the document stresses. “Not every patient with CKD will be appropriate to target to less than 120,” Dr. Chang said. However, “we want people to at least consider less than 120,” she added, to avoid therapeutic inertia.

“If you take the blood pressure in a standardized manner – such as in the ACCORD trial and in the SPRINT trial – even patients over 75 years old, or people over 80 years old, they have very little side effects,” Dr. Cheung noted.

“In the overall cohort,” he continued, “they do not have a significant increase in serious adverse events, do not have adverse events of postural hypotension, syncope, bradycardia, injurious falls – so people are worried about it, but it’s not borne out by the data.

“That said, I have two cautions,” Dr. Cheung noted. “One. If you drop somebody’s blood pressure rapidly over a week, you may be more likely to get in trouble. If you drop the blood pressure gradually over several weeks, several months, you’re much less likely to get into trouble.”

“Two. If the patient is old, you know the patient has carotid stenosis and already has postural dizziness, you may not want to try on that patient – but just because the patient is old is not the reason not to target 120.”
 

ACE inhibitors and ARBs beneficial in albuminuria, underused

“How do you get to less than 120? The short answer is, use whatever medications you need to – there is no necessarily right cocktail,” Dr. Chang said.

“We’ve known that angiotensin-converting enzyme (ACE) inhibitors and ARBs [angiotensin II receptor blockers] are beneficial in patients with CKD and in particular those with heavier albuminuria,” she continued. “We’ve known this for over 20 years.”

Yet, the study identified underutilization – “a persistent gap, just like blood pressure control and awareness,” she noted. “We’re just not making much headway.

“We are not recommending ACE inhibitors or ARBs for all the patients,” Dr. Cheung clarified. “If you are diabetic and have heavy proteinuria, that’s when the use of ACE inhibitors and ARBs are most indicated.”
 

Public health implications

SPRINT showed that treating to a systolic blood pressure of less than 120 mm Hg vs. less than 140 mm Hg reduced the risk for cardiovascular disease by 25% and all-cause mortality by 27% for participants with and those without CKD, Dr. Foti and colleagues stress.

They aimed to estimate how the new guideline would affect (1) the number of U.S. patients with CKD who would be eligible for blood pressure lowering treatment, and (2) the proportion of those with albuminuria who would be eligible for an ACE inhibitor or an ARB.

The researchers analyzed data from 1,699 adults with CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m² or a urinary albumin-to-creatinine ratio of ≥30 mg/g) who participated in the 2015-2018 National Health and Nutrition Examination Survey.

Both the 2021 and 2012 KDIGO guidelines recommend that patients with albuminuria and blood pressure higher than the target value who are not kidney transplant recipients should be treated with an ACE inhibitor or an ARB.

On the basis of the new target, 78% of patients with CKD and albuminuria were eligible for ACE inhibitor/ARB treatment by the 2021 KDIGO guideline, compared with 71% by the 2012 KDIGO guideline. However, only 39% were taking one of these drugs.

These findings show that “with the new guideline and with the lower blood pressure target, you potentially have an even larger pool of people who have blood pressure that’s not under control, and a potential larger group of people who may benefit from ACE inhibitors and ARBs,” Dr. Chang said.

“Our paper is not the only one to show that we haven’t made a whole lot of progress,” she said, “and now that the bar has been lowered, there [have] to be some renewed efforts on controlling blood pressure, because we know that blood pressure control is such an important risk factor for cardiovascular outcomes.”

Dr. Foti is supported by an NIH/National Heart, Lung, and Blood Institute grant. Dr. Cheung has received consultancy fees from Amgen, Bard, Boehringer Ingelheim, Calliditas, Tricida, and UpToDate, and grant/research support from the National Institutes of Health for SPRINT (monies paid to institution). Dr. Chang has received consultancy fees from Bayer, Gilead, Janssen Research and Development, Novo Nordisk, Tricida, and Vascular Dynamics; grant/research support from AstraZeneca and Satellite Healthcare (monies paid to institution), the NIH, and the American Heart Association; is on advisory boards for AstraZeneca and Fresenius Medical Care Renal Therapies Group; and has received workshop honoraria from Fresenius. Disclosures of relevant financial relationships of the other authors are listed in the original articles.

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

The new 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for blood pressure management for adults with chronic kidney disease (CKD) who are not receiving dialysis advises treating to a target systolic blood pressure of less than 120 mm Hg, provided measurements are “standardized” and that blood pressure is “measured properly.”

This blood pressure target – largely based on evidence from the Systolic Blood Pressure Intervention Trial (SPRINT) – represents “a major update” from the 2012 KDIGO guideline, which advised clinicians to treat to a target blood pressure of less than or equal to 130/80 mm Hg for patients with albuminuria or less than or equal to 140/90 mm Hg for patients without albuminuria.

The new goal is also lower than the less than 130/80 mm Hg target in the 2017 American College of Cardiology/American Heart Association guideline.

In a study of the public health implications of the guideline, Kathryn Foti, PhD, and colleagues determined that 70% of U.S. adults with CKD would now be eligible for treatment to lower blood pressure, as opposed to 50% under the previous KDIGO guideline and 56% under the ACC/AHA guideline.

“This is a major update of an influential set of guidelines for chronic kidney disease patients” at a time when blood pressure control is worsening in the United States, Dr. Foti, a postdoctoral researcher in the department of epidemiology at Johns Hopkins Bloomberg School of Public Health, Baltimore, said in a statement from her institution.

The 2021 KDIGO blood pressure guideline and executive summary and the public health implications study are published online in Kidney International.
 

First, ‘take blood pressure well’

The cochair of the new KDIGO guidelines, Alfred K. Cheung, MD, from the University of Utah, Salt Lake City, said in an interview that the guideline has “two important points.”

First, “take that blood pressure well,” he said. “That has a lot to do with patient preparation rather than any fancy instrument,” he emphasized.

Second, the guideline proposes a systolic blood pressure target of less than 120 mm Hg for most people with CKD not receiving dialysis, except for children and kidney transplant recipients. This target is “contingent on ‘standardized’ blood pressure measurement.”

The document provides a checklist for obtaining a standardized blood pressure measurement, adapted from the 2017 ACC/AHA blood pressure guidelines. It starts with the patient relaxed and sitting on a chair for more than 5 minutes.

In contrast to this measurement, a “routine” or “casual” office blood pressure measurement could be off by plus or minus 10 mm Hg, Dr. Cheung noted.

In a typical scenario, he continued, a patient cannot find a place to park, rushes into the clinic, and has his or her blood pressure checked right away, which would provide a “totally unreliable” reading. Adding a “fudge factor” (correction factor) would not provide an accurate reading.

Clinicians “would not settle for a potassium measurement that is 5.0 mmol/L plus or minus a few decimal points” to guide treatment, he pointed out.
 

Second, target 120, properly measured

“The very first chapter of the guidelines is devoted to blood pressure measurement, because we recognize if we’re going to do 120 [mm Hg] – the emphasis is on 120 measured properly – so we try to drive that point home,” Tara I. Chang, MD, guideline second author and a coauthor of the public health implications study, pointed out in an interview.

“There are a lot of other things that we base clinical decisions on where we really require some degree of precision, and blood pressure is important enough that to us it’s kind of in the same boat,” said Dr. Chang, from Stanford (Calif.) University.

“In SPRINT, people were randomized to less than less than 120 vs. less than 140 (they weren’t randomized to <130),” she noted.

“The recommendation should be widely adopted in clinical practice,” the guideline authors write, “since accurate measurements will ensure that proper guidance is being applied to the management of BP, as it is to the management of other risk factors.”
 

Still need individual treatment

Nevertheless, patients still need individualized treatment, the document stresses. “Not every patient with CKD will be appropriate to target to less than 120,” Dr. Chang said. However, “we want people to at least consider less than 120,” she added, to avoid therapeutic inertia.

“If you take the blood pressure in a standardized manner – such as in the ACCORD trial and in the SPRINT trial – even patients over 75 years old, or people over 80 years old, they have very little side effects,” Dr. Cheung noted.

“In the overall cohort,” he continued, “they do not have a significant increase in serious adverse events, do not have adverse events of postural hypotension, syncope, bradycardia, injurious falls – so people are worried about it, but it’s not borne out by the data.

“That said, I have two cautions,” Dr. Cheung noted. “One. If you drop somebody’s blood pressure rapidly over a week, you may be more likely to get in trouble. If you drop the blood pressure gradually over several weeks, several months, you’re much less likely to get into trouble.”

“Two. If the patient is old, you know the patient has carotid stenosis and already has postural dizziness, you may not want to try on that patient – but just because the patient is old is not the reason not to target 120.”
 

ACE inhibitors and ARBs beneficial in albuminuria, underused

“How do you get to less than 120? The short answer is, use whatever medications you need to – there is no necessarily right cocktail,” Dr. Chang said.

“We’ve known that angiotensin-converting enzyme (ACE) inhibitors and ARBs [angiotensin II receptor blockers] are beneficial in patients with CKD and in particular those with heavier albuminuria,” she continued. “We’ve known this for over 20 years.”

Yet, the study identified underutilization – “a persistent gap, just like blood pressure control and awareness,” she noted. “We’re just not making much headway.

“We are not recommending ACE inhibitors or ARBs for all the patients,” Dr. Cheung clarified. “If you are diabetic and have heavy proteinuria, that’s when the use of ACE inhibitors and ARBs are most indicated.”
 

Public health implications

SPRINT showed that treating to a systolic blood pressure of less than 120 mm Hg vs. less than 140 mm Hg reduced the risk for cardiovascular disease by 25% and all-cause mortality by 27% for participants with and those without CKD, Dr. Foti and colleagues stress.

They aimed to estimate how the new guideline would affect (1) the number of U.S. patients with CKD who would be eligible for blood pressure lowering treatment, and (2) the proportion of those with albuminuria who would be eligible for an ACE inhibitor or an ARB.

The researchers analyzed data from 1,699 adults with CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m² or a urinary albumin-to-creatinine ratio of ≥30 mg/g) who participated in the 2015-2018 National Health and Nutrition Examination Survey.

Both the 2021 and 2012 KDIGO guidelines recommend that patients with albuminuria and blood pressure higher than the target value who are not kidney transplant recipients should be treated with an ACE inhibitor or an ARB.

On the basis of the new target, 78% of patients with CKD and albuminuria were eligible for ACE inhibitor/ARB treatment by the 2021 KDIGO guideline, compared with 71% by the 2012 KDIGO guideline. However, only 39% were taking one of these drugs.

These findings show that “with the new guideline and with the lower blood pressure target, you potentially have an even larger pool of people who have blood pressure that’s not under control, and a potential larger group of people who may benefit from ACE inhibitors and ARBs,” Dr. Chang said.

“Our paper is not the only one to show that we haven’t made a whole lot of progress,” she said, “and now that the bar has been lowered, there [have] to be some renewed efforts on controlling blood pressure, because we know that blood pressure control is such an important risk factor for cardiovascular outcomes.”

Dr. Foti is supported by an NIH/National Heart, Lung, and Blood Institute grant. Dr. Cheung has received consultancy fees from Amgen, Bard, Boehringer Ingelheim, Calliditas, Tricida, and UpToDate, and grant/research support from the National Institutes of Health for SPRINT (monies paid to institution). Dr. Chang has received consultancy fees from Bayer, Gilead, Janssen Research and Development, Novo Nordisk, Tricida, and Vascular Dynamics; grant/research support from AstraZeneca and Satellite Healthcare (monies paid to institution), the NIH, and the American Heart Association; is on advisory boards for AstraZeneca and Fresenius Medical Care Renal Therapies Group; and has received workshop honoraria from Fresenius. Disclosures of relevant financial relationships of the other authors are listed in the original articles.

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

Vivek H. Murthy, MD, was named by President Joe Biden as his selection for Surgeon General of the United States. Dr. Murthy filled the same role from 2014-17 during President Barack Obama’s administration.

Dr. Murthy was a hospitalist and an instructor at Brigham and Women’s Hospital at Harvard Medical School prior to becoming surgeon general the first time. He also is the founder of Doctors for America.
 

David Tupponce, MD, recently was named the new president of Allegheny Health Network’s Grove City (Pa.) Medical Center. He takes over for interim president Allan Klapper, MD, who filled the position since August 2020.

Dr. Tupponce comes to Grove City Medical Center after a successful tenure as president of Central Maine Medical Center (Lewiston, Maine), where he grew its physician group and fine-tuned the hospital quality program. Prior to that, he was chief executive officer at Tenet Healthcare’s Abrazo Scottsdale (Ariz.) Campus and CEO at Paradise Valley Hospital (Phoenix, Ariz.).

Malcolm Mar Fan, MD, has been elevated to medical director of the Hospitalist Group at Evangelical Community Hospital (Lewisburg, Pa.). In the newly established position, Dr. Mar Fan will oversee all operations for the facility’s hospitalist program.

Dr. Mar Fan has been a hospitalist at Evangelical since 2014 after completing his internist residency at Albert Einstein Medical Center in Philadelphia. He has played a major role on Evangelical’s Peri-operative Glucose Management Committee and its Informatics Committee for Impatient and Outpatient Electronic Health Records.
 

Lyon County (Kansas) recently announced that Ladun Oyenuga, MD, has been appointed as public health officer for the county. She began her tenure on January 1.

Dr. Oyenuga is a hospitalist at Newman Regional Health (Emporia, Kan.). She is a native of Nigeria and did her residency at Harlem (N.Y.) Hospital Center. She has been with Newman since 2017.
 

Cherese Mari Laulhere BirthCare Center (Long Beach, Calif.) recently announced the addition of an OB hospitalist program at Miller Children’s & Women’s Hospital. OB hospitalists, or laborists, care for women with obstetrical issues while in the hospital.

At Cherese Mari Laulhere, OB hospitalists will be on hand 24 hours a day to assist patients’ OB/GYNs or to fill in if the personal physician cannot get to the hospital quickly.
 

Hospitalists at Nationwide Children’s (Columbus, Ohio) are now providing care for children who are hospitalized at Adena Regional Medical Center (Chillicothe, Ohio).

It is an expansion of an ongoing partnership between the two hospitals. Adena and Nationwide Children’s have been working together in helping to care for children in the south central and southern Ohio region since 2011. Nationwide Children’s hospitalists will round in special care and the well-baby nursery at Adena, as well as provide education programs for Adena providers and staff.
 

MultiCare Health System (Tacoma, Wash.) has announced that it will expand its hospitalist program partnership with Sound Physicians, also based in Tacoma, to create a region-wide, cohesive group of providers. The goal is to help ensure efficient management of inpatient populations as a region instead of at the individual hospital level, and will allow MultiCare to implement standard tools, processes and regionwide best practices.

The hospitalist programs at Tacoma General Hospital, Allenmore Hospital and Covington Medical Center will transition to Sound Physicians on April 5, 2021. Sound hospitalists are already working at three other MultiCare facilities – Tacoma General Hospital, Allenmore Hospital, and Covington Medical Center.

Vivek H. Murthy, MD, was named by President Joe Biden as his selection for Surgeon General of the United States. Dr. Murthy filled the same role from 2014-17 during President Barack Obama’s administration.

Dr. Murthy was a hospitalist and an instructor at Brigham and Women’s Hospital at Harvard Medical School prior to becoming surgeon general the first time. He also is the founder of Doctors for America.
 

David Tupponce, MD, recently was named the new president of Allegheny Health Network’s Grove City (Pa.) Medical Center. He takes over for interim president Allan Klapper, MD, who filled the position since August 2020.

Dr. Tupponce comes to Grove City Medical Center after a successful tenure as president of Central Maine Medical Center (Lewiston, Maine), where he grew its physician group and fine-tuned the hospital quality program. Prior to that, he was chief executive officer at Tenet Healthcare’s Abrazo Scottsdale (Ariz.) Campus and CEO at Paradise Valley Hospital (Phoenix, Ariz.).

Malcolm Mar Fan, MD, has been elevated to medical director of the Hospitalist Group at Evangelical Community Hospital (Lewisburg, Pa.). In the newly established position, Dr. Mar Fan will oversee all operations for the facility’s hospitalist program.

Dr. Mar Fan has been a hospitalist at Evangelical since 2014 after completing his internist residency at Albert Einstein Medical Center in Philadelphia. He has played a major role on Evangelical’s Peri-operative Glucose Management Committee and its Informatics Committee for Impatient and Outpatient Electronic Health Records.
 

Lyon County (Kansas) recently announced that Ladun Oyenuga, MD, has been appointed as public health officer for the county. She began her tenure on January 1.

Dr. Oyenuga is a hospitalist at Newman Regional Health (Emporia, Kan.). She is a native of Nigeria and did her residency at Harlem (N.Y.) Hospital Center. She has been with Newman since 2017.
 

Cherese Mari Laulhere BirthCare Center (Long Beach, Calif.) recently announced the addition of an OB hospitalist program at Miller Children’s & Women’s Hospital. OB hospitalists, or laborists, care for women with obstetrical issues while in the hospital.

At Cherese Mari Laulhere, OB hospitalists will be on hand 24 hours a day to assist patients’ OB/GYNs or to fill in if the personal physician cannot get to the hospital quickly.
 

Hospitalists at Nationwide Children’s (Columbus, Ohio) are now providing care for children who are hospitalized at Adena Regional Medical Center (Chillicothe, Ohio).

It is an expansion of an ongoing partnership between the two hospitals. Adena and Nationwide Children’s have been working together in helping to care for children in the south central and southern Ohio region since 2011. Nationwide Children’s hospitalists will round in special care and the well-baby nursery at Adena, as well as provide education programs for Adena providers and staff.
 

MultiCare Health System (Tacoma, Wash.) has announced that it will expand its hospitalist program partnership with Sound Physicians, also based in Tacoma, to create a region-wide, cohesive group of providers. The goal is to help ensure efficient management of inpatient populations as a region instead of at the individual hospital level, and will allow MultiCare to implement standard tools, processes and regionwide best practices.

The hospitalist programs at Tacoma General Hospital, Allenmore Hospital and Covington Medical Center will transition to Sound Physicians on April 5, 2021. Sound hospitalists are already working at three other MultiCare facilities – Tacoma General Hospital, Allenmore Hospital, and Covington Medical Center.

Vivek H. Murthy, MD, was named by President Joe Biden as his selection for Surgeon General of the United States. Dr. Murthy filled the same role from 2014-17 during President Barack Obama’s administration.

Dr. Murthy was a hospitalist and an instructor at Brigham and Women’s Hospital at Harvard Medical School prior to becoming surgeon general the first time. He also is the founder of Doctors for America.
 

David Tupponce, MD, recently was named the new president of Allegheny Health Network’s Grove City (Pa.) Medical Center. He takes over for interim president Allan Klapper, MD, who filled the position since August 2020.

Dr. Tupponce comes to Grove City Medical Center after a successful tenure as president of Central Maine Medical Center (Lewiston, Maine), where he grew its physician group and fine-tuned the hospital quality program. Prior to that, he was chief executive officer at Tenet Healthcare’s Abrazo Scottsdale (Ariz.) Campus and CEO at Paradise Valley Hospital (Phoenix, Ariz.).

Malcolm Mar Fan, MD, has been elevated to medical director of the Hospitalist Group at Evangelical Community Hospital (Lewisburg, Pa.). In the newly established position, Dr. Mar Fan will oversee all operations for the facility’s hospitalist program.

Dr. Mar Fan has been a hospitalist at Evangelical since 2014 after completing his internist residency at Albert Einstein Medical Center in Philadelphia. He has played a major role on Evangelical’s Peri-operative Glucose Management Committee and its Informatics Committee for Impatient and Outpatient Electronic Health Records.
 

Lyon County (Kansas) recently announced that Ladun Oyenuga, MD, has been appointed as public health officer for the county. She began her tenure on January 1.

Dr. Oyenuga is a hospitalist at Newman Regional Health (Emporia, Kan.). She is a native of Nigeria and did her residency at Harlem (N.Y.) Hospital Center. She has been with Newman since 2017.
 

Cherese Mari Laulhere BirthCare Center (Long Beach, Calif.) recently announced the addition of an OB hospitalist program at Miller Children’s & Women’s Hospital. OB hospitalists, or laborists, care for women with obstetrical issues while in the hospital.

At Cherese Mari Laulhere, OB hospitalists will be on hand 24 hours a day to assist patients’ OB/GYNs or to fill in if the personal physician cannot get to the hospital quickly.
 

Hospitalists at Nationwide Children’s (Columbus, Ohio) are now providing care for children who are hospitalized at Adena Regional Medical Center (Chillicothe, Ohio).

It is an expansion of an ongoing partnership between the two hospitals. Adena and Nationwide Children’s have been working together in helping to care for children in the south central and southern Ohio region since 2011. Nationwide Children’s hospitalists will round in special care and the well-baby nursery at Adena, as well as provide education programs for Adena providers and staff.
 

MultiCare Health System (Tacoma, Wash.) has announced that it will expand its hospitalist program partnership with Sound Physicians, also based in Tacoma, to create a region-wide, cohesive group of providers. The goal is to help ensure efficient management of inpatient populations as a region instead of at the individual hospital level, and will allow MultiCare to implement standard tools, processes and regionwide best practices.

The hospitalist programs at Tacoma General Hospital, Allenmore Hospital and Covington Medical Center will transition to Sound Physicians on April 5, 2021. Sound hospitalists are already working at three other MultiCare facilities – Tacoma General Hospital, Allenmore Hospital, and Covington Medical Center.

Among patients with nonalcoholic fatty liver disease (NAFLD) and compensated advanced chronic liver disease, liver stiffness measurements (LSMs) are associated with risks of hepatic events, according to a retrospective analysis of more than 1,000 patients.

“[N]oninvasive markers that can predict liver disease severity and outcomes in patients with NAFLD and advanced fibrosis are a major unmet need,” wrote lead author Salvatore Petta, MD, of the University of Palermo, Italy, and colleagues. Their report is in Clinical Gastroenterology and Hepatology. “Data about the accuracy of LSM in the prediction of events in NAFLD, and especially in patients with NAFLD and F3-F4 fibrosis, are scarce.”

To address this knowledge gap, the investigators retrospectively analyzed data from 1,039 consecutive patients with NAFLD who had baseline LSMs of more than 10 kPa and/or histologically diagnosed F3-F4 fibrosis. Patients were prospectively recruited at 10 centers in 6 countries, then followed for a median of 35 months, ranging from 19 to 63 months.

All patients had their liver stiffness measured with an M or XL probe at baseline. In addition, approximately half of the patients (n = 533) had a follow-up measurement using the same method, generating a subgroup with changes in liver stiffness. “Improved” liver stiffness was defined as a decrease in LSM greater than 20% from baseline, “impaired” liver stiffness was defined as an increase in LSM greater than 20% from baseline, and “stable” liver stiffness was defined as a change falling between 20% lower and 20% higher than baseline.

At baseline, mean LSM was 17.6 kPa. Cox regression analysis revealed that baseline LSM was independently associated with HCC (hazard ratio, 1.03; 95% confidence interval, 1.00-1.04; P = .003), liver decompensation (HR, 1.03; 95% CI, 1.02-1.04; P < .001), and liver-related death (HR, 1.02; 95% CI, 1.00-1.03; P = .005), but not extrahepatic events.

According to the investigators, the association between LSM at baseline and risk of liver decompensation was maintained after adjustment for the severity of liver disease and for surrogate markers of portal hypertension, they noted. Furthermore, patients with a baseline LSM of at least 21 kPa – which indicates high risk of clinically significant portal hypertension (CSPH) – were at greater risk of liver decompensation than were those with an LSM less than 21 kPa (HR, 3.71; 95% CI, 1.89-6.78; P = .04).

In the subgroup with follow-up measurements, approximately half of the patients had an improved LSM (53.3%), while 27.2% had a stable LSM, and 19.5% had an impaired LSM, a pattern that was significantly associated with diabetes at baseline (P = .01).

“These data agree with the available literature identifying diabetes as a risk factor for liver disease progression and liver-related complications,” the investigators wrote.

Cox regression showed that, among those with follow-up LSM, changes in LSM were independently associated with HCC (HR, 1.72; 95% CI, 1.01-3.02; P = .04), liver decompensation (HR, 1.56; 95% CI, 1.05-2.51; P = . 04), liver-related mortality (HR, 1.96; 95% CI, 1.10-3.38; P = .02), and mortality of any cause (HR, 1.73; 95% CI, 1.11-2.69; P = .01).

These risks could be further stratified by level of change in liver stiffness, with greater impairment predicting greater risk: The crude rate of liver decompensation was 14.4% among those with impaired LSM, compared with 6.2% among those with stable LSM and 3.8% among those with LSM improvement. That said, the categories of changes in LSM were not predictive of decompensation among patients with high risk of CSPH at baseline; however, they remained predictive among those with low risk of CSPH at baseline.

“[T]his study … showed that an integrated assessment of baseline LSM or [changes in LSM] can help in stratifying the risk of development of liver-related complications and of both hepatic and overall mortality,” the investigators concluded. “These data, if further validated, could help personalize prognosis and follow-up in NAFLD with [compensated advanced chronic liver disease].”

The investigators disclosed relationships with AbbVie, Novo Nordisk, Gilead, and others.

Among patients with nonalcoholic fatty liver disease (NAFLD) and compensated advanced chronic liver disease, liver stiffness measurements (LSMs) are associated with risks of hepatic events, according to a retrospective analysis of more than 1,000 patients.

“[N]oninvasive markers that can predict liver disease severity and outcomes in patients with NAFLD and advanced fibrosis are a major unmet need,” wrote lead author Salvatore Petta, MD, of the University of Palermo, Italy, and colleagues. Their report is in Clinical Gastroenterology and Hepatology. “Data about the accuracy of LSM in the prediction of events in NAFLD, and especially in patients with NAFLD and F3-F4 fibrosis, are scarce.”

To address this knowledge gap, the investigators retrospectively analyzed data from 1,039 consecutive patients with NAFLD who had baseline LSMs of more than 10 kPa and/or histologically diagnosed F3-F4 fibrosis. Patients were prospectively recruited at 10 centers in 6 countries, then followed for a median of 35 months, ranging from 19 to 63 months.

All patients had their liver stiffness measured with an M or XL probe at baseline. In addition, approximately half of the patients (n = 533) had a follow-up measurement using the same method, generating a subgroup with changes in liver stiffness. “Improved” liver stiffness was defined as a decrease in LSM greater than 20% from baseline, “impaired” liver stiffness was defined as an increase in LSM greater than 20% from baseline, and “stable” liver stiffness was defined as a change falling between 20% lower and 20% higher than baseline.

At baseline, mean LSM was 17.6 kPa. Cox regression analysis revealed that baseline LSM was independently associated with HCC (hazard ratio, 1.03; 95% confidence interval, 1.00-1.04; P = .003), liver decompensation (HR, 1.03; 95% CI, 1.02-1.04; P < .001), and liver-related death (HR, 1.02; 95% CI, 1.00-1.03; P = .005), but not extrahepatic events.

According to the investigators, the association between LSM at baseline and risk of liver decompensation was maintained after adjustment for the severity of liver disease and for surrogate markers of portal hypertension, they noted. Furthermore, patients with a baseline LSM of at least 21 kPa – which indicates high risk of clinically significant portal hypertension (CSPH) – were at greater risk of liver decompensation than were those with an LSM less than 21 kPa (HR, 3.71; 95% CI, 1.89-6.78; P = .04).

In the subgroup with follow-up measurements, approximately half of the patients had an improved LSM (53.3%), while 27.2% had a stable LSM, and 19.5% had an impaired LSM, a pattern that was significantly associated with diabetes at baseline (P = .01).

“These data agree with the available literature identifying diabetes as a risk factor for liver disease progression and liver-related complications,” the investigators wrote.

Cox regression showed that, among those with follow-up LSM, changes in LSM were independently associated with HCC (HR, 1.72; 95% CI, 1.01-3.02; P = .04), liver decompensation (HR, 1.56; 95% CI, 1.05-2.51; P = . 04), liver-related mortality (HR, 1.96; 95% CI, 1.10-3.38; P = .02), and mortality of any cause (HR, 1.73; 95% CI, 1.11-2.69; P = .01).

These risks could be further stratified by level of change in liver stiffness, with greater impairment predicting greater risk: The crude rate of liver decompensation was 14.4% among those with impaired LSM, compared with 6.2% among those with stable LSM and 3.8% among those with LSM improvement. That said, the categories of changes in LSM were not predictive of decompensation among patients with high risk of CSPH at baseline; however, they remained predictive among those with low risk of CSPH at baseline.

“[T]his study … showed that an integrated assessment of baseline LSM or [changes in LSM] can help in stratifying the risk of development of liver-related complications and of both hepatic and overall mortality,” the investigators concluded. “These data, if further validated, could help personalize prognosis and follow-up in NAFLD with [compensated advanced chronic liver disease].”

The investigators disclosed relationships with AbbVie, Novo Nordisk, Gilead, and others.

Among patients with nonalcoholic fatty liver disease (NAFLD) and compensated advanced chronic liver disease, liver stiffness measurements (LSMs) are associated with risks of hepatic events, according to a retrospective analysis of more than 1,000 patients.

“[N]oninvasive markers that can predict liver disease severity and outcomes in patients with NAFLD and advanced fibrosis are a major unmet need,” wrote lead author Salvatore Petta, MD, of the University of Palermo, Italy, and colleagues. Their report is in Clinical Gastroenterology and Hepatology. “Data about the accuracy of LSM in the prediction of events in NAFLD, and especially in patients with NAFLD and F3-F4 fibrosis, are scarce.”

To address this knowledge gap, the investigators retrospectively analyzed data from 1,039 consecutive patients with NAFLD who had baseline LSMs of more than 10 kPa and/or histologically diagnosed F3-F4 fibrosis. Patients were prospectively recruited at 10 centers in 6 countries, then followed for a median of 35 months, ranging from 19 to 63 months.

All patients had their liver stiffness measured with an M or XL probe at baseline. In addition, approximately half of the patients (n = 533) had a follow-up measurement using the same method, generating a subgroup with changes in liver stiffness. “Improved” liver stiffness was defined as a decrease in LSM greater than 20% from baseline, “impaired” liver stiffness was defined as an increase in LSM greater than 20% from baseline, and “stable” liver stiffness was defined as a change falling between 20% lower and 20% higher than baseline.

At baseline, mean LSM was 17.6 kPa. Cox regression analysis revealed that baseline LSM was independently associated with HCC (hazard ratio, 1.03; 95% confidence interval, 1.00-1.04; P = .003), liver decompensation (HR, 1.03; 95% CI, 1.02-1.04; P < .001), and liver-related death (HR, 1.02; 95% CI, 1.00-1.03; P = .005), but not extrahepatic events.

According to the investigators, the association between LSM at baseline and risk of liver decompensation was maintained after adjustment for the severity of liver disease and for surrogate markers of portal hypertension, they noted. Furthermore, patients with a baseline LSM of at least 21 kPa – which indicates high risk of clinically significant portal hypertension (CSPH) – were at greater risk of liver decompensation than were those with an LSM less than 21 kPa (HR, 3.71; 95% CI, 1.89-6.78; P = .04).

In the subgroup with follow-up measurements, approximately half of the patients had an improved LSM (53.3%), while 27.2% had a stable LSM, and 19.5% had an impaired LSM, a pattern that was significantly associated with diabetes at baseline (P = .01).

“These data agree with the available literature identifying diabetes as a risk factor for liver disease progression and liver-related complications,” the investigators wrote.

Cox regression showed that, among those with follow-up LSM, changes in LSM were independently associated with HCC (HR, 1.72; 95% CI, 1.01-3.02; P = .04), liver decompensation (HR, 1.56; 95% CI, 1.05-2.51; P = . 04), liver-related mortality (HR, 1.96; 95% CI, 1.10-3.38; P = .02), and mortality of any cause (HR, 1.73; 95% CI, 1.11-2.69; P = .01).

These risks could be further stratified by level of change in liver stiffness, with greater impairment predicting greater risk: The crude rate of liver decompensation was 14.4% among those with impaired LSM, compared with 6.2% among those with stable LSM and 3.8% among those with LSM improvement. That said, the categories of changes in LSM were not predictive of decompensation among patients with high risk of CSPH at baseline; however, they remained predictive among those with low risk of CSPH at baseline.

“[T]his study … showed that an integrated assessment of baseline LSM or [changes in LSM] can help in stratifying the risk of development of liver-related complications and of both hepatic and overall mortality,” the investigators concluded. “These data, if further validated, could help personalize prognosis and follow-up in NAFLD with [compensated advanced chronic liver disease].”

The investigators disclosed relationships with AbbVie, Novo Nordisk, Gilead, and others.

Novel therapies have transformed the treatment of hemophilia in recent decades, but these new approaches also raise new challenges for clinicians who monitor joint health in persons with hemophilia, a specialist said.

“Patient-reported outcomes should be combined with other, more objective outcome measures for joint health monitoring, and joint ultrasound is a promising tool for objective joint health monitoring, although, due to its relatively recent introduction in clinical practice, we lack objective data and standardization,” said Roberta Gualtierotti, MD, PhD, from the Università Degli Studi of Milan.

She reviewed the challenges and approaches to monitoring joint health in persons with hemophilia during the annual congress of the European Association for Haemophilia and Allied Disorders.

Over the last decades the target of hemophilia treatment has shifted from prolonging survival to improving joint health and quality of life, and care has improved with the introduction of novel therapies such as extended half-life replacement products, nonreplacement therapies, and gene therapy, she noted.

However, “due to different pharmacodynamics and pharmacokinetics profiles, the currently available therapies cannot be compared to each other on several levels,” Dr. Gualtierotti said.

Laboratory monitoring of replacement therapies with standard coagulation assays may be unreliable, and depending on the mechanism of action and type of administration of nonreplacement agents, patients may experience breakthrough bleeding, especially after traumatic injury, she said.

Until the specific noncoagulatory effects of factor VIII on bone and joint health is better understood, close monitoring of patients will be required, she added.
 

Outcome measures

Subjective measures of joint health include patient-reported bleeding rates and health-related quality of life. These are practical for home management, but patients may not be able to distinguish symptoms of acute joint bleeding from chronic arthritis pain, with the potential for either under- or overtreatment, and subjective reporting is likely to miss subclinical bleeding that can occur even when patients are on prophylaxis.

Health-related quality of life tools, whether generic or specific for hemophilia, are not sensitive to small improvements, and they are not always used in routine clinical practice.

Objective measures include physical examination with scoring according to the World Federation of Hemophilia (Gilbert Scale) score or Hemophilia Joint Health Score, but these measures have limited ability to identify early or subclinical joint abnormalities.

“Therefore, joint physical examination on its own is not a sufficient measure of treatment efficacy, and it should be used in combination with other tools more objective, such as imaging,” Dr. Gualtierotti said.
 

Get the picture?

Imaging with x-rays, MRI, and, recently in some centers, point-of-care ultrasound can provide clinicians with important real-time information about the joint stability and health.

Point-of-care ultrasound in particular offers promise as a practical tool, with no ionizing radiation and high sensitivity for synovial hyperplasia subclinical joint effusion. It’s relatively inexpensive, can be used to image multiple joints, and allows for ease of follow-up, she said. The technique requires specialized training, however, and there is a lack of prospective data about its utility in hemophilia.

Various ultrasound scoring systems have been proposed, and home-based ultrasound is currently being explored in several clinical trials, Dr. Gualtierotti noted.

Other avenues for remote joint health monitoring under consideration are serum or synovial biomarkers for joint bleeding and arthropathy that could be employed at bedside or at home, smartphone apps for breakthrough bleeding and patient-reported outcomes, and sensors for detecting abnormalities in gait that may signal joint dysfunction, she said.
 

Best practice

In the question-and-answer session following the talk, Fernando Zikan, MD, from the Federal University of Rio de Janeiro noted that, “in underdeveloped countries, we still find it very difficult to guide good practices for joint health control by the patient and family members. Which strategy do you think is fundamental for the patient to feel safe to notice changes in his body?”

“It would be useful to educate patients to come to the center whenever the patient has trauma and whenever an increase in his physical activity occurs. If this is far, a bedside ultrasound evaluation by the general practitioner could help avoid joint damage. Finally, a correct rehabilitation is fundamental,” Dr. Gualtierotti replied.

Asked by several others whether she used ultrasound in her daily practice, Dr. Gualtierotti said that “we use joint ultrasound in our clinical practice in the regular annual check-up examination and whenever the patient suspects and reports hemarthrosis.”

Dr. Gualtierotti reported participation in advisory boards for Biomarin, Pfizer, Bayer, and Takeda, and in educational seminars sponsored by Pfizer, Sobi, and Roche. She has received support for congress travel and/or attendance by Bayer and Pfizer. Dr. Zikan reported no relevant disclosures.

Novel therapies have transformed the treatment of hemophilia in recent decades, but these new approaches also raise new challenges for clinicians who monitor joint health in persons with hemophilia, a specialist said.

“Patient-reported outcomes should be combined with other, more objective outcome measures for joint health monitoring, and joint ultrasound is a promising tool for objective joint health monitoring, although, due to its relatively recent introduction in clinical practice, we lack objective data and standardization,” said Roberta Gualtierotti, MD, PhD, from the Università Degli Studi of Milan.

She reviewed the challenges and approaches to monitoring joint health in persons with hemophilia during the annual congress of the European Association for Haemophilia and Allied Disorders.

Over the last decades the target of hemophilia treatment has shifted from prolonging survival to improving joint health and quality of life, and care has improved with the introduction of novel therapies such as extended half-life replacement products, nonreplacement therapies, and gene therapy, she noted.

However, “due to different pharmacodynamics and pharmacokinetics profiles, the currently available therapies cannot be compared to each other on several levels,” Dr. Gualtierotti said.

Laboratory monitoring of replacement therapies with standard coagulation assays may be unreliable, and depending on the mechanism of action and type of administration of nonreplacement agents, patients may experience breakthrough bleeding, especially after traumatic injury, she said.

Until the specific noncoagulatory effects of factor VIII on bone and joint health is better understood, close monitoring of patients will be required, she added.
 

Outcome measures

Subjective measures of joint health include patient-reported bleeding rates and health-related quality of life. These are practical for home management, but patients may not be able to distinguish symptoms of acute joint bleeding from chronic arthritis pain, with the potential for either under- or overtreatment, and subjective reporting is likely to miss subclinical bleeding that can occur even when patients are on prophylaxis.

Health-related quality of life tools, whether generic or specific for hemophilia, are not sensitive to small improvements, and they are not always used in routine clinical practice.

Objective measures include physical examination with scoring according to the World Federation of Hemophilia (Gilbert Scale) score or Hemophilia Joint Health Score, but these measures have limited ability to identify early or subclinical joint abnormalities.

“Therefore, joint physical examination on its own is not a sufficient measure of treatment efficacy, and it should be used in combination with other tools more objective, such as imaging,” Dr. Gualtierotti said.
 

Get the picture?

Imaging with x-rays, MRI, and, recently in some centers, point-of-care ultrasound can provide clinicians with important real-time information about the joint stability and health.

Point-of-care ultrasound in particular offers promise as a practical tool, with no ionizing radiation and high sensitivity for synovial hyperplasia subclinical joint effusion. It’s relatively inexpensive, can be used to image multiple joints, and allows for ease of follow-up, she said. The technique requires specialized training, however, and there is a lack of prospective data about its utility in hemophilia.

Various ultrasound scoring systems have been proposed, and home-based ultrasound is currently being explored in several clinical trials, Dr. Gualtierotti noted.

Other avenues for remote joint health monitoring under consideration are serum or synovial biomarkers for joint bleeding and arthropathy that could be employed at bedside or at home, smartphone apps for breakthrough bleeding and patient-reported outcomes, and sensors for detecting abnormalities in gait that may signal joint dysfunction, she said.
 

Best practice

In the question-and-answer session following the talk, Fernando Zikan, MD, from the Federal University of Rio de Janeiro noted that, “in underdeveloped countries, we still find it very difficult to guide good practices for joint health control by the patient and family members. Which strategy do you think is fundamental for the patient to feel safe to notice changes in his body?”

“It would be useful to educate patients to come to the center whenever the patient has trauma and whenever an increase in his physical activity occurs. If this is far, a bedside ultrasound evaluation by the general practitioner could help avoid joint damage. Finally, a correct rehabilitation is fundamental,” Dr. Gualtierotti replied.

Asked by several others whether she used ultrasound in her daily practice, Dr. Gualtierotti said that “we use joint ultrasound in our clinical practice in the regular annual check-up examination and whenever the patient suspects and reports hemarthrosis.”

Dr. Gualtierotti reported participation in advisory boards for Biomarin, Pfizer, Bayer, and Takeda, and in educational seminars sponsored by Pfizer, Sobi, and Roche. She has received support for congress travel and/or attendance by Bayer and Pfizer. Dr. Zikan reported no relevant disclosures.

Novel therapies have transformed the treatment of hemophilia in recent decades, but these new approaches also raise new challenges for clinicians who monitor joint health in persons with hemophilia, a specialist said.

“Patient-reported outcomes should be combined with other, more objective outcome measures for joint health monitoring, and joint ultrasound is a promising tool for objective joint health monitoring, although, due to its relatively recent introduction in clinical practice, we lack objective data and standardization,” said Roberta Gualtierotti, MD, PhD, from the Università Degli Studi of Milan.

She reviewed the challenges and approaches to monitoring joint health in persons with hemophilia during the annual congress of the European Association for Haemophilia and Allied Disorders.

Over the last decades the target of hemophilia treatment has shifted from prolonging survival to improving joint health and quality of life, and care has improved with the introduction of novel therapies such as extended half-life replacement products, nonreplacement therapies, and gene therapy, she noted.

However, “due to different pharmacodynamics and pharmacokinetics profiles, the currently available therapies cannot be compared to each other on several levels,” Dr. Gualtierotti said.

Laboratory monitoring of replacement therapies with standard coagulation assays may be unreliable, and depending on the mechanism of action and type of administration of nonreplacement agents, patients may experience breakthrough bleeding, especially after traumatic injury, she said.

Until the specific noncoagulatory effects of factor VIII on bone and joint health is better understood, close monitoring of patients will be required, she added.
 

Outcome measures

Subjective measures of joint health include patient-reported bleeding rates and health-related quality of life. These are practical for home management, but patients may not be able to distinguish symptoms of acute joint bleeding from chronic arthritis pain, with the potential for either under- or overtreatment, and subjective reporting is likely to miss subclinical bleeding that can occur even when patients are on prophylaxis.

Health-related quality of life tools, whether generic or specific for hemophilia, are not sensitive to small improvements, and they are not always used in routine clinical practice.

Objective measures include physical examination with scoring according to the World Federation of Hemophilia (Gilbert Scale) score or Hemophilia Joint Health Score, but these measures have limited ability to identify early or subclinical joint abnormalities.

“Therefore, joint physical examination on its own is not a sufficient measure of treatment efficacy, and it should be used in combination with other tools more objective, such as imaging,” Dr. Gualtierotti said.
 

Get the picture?

Imaging with x-rays, MRI, and, recently in some centers, point-of-care ultrasound can provide clinicians with important real-time information about the joint stability and health.

Point-of-care ultrasound in particular offers promise as a practical tool, with no ionizing radiation and high sensitivity for synovial hyperplasia subclinical joint effusion. It’s relatively inexpensive, can be used to image multiple joints, and allows for ease of follow-up, she said. The technique requires specialized training, however, and there is a lack of prospective data about its utility in hemophilia.

Various ultrasound scoring systems have been proposed, and home-based ultrasound is currently being explored in several clinical trials, Dr. Gualtierotti noted.

Other avenues for remote joint health monitoring under consideration are serum or synovial biomarkers for joint bleeding and arthropathy that could be employed at bedside or at home, smartphone apps for breakthrough bleeding and patient-reported outcomes, and sensors for detecting abnormalities in gait that may signal joint dysfunction, she said.
 

Best practice

In the question-and-answer session following the talk, Fernando Zikan, MD, from the Federal University of Rio de Janeiro noted that, “in underdeveloped countries, we still find it very difficult to guide good practices for joint health control by the patient and family members. Which strategy do you think is fundamental for the patient to feel safe to notice changes in his body?”

“It would be useful to educate patients to come to the center whenever the patient has trauma and whenever an increase in his physical activity occurs. If this is far, a bedside ultrasound evaluation by the general practitioner could help avoid joint damage. Finally, a correct rehabilitation is fundamental,” Dr. Gualtierotti replied.

Asked by several others whether she used ultrasound in her daily practice, Dr. Gualtierotti said that “we use joint ultrasound in our clinical practice in the regular annual check-up examination and whenever the patient suspects and reports hemarthrosis.”

Dr. Gualtierotti reported participation in advisory boards for Biomarin, Pfizer, Bayer, and Takeda, and in educational seminars sponsored by Pfizer, Sobi, and Roche. She has received support for congress travel and/or attendance by Bayer and Pfizer. Dr. Zikan reported no relevant disclosures.

Elevated vaginal pH at the time of cervical intraepithelial neoplasia 2 diagnosis may be a useful marker of CIN 2 persistence/progression, as well as the rate of persistence/progression in HIV-positive women, new research suggests.

“We analyzed data from the Women’s Interagency HIV Study [WIHS], an observational, longitudinal cohort of women with and without HIV to determine factors that may influence CIN 2 natural history,” said Kate Michel, PhD, MPH, of Georgetown University, Washington. She presented the results at the Conference on Retroviruses and Opportunistic Infections.

As previous data have shown a high incidence of CIN 2 progression among women with HIV, the researchers evaluated the role of human papillomavirus (HPV) type, local immune response, and markers of the cervicovaginal microbiome on the risk of CIN 2 persistence/progression.

Within the cohort, follow-up visits occur every 6 months, and clinical data is collected via questionnaires, physical and gynecologic exams, and biological samples. As no specific treatment is offered in the WIHS, treatment for cervical abnormalities is abstracted from medical records.

In the present study, Dr. Michel and colleagues selected up to four banked cervicovaginal lavage (CVL) samples per woman, with the first sample selected 6-12 months prior to CIN 2 diagnosis, the second at CIN 2 diagnosis, the third between CIN 2 diagnosis and outcome, and the fourth at the outcome visit.

The investigators performed HPV typing and muiltiplex immune mediator testing on each CVL sample. Lab results from WIHS core testing were also extracted, including plasma CD4+ T-cell count and HIV viral load, as well as vaginal pH and Nugent’s score.

Study outcomes included persistence/progression and regression, defined as a subsequent CIN 2 or CIN 3 diagnosis and subsequent CIN 1 or normal diagnosis, respectively. Logistic regression models were used to determine CIN 2 regression versus persistence/progression.
 

Results

A total of 337 samples were obtained and 94 women were included in the analysis. Key demographic and behavioral factor were similar at CIN 2 diagnosis.

The majority of participants were African American (53.2%) and on antiretroviral therapy (66.0%). The most prevalent high-risk types were HPV-58 (18.4%) and HPV-16 (17.5%).

After a median 12.5 years of follow-up, 33 participants (35.1%) with incident CIN 2 had a subsequent CIN 2/CIN 3 diagnosis and those who regressed had a higher CD4 T-cell count at CIN 2 diagnosis (P = .02).

Each subsequent high-risk HPV type identified at the pre–CIN 2 visit was associated with higher odds of CIN2 persistence/progression (odds ratio, 2.27; 95% confidence interval, 1.15-4.50).

Bacterial vaginosis (adjusted OR, 5.08; 95% CI, 1.30-19.94) and vaginal pH (aOR, 2.27; 95% CI, 1.15-4.50) at the CIN 2 diagnosis visit were each associated with increased odds of CIN 2 persistence/progression.

Vaginal pH greater than 4.5 at CIN 2 diagnosis was also associated with unadjusted time to CIN 2 persistence/progression (log rank P = .002) and an increased rate of CIN 2 persistence/progression (adjusted hazard ratio, 3.37; 95% CI, 1.26-8.99).

Furthermore, among participants who did not receive CIN 2 treatment, vaginal pH remained associated with greater odds of CIN 2 persistence/progression (OR, 2.46; 95% CI, 1.19-5.13). Cervicovaginal immune mediator levels were not associated with CIN 2 persistence/progression.

“The most striking finding from this work was that vaginal pH was associated with higher odds of, quicker time to, and increased hazard of CIN 2 persistence/progression,” Dr. Michel said. “We postulate this effect is mediated by the cervical microbiome, but more work is needed to establish the exact mechanism.”

“It would be interesting to test whether this association might be explained by different vaginal cleaning techniques, such as douching,” said moderator Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles.

“We’re currently working on an analysis of cervicovaginal bacterial species to explore the microbiome in more detail,” Dr. Michel concluded.

Dr. Michel disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Georgetown-Howard Universities Center for Clinical and Translational Science.

Elevated vaginal pH at the time of cervical intraepithelial neoplasia 2 diagnosis may be a useful marker of CIN 2 persistence/progression, as well as the rate of persistence/progression in HIV-positive women, new research suggests.

“We analyzed data from the Women’s Interagency HIV Study [WIHS], an observational, longitudinal cohort of women with and without HIV to determine factors that may influence CIN 2 natural history,” said Kate Michel, PhD, MPH, of Georgetown University, Washington. She presented the results at the Conference on Retroviruses and Opportunistic Infections.

As previous data have shown a high incidence of CIN 2 progression among women with HIV, the researchers evaluated the role of human papillomavirus (HPV) type, local immune response, and markers of the cervicovaginal microbiome on the risk of CIN 2 persistence/progression.

Within the cohort, follow-up visits occur every 6 months, and clinical data is collected via questionnaires, physical and gynecologic exams, and biological samples. As no specific treatment is offered in the WIHS, treatment for cervical abnormalities is abstracted from medical records.

In the present study, Dr. Michel and colleagues selected up to four banked cervicovaginal lavage (CVL) samples per woman, with the first sample selected 6-12 months prior to CIN 2 diagnosis, the second at CIN 2 diagnosis, the third between CIN 2 diagnosis and outcome, and the fourth at the outcome visit.

The investigators performed HPV typing and muiltiplex immune mediator testing on each CVL sample. Lab results from WIHS core testing were also extracted, including plasma CD4+ T-cell count and HIV viral load, as well as vaginal pH and Nugent’s score.

Study outcomes included persistence/progression and regression, defined as a subsequent CIN 2 or CIN 3 diagnosis and subsequent CIN 1 or normal diagnosis, respectively. Logistic regression models were used to determine CIN 2 regression versus persistence/progression.
 

Results

A total of 337 samples were obtained and 94 women were included in the analysis. Key demographic and behavioral factor were similar at CIN 2 diagnosis.

The majority of participants were African American (53.2%) and on antiretroviral therapy (66.0%). The most prevalent high-risk types were HPV-58 (18.4%) and HPV-16 (17.5%).

After a median 12.5 years of follow-up, 33 participants (35.1%) with incident CIN 2 had a subsequent CIN 2/CIN 3 diagnosis and those who regressed had a higher CD4 T-cell count at CIN 2 diagnosis (P = .02).

Each subsequent high-risk HPV type identified at the pre–CIN 2 visit was associated with higher odds of CIN2 persistence/progression (odds ratio, 2.27; 95% confidence interval, 1.15-4.50).

Bacterial vaginosis (adjusted OR, 5.08; 95% CI, 1.30-19.94) and vaginal pH (aOR, 2.27; 95% CI, 1.15-4.50) at the CIN 2 diagnosis visit were each associated with increased odds of CIN 2 persistence/progression.

Vaginal pH greater than 4.5 at CIN 2 diagnosis was also associated with unadjusted time to CIN 2 persistence/progression (log rank P = .002) and an increased rate of CIN 2 persistence/progression (adjusted hazard ratio, 3.37; 95% CI, 1.26-8.99).

Furthermore, among participants who did not receive CIN 2 treatment, vaginal pH remained associated with greater odds of CIN 2 persistence/progression (OR, 2.46; 95% CI, 1.19-5.13). Cervicovaginal immune mediator levels were not associated with CIN 2 persistence/progression.

“The most striking finding from this work was that vaginal pH was associated with higher odds of, quicker time to, and increased hazard of CIN 2 persistence/progression,” Dr. Michel said. “We postulate this effect is mediated by the cervical microbiome, but more work is needed to establish the exact mechanism.”

“It would be interesting to test whether this association might be explained by different vaginal cleaning techniques, such as douching,” said moderator Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles.

“We’re currently working on an analysis of cervicovaginal bacterial species to explore the microbiome in more detail,” Dr. Michel concluded.

Dr. Michel disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Georgetown-Howard Universities Center for Clinical and Translational Science.

Elevated vaginal pH at the time of cervical intraepithelial neoplasia 2 diagnosis may be a useful marker of CIN 2 persistence/progression, as well as the rate of persistence/progression in HIV-positive women, new research suggests.

“We analyzed data from the Women’s Interagency HIV Study [WIHS], an observational, longitudinal cohort of women with and without HIV to determine factors that may influence CIN 2 natural history,” said Kate Michel, PhD, MPH, of Georgetown University, Washington. She presented the results at the Conference on Retroviruses and Opportunistic Infections.

As previous data have shown a high incidence of CIN 2 progression among women with HIV, the researchers evaluated the role of human papillomavirus (HPV) type, local immune response, and markers of the cervicovaginal microbiome on the risk of CIN 2 persistence/progression.

Within the cohort, follow-up visits occur every 6 months, and clinical data is collected via questionnaires, physical and gynecologic exams, and biological samples. As no specific treatment is offered in the WIHS, treatment for cervical abnormalities is abstracted from medical records.

In the present study, Dr. Michel and colleagues selected up to four banked cervicovaginal lavage (CVL) samples per woman, with the first sample selected 6-12 months prior to CIN 2 diagnosis, the second at CIN 2 diagnosis, the third between CIN 2 diagnosis and outcome, and the fourth at the outcome visit.

The investigators performed HPV typing and muiltiplex immune mediator testing on each CVL sample. Lab results from WIHS core testing were also extracted, including plasma CD4+ T-cell count and HIV viral load, as well as vaginal pH and Nugent’s score.

Study outcomes included persistence/progression and regression, defined as a subsequent CIN 2 or CIN 3 diagnosis and subsequent CIN 1 or normal diagnosis, respectively. Logistic regression models were used to determine CIN 2 regression versus persistence/progression.
 

Results

A total of 337 samples were obtained and 94 women were included in the analysis. Key demographic and behavioral factor were similar at CIN 2 diagnosis.

The majority of participants were African American (53.2%) and on antiretroviral therapy (66.0%). The most prevalent high-risk types were HPV-58 (18.4%) and HPV-16 (17.5%).

After a median 12.5 years of follow-up, 33 participants (35.1%) with incident CIN 2 had a subsequent CIN 2/CIN 3 diagnosis and those who regressed had a higher CD4 T-cell count at CIN 2 diagnosis (P = .02).

Each subsequent high-risk HPV type identified at the pre–CIN 2 visit was associated with higher odds of CIN2 persistence/progression (odds ratio, 2.27; 95% confidence interval, 1.15-4.50).

Bacterial vaginosis (adjusted OR, 5.08; 95% CI, 1.30-19.94) and vaginal pH (aOR, 2.27; 95% CI, 1.15-4.50) at the CIN 2 diagnosis visit were each associated with increased odds of CIN 2 persistence/progression.

Vaginal pH greater than 4.5 at CIN 2 diagnosis was also associated with unadjusted time to CIN 2 persistence/progression (log rank P = .002) and an increased rate of CIN 2 persistence/progression (adjusted hazard ratio, 3.37; 95% CI, 1.26-8.99).

Furthermore, among participants who did not receive CIN 2 treatment, vaginal pH remained associated with greater odds of CIN 2 persistence/progression (OR, 2.46; 95% CI, 1.19-5.13). Cervicovaginal immune mediator levels were not associated with CIN 2 persistence/progression.

“The most striking finding from this work was that vaginal pH was associated with higher odds of, quicker time to, and increased hazard of CIN 2 persistence/progression,” Dr. Michel said. “We postulate this effect is mediated by the cervical microbiome, but more work is needed to establish the exact mechanism.”

“It would be interesting to test whether this association might be explained by different vaginal cleaning techniques, such as douching,” said moderator Ronald T. Mitsuyasu, MD, of the University of California, Los Angeles.

“We’re currently working on an analysis of cervicovaginal bacterial species to explore the microbiome in more detail,” Dr. Michel concluded.

Dr. Michel disclosed no conflicts of interest. The study was supported by multiple sources, including the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the Georgetown-Howard Universities Center for Clinical and Translational Science.

Edward H. Livingston, MD, has resigned as deputy editor of JAMA after he and the journal faced significant backlash over a February 2021 podcast that questioned the existence of structural racism.

JAMA editor in chief Howard Bauchner, MD, apologized to JAMA staff and stakeholders and asked for and received Dr. Livingston’s resignation, according to a statement from AMA CEO James Madara.

More than 2,000 people have signed a petition on Change.org calling for an investigation at JAMA over the podcast, called “Structural Racism for Doctors: What Is It?”

It appears they are now getting their wish. Dr. Bauchner announced that the journal’s oversight committee is investigating how the podcast and a tweet promoting the episode were developed, reviewed, and ultimately posted.

“This investigation and report of its findings will be thorough and completed rapidly,” Dr. Bauchner said.

Dr. Livingston, the host of the podcast, has been heavily criticized across social media. During the podcast, Dr. Livingston, who is White, said: “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”

The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released last week, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”

Dr. Katz is an editor at JAMA Internal Medicine and CEO of NYC Health + Hospitals in New York.

Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”

The incident was met with anger and confusion in the medical community.

Herbert C. Smitherman, MD, vice dean of diversity and community affairs at Wayne State University, Detroit, noted after hearing the podcast that it was a symptom of a much larger problem.

“At its core, this podcast had racist tendencies. Those attitudes are why you don’t have as many articles by Black and Brown people in JAMA,” he said. “People’s attitudes, whether conscious or unconscious, are what drive the policies and practices which create the structural racism.”

Dr. Katz responded to the backlash last week with the following statement: “Systemic racism exists in our country. The disparate effects of the pandemic have made this painfully clear in New York City and across the country.

“As clinicians, we must understand how these structures and policies have a direct impact on the health outcomes of the patients and communities we serve. It is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it, or that we should avoid the term ‘systematic racism’ because it makes people uncomfortable. We must and can do better.”

JAMA, an independent arm of the AMA, is taking other steps to address concerns. Its executive publisher, Thomas Easley, held an employee town hall this week, and said JAMA acknowledges that “structural racism is real, pernicious, and pervasive in health care.” The journal is also starting an “end-to-end review” of all editorial processes across all JAMA publications. Finally, the journal will also create a new associate editor’s position who will provide “insight and counsel” on racism and structural racism in health care.

A version of this article first appeared on WebMD.com .

Edward H. Livingston, MD, has resigned as deputy editor of JAMA after he and the journal faced significant backlash over a February 2021 podcast that questioned the existence of structural racism.

JAMA editor in chief Howard Bauchner, MD, apologized to JAMA staff and stakeholders and asked for and received Dr. Livingston’s resignation, according to a statement from AMA CEO James Madara.

More than 2,000 people have signed a petition on Change.org calling for an investigation at JAMA over the podcast, called “Structural Racism for Doctors: What Is It?”

It appears they are now getting their wish. Dr. Bauchner announced that the journal’s oversight committee is investigating how the podcast and a tweet promoting the episode were developed, reviewed, and ultimately posted.

“This investigation and report of its findings will be thorough and completed rapidly,” Dr. Bauchner said.

Dr. Livingston, the host of the podcast, has been heavily criticized across social media. During the podcast, Dr. Livingston, who is White, said: “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”

The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released last week, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”

Dr. Katz is an editor at JAMA Internal Medicine and CEO of NYC Health + Hospitals in New York.

Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”

The incident was met with anger and confusion in the medical community.

Herbert C. Smitherman, MD, vice dean of diversity and community affairs at Wayne State University, Detroit, noted after hearing the podcast that it was a symptom of a much larger problem.

“At its core, this podcast had racist tendencies. Those attitudes are why you don’t have as many articles by Black and Brown people in JAMA,” he said. “People’s attitudes, whether conscious or unconscious, are what drive the policies and practices which create the structural racism.”

Dr. Katz responded to the backlash last week with the following statement: “Systemic racism exists in our country. The disparate effects of the pandemic have made this painfully clear in New York City and across the country.

“As clinicians, we must understand how these structures and policies have a direct impact on the health outcomes of the patients and communities we serve. It is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it, or that we should avoid the term ‘systematic racism’ because it makes people uncomfortable. We must and can do better.”

JAMA, an independent arm of the AMA, is taking other steps to address concerns. Its executive publisher, Thomas Easley, held an employee town hall this week, and said JAMA acknowledges that “structural racism is real, pernicious, and pervasive in health care.” The journal is also starting an “end-to-end review” of all editorial processes across all JAMA publications. Finally, the journal will also create a new associate editor’s position who will provide “insight and counsel” on racism and structural racism in health care.

A version of this article first appeared on WebMD.com .

Edward H. Livingston, MD, has resigned as deputy editor of JAMA after he and the journal faced significant backlash over a February 2021 podcast that questioned the existence of structural racism.

JAMA editor in chief Howard Bauchner, MD, apologized to JAMA staff and stakeholders and asked for and received Dr. Livingston’s resignation, according to a statement from AMA CEO James Madara.

More than 2,000 people have signed a petition on Change.org calling for an investigation at JAMA over the podcast, called “Structural Racism for Doctors: What Is It?”

It appears they are now getting their wish. Dr. Bauchner announced that the journal’s oversight committee is investigating how the podcast and a tweet promoting the episode were developed, reviewed, and ultimately posted.

“This investigation and report of its findings will be thorough and completed rapidly,” Dr. Bauchner said.

Dr. Livingston, the host of the podcast, has been heavily criticized across social media. During the podcast, Dr. Livingston, who is White, said: “Structural racism is an unfortunate term. Personally, I think taking racism out of the conversation will help. Many of us are offended by the concept that we are racist.”

The audio of the podcast has been deleted from JAMA’s website. In its place is audio of a statement from Dr. Bauchner. In his statement, which he released last week, he said the comments in the podcast, which also featured Mitch Katz, MD, were “inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA.”

Dr. Katz is an editor at JAMA Internal Medicine and CEO of NYC Health + Hospitals in New York.

Also deleted was a JAMA tweet promoting the podcast episode. The tweet said: “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”

The incident was met with anger and confusion in the medical community.

Herbert C. Smitherman, MD, vice dean of diversity and community affairs at Wayne State University, Detroit, noted after hearing the podcast that it was a symptom of a much larger problem.

“At its core, this podcast had racist tendencies. Those attitudes are why you don’t have as many articles by Black and Brown people in JAMA,” he said. “People’s attitudes, whether conscious or unconscious, are what drive the policies and practices which create the structural racism.”

Dr. Katz responded to the backlash last week with the following statement: “Systemic racism exists in our country. The disparate effects of the pandemic have made this painfully clear in New York City and across the country.

“As clinicians, we must understand how these structures and policies have a direct impact on the health outcomes of the patients and communities we serve. It is woefully naive to say that no physician is a racist just because the Civil Rights Act of 1964 forbade it, or that we should avoid the term ‘systematic racism’ because it makes people uncomfortable. We must and can do better.”

JAMA, an independent arm of the AMA, is taking other steps to address concerns. Its executive publisher, Thomas Easley, held an employee town hall this week, and said JAMA acknowledges that “structural racism is real, pernicious, and pervasive in health care.” The journal is also starting an “end-to-end review” of all editorial processes across all JAMA publications. Finally, the journal will also create a new associate editor’s position who will provide “insight and counsel” on racism and structural racism in health care.

A version of this article first appeared on WebMD.com .

Bremelanotide, a Food and Drug Administration–approved treatment for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women, may be of limited use, suggests Glen I. Spielmans, PhD, in a new analysis paper.

Dr. Spielmans, professor of psychology at Metropolitan State University in Saint Paul, Minn., examined data from the FDA application for bremelanotide, clinicaltrials.gov entries for two phase 3 trials of the drug, and a 2019 article published in Obstetrics & Gynecology that described results from the 24-week trials.

In Dr. Speilman’s analysis, which was published online March 7 in the Journal of Sex Research, he notes that 42.1% of trial participants who received bremelanotide did not complete the trial, compared with 20.48% of participants who received placebo.

Of those who completed the study, 87.22% who received placebo wanted to continue treatment in an open-label extension, compared with 69.97% who received bremelanotide, he wrote.

Women “should be aware of the small degree of bremelanotide’s efficacy, that the protocol-specified outcomes of bremelanotide are mostly unknown, and that participants would rather take a placebo than bremelanotide,” Dr. Spielmans said.

Anita H. Clayton, MD, an author of the Obstetrics & Gynecology paper addressed in Dr. Spielmans’ analysis, says the Journal of Sex Research article does not provide new information and is a disservice to women because it questions accurate scientific data.

Measuring outcomes in HSDD is an evolving field, Dr. Clayton, a psychiatrist at the University of Virginia in Charlottesville, said in an interview. Initial FDA guidance relied on satisfying sexual events as an outcome measure, but this measure was derived from erectile dysfunction studies and is not necessarily adequate for assessing HSDD, she said. The FDA and drug developers agreed to use the desire subscale of the Female Sexual Function Index (FSFI-D) as a coprimary outcome measure instead, she noted.
 

Dr. Spielmans’ critique of Obstetrics & Gynecology paper

The article published in Obstetrics & Gynecology reporting bremelanotide trial results was noteworthy, although the various issues involved can be seen in reports about other drug trials, Dr. Spielmans said in an interview.

“It is well-established that journal articles reporting clinical trial data overstate benefits and understate harms,” he continued. In this case, “the very incomplete data reporting, reliance on many post-hoc measures of questionable validity, hiding the concerning number of dropouts due to adverse events, and putting a positive spin on efficacy and tolerability is both remarkable and highly problematic,” Dr. Spielmans said.
 

Dr. Clayton’s reaction

Data about dropout rates due to adverse events have been reported and presented at national meetings, she said in an interview. In addition, a questionnaire found that bremelanotide was superior to placebo in terms of patients feeling that the treatment had provided clinically meaningful benefit, Dr. Clayton said.

The available information enables patients to make informed treatment decisions, Dr. Clayton continued. “There is really this sexist attitude of women needing protection from their own decisions,” she said.
 

Diagnosing and treating HSDD

Eight of 11 efficacy outcomes in the clinicaltrials.gov study protocols for bremelanotide were not reported in the Obstetrics & Gynecology article in a way that was consistent with the protocols, Dr. Spielmans said. Changing a coprimary outcome to the key secondary outcome “occurred over a year after the trials had begun,” and the authors of the journal article “did not mention that this change occurred,” Dr. Spielmans wrote.

For the coprimary outcome measures of mean change on FSFI-D and Female Sexual Distress Scale–Desire/Arousal/Orgasm #13, “bremelanotide offers modest benefits over placebo,” Dr. Spielmans reported.

In addition to outlining his concerns about transparency in the reporting of trial data and raising questions about the outcome measures used in the Obstetrics & Gynecology article, Dr. Spielmans wrote that the diagnosis of HSDD is problematic.

“The lack of specifying symptom duration, questionable validity for the lack of sexual fantasies as a diagnostic criterion, difficulty in disentangling individual sexual problems from relational problems, and the failure to consider cultural influence (including the pressure on women to satisfy the sexual desires of their male partners) in the experience of sexuality all render HSDD as a problematic entity,” Dr. Spielmans wrote.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders replaced HSDD and female sexual arousal disorder with the combined condition female sexual interest/arousal disorder. HSDD is in the 11th edition of the International Classification of Diseases and can be applied to men or women, Dr. Spielmans said.
 

FDA acknowledged HSDD as an unmet medical need

Dr. Clayton pointed out that HSDD was described decades ago and the FDA acknowledged it as an unmet medical need, and she expressed dissatisfaction with the fact the hypoactive sexual desire disorder appears with quotation marks around it in the title of Dr. Spielmans’ article. This way of presenting HSDD indicates that “the author has no concept of sexual health or sexual dysfunction,” Dr. Clayton said. “Basically this is sort of a dramatic tool, I think, to act like this is not a real disorder,” she added.

Carl Spana, PhD, CEO and president of Palatin Technologies, the developer of bremelanotide, defined the article in the Journal of Sex Research as a “retrospective meta-analysis, and not a re-analysis of the data.

“As a meta-analysis, it is open to various interpretations and reflects the author’s interpretations, which appear to have clear biases,” Dr. Spana said in an interview. “We believe several of this author’s interpretations are contrary to the FDA’s positive assessment that led to Vyleesi’s approval as a safe and effective treatment for women suffering from hypoactive sexual desire disorder.”

The author is unaware of the validation that was conducted at the direction of the FDA to establish clinically meaningful cutoffs for patient-reported outcomes and to establish metrics that define clinical benefit, Dr. Spana said

“Vyleesi was approved by the FDA after a thorough analysis of data from two well-controlled phase 3 clinical studies and multiple clinical and preclinical safety studies,” he said. “The analyses in the New Drug Application were prespecified and conducted according to a statistical analysis plan that the sponsor and FDA agreed to prior to database lock.”

Dr. Spielmans disclosed holdings in Vanguard Healthcare, a mutual fund that invests in pharmaceutical firms. Dr. Clayton has received financial support from Palatin and AMAG Pharmaceuticals, the companies that developed bremelanotide, in previous years.

[email protected]

Bremelanotide, a Food and Drug Administration–approved treatment for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women, may be of limited use, suggests Glen I. Spielmans, PhD, in a new analysis paper.

Dr. Spielmans, professor of psychology at Metropolitan State University in Saint Paul, Minn., examined data from the FDA application for bremelanotide, clinicaltrials.gov entries for two phase 3 trials of the drug, and a 2019 article published in Obstetrics & Gynecology that described results from the 24-week trials.

In Dr. Speilman’s analysis, which was published online March 7 in the Journal of Sex Research, he notes that 42.1% of trial participants who received bremelanotide did not complete the trial, compared with 20.48% of participants who received placebo.

Of those who completed the study, 87.22% who received placebo wanted to continue treatment in an open-label extension, compared with 69.97% who received bremelanotide, he wrote.

Women “should be aware of the small degree of bremelanotide’s efficacy, that the protocol-specified outcomes of bremelanotide are mostly unknown, and that participants would rather take a placebo than bremelanotide,” Dr. Spielmans said.

Anita H. Clayton, MD, an author of the Obstetrics & Gynecology paper addressed in Dr. Spielmans’ analysis, says the Journal of Sex Research article does not provide new information and is a disservice to women because it questions accurate scientific data.

Measuring outcomes in HSDD is an evolving field, Dr. Clayton, a psychiatrist at the University of Virginia in Charlottesville, said in an interview. Initial FDA guidance relied on satisfying sexual events as an outcome measure, but this measure was derived from erectile dysfunction studies and is not necessarily adequate for assessing HSDD, she said. The FDA and drug developers agreed to use the desire subscale of the Female Sexual Function Index (FSFI-D) as a coprimary outcome measure instead, she noted.
 

Dr. Spielmans’ critique of Obstetrics & Gynecology paper

The article published in Obstetrics & Gynecology reporting bremelanotide trial results was noteworthy, although the various issues involved can be seen in reports about other drug trials, Dr. Spielmans said in an interview.

“It is well-established that journal articles reporting clinical trial data overstate benefits and understate harms,” he continued. In this case, “the very incomplete data reporting, reliance on many post-hoc measures of questionable validity, hiding the concerning number of dropouts due to adverse events, and putting a positive spin on efficacy and tolerability is both remarkable and highly problematic,” Dr. Spielmans said.
 

Dr. Clayton’s reaction

Data about dropout rates due to adverse events have been reported and presented at national meetings, she said in an interview. In addition, a questionnaire found that bremelanotide was superior to placebo in terms of patients feeling that the treatment had provided clinically meaningful benefit, Dr. Clayton said.

The available information enables patients to make informed treatment decisions, Dr. Clayton continued. “There is really this sexist attitude of women needing protection from their own decisions,” she said.
 

Diagnosing and treating HSDD

Eight of 11 efficacy outcomes in the clinicaltrials.gov study protocols for bremelanotide were not reported in the Obstetrics & Gynecology article in a way that was consistent with the protocols, Dr. Spielmans said. Changing a coprimary outcome to the key secondary outcome “occurred over a year after the trials had begun,” and the authors of the journal article “did not mention that this change occurred,” Dr. Spielmans wrote.

For the coprimary outcome measures of mean change on FSFI-D and Female Sexual Distress Scale–Desire/Arousal/Orgasm #13, “bremelanotide offers modest benefits over placebo,” Dr. Spielmans reported.

In addition to outlining his concerns about transparency in the reporting of trial data and raising questions about the outcome measures used in the Obstetrics & Gynecology article, Dr. Spielmans wrote that the diagnosis of HSDD is problematic.

“The lack of specifying symptom duration, questionable validity for the lack of sexual fantasies as a diagnostic criterion, difficulty in disentangling individual sexual problems from relational problems, and the failure to consider cultural influence (including the pressure on women to satisfy the sexual desires of their male partners) in the experience of sexuality all render HSDD as a problematic entity,” Dr. Spielmans wrote.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders replaced HSDD and female sexual arousal disorder with the combined condition female sexual interest/arousal disorder. HSDD is in the 11th edition of the International Classification of Diseases and can be applied to men or women, Dr. Spielmans said.
 

FDA acknowledged HSDD as an unmet medical need

Dr. Clayton pointed out that HSDD was described decades ago and the FDA acknowledged it as an unmet medical need, and she expressed dissatisfaction with the fact the hypoactive sexual desire disorder appears with quotation marks around it in the title of Dr. Spielmans’ article. This way of presenting HSDD indicates that “the author has no concept of sexual health or sexual dysfunction,” Dr. Clayton said. “Basically this is sort of a dramatic tool, I think, to act like this is not a real disorder,” she added.

Carl Spana, PhD, CEO and president of Palatin Technologies, the developer of bremelanotide, defined the article in the Journal of Sex Research as a “retrospective meta-analysis, and not a re-analysis of the data.

“As a meta-analysis, it is open to various interpretations and reflects the author’s interpretations, which appear to have clear biases,” Dr. Spana said in an interview. “We believe several of this author’s interpretations are contrary to the FDA’s positive assessment that led to Vyleesi’s approval as a safe and effective treatment for women suffering from hypoactive sexual desire disorder.”

The author is unaware of the validation that was conducted at the direction of the FDA to establish clinically meaningful cutoffs for patient-reported outcomes and to establish metrics that define clinical benefit, Dr. Spana said

“Vyleesi was approved by the FDA after a thorough analysis of data from two well-controlled phase 3 clinical studies and multiple clinical and preclinical safety studies,” he said. “The analyses in the New Drug Application were prespecified and conducted according to a statistical analysis plan that the sponsor and FDA agreed to prior to database lock.”

Dr. Spielmans disclosed holdings in Vanguard Healthcare, a mutual fund that invests in pharmaceutical firms. Dr. Clayton has received financial support from Palatin and AMAG Pharmaceuticals, the companies that developed bremelanotide, in previous years.

[email protected]

Bremelanotide, a Food and Drug Administration–approved treatment for acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women, may be of limited use, suggests Glen I. Spielmans, PhD, in a new analysis paper.

Dr. Spielmans, professor of psychology at Metropolitan State University in Saint Paul, Minn., examined data from the FDA application for bremelanotide, clinicaltrials.gov entries for two phase 3 trials of the drug, and a 2019 article published in Obstetrics & Gynecology that described results from the 24-week trials.

In Dr. Speilman’s analysis, which was published online March 7 in the Journal of Sex Research, he notes that 42.1% of trial participants who received bremelanotide did not complete the trial, compared with 20.48% of participants who received placebo.

Of those who completed the study, 87.22% who received placebo wanted to continue treatment in an open-label extension, compared with 69.97% who received bremelanotide, he wrote.

Women “should be aware of the small degree of bremelanotide’s efficacy, that the protocol-specified outcomes of bremelanotide are mostly unknown, and that participants would rather take a placebo than bremelanotide,” Dr. Spielmans said.

Anita H. Clayton, MD, an author of the Obstetrics & Gynecology paper addressed in Dr. Spielmans’ analysis, says the Journal of Sex Research article does not provide new information and is a disservice to women because it questions accurate scientific data.

Measuring outcomes in HSDD is an evolving field, Dr. Clayton, a psychiatrist at the University of Virginia in Charlottesville, said in an interview. Initial FDA guidance relied on satisfying sexual events as an outcome measure, but this measure was derived from erectile dysfunction studies and is not necessarily adequate for assessing HSDD, she said. The FDA and drug developers agreed to use the desire subscale of the Female Sexual Function Index (FSFI-D) as a coprimary outcome measure instead, she noted.
 

Dr. Spielmans’ critique of Obstetrics & Gynecology paper

The article published in Obstetrics & Gynecology reporting bremelanotide trial results was noteworthy, although the various issues involved can be seen in reports about other drug trials, Dr. Spielmans said in an interview.

“It is well-established that journal articles reporting clinical trial data overstate benefits and understate harms,” he continued. In this case, “the very incomplete data reporting, reliance on many post-hoc measures of questionable validity, hiding the concerning number of dropouts due to adverse events, and putting a positive spin on efficacy and tolerability is both remarkable and highly problematic,” Dr. Spielmans said.
 

Dr. Clayton’s reaction

Data about dropout rates due to adverse events have been reported and presented at national meetings, she said in an interview. In addition, a questionnaire found that bremelanotide was superior to placebo in terms of patients feeling that the treatment had provided clinically meaningful benefit, Dr. Clayton said.

The available information enables patients to make informed treatment decisions, Dr. Clayton continued. “There is really this sexist attitude of women needing protection from their own decisions,” she said.
 

Diagnosing and treating HSDD

Eight of 11 efficacy outcomes in the clinicaltrials.gov study protocols for bremelanotide were not reported in the Obstetrics & Gynecology article in a way that was consistent with the protocols, Dr. Spielmans said. Changing a coprimary outcome to the key secondary outcome “occurred over a year after the trials had begun,” and the authors of the journal article “did not mention that this change occurred,” Dr. Spielmans wrote.

For the coprimary outcome measures of mean change on FSFI-D and Female Sexual Distress Scale–Desire/Arousal/Orgasm #13, “bremelanotide offers modest benefits over placebo,” Dr. Spielmans reported.

In addition to outlining his concerns about transparency in the reporting of trial data and raising questions about the outcome measures used in the Obstetrics & Gynecology article, Dr. Spielmans wrote that the diagnosis of HSDD is problematic.

“The lack of specifying symptom duration, questionable validity for the lack of sexual fantasies as a diagnostic criterion, difficulty in disentangling individual sexual problems from relational problems, and the failure to consider cultural influence (including the pressure on women to satisfy the sexual desires of their male partners) in the experience of sexuality all render HSDD as a problematic entity,” Dr. Spielmans wrote.

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders replaced HSDD and female sexual arousal disorder with the combined condition female sexual interest/arousal disorder. HSDD is in the 11th edition of the International Classification of Diseases and can be applied to men or women, Dr. Spielmans said.
 

FDA acknowledged HSDD as an unmet medical need

Dr. Clayton pointed out that HSDD was described decades ago and the FDA acknowledged it as an unmet medical need, and she expressed dissatisfaction with the fact the hypoactive sexual desire disorder appears with quotation marks around it in the title of Dr. Spielmans’ article. This way of presenting HSDD indicates that “the author has no concept of sexual health or sexual dysfunction,” Dr. Clayton said. “Basically this is sort of a dramatic tool, I think, to act like this is not a real disorder,” she added.

Carl Spana, PhD, CEO and president of Palatin Technologies, the developer of bremelanotide, defined the article in the Journal of Sex Research as a “retrospective meta-analysis, and not a re-analysis of the data.

“As a meta-analysis, it is open to various interpretations and reflects the author’s interpretations, which appear to have clear biases,” Dr. Spana said in an interview. “We believe several of this author’s interpretations are contrary to the FDA’s positive assessment that led to Vyleesi’s approval as a safe and effective treatment for women suffering from hypoactive sexual desire disorder.”

The author is unaware of the validation that was conducted at the direction of the FDA to establish clinically meaningful cutoffs for patient-reported outcomes and to establish metrics that define clinical benefit, Dr. Spana said

“Vyleesi was approved by the FDA after a thorough analysis of data from two well-controlled phase 3 clinical studies and multiple clinical and preclinical safety studies,” he said. “The analyses in the New Drug Application were prespecified and conducted according to a statistical analysis plan that the sponsor and FDA agreed to prior to database lock.”

Dr. Spielmans disclosed holdings in Vanguard Healthcare, a mutual fund that invests in pharmaceutical firms. Dr. Clayton has received financial support from Palatin and AMAG Pharmaceuticals, the companies that developed bremelanotide, in previous years.

[email protected]

On a busy call day, Oviea (a second-year gastroenterology fellow), paused in the hallway to listen to a conversation between an endoscopy nurse and a patient. The nurse was requesting the patient’s permission for a gastroenterology fellow to participate in their care and the patient, well acquainted with the role from prior procedures, immediately agreed. Oviea entered the patient’s room, introduced himself as “Dr. Akpotaire, the gastroenterology fellow,” as he had with hundreds of other patients during his fellowship, and completed the informed consent. The interaction was brief but pleasant. As Oviea was leaving the room, the patient asked: “When will I meet the doctor”?

This question was familiar to Oviea. Despite always introducing himself by title and wearing matching identification, many patients had dismissed his credentials since graduating from medical school. His answer was equally familiar: “I am a doctor, and Dr. X, the supervising physician, will meet you soon.” With the patient seemingly placated, Oviea delivered the consent form to the procedure room. Minutes later, he was surprised to learn that the patient specifically requested that he not be allowed to participate in their care. This in combination with the patient’s initial dismissal of Oviea’s credentials, left a sting. While none of the other team members outwardly questioned the reason for the patient’s change of heart, Oviea continued to wonder if the patient’s decision was because of his race.

Beyond gastroenterology, similar experiences are common in other spheres. The Twitter thread #BlackintheIvory recounts stories of microaggressions and structural racism in medicine and academia. The cumulative toll of these experiences leads to departures of Black physicians including Uché Blackstock, MD;¹ Aysha Khoury, MD, MPH;² Ben Danielson, MD;³ Princess Dennar, MD;⁴ and others.
 

Microaggressions as proxy for bias

The term microaggression was coined by Chester Pierce, MD, the first Black tenured professor at Massachusetts General Hospital in the 1970’s, to describe the frequent, yet subtle dismissals Black Americans experienced in society. Over time, the term has been expanded to include “brief and commonplace daily verbal, behavioral, or environmental indignities, intentional or unintentional, that communicate hostile, derogatory, or negative slights and insults” to any marginalized group.⁵

While the term microaggressions is useful in contextualizing individual experiences, it narrowly focuses on conscious or unconscious interpersonal prejudices. In medicine, this misdirects attention away from the policies and practices that create and reinforce prejudices; these policies and practices do so by systematically excluding underrepresented minority (URM) physicians,⁶ defined by the American Association of Medical Colleges as physicians who are Black, Hispanic, Native Americans, and Alaska Natives,⁷ from the medical workforce. Ultimately, this leads to and exacerbates poor health outcomes for racial and ethnic minority patients.

Microaggressions represent our society’s deepest and oldest biases and are rooted in structural racism, as well as misogyny, homophobia, transphobia, xenophobia, ableism, and other prejudices.⁸ For URM physicians, experiences like the example above are frequently caused by structural racism.
 

Structural racism in medicine

Structural racism refers to the policies, practices, cultural representations, and norms that reinforce inequities by providing privileges to White people at the disadvantage of non-White people.⁹ In 1910, Abraham Flexner, commissioned by the Carnegie Foundation and the American Medical Association, wrote that African American physicians should be trained in hygiene rather than surgery and should primarily serve as “sanitarians” whose purpose was to “protect Whites” from common diseases like tuberculosis.¹⁰ The 1910 Flexner Report also emphasized the importance of prerequisite basic sciences education and recommended that only two of the seven existing Black medical schools remain open because Flexner believed that only these schools had the potential to meet the new requirements for medical education.¹¹ A recent analysis found that, had the other five medical schools affiliated with historically Black colleges and universities remained open, this would have resulted in an additional 33,315 Black medical school graduates by 2019.¹² Structural racism explains why the majority of practicing physicians, medical educators, National Institutes of Health–funded researchers, and hospital executives are White and, similarly, why White patients are overrepresented in clinical trials, have better health outcomes, and live longer lives than several racial and ethnic minority groups.¹³

The murders of Ahmaud Arbery, Breonna Taylor, and George Floyd and the inequitable toll of the COVID-19 pandemic on Black, Hispanic, and Native American people renewed the dialogue regarding structural racism in America. Beyond criminal justice and police reform, the current social justice movement demands that structural racism is examined in all spheres. In medicine and health care, acknowledging the history of exclusion and exploitation of Black people and other URM groups is an important first step, but this must be followed by a commitment to an antiracist future for the benefit of all medical professionals and patients.^14,15

Antiracism as a path forward

Antiracism refers to actions and policies that seek to dismantle structural racism. While individuals can and should engage in antiracist actions, it is equally important for organizations and government to actively participate in this process as well.



Individual and interpersonal levels

Gastroenterologists should advocate an end to racist practices within their organizations (e.g., unjustified use of race-based corrections in diagnostic algorithms and practice guidelines),¹⁶ and interrupt microaggressions and racist actions in real time (e.g., overpolicing of underrepresented groups in health care settings).¹⁷ Gastroenterologists from underrepresented groups may also need to unlearn internalized racism, which is defined as acceptance by members of disadvantaged races of the negative messages about their own abilities and intrinsic worth.¹⁸



Organizational level

Gastroenterology divisions and practices must ensure that the entire workforce, including leadership, reflects the diversity of our country. Underrepresented groups represent 33% of the U.S. population, but only 9.1% of gastroenterology fellows and 10% of gastroenterology faculty are from underrepresented groups.¹⁹ In addition to diversifying the field of gastroenterology through financial and operational support of pipeline educational programs, organizations should also promote the scholarship of URM groups, whose work is often undervalued, and redistribute power by elevating voices that have been historically absent.²⁰ Gastroenterology practices should also collect high-quality patient data disaggregated by demographic factors. Doing so will enable rapid identification of disparate health outcomes by demographic variables and inform interventions to eliminate identified disparities.



Government level

The “Executive Order On Advancing Racial Equity and Support for Underserved Communities Through the Federal Government” issued by President Biden on Jan. 20, 2021, is an example of how government can promote antiracism.²¹ The executive order states that domestic policies cause group inequities and calls for the removal of systemic barriers in current and future domestic policies. The executive order outlines several additional ways to improve equity in current and future policy, including engagement, consultation, and coordination with members of underserved communities. The details outlined in the executive order should serve as the foundation for establishing new standards at the state, county, and city levels as well. Gastroenterologists can influence government by voting for officials at all levels that support and promote these standards.

Conclusion

Beyond calling out microaggressions in real time, we must also interrogate the biases, policies, and practices that support them in medicine and beyond. As Black gastroenterologists who have experienced microaggressions and overt acts of racism, we ground Oviea’s experience in structural racism and offer strategies that individuals, organizations, and governing institutions can adopt toward an antiracist future. This model can be applied to experiences rooted in misogyny, homophobia, transphobia, xenophobia, ableism, and other prejudices.

As a nation, we must make an active and collective choice to address structural racism. In health care, doing so will strengthen communities, enhance the lived experiences of URM physician colleagues, and save patient lives. Gastroenterologists, as trusted health care providers, are uniquely positioned to lead the way.

Dr. Akpotaire is a second-year GI fellow in the division of gastroenterology at the University of Washington, Seattle. Dr. Issaka is an assistant professor with both the Fred Hutchinson Cancer Research Center, Seattle, and the division of gastroenterology at the University of Washington.

References

1. Blackstock U. “Why Black doctors like me are leaving faculty positions in academic medical centers.” STAT News, 2020.

2. Asare JG. “One Doctor Shares Her Story of Racism in Medicine.” Forbes. 2021 Feb 1.

3. Kroman D. “Revered doctor steps down, accusing Seattle Children’s Hospital of racism.” Crosscut. 2020 Dec 31.

4. United States District Court Eastern District of Louisiana. Princess Dennar, M.D. v. The Administrators of the Tulane Educational Fund, 2020.

5. Sue DW. Microaggressions in Everyday Life: Race, Gender, and Sexual Orientation. Hoboken, N.J.: Wiley, 2010.

6. Boyd RW. Lancet. 2019 Jun 22;393(10190):2484-5.

7. AAMC. Diversity in Medicine Facts and Figures 2019. Washington, D.C., 2019.

8. Overland MK et al. PM R. 2019 Sep;11(9):1004-12.

9. Jones CP. Ethn Dis. 2018 Aug 9;28(Suppl 1):231-4.

10. Hlavinka E. “Racial Bias in Flexner Report Permeates Medical Education Today.” Medpage Today. 2020 Jun 18.

11. Flexner A. Medical Education in the United States and Canada. New York: 1910. Republished: Bull World Health Organ. 2002;80(7):594-602.

12. Campbell KM et al. JAMA Netw Open. 2020 Aug 3;3(8):e2015220.

13. Malat J et al. Soc Sci Med. 2018 Feb;199:148-56.

14. Kendi IX. How to be an antiracist. New York: Random House Books, 2019.

15. Gray DM 2nd et al. Nat Rev Gastroenterol Hepatol. 2020 Oct;17(10):589-90.

16. Vyas DA et al. N Engl J Med. 2020 Aug 27;383(9):874-82.

17. Green CR et al. J Natl Med Assoc. 2018 Feb;110(1):37-43.

18. Jones CP. Am J Public Health. 2000 Aug;90(8):1212-5.

19. Anyane-Yeboa A et al. Am J Gastroenterol. 2020 Aug;115(8):1147-9.

20. Issaka RB. JAMA. 2020 Aug 11;324(6):556-7.

21. Biden JR. Executive Order On Advancing Racial Equity and Support for Underserved Communities Through the Federal Government. Washington, D.C.: The White House, 2021.

On a busy call day, Oviea (a second-year gastroenterology fellow), paused in the hallway to listen to a conversation between an endoscopy nurse and a patient. The nurse was requesting the patient’s permission for a gastroenterology fellow to participate in their care and the patient, well acquainted with the role from prior procedures, immediately agreed. Oviea entered the patient’s room, introduced himself as “Dr. Akpotaire, the gastroenterology fellow,” as he had with hundreds of other patients during his fellowship, and completed the informed consent. The interaction was brief but pleasant. As Oviea was leaving the room, the patient asked: “When will I meet the doctor”?

This question was familiar to Oviea. Despite always introducing himself by title and wearing matching identification, many patients had dismissed his credentials since graduating from medical school. His answer was equally familiar: “I am a doctor, and Dr. X, the supervising physician, will meet you soon.” With the patient seemingly placated, Oviea delivered the consent form to the procedure room. Minutes later, he was surprised to learn that the patient specifically requested that he not be allowed to participate in their care. This in combination with the patient’s initial dismissal of Oviea’s credentials, left a sting. While none of the other team members outwardly questioned the reason for the patient’s change of heart, Oviea continued to wonder if the patient’s decision was because of his race.

Beyond gastroenterology, similar experiences are common in other spheres. The Twitter thread #BlackintheIvory recounts stories of microaggressions and structural racism in medicine and academia. The cumulative toll of these experiences leads to departures of Black physicians including Uché Blackstock, MD;¹ Aysha Khoury, MD, MPH;² Ben Danielson, MD;³ Princess Dennar, MD;⁴ and others.
 

Microaggressions as proxy for bias

The term microaggression was coined by Chester Pierce, MD, the first Black tenured professor at Massachusetts General Hospital in the 1970’s, to describe the frequent, yet subtle dismissals Black Americans experienced in society. Over time, the term has been expanded to include “brief and commonplace daily verbal, behavioral, or environmental indignities, intentional or unintentional, that communicate hostile, derogatory, or negative slights and insults” to any marginalized group.⁵

While the term microaggressions is useful in contextualizing individual experiences, it narrowly focuses on conscious or unconscious interpersonal prejudices. In medicine, this misdirects attention away from the policies and practices that create and reinforce prejudices; these policies and practices do so by systematically excluding underrepresented minority (URM) physicians,⁶ defined by the American Association of Medical Colleges as physicians who are Black, Hispanic, Native Americans, and Alaska Natives,⁷ from the medical workforce. Ultimately, this leads to and exacerbates poor health outcomes for racial and ethnic minority patients.

Microaggressions represent our society’s deepest and oldest biases and are rooted in structural racism, as well as misogyny, homophobia, transphobia, xenophobia, ableism, and other prejudices.⁸ For URM physicians, experiences like the example above are frequently caused by structural racism.
 

Structural racism in medicine

Structural racism refers to the policies, practices, cultural representations, and norms that reinforce inequities by providing privileges to White people at the disadvantage of non-White people.⁹ In 1910, Abraham Flexner, commissioned by the Carnegie Foundation and the American Medical Association, wrote that African American physicians should be trained in hygiene rather than surgery and should primarily serve as “sanitarians” whose purpose was to “protect Whites” from common diseases like tuberculosis.¹⁰ The 1910 Flexner Report also emphasized the importance of prerequisite basic sciences education and recommended that only two of the seven existing Black medical schools remain open because Flexner believed that only these schools had the potential to meet the new requirements for medical education.¹¹ A recent analysis found that, had the other five medical schools affiliated with historically Black colleges and universities remained open, this would have resulted in an additional 33,315 Black medical school graduates by 2019.¹² Structural racism explains why the majority of practicing physicians, medical educators, National Institutes of Health–funded researchers, and hospital executives are White and, similarly, why White patients are overrepresented in clinical trials, have better health outcomes, and live longer lives than several racial and ethnic minority groups.¹³

The murders of Ahmaud Arbery, Breonna Taylor, and George Floyd and the inequitable toll of the COVID-19 pandemic on Black, Hispanic, and Native American people renewed the dialogue regarding structural racism in America. Beyond criminal justice and police reform, the current social justice movement demands that structural racism is examined in all spheres. In medicine and health care, acknowledging the history of exclusion and exploitation of Black people and other URM groups is an important first step, but this must be followed by a commitment to an antiracist future for the benefit of all medical professionals and patients.^14,15

Antiracism as a path forward

Antiracism refers to actions and policies that seek to dismantle structural racism. While individuals can and should engage in antiracist actions, it is equally important for organizations and government to actively participate in this process as well.



Individual and interpersonal levels

Gastroenterologists should advocate an end to racist practices within their organizations (e.g., unjustified use of race-based corrections in diagnostic algorithms and practice guidelines),¹⁶ and interrupt microaggressions and racist actions in real time (e.g., overpolicing of underrepresented groups in health care settings).¹⁷ Gastroenterologists from underrepresented groups may also need to unlearn internalized racism, which is defined as acceptance by members of disadvantaged races of the negative messages about their own abilities and intrinsic worth.¹⁸



Organizational level

Gastroenterology divisions and practices must ensure that the entire workforce, including leadership, reflects the diversity of our country. Underrepresented groups represent 33% of the U.S. population, but only 9.1% of gastroenterology fellows and 10% of gastroenterology faculty are from underrepresented groups.¹⁹ In addition to diversifying the field of gastroenterology through financial and operational support of pipeline educational programs, organizations should also promote the scholarship of URM groups, whose work is often undervalued, and redistribute power by elevating voices that have been historically absent.²⁰ Gastroenterology practices should also collect high-quality patient data disaggregated by demographic factors. Doing so will enable rapid identification of disparate health outcomes by demographic variables and inform interventions to eliminate identified disparities.



Government level

The “Executive Order On Advancing Racial Equity and Support for Underserved Communities Through the Federal Government” issued by President Biden on Jan. 20, 2021, is an example of how government can promote antiracism.²¹ The executive order states that domestic policies cause group inequities and calls for the removal of systemic barriers in current and future domestic policies. The executive order outlines several additional ways to improve equity in current and future policy, including engagement, consultation, and coordination with members of underserved communities. The details outlined in the executive order should serve as the foundation for establishing new standards at the state, county, and city levels as well. Gastroenterologists can influence government by voting for officials at all levels that support and promote these standards.

Conclusion

Beyond calling out microaggressions in real time, we must also interrogate the biases, policies, and practices that support them in medicine and beyond. As Black gastroenterologists who have experienced microaggressions and overt acts of racism, we ground Oviea’s experience in structural racism and offer strategies that individuals, organizations, and governing institutions can adopt toward an antiracist future. This model can be applied to experiences rooted in misogyny, homophobia, transphobia, xenophobia, ableism, and other prejudices.

As a nation, we must make an active and collective choice to address structural racism. In health care, doing so will strengthen communities, enhance the lived experiences of URM physician colleagues, and save patient lives. Gastroenterologists, as trusted health care providers, are uniquely positioned to lead the way.

Dr. Akpotaire is a second-year GI fellow in the division of gastroenterology at the University of Washington, Seattle. Dr. Issaka is an assistant professor with both the Fred Hutchinson Cancer Research Center, Seattle, and the division of gastroenterology at the University of Washington.

References

1. Blackstock U. “Why Black doctors like me are leaving faculty positions in academic medical centers.” STAT News, 2020.

2. Asare JG. “One Doctor Shares Her Story of Racism in Medicine.” Forbes. 2021 Feb 1.

3. Kroman D. “Revered doctor steps down, accusing Seattle Children’s Hospital of racism.” Crosscut. 2020 Dec 31.

4. United States District Court Eastern District of Louisiana. Princess Dennar, M.D. v. The Administrators of the Tulane Educational Fund, 2020.

5. Sue DW. Microaggressions in Everyday Life: Race, Gender, and Sexual Orientation. Hoboken, N.J.: Wiley, 2010.

6. Boyd RW. Lancet. 2019 Jun 22;393(10190):2484-5.

7. AAMC. Diversity in Medicine Facts and Figures 2019. Washington, D.C., 2019.

8. Overland MK et al. PM R. 2019 Sep;11(9):1004-12.

9. Jones CP. Ethn Dis. 2018 Aug 9;28(Suppl 1):231-4.

10. Hlavinka E. “Racial Bias in Flexner Report Permeates Medical Education Today.” Medpage Today. 2020 Jun 18.

11. Flexner A. Medical Education in the United States and Canada. New York: 1910. Republished: Bull World Health Organ. 2002;80(7):594-602.

12. Campbell KM et al. JAMA Netw Open. 2020 Aug 3;3(8):e2015220.

13. Malat J et al. Soc Sci Med. 2018 Feb;199:148-56.

14. Kendi IX. How to be an antiracist. New York: Random House Books, 2019.

15. Gray DM 2nd et al. Nat Rev Gastroenterol Hepatol. 2020 Oct;17(10):589-90.

16. Vyas DA et al. N Engl J Med. 2020 Aug 27;383(9):874-82.

17. Green CR et al. J Natl Med Assoc. 2018 Feb;110(1):37-43.

18. Jones CP. Am J Public Health. 2000 Aug;90(8):1212-5.

19. Anyane-Yeboa A et al. Am J Gastroenterol. 2020 Aug;115(8):1147-9.

20. Issaka RB. JAMA. 2020 Aug 11;324(6):556-7.

21. Biden JR. Executive Order On Advancing Racial Equity and Support for Underserved Communities Through the Federal Government. Washington, D.C.: The White House, 2021.

On a busy call day, Oviea (a second-year gastroenterology fellow), paused in the hallway to listen to a conversation between an endoscopy nurse and a patient. The nurse was requesting the patient’s permission for a gastroenterology fellow to participate in their care and the patient, well acquainted with the role from prior procedures, immediately agreed. Oviea entered the patient’s room, introduced himself as “Dr. Akpotaire, the gastroenterology fellow,” as he had with hundreds of other patients during his fellowship, and completed the informed consent. The interaction was brief but pleasant. As Oviea was leaving the room, the patient asked: “When will I meet the doctor”?

This question was familiar to Oviea. Despite always introducing himself by title and wearing matching identification, many patients had dismissed his credentials since graduating from medical school. His answer was equally familiar: “I am a doctor, and Dr. X, the supervising physician, will meet you soon.” With the patient seemingly placated, Oviea delivered the consent form to the procedure room. Minutes later, he was surprised to learn that the patient specifically requested that he not be allowed to participate in their care. This in combination with the patient’s initial dismissal of Oviea’s credentials, left a sting. While none of the other team members outwardly questioned the reason for the patient’s change of heart, Oviea continued to wonder if the patient’s decision was because of his race.

Beyond gastroenterology, similar experiences are common in other spheres. The Twitter thread #BlackintheIvory recounts stories of microaggressions and structural racism in medicine and academia. The cumulative toll of these experiences leads to departures of Black physicians including Uché Blackstock, MD;¹ Aysha Khoury, MD, MPH;² Ben Danielson, MD;³ Princess Dennar, MD;⁴ and others.
 

Microaggressions as proxy for bias

The term microaggression was coined by Chester Pierce, MD, the first Black tenured professor at Massachusetts General Hospital in the 1970’s, to describe the frequent, yet subtle dismissals Black Americans experienced in society. Over time, the term has been expanded to include “brief and commonplace daily verbal, behavioral, or environmental indignities, intentional or unintentional, that communicate hostile, derogatory, or negative slights and insults” to any marginalized group.⁵

While the term microaggressions is useful in contextualizing individual experiences, it narrowly focuses on conscious or unconscious interpersonal prejudices. In medicine, this misdirects attention away from the policies and practices that create and reinforce prejudices; these policies and practices do so by systematically excluding underrepresented minority (URM) physicians,⁶ defined by the American Association of Medical Colleges as physicians who are Black, Hispanic, Native Americans, and Alaska Natives,⁷ from the medical workforce. Ultimately, this leads to and exacerbates poor health outcomes for racial and ethnic minority patients.

Microaggressions represent our society’s deepest and oldest biases and are rooted in structural racism, as well as misogyny, homophobia, transphobia, xenophobia, ableism, and other prejudices.⁸ For URM physicians, experiences like the example above are frequently caused by structural racism.
 

Structural racism in medicine

Structural racism refers to the policies, practices, cultural representations, and norms that reinforce inequities by providing privileges to White people at the disadvantage of non-White people.⁹ In 1910, Abraham Flexner, commissioned by the Carnegie Foundation and the American Medical Association, wrote that African American physicians should be trained in hygiene rather than surgery and should primarily serve as “sanitarians” whose purpose was to “protect Whites” from common diseases like tuberculosis.¹⁰ The 1910 Flexner Report also emphasized the importance of prerequisite basic sciences education and recommended that only two of the seven existing Black medical schools remain open because Flexner believed that only these schools had the potential to meet the new requirements for medical education.¹¹ A recent analysis found that, had the other five medical schools affiliated with historically Black colleges and universities remained open, this would have resulted in an additional 33,315 Black medical school graduates by 2019.¹² Structural racism explains why the majority of practicing physicians, medical educators, National Institutes of Health–funded researchers, and hospital executives are White and, similarly, why White patients are overrepresented in clinical trials, have better health outcomes, and live longer lives than several racial and ethnic minority groups.¹³

The murders of Ahmaud Arbery, Breonna Taylor, and George Floyd and the inequitable toll of the COVID-19 pandemic on Black, Hispanic, and Native American people renewed the dialogue regarding structural racism in America. Beyond criminal justice and police reform, the current social justice movement demands that structural racism is examined in all spheres. In medicine and health care, acknowledging the history of exclusion and exploitation of Black people and other URM groups is an important first step, but this must be followed by a commitment to an antiracist future for the benefit of all medical professionals and patients.^14,15

Antiracism as a path forward

Antiracism refers to actions and policies that seek to dismantle structural racism. While individuals can and should engage in antiracist actions, it is equally important for organizations and government to actively participate in this process as well.



Individual and interpersonal levels

Gastroenterologists should advocate an end to racist practices within their organizations (e.g., unjustified use of race-based corrections in diagnostic algorithms and practice guidelines),¹⁶ and interrupt microaggressions and racist actions in real time (e.g., overpolicing of underrepresented groups in health care settings).¹⁷ Gastroenterologists from underrepresented groups may also need to unlearn internalized racism, which is defined as acceptance by members of disadvantaged races of the negative messages about their own abilities and intrinsic worth.¹⁸



Organizational level

Gastroenterology divisions and practices must ensure that the entire workforce, including leadership, reflects the diversity of our country. Underrepresented groups represent 33% of the U.S. population, but only 9.1% of gastroenterology fellows and 10% of gastroenterology faculty are from underrepresented groups.¹⁹ In addition to diversifying the field of gastroenterology through financial and operational support of pipeline educational programs, organizations should also promote the scholarship of URM groups, whose work is often undervalued, and redistribute power by elevating voices that have been historically absent.²⁰ Gastroenterology practices should also collect high-quality patient data disaggregated by demographic factors. Doing so will enable rapid identification of disparate health outcomes by demographic variables and inform interventions to eliminate identified disparities.



Government level

The “Executive Order On Advancing Racial Equity and Support for Underserved Communities Through the Federal Government” issued by President Biden on Jan. 20, 2021, is an example of how government can promote antiracism.²¹ The executive order states that domestic policies cause group inequities and calls for the removal of systemic barriers in current and future domestic policies. The executive order outlines several additional ways to improve equity in current and future policy, including engagement, consultation, and coordination with members of underserved communities. The details outlined in the executive order should serve as the foundation for establishing new standards at the state, county, and city levels as well. Gastroenterologists can influence government by voting for officials at all levels that support and promote these standards.

Conclusion

Beyond calling out microaggressions in real time, we must also interrogate the biases, policies, and practices that support them in medicine and beyond. As Black gastroenterologists who have experienced microaggressions and overt acts of racism, we ground Oviea’s experience in structural racism and offer strategies that individuals, organizations, and governing institutions can adopt toward an antiracist future. This model can be applied to experiences rooted in misogyny, homophobia, transphobia, xenophobia, ableism, and other prejudices.

As a nation, we must make an active and collective choice to address structural racism. In health care, doing so will strengthen communities, enhance the lived experiences of URM physician colleagues, and save patient lives. Gastroenterologists, as trusted health care providers, are uniquely positioned to lead the way.

Dr. Akpotaire is a second-year GI fellow in the division of gastroenterology at the University of Washington, Seattle. Dr. Issaka is an assistant professor with both the Fred Hutchinson Cancer Research Center, Seattle, and the division of gastroenterology at the University of Washington.

References

1. Blackstock U. “Why Black doctors like me are leaving faculty positions in academic medical centers.” STAT News, 2020.

2. Asare JG. “One Doctor Shares Her Story of Racism in Medicine.” Forbes. 2021 Feb 1.

3. Kroman D. “Revered doctor steps down, accusing Seattle Children’s Hospital of racism.” Crosscut. 2020 Dec 31.

4. United States District Court Eastern District of Louisiana. Princess Dennar, M.D. v. The Administrators of the Tulane Educational Fund, 2020.

5. Sue DW. Microaggressions in Everyday Life: Race, Gender, and Sexual Orientation. Hoboken, N.J.: Wiley, 2010.

6. Boyd RW. Lancet. 2019 Jun 22;393(10190):2484-5.

7. AAMC. Diversity in Medicine Facts and Figures 2019. Washington, D.C., 2019.

8. Overland MK et al. PM R. 2019 Sep;11(9):1004-12.

9. Jones CP. Ethn Dis. 2018 Aug 9;28(Suppl 1):231-4.

10. Hlavinka E. “Racial Bias in Flexner Report Permeates Medical Education Today.” Medpage Today. 2020 Jun 18.

11. Flexner A. Medical Education in the United States and Canada. New York: 1910. Republished: Bull World Health Organ. 2002;80(7):594-602.

12. Campbell KM et al. JAMA Netw Open. 2020 Aug 3;3(8):e2015220.

13. Malat J et al. Soc Sci Med. 2018 Feb;199:148-56.

14. Kendi IX. How to be an antiracist. New York: Random House Books, 2019.

15. Gray DM 2nd et al. Nat Rev Gastroenterol Hepatol. 2020 Oct;17(10):589-90.

16. Vyas DA et al. N Engl J Med. 2020 Aug 27;383(9):874-82.

17. Green CR et al. J Natl Med Assoc. 2018 Feb;110(1):37-43.

18. Jones CP. Am J Public Health. 2000 Aug;90(8):1212-5.

19. Anyane-Yeboa A et al. Am J Gastroenterol. 2020 Aug;115(8):1147-9.

20. Issaka RB. JAMA. 2020 Aug 11;324(6):556-7.

21. Biden JR. Executive Order On Advancing Racial Equity and Support for Underserved Communities Through the Federal Government. Washington, D.C.: The White House, 2021.

There are no currently US Food and Drug Administration (FDA)-approved therapies for testosterone use in women. Its use by clinicians is through dose modification of FDA-approved therapies for men, or preparations created by compounding pharmacies. Recently, several professional organizations, including the American College of Obstetricians and Gynecologists (ACOG), North American Menopause Society, International Society for the Study of Women’s Sexual Health, and the International Society for Sexual Medicine, convened an expert panel to develop a global position statement on testosterone therapy for women.¹ In this roundtable for OBG Management, moderated by Mickey Karram, MD, several experts discuss this position statement as well as the overall clinical advantages and drawbacks of using testosterone in women.

Testosterone indications

Mickey Karram, MD: For which indications do you prescribe testosterone supplementation in women?

Lauren Streicher, MD: I offer systemic testosterone therapy to postmenopausal women who have hypoactive sexual desire disorder (HSDD) and low serum testosterone levels, with one caveat—it is important that the patient’s reported distressing lack of libido is not explained by another condition or circumstance. Many women present reporting low libido but, on further questioning, it is typically revealed that dyspareunia precipitated their loss of interest in sex. It is normal to not want to do something that is painful. In addition, low libido can often be explained by chronic disease, such as diabetes, cancer, or clinical depression.

Some medications, including selective serotonin reuptake inhibitors (SSRIs), frequently cause a decline in sexual interest. Finally, psychosocial and partner issues may be the culprit.

James Simon, MD, CCP, NCMP, IF: Much of the beneficial data for testosterone’s use is for sexual function in postmenopausal women.² Female sexual dysfunction is highly prevalent among women during the postmenopause.³ Androgen levels progressively decrease throughout adult life in all women, so the postmenopausal additional lack of estrogen has a recognized effect on genitourinary health. There is evidence that the insufficiency of androgens as well as estrogens after menopause can lead to genitourinary symptoms of menopause (GSM).⁴

Testosterone also is used for increasing strength, lean muscle mass, bone mineral density, and sense of well-being.⁵

Rebecca Glaser, MD: I consider testosterone supplementation in my clinical practice in both premenopausal and postmenopausal women for symptoms of androgen/hormone deficiency, including diminished sense of well-being; dysphoric mood; anxiety; irritability; fatigue; decreased libido, sexual activity, or pleasure; vasomotor instability; bone loss; decreased muscle strength; insomnia; changes in cognition; memory loss; urinary symptoms; incontinence; vaginal atrophy and dryness; and joint and muscular pain. We also have shown through preliminary and short-term data and case studies that testosterone therapy has a potential beneficial effect on migraine headaches, as well as active breast cancers in both premenopausal and postmenopausal women.^6-10

Continue to: What is appropriate bloodwork?...

 

 

What is appropriate bloodwork?

Dr. Karram: Do you obtain blood work before initiating testosterone treatment? If so, what tests do you order and what testosterone levels are considered to be normal for premenopausal and postmenopausal women?

Dr. Streicher: Unlike estrogen, which is predictably low in a postmenopausal woman, serum testosterone (T) levels are highly variable because of the adrenal component. Ovarian testosterone production does not cease at the same time as estrogen production. So I do obtain total and free T levels, prior to initiating treatment. Having said that, it has been well established that T levels correlate poorly with level of sexual interest, and there is no specific blood level that can be used to differentiate women with and without sexual dysfunction. We all have patients who have nonexistent T levels and have a very healthy libido, and other women with sky-high levels who have no libido. But it is useful to know levels prior to initiating therapy to be able to monitor levels throughout treatment. Also, if levels are in the premenopausal physiologic range, not only is she unlikely to respond but she is also at risk for developing androgenic adverse effects, such as acne and hair growth. In general, a low free T level (even if it is in the normal postmenopausal range) in a clinical setting of HSDD supports supplementation.

The assessment and interpretation of T levels can be challenging, particularly as the majority of testosterone is protein-bound and biologically inactive. Free T levels (the biologically active testosterone) in many labs are unreliable and need to be calculated.

In addition to total and free T, I check levels of sex hormone-binding globulin (SHBG), the protein that binds testosterone and renders it biologically inactive. If someone has high SHBG levels and is taking an oral estrogen, simply switching to a transdermal estrogen will result in decreased SHBG and increased free T.

Levels of total and free T vary from lab to lab, so it is best to be familiar with those ranges and then be consistent in which lab you choose.

Dr. Glaser: Although I personally do order blood work on most patients (T, free T, estradiol, complete blood count, thyroid-stimulating hormone, and follicle-stimulating hormone), after 15 years of research and publishing data on testosterone implants, I do not believe that T levels are absolutely necessary or even beneficial in most cases. It rarely changes management in my patients.

As Lauren said, it is well known that T levels do not correlate with androgen deficiency symptoms or clinical conditions caused by androgen deficiency. If a patient has symptoms of androgen deficiency, a trial of testosterone therapy should be given.

T levels are not a valid marker of tissue exposure in women, reflecting less than 20% of total androgen activity. The major source of testosterone in pre and postmenopausal women is the local intracrine production of testosterone from the adrenal precursor steroids dehydroepiandrosterone (DHEA) and androstenedione, which would not be reflected in T levels.

In our study involving 300 women, we found no relationship between baseline T levels, presenting symptoms, or response to therapy.⁶ Premenopausal and postmenopausal women had similar baseline T levels and similar response to therapy. Even women with baseline T levels in the mid-range responded to therapy.

Some of the most controversial topics in treating women with testosterone are related to dosing and T levels throughout therapy. Guideline authors often use the terms ‘physiologic dosing’ and ‘physiologic ranges’ when making recommendations for therapy. Although “physiologic” sounds appropriate/ scientific, these rigid opinions/recommendations are not evidence based. There are no data supporting the use of endogenous T ranges to guide dosing or monitor testosterone therapy.

The decision to initiate testosterone therapy is a clinical decision between the doctor and the patient based on the patient’s symptomatology, which is the therapeutic endpoint. Testosterone therapy must be done with adequate doses determined by clinical effect (benefits) versus side effects or adverse events (risks). T levels may be helpful, along with clinical evaluation when troubleshooting.

Utilizing data from thousands of patients, we have developed serum ranges for testosterone implants.¹¹ Even so, no two patients are the same, nor do they respond to therapy the same. It is always a clinical decision.

Continue to: Dr. Simon...

Dr. Simon: In the recent global consensus statement on testosterone use,¹ the experts were in agreement that “no cut-off blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction.” They give their recommendation a C, and I agree that testosterone supplementation, with specific dosage levels, are a clinical decision.

Before initiating testosterone therapy, it is recommended that liver function and fasting lipids are assessed, as liver disease and hyperlipidemia are contraindications to treatment. These levels should be monitored twice in the first year and annually thereafter while the patient is taking testosterone. Breast and pelvic examinations, mammography, and evaluation for abnormal bleeding should be performed as well as the blood tests.¹² These recommendations are focused on safety not efficacy.

Administration route

Dr. Karram: How do you administer testosterone, and why?

Dr. Streicher: As there are no FDA approved testosterone products for women, clinicians must determine the dosage and route of delivery based on published clinical trials.

Dr. Glaser: I treat patients with subcutaneous pellet implants. The implants provide consistent and continuous delivery of therapeutic amounts of testosterone. There is a reason testosterone pellets have been used for more than 80 years and are more popular now than ever—they work. The insertion procedure is simple and takes about 2 minutes. The treatment is cost-effective, avoids first pass, has no adverse effect on the liver or clotting factors, and there is no transference. Decades of data support both the efficacy and safety of testosterone implants.⁶ However, testosterone implants are not regulated by the FDA and all patients are required to sign a consent informing them of off-label use, benefits, and risks of testosterone implant therapy.

Dr. Simon: I think the consent is important, as there is no package labeling to warn of possible side effects.

Dr. Streicher: Oral testosterone therapy, because of its first pass through the liver and association with adverse lipid profiles with negative effects on high- and low-density lipoprotein cholesterol levels, is not recommended. I prefer a transdermal approach. Pellets, implants, and injections have the potential to result in supraphysiologic blood concentrations. It must be emphasized that the goal of treatment is to approximate premenopausal physiologic levels. More is not better; excessive levels do not demonstrate a greater sexual response and are in fact more likely to have a negative impact due to androgenic side effects.

In most clinical trials, a 300 mg/d testosterone patch was effective, but these patches are not commercially available so I rely on transdermal gel from a compounding pharmacy. The typical dose needed to raise levels into the high to normal range for most women is 2.5 mg up to 5 mg per day of testosterone 1%, which translates to roughly 1 mL. Many pharmacies provide a dispenser, which allots the appropriate dose. Alternatively, I instruct the patient to place a dollop on her thigh (roughly in size of a single M&M candy).

I always tell my patients that the response is not immediate, typically taking 8 to 12 weeks for the effect to become clinically significant. I generally see a patient back 8 weeks after initiation of treatment to check T levels and evaluate response.

Dr. Simon: There are some data demonstrating that intravaginal testosterone can be a potential treatment for GSM. Intravaginal testosterone coupled with aromatase inhibitor therapy used for breast cancer treatment resulted in supraphysiologic T levels and reportedly improved vaginal maturation index and reduced dyspareunia. More study is needed.¹³

Dr. Streicher: Agreed. The lower third of the vagina and the vestibule is rich in testosterone receptors. Like Dr. Simon, in some cases of vaginal atrophy I prescribe a compounded local vaginal testosterone.

Continue to: Testosterone and premenopausal women...

Testosterone and premenopausal women

Dr. Karram: Is there a role for testosterone supplementation in premenopausal women with normal estrogen production?

Dr. Glaser: Yes. In fact, in our study, more than one-third of the patients were premenopausal, which makes sense.⁶ There is a marked decline of T levels and the adrenal precursor steroids (DHEA and androstenedione) in women between the ages of 20–30 years and around age 50. As we said, symptoms of androgen deficiency often occur prior to menopause and are not related to estrogen levels. In our study, testosterone implant therapy relieved symptoms of hormone (androgen) deficiency, including vasomotor symptoms, sleep problems, depressive mood, irritability, anxiety, physical and mental exhaustion (fatigue, memory issues), sexual problems, bladder problems (incontinence, frequency), vaginal dryness, and joint and muscular pain. Premenopausal and postmenopausal patients reported similar hormone deficiency symptoms. Premenopausal women did report a higher incidence of psychological complaints (depressive mood, anxiety, and irritability), while postmenopausal women reported more hot flashes, vaginal dryness, and urologic symptoms. Both groups demonstrated similar improvement in symptoms.

In addition, we have seen relief of severe migraine headache in premenopausal (as well as postmenopausal) women treated with testosterone implant therapy.^6,7

Dr. Streicher: The goal of testosterone supplementation is to approximate physiological testosterone concentrations for premenopausal women. While testosterone may improve well-being and sexual function in premenopausal women, the data are limited and really inconclusive. More study is needed given that there is likely a wide therapeutic range with many variables. Having said that, there are some data that indicate that testosterone in premenopausal women may enhance general sense of well-being.¹⁴

Why is there no FDA-approved agent?

Dr. Karram: Why do you think the FDA has been reluctant to approve a testosterone agent for women?

Dr. Simon: Three potential testosterone drugs for use in women have been unsuccessfully brought to market after the FDA did not approve them. There are 31 approved products for men, each of which were approved because they safely restored normal testosterone concentrations in men with reduced levels and an associated medical condition. Unlike this scenario for men, for women, the FDA has required products to show clinical effectiveness in trials. For instance, Estratest, a combination estrogen-testosterone product, was in use in the 1960s—approved for women with estrogen-resistant hot flushes, and used in practice for sexual dysfunction. After the FDA implemented its Drug Efficacy Study and Implementation regulation system after 2000, which required safety and efficacy trial(s) before drug approval, the manufacturer removed the drug from market when presented efficacy study data for the added testosterone in the drug were deemed inadequate.¹⁵

Dr. Streicher: We have yet another example of the disparity between the FDA approval processes for sexual function drugs for men versus women. Take Intrinsia as another example. It was a 300-mg testosterone patch that underwent clinical trials in women who were post-oophorectomy with HSDD. The patch had demonstrated efficacy with minimal adverse effects and no statistically significant dangerous effects. However, the FDA declined approval, citing “safety considerations” and requested longer-term clinical trials to evaluate potential cardiovascular or breast problems. Given that Intrinsia supplementation simply restored normal physiologic testosterone levels, and there was no such requirement in men who received supplementation post-orchiectomy, this requirement was nonsensical and unjustified.

Compounded formulations

Dr. Karram: Are compounding pharmacies appropriately regulated, and how can you be assured that the source of your testosterone is appropriate?

Dr. Glaser: Compounding pharmacies are regulated by the State Boards of Pharmacy, Drug Enforcement Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, State Bureaus of Narcotics and Dangerous Drugs, and Departments of Health (in some states).

Compounding is a highly regulated profession that is constantly under scrutiny by agencies, patients, and physicians. Any additional regulations could adversely impact the accessibility of patients to individually compounded medications including intravenous and oncology medications. Over the past 20 years, I have treated hundreds of patients with breast cancer with compounded vaginal testosterone (with or without estriol) and subcutaneous testosterone (with or without anastrozole), greatly improving quality of life in women suffering from severe symptoms. Without the availability of compounded medications, there would have been no or limited alternatives for adequate and much needed therapy. Notably, there have been no adverse events or safety-related issues in more than 20 years.

Regarding whether or not “the source of your testosterone is appropriate,” pharmacists can only use United States Pharmacopeia (USP) grades of testosterone. Testosterone used in compounding is required by the FDA to be of USP grade from an FDA registered and compliant facility. In addition, compounding support companies run additional USP tests to confirm their products meet USP standards prior to being delivered to individual compounding pharmacies.

Dr. Streicher: However, there potentially can be substantial variability between formulations and batches. Product purity can also be an issue. It is reassuring if the compounding pharmacy is compliant with purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice rules and guidelines that assure the minimum requirements to assure high quality and batch-to-batch consistency. I find it helpful to always work with the same pharmacy once you have established uniformity and reliability. If there is concern, it is appropriate to check a patient’s serum level 2 weeks after initiation of therapy.

Dr. Simon: I think the problem with some compounding pharmacies is that there may be incentives back and forth with the clinician to use a certain outlet, whereby the patient’s best interest may not be served. I do believe that there is a role for compounding pharmacies, however. We also use them because some women may have strange reactions or be allergic to the preservatives, formulating agents, or even lactose, in various pills and patches, gels, and creams.

Continue to: Testosterone for aging and cognition?...

Testosterone for aging and cognition?

Dr. Karram: Do you think that testosterone supplementation in the elderly can have a positive impact on aging, Alzheimer disease, and dementia?

Dr. Streicher: The jury is still out on the cognitive effects of postmenopausal androgen supplementation. There is currently insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline. I prescribe testosterone only to treat HSDD, but I do tell my patient that she may possibly also benefit in terms of cognitive function, musculoskeletal parameters, and well-being. Large RCTs are needed in those areas to justify prescribing for those benefits alone.

Dr. Simon: I would say this is the place for future development, but where there is very likely to be a benefit is on sarcopenia.

Dr. Glaser: There is some evidence that testosterone is neuroprotective.¹⁶ In my clinical practice I have seen “self-reported” memory issues improved on therapy, often returning toward the end of the testosterone implant cycle. Adequate amounts of bioavailable testosterone at the androgen receptor are critical for optimal health, immune function, and disease prevention.

Dr. Karram: In conclusion, this expert panel agrees that testosterone supplementation is beneficial for sexual dysfunction in postmenopausal women, with also many other potential benefits that require further investigation. Route of administration preferred by Dr. Simon and Dr. Streicher is transdermal or a transvaginal cream. Dr. Glaser uses a subcutaneous pellet approach. Thank you all for an engaging and informative discussion. ●

There are no currently US Food and Drug Administration (FDA)-approved therapies for testosterone use in women. Its use by clinicians is through dose modification of FDA-approved therapies for men, or preparations created by compounding pharmacies. Recently, several professional organizations, including the American College of Obstetricians and Gynecologists (ACOG), North American Menopause Society, International Society for the Study of Women’s Sexual Health, and the International Society for Sexual Medicine, convened an expert panel to develop a global position statement on testosterone therapy for women.¹ In this roundtable for OBG Management, moderated by Mickey Karram, MD, several experts discuss this position statement as well as the overall clinical advantages and drawbacks of using testosterone in women.

Testosterone indications

Mickey Karram, MD: For which indications do you prescribe testosterone supplementation in women?

Lauren Streicher, MD: I offer systemic testosterone therapy to postmenopausal women who have hypoactive sexual desire disorder (HSDD) and low serum testosterone levels, with one caveat—it is important that the patient’s reported distressing lack of libido is not explained by another condition or circumstance. Many women present reporting low libido but, on further questioning, it is typically revealed that dyspareunia precipitated their loss of interest in sex. It is normal to not want to do something that is painful. In addition, low libido can often be explained by chronic disease, such as diabetes, cancer, or clinical depression.

Some medications, including selective serotonin reuptake inhibitors (SSRIs), frequently cause a decline in sexual interest. Finally, psychosocial and partner issues may be the culprit.

James Simon, MD, CCP, NCMP, IF: Much of the beneficial data for testosterone’s use is for sexual function in postmenopausal women.² Female sexual dysfunction is highly prevalent among women during the postmenopause.³ Androgen levels progressively decrease throughout adult life in all women, so the postmenopausal additional lack of estrogen has a recognized effect on genitourinary health. There is evidence that the insufficiency of androgens as well as estrogens after menopause can lead to genitourinary symptoms of menopause (GSM).⁴

Testosterone also is used for increasing strength, lean muscle mass, bone mineral density, and sense of well-being.⁵

Rebecca Glaser, MD: I consider testosterone supplementation in my clinical practice in both premenopausal and postmenopausal women for symptoms of androgen/hormone deficiency, including diminished sense of well-being; dysphoric mood; anxiety; irritability; fatigue; decreased libido, sexual activity, or pleasure; vasomotor instability; bone loss; decreased muscle strength; insomnia; changes in cognition; memory loss; urinary symptoms; incontinence; vaginal atrophy and dryness; and joint and muscular pain. We also have shown through preliminary and short-term data and case studies that testosterone therapy has a potential beneficial effect on migraine headaches, as well as active breast cancers in both premenopausal and postmenopausal women.^6-10

Continue to: What is appropriate bloodwork?...

 

 

What is appropriate bloodwork?

Dr. Karram: Do you obtain blood work before initiating testosterone treatment? If so, what tests do you order and what testosterone levels are considered to be normal for premenopausal and postmenopausal women?

Dr. Streicher: Unlike estrogen, which is predictably low in a postmenopausal woman, serum testosterone (T) levels are highly variable because of the adrenal component. Ovarian testosterone production does not cease at the same time as estrogen production. So I do obtain total and free T levels, prior to initiating treatment. Having said that, it has been well established that T levels correlate poorly with level of sexual interest, and there is no specific blood level that can be used to differentiate women with and without sexual dysfunction. We all have patients who have nonexistent T levels and have a very healthy libido, and other women with sky-high levels who have no libido. But it is useful to know levels prior to initiating therapy to be able to monitor levels throughout treatment. Also, if levels are in the premenopausal physiologic range, not only is she unlikely to respond but she is also at risk for developing androgenic adverse effects, such as acne and hair growth. In general, a low free T level (even if it is in the normal postmenopausal range) in a clinical setting of HSDD supports supplementation.

The assessment and interpretation of T levels can be challenging, particularly as the majority of testosterone is protein-bound and biologically inactive. Free T levels (the biologically active testosterone) in many labs are unreliable and need to be calculated.

In addition to total and free T, I check levels of sex hormone-binding globulin (SHBG), the protein that binds testosterone and renders it biologically inactive. If someone has high SHBG levels and is taking an oral estrogen, simply switching to a transdermal estrogen will result in decreased SHBG and increased free T.

Levels of total and free T vary from lab to lab, so it is best to be familiar with those ranges and then be consistent in which lab you choose.

Dr. Glaser: Although I personally do order blood work on most patients (T, free T, estradiol, complete blood count, thyroid-stimulating hormone, and follicle-stimulating hormone), after 15 years of research and publishing data on testosterone implants, I do not believe that T levels are absolutely necessary or even beneficial in most cases. It rarely changes management in my patients.

As Lauren said, it is well known that T levels do not correlate with androgen deficiency symptoms or clinical conditions caused by androgen deficiency. If a patient has symptoms of androgen deficiency, a trial of testosterone therapy should be given.

T levels are not a valid marker of tissue exposure in women, reflecting less than 20% of total androgen activity. The major source of testosterone in pre and postmenopausal women is the local intracrine production of testosterone from the adrenal precursor steroids dehydroepiandrosterone (DHEA) and androstenedione, which would not be reflected in T levels.

In our study involving 300 women, we found no relationship between baseline T levels, presenting symptoms, or response to therapy.⁶ Premenopausal and postmenopausal women had similar baseline T levels and similar response to therapy. Even women with baseline T levels in the mid-range responded to therapy.

Some of the most controversial topics in treating women with testosterone are related to dosing and T levels throughout therapy. Guideline authors often use the terms ‘physiologic dosing’ and ‘physiologic ranges’ when making recommendations for therapy. Although “physiologic” sounds appropriate/ scientific, these rigid opinions/recommendations are not evidence based. There are no data supporting the use of endogenous T ranges to guide dosing or monitor testosterone therapy.

The decision to initiate testosterone therapy is a clinical decision between the doctor and the patient based on the patient’s symptomatology, which is the therapeutic endpoint. Testosterone therapy must be done with adequate doses determined by clinical effect (benefits) versus side effects or adverse events (risks). T levels may be helpful, along with clinical evaluation when troubleshooting.

Utilizing data from thousands of patients, we have developed serum ranges for testosterone implants.¹¹ Even so, no two patients are the same, nor do they respond to therapy the same. It is always a clinical decision.

Continue to: Dr. Simon...

Dr. Simon: In the recent global consensus statement on testosterone use,¹ the experts were in agreement that “no cut-off blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction.” They give their recommendation a C, and I agree that testosterone supplementation, with specific dosage levels, are a clinical decision.

Before initiating testosterone therapy, it is recommended that liver function and fasting lipids are assessed, as liver disease and hyperlipidemia are contraindications to treatment. These levels should be monitored twice in the first year and annually thereafter while the patient is taking testosterone. Breast and pelvic examinations, mammography, and evaluation for abnormal bleeding should be performed as well as the blood tests.¹² These recommendations are focused on safety not efficacy.

Administration route

Dr. Karram: How do you administer testosterone, and why?

Dr. Streicher: As there are no FDA approved testosterone products for women, clinicians must determine the dosage and route of delivery based on published clinical trials.

Dr. Glaser: I treat patients with subcutaneous pellet implants. The implants provide consistent and continuous delivery of therapeutic amounts of testosterone. There is a reason testosterone pellets have been used for more than 80 years and are more popular now than ever—they work. The insertion procedure is simple and takes about 2 minutes. The treatment is cost-effective, avoids first pass, has no adverse effect on the liver or clotting factors, and there is no transference. Decades of data support both the efficacy and safety of testosterone implants.⁶ However, testosterone implants are not regulated by the FDA and all patients are required to sign a consent informing them of off-label use, benefits, and risks of testosterone implant therapy.

Dr. Simon: I think the consent is important, as there is no package labeling to warn of possible side effects.

Dr. Streicher: Oral testosterone therapy, because of its first pass through the liver and association with adverse lipid profiles with negative effects on high- and low-density lipoprotein cholesterol levels, is not recommended. I prefer a transdermal approach. Pellets, implants, and injections have the potential to result in supraphysiologic blood concentrations. It must be emphasized that the goal of treatment is to approximate premenopausal physiologic levels. More is not better; excessive levels do not demonstrate a greater sexual response and are in fact more likely to have a negative impact due to androgenic side effects.

In most clinical trials, a 300 mg/d testosterone patch was effective, but these patches are not commercially available so I rely on transdermal gel from a compounding pharmacy. The typical dose needed to raise levels into the high to normal range for most women is 2.5 mg up to 5 mg per day of testosterone 1%, which translates to roughly 1 mL. Many pharmacies provide a dispenser, which allots the appropriate dose. Alternatively, I instruct the patient to place a dollop on her thigh (roughly in size of a single M&M candy).

I always tell my patients that the response is not immediate, typically taking 8 to 12 weeks for the effect to become clinically significant. I generally see a patient back 8 weeks after initiation of treatment to check T levels and evaluate response.

Dr. Simon: There are some data demonstrating that intravaginal testosterone can be a potential treatment for GSM. Intravaginal testosterone coupled with aromatase inhibitor therapy used for breast cancer treatment resulted in supraphysiologic T levels and reportedly improved vaginal maturation index and reduced dyspareunia. More study is needed.¹³

Dr. Streicher: Agreed. The lower third of the vagina and the vestibule is rich in testosterone receptors. Like Dr. Simon, in some cases of vaginal atrophy I prescribe a compounded local vaginal testosterone.

Continue to: Testosterone and premenopausal women...

Testosterone and premenopausal women

Dr. Karram: Is there a role for testosterone supplementation in premenopausal women with normal estrogen production?

Dr. Glaser: Yes. In fact, in our study, more than one-third of the patients were premenopausal, which makes sense.⁶ There is a marked decline of T levels and the adrenal precursor steroids (DHEA and androstenedione) in women between the ages of 20–30 years and around age 50. As we said, symptoms of androgen deficiency often occur prior to menopause and are not related to estrogen levels. In our study, testosterone implant therapy relieved symptoms of hormone (androgen) deficiency, including vasomotor symptoms, sleep problems, depressive mood, irritability, anxiety, physical and mental exhaustion (fatigue, memory issues), sexual problems, bladder problems (incontinence, frequency), vaginal dryness, and joint and muscular pain. Premenopausal and postmenopausal patients reported similar hormone deficiency symptoms. Premenopausal women did report a higher incidence of psychological complaints (depressive mood, anxiety, and irritability), while postmenopausal women reported more hot flashes, vaginal dryness, and urologic symptoms. Both groups demonstrated similar improvement in symptoms.

In addition, we have seen relief of severe migraine headache in premenopausal (as well as postmenopausal) women treated with testosterone implant therapy.^6,7

Dr. Streicher: The goal of testosterone supplementation is to approximate physiological testosterone concentrations for premenopausal women. While testosterone may improve well-being and sexual function in premenopausal women, the data are limited and really inconclusive. More study is needed given that there is likely a wide therapeutic range with many variables. Having said that, there are some data that indicate that testosterone in premenopausal women may enhance general sense of well-being.¹⁴

Why is there no FDA-approved agent?

Dr. Karram: Why do you think the FDA has been reluctant to approve a testosterone agent for women?

Dr. Simon: Three potential testosterone drugs for use in women have been unsuccessfully brought to market after the FDA did not approve them. There are 31 approved products for men, each of which were approved because they safely restored normal testosterone concentrations in men with reduced levels and an associated medical condition. Unlike this scenario for men, for women, the FDA has required products to show clinical effectiveness in trials. For instance, Estratest, a combination estrogen-testosterone product, was in use in the 1960s—approved for women with estrogen-resistant hot flushes, and used in practice for sexual dysfunction. After the FDA implemented its Drug Efficacy Study and Implementation regulation system after 2000, which required safety and efficacy trial(s) before drug approval, the manufacturer removed the drug from market when presented efficacy study data for the added testosterone in the drug were deemed inadequate.¹⁵

Dr. Streicher: We have yet another example of the disparity between the FDA approval processes for sexual function drugs for men versus women. Take Intrinsia as another example. It was a 300-mg testosterone patch that underwent clinical trials in women who were post-oophorectomy with HSDD. The patch had demonstrated efficacy with minimal adverse effects and no statistically significant dangerous effects. However, the FDA declined approval, citing “safety considerations” and requested longer-term clinical trials to evaluate potential cardiovascular or breast problems. Given that Intrinsia supplementation simply restored normal physiologic testosterone levels, and there was no such requirement in men who received supplementation post-orchiectomy, this requirement was nonsensical and unjustified.

Compounded formulations

Dr. Karram: Are compounding pharmacies appropriately regulated, and how can you be assured that the source of your testosterone is appropriate?

Dr. Glaser: Compounding pharmacies are regulated by the State Boards of Pharmacy, Drug Enforcement Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, State Bureaus of Narcotics and Dangerous Drugs, and Departments of Health (in some states).

Compounding is a highly regulated profession that is constantly under scrutiny by agencies, patients, and physicians. Any additional regulations could adversely impact the accessibility of patients to individually compounded medications including intravenous and oncology medications. Over the past 20 years, I have treated hundreds of patients with breast cancer with compounded vaginal testosterone (with or without estriol) and subcutaneous testosterone (with or without anastrozole), greatly improving quality of life in women suffering from severe symptoms. Without the availability of compounded medications, there would have been no or limited alternatives for adequate and much needed therapy. Notably, there have been no adverse events or safety-related issues in more than 20 years.

Regarding whether or not “the source of your testosterone is appropriate,” pharmacists can only use United States Pharmacopeia (USP) grades of testosterone. Testosterone used in compounding is required by the FDA to be of USP grade from an FDA registered and compliant facility. In addition, compounding support companies run additional USP tests to confirm their products meet USP standards prior to being delivered to individual compounding pharmacies.

Dr. Streicher: However, there potentially can be substantial variability between formulations and batches. Product purity can also be an issue. It is reassuring if the compounding pharmacy is compliant with purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice rules and guidelines that assure the minimum requirements to assure high quality and batch-to-batch consistency. I find it helpful to always work with the same pharmacy once you have established uniformity and reliability. If there is concern, it is appropriate to check a patient’s serum level 2 weeks after initiation of therapy.

Dr. Simon: I think the problem with some compounding pharmacies is that there may be incentives back and forth with the clinician to use a certain outlet, whereby the patient’s best interest may not be served. I do believe that there is a role for compounding pharmacies, however. We also use them because some women may have strange reactions or be allergic to the preservatives, formulating agents, or even lactose, in various pills and patches, gels, and creams.

Continue to: Testosterone for aging and cognition?...

Testosterone for aging and cognition?

Dr. Karram: Do you think that testosterone supplementation in the elderly can have a positive impact on aging, Alzheimer disease, and dementia?

Dr. Streicher: The jury is still out on the cognitive effects of postmenopausal androgen supplementation. There is currently insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline. I prescribe testosterone only to treat HSDD, but I do tell my patient that she may possibly also benefit in terms of cognitive function, musculoskeletal parameters, and well-being. Large RCTs are needed in those areas to justify prescribing for those benefits alone.

Dr. Simon: I would say this is the place for future development, but where there is very likely to be a benefit is on sarcopenia.

Dr. Glaser: There is some evidence that testosterone is neuroprotective.¹⁶ In my clinical practice I have seen “self-reported” memory issues improved on therapy, often returning toward the end of the testosterone implant cycle. Adequate amounts of bioavailable testosterone at the androgen receptor are critical for optimal health, immune function, and disease prevention.

Dr. Karram: In conclusion, this expert panel agrees that testosterone supplementation is beneficial for sexual dysfunction in postmenopausal women, with also many other potential benefits that require further investigation. Route of administration preferred by Dr. Simon and Dr. Streicher is transdermal or a transvaginal cream. Dr. Glaser uses a subcutaneous pellet approach. Thank you all for an engaging and informative discussion. ●

There are no currently US Food and Drug Administration (FDA)-approved therapies for testosterone use in women. Its use by clinicians is through dose modification of FDA-approved therapies for men, or preparations created by compounding pharmacies. Recently, several professional organizations, including the American College of Obstetricians and Gynecologists (ACOG), North American Menopause Society, International Society for the Study of Women’s Sexual Health, and the International Society for Sexual Medicine, convened an expert panel to develop a global position statement on testosterone therapy for women.¹ In this roundtable for OBG Management, moderated by Mickey Karram, MD, several experts discuss this position statement as well as the overall clinical advantages and drawbacks of using testosterone in women.

Testosterone indications

Mickey Karram, MD: For which indications do you prescribe testosterone supplementation in women?

Lauren Streicher, MD: I offer systemic testosterone therapy to postmenopausal women who have hypoactive sexual desire disorder (HSDD) and low serum testosterone levels, with one caveat—it is important that the patient’s reported distressing lack of libido is not explained by another condition or circumstance. Many women present reporting low libido but, on further questioning, it is typically revealed that dyspareunia precipitated their loss of interest in sex. It is normal to not want to do something that is painful. In addition, low libido can often be explained by chronic disease, such as diabetes, cancer, or clinical depression.

Some medications, including selective serotonin reuptake inhibitors (SSRIs), frequently cause a decline in sexual interest. Finally, psychosocial and partner issues may be the culprit.

James Simon, MD, CCP, NCMP, IF: Much of the beneficial data for testosterone’s use is for sexual function in postmenopausal women.² Female sexual dysfunction is highly prevalent among women during the postmenopause.³ Androgen levels progressively decrease throughout adult life in all women, so the postmenopausal additional lack of estrogen has a recognized effect on genitourinary health. There is evidence that the insufficiency of androgens as well as estrogens after menopause can lead to genitourinary symptoms of menopause (GSM).⁴

Testosterone also is used for increasing strength, lean muscle mass, bone mineral density, and sense of well-being.⁵

Rebecca Glaser, MD: I consider testosterone supplementation in my clinical practice in both premenopausal and postmenopausal women for symptoms of androgen/hormone deficiency, including diminished sense of well-being; dysphoric mood; anxiety; irritability; fatigue; decreased libido, sexual activity, or pleasure; vasomotor instability; bone loss; decreased muscle strength; insomnia; changes in cognition; memory loss; urinary symptoms; incontinence; vaginal atrophy and dryness; and joint and muscular pain. We also have shown through preliminary and short-term data and case studies that testosterone therapy has a potential beneficial effect on migraine headaches, as well as active breast cancers in both premenopausal and postmenopausal women.^6-10

Continue to: What is appropriate bloodwork?...

 

 

What is appropriate bloodwork?

Dr. Karram: Do you obtain blood work before initiating testosterone treatment? If so, what tests do you order and what testosterone levels are considered to be normal for premenopausal and postmenopausal women?

Dr. Streicher: Unlike estrogen, which is predictably low in a postmenopausal woman, serum testosterone (T) levels are highly variable because of the adrenal component. Ovarian testosterone production does not cease at the same time as estrogen production. So I do obtain total and free T levels, prior to initiating treatment. Having said that, it has been well established that T levels correlate poorly with level of sexual interest, and there is no specific blood level that can be used to differentiate women with and without sexual dysfunction. We all have patients who have nonexistent T levels and have a very healthy libido, and other women with sky-high levels who have no libido. But it is useful to know levels prior to initiating therapy to be able to monitor levels throughout treatment. Also, if levels are in the premenopausal physiologic range, not only is she unlikely to respond but she is also at risk for developing androgenic adverse effects, such as acne and hair growth. In general, a low free T level (even if it is in the normal postmenopausal range) in a clinical setting of HSDD supports supplementation.

The assessment and interpretation of T levels can be challenging, particularly as the majority of testosterone is protein-bound and biologically inactive. Free T levels (the biologically active testosterone) in many labs are unreliable and need to be calculated.

In addition to total and free T, I check levels of sex hormone-binding globulin (SHBG), the protein that binds testosterone and renders it biologically inactive. If someone has high SHBG levels and is taking an oral estrogen, simply switching to a transdermal estrogen will result in decreased SHBG and increased free T.

Levels of total and free T vary from lab to lab, so it is best to be familiar with those ranges and then be consistent in which lab you choose.

Dr. Glaser: Although I personally do order blood work on most patients (T, free T, estradiol, complete blood count, thyroid-stimulating hormone, and follicle-stimulating hormone), after 15 years of research and publishing data on testosterone implants, I do not believe that T levels are absolutely necessary or even beneficial in most cases. It rarely changes management in my patients.

As Lauren said, it is well known that T levels do not correlate with androgen deficiency symptoms or clinical conditions caused by androgen deficiency. If a patient has symptoms of androgen deficiency, a trial of testosterone therapy should be given.

T levels are not a valid marker of tissue exposure in women, reflecting less than 20% of total androgen activity. The major source of testosterone in pre and postmenopausal women is the local intracrine production of testosterone from the adrenal precursor steroids dehydroepiandrosterone (DHEA) and androstenedione, which would not be reflected in T levels.

In our study involving 300 women, we found no relationship between baseline T levels, presenting symptoms, or response to therapy.⁶ Premenopausal and postmenopausal women had similar baseline T levels and similar response to therapy. Even women with baseline T levels in the mid-range responded to therapy.

Some of the most controversial topics in treating women with testosterone are related to dosing and T levels throughout therapy. Guideline authors often use the terms ‘physiologic dosing’ and ‘physiologic ranges’ when making recommendations for therapy. Although “physiologic” sounds appropriate/ scientific, these rigid opinions/recommendations are not evidence based. There are no data supporting the use of endogenous T ranges to guide dosing or monitor testosterone therapy.

The decision to initiate testosterone therapy is a clinical decision between the doctor and the patient based on the patient’s symptomatology, which is the therapeutic endpoint. Testosterone therapy must be done with adequate doses determined by clinical effect (benefits) versus side effects or adverse events (risks). T levels may be helpful, along with clinical evaluation when troubleshooting.

Utilizing data from thousands of patients, we have developed serum ranges for testosterone implants.¹¹ Even so, no two patients are the same, nor do they respond to therapy the same. It is always a clinical decision.

Continue to: Dr. Simon...

Dr. Simon: In the recent global consensus statement on testosterone use,¹ the experts were in agreement that “no cut-off blood level can be used for any measured circulating androgen to differentiate women with and without sexual dysfunction.” They give their recommendation a C, and I agree that testosterone supplementation, with specific dosage levels, are a clinical decision.

Before initiating testosterone therapy, it is recommended that liver function and fasting lipids are assessed, as liver disease and hyperlipidemia are contraindications to treatment. These levels should be monitored twice in the first year and annually thereafter while the patient is taking testosterone. Breast and pelvic examinations, mammography, and evaluation for abnormal bleeding should be performed as well as the blood tests.¹² These recommendations are focused on safety not efficacy.

Administration route

Dr. Karram: How do you administer testosterone, and why?

Dr. Streicher: As there are no FDA approved testosterone products for women, clinicians must determine the dosage and route of delivery based on published clinical trials.

Dr. Glaser: I treat patients with subcutaneous pellet implants. The implants provide consistent and continuous delivery of therapeutic amounts of testosterone. There is a reason testosterone pellets have been used for more than 80 years and are more popular now than ever—they work. The insertion procedure is simple and takes about 2 minutes. The treatment is cost-effective, avoids first pass, has no adverse effect on the liver or clotting factors, and there is no transference. Decades of data support both the efficacy and safety of testosterone implants.⁶ However, testosterone implants are not regulated by the FDA and all patients are required to sign a consent informing them of off-label use, benefits, and risks of testosterone implant therapy.

Dr. Simon: I think the consent is important, as there is no package labeling to warn of possible side effects.

Dr. Streicher: Oral testosterone therapy, because of its first pass through the liver and association with adverse lipid profiles with negative effects on high- and low-density lipoprotein cholesterol levels, is not recommended. I prefer a transdermal approach. Pellets, implants, and injections have the potential to result in supraphysiologic blood concentrations. It must be emphasized that the goal of treatment is to approximate premenopausal physiologic levels. More is not better; excessive levels do not demonstrate a greater sexual response and are in fact more likely to have a negative impact due to androgenic side effects.

In most clinical trials, a 300 mg/d testosterone patch was effective, but these patches are not commercially available so I rely on transdermal gel from a compounding pharmacy. The typical dose needed to raise levels into the high to normal range for most women is 2.5 mg up to 5 mg per day of testosterone 1%, which translates to roughly 1 mL. Many pharmacies provide a dispenser, which allots the appropriate dose. Alternatively, I instruct the patient to place a dollop on her thigh (roughly in size of a single M&M candy).

I always tell my patients that the response is not immediate, typically taking 8 to 12 weeks for the effect to become clinically significant. I generally see a patient back 8 weeks after initiation of treatment to check T levels and evaluate response.

Dr. Simon: There are some data demonstrating that intravaginal testosterone can be a potential treatment for GSM. Intravaginal testosterone coupled with aromatase inhibitor therapy used for breast cancer treatment resulted in supraphysiologic T levels and reportedly improved vaginal maturation index and reduced dyspareunia. More study is needed.¹³

Dr. Streicher: Agreed. The lower third of the vagina and the vestibule is rich in testosterone receptors. Like Dr. Simon, in some cases of vaginal atrophy I prescribe a compounded local vaginal testosterone.

Continue to: Testosterone and premenopausal women...

Testosterone and premenopausal women

Dr. Karram: Is there a role for testosterone supplementation in premenopausal women with normal estrogen production?

Dr. Glaser: Yes. In fact, in our study, more than one-third of the patients were premenopausal, which makes sense.⁶ There is a marked decline of T levels and the adrenal precursor steroids (DHEA and androstenedione) in women between the ages of 20–30 years and around age 50. As we said, symptoms of androgen deficiency often occur prior to menopause and are not related to estrogen levels. In our study, testosterone implant therapy relieved symptoms of hormone (androgen) deficiency, including vasomotor symptoms, sleep problems, depressive mood, irritability, anxiety, physical and mental exhaustion (fatigue, memory issues), sexual problems, bladder problems (incontinence, frequency), vaginal dryness, and joint and muscular pain. Premenopausal and postmenopausal patients reported similar hormone deficiency symptoms. Premenopausal women did report a higher incidence of psychological complaints (depressive mood, anxiety, and irritability), while postmenopausal women reported more hot flashes, vaginal dryness, and urologic symptoms. Both groups demonstrated similar improvement in symptoms.

In addition, we have seen relief of severe migraine headache in premenopausal (as well as postmenopausal) women treated with testosterone implant therapy.^6,7

Dr. Streicher: The goal of testosterone supplementation is to approximate physiological testosterone concentrations for premenopausal women. While testosterone may improve well-being and sexual function in premenopausal women, the data are limited and really inconclusive. More study is needed given that there is likely a wide therapeutic range with many variables. Having said that, there are some data that indicate that testosterone in premenopausal women may enhance general sense of well-being.¹⁴

Why is there no FDA-approved agent?

Dr. Karram: Why do you think the FDA has been reluctant to approve a testosterone agent for women?

Dr. Simon: Three potential testosterone drugs for use in women have been unsuccessfully brought to market after the FDA did not approve them. There are 31 approved products for men, each of which were approved because they safely restored normal testosterone concentrations in men with reduced levels and an associated medical condition. Unlike this scenario for men, for women, the FDA has required products to show clinical effectiveness in trials. For instance, Estratest, a combination estrogen-testosterone product, was in use in the 1960s—approved for women with estrogen-resistant hot flushes, and used in practice for sexual dysfunction. After the FDA implemented its Drug Efficacy Study and Implementation regulation system after 2000, which required safety and efficacy trial(s) before drug approval, the manufacturer removed the drug from market when presented efficacy study data for the added testosterone in the drug were deemed inadequate.¹⁵

Dr. Streicher: We have yet another example of the disparity between the FDA approval processes for sexual function drugs for men versus women. Take Intrinsia as another example. It was a 300-mg testosterone patch that underwent clinical trials in women who were post-oophorectomy with HSDD. The patch had demonstrated efficacy with minimal adverse effects and no statistically significant dangerous effects. However, the FDA declined approval, citing “safety considerations” and requested longer-term clinical trials to evaluate potential cardiovascular or breast problems. Given that Intrinsia supplementation simply restored normal physiologic testosterone levels, and there was no such requirement in men who received supplementation post-orchiectomy, this requirement was nonsensical and unjustified.

Compounded formulations

Dr. Karram: Are compounding pharmacies appropriately regulated, and how can you be assured that the source of your testosterone is appropriate?

Dr. Glaser: Compounding pharmacies are regulated by the State Boards of Pharmacy, Drug Enforcement Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, State Bureaus of Narcotics and Dangerous Drugs, and Departments of Health (in some states).

Compounding is a highly regulated profession that is constantly under scrutiny by agencies, patients, and physicians. Any additional regulations could adversely impact the accessibility of patients to individually compounded medications including intravenous and oncology medications. Over the past 20 years, I have treated hundreds of patients with breast cancer with compounded vaginal testosterone (with or without estriol) and subcutaneous testosterone (with or without anastrozole), greatly improving quality of life in women suffering from severe symptoms. Without the availability of compounded medications, there would have been no or limited alternatives for adequate and much needed therapy. Notably, there have been no adverse events or safety-related issues in more than 20 years.

Regarding whether or not “the source of your testosterone is appropriate,” pharmacists can only use United States Pharmacopeia (USP) grades of testosterone. Testosterone used in compounding is required by the FDA to be of USP grade from an FDA registered and compliant facility. In addition, compounding support companies run additional USP tests to confirm their products meet USP standards prior to being delivered to individual compounding pharmacies.

Dr. Streicher: However, there potentially can be substantial variability between formulations and batches. Product purity can also be an issue. It is reassuring if the compounding pharmacy is compliant with purity of Active Pharmaceutical Ingredients and Good Manufacturing Practice rules and guidelines that assure the minimum requirements to assure high quality and batch-to-batch consistency. I find it helpful to always work with the same pharmacy once you have established uniformity and reliability. If there is concern, it is appropriate to check a patient’s serum level 2 weeks after initiation of therapy.

Dr. Simon: I think the problem with some compounding pharmacies is that there may be incentives back and forth with the clinician to use a certain outlet, whereby the patient’s best interest may not be served. I do believe that there is a role for compounding pharmacies, however. We also use them because some women may have strange reactions or be allergic to the preservatives, formulating agents, or even lactose, in various pills and patches, gels, and creams.

Continue to: Testosterone for aging and cognition?...

Testosterone for aging and cognition?

Dr. Karram: Do you think that testosterone supplementation in the elderly can have a positive impact on aging, Alzheimer disease, and dementia?

Dr. Streicher: The jury is still out on the cognitive effects of postmenopausal androgen supplementation. There is currently insufficient evidence to support the use of testosterone to enhance cognitive performance, or to delay cognitive decline. I prescribe testosterone only to treat HSDD, but I do tell my patient that she may possibly also benefit in terms of cognitive function, musculoskeletal parameters, and well-being. Large RCTs are needed in those areas to justify prescribing for those benefits alone.

Dr. Simon: I would say this is the place for future development, but where there is very likely to be a benefit is on sarcopenia.

Dr. Glaser: There is some evidence that testosterone is neuroprotective.¹⁶ In my clinical practice I have seen “self-reported” memory issues improved on therapy, often returning toward the end of the testosterone implant cycle. Adequate amounts of bioavailable testosterone at the androgen receptor are critical for optimal health, immune function, and disease prevention.

Dr. Karram: In conclusion, this expert panel agrees that testosterone supplementation is beneficial for sexual dysfunction in postmenopausal women, with also many other potential benefits that require further investigation. Route of administration preferred by Dr. Simon and Dr. Streicher is transdermal or a transvaginal cream. Dr. Glaser uses a subcutaneous pellet approach. Thank you all for an engaging and informative discussion. ●

Skin microbiome therapy to protect against Staphylococcus aureus in patients with atopic dermatitis (AD) proved safe in a phase 1 randomized clinical trial that also demonstrated “encouraging clinical and mechanistic results,” Richard L. Gallo, MD, PhD, and his coinvestigators have reported in Nature Medicine.

Findings from the 1-week, 54-patient trial of a topical formulation containing Staphylococcus hominis A9 (ShA9) offer evidence that the strain directly kills S. aureus, inhibits the production of S. aureus–generated toxins, and enables expansion of a healthy bacterial community, “allowing the rest of the microbiome to start to recover to normal,” Dr. Gallo, professor and chairman of the department of dermatology at the University of California, San Diego, said in an interview.

“And perhaps most exciting,” Dr. Gallo added, is the finding that the subset of patients with AD who were most responsive to the ShA9 compound – approximately two-thirds of the participants who were randomized to receive it – showed improvement in local EASI (Eczema Area and Severity Index) and SCORAD (Scoring Atopic Dermatitis) scores used to assess inflammation. Plans are underway for a larger and longer trial, he said.

S. aureus commonly colonizes patients with AD and exacerbates disease by causing inflammation. In recent years, Dr. Gallo and other investigators have come to believe that AD is a cyclic disease in which the skin’s microbiome affects the host, and the host affects the microbiome. The goal of bacteriotherapy is to break the cycle of S. aureus colonization and improve the skin immune and barrier dysfunction characteristics of AD, Dr. Gallo said.

ShA9, a bacterium isolated from healthy human skin, was chosen as a potential topical therapy for AD based on its capacity both to selectively kill S. aureus and to inhibit toxin production by S. aureus. Dr. Gallo’s team’s preclinical work involved screening thousands of isolates of coagulase-negative staphylococci for gene products that perform these two functions by expressing both antimicrobial peptides (AMPs) and autoinducing peptides (AIPs), the latter of which inhibit the S. aureus quorum-sending system that leads to toxin production. Most patients with AD lack protective strains of coagulase-negative staphylococci, including S. hominis, prior research has found.

The double-blind phase 1 trial randomized 54 adults with moderate-severe AD affecting the ventral forearms in a 2:1 fashion to receive the proprietary lyophilized preparation of ShA9 or an ShA9-free formulation twice daily for 1 week. All participants were culture positive for S. aureus.

Clinical assessments and skin swabs were obtained before and within an hour after the first application of day 1, and swabs were collected on days 4 and 7 within 4 hours of the first application.

Blinded physician assessments and skin swabs were also obtained at 24, 48, and 96 hours after the final dose on day 7.

Based on structured daily diaries, there were no serious adverse events, and significantly fewer adverse events in those treated with ShA9, compared with the vehicle alone; 55.6% versus 83.3%, respectively, were considered to have adverse events.

The adverse event–reporting system captured the normal fluctuation of eczema and considered any report of fluctuation above baseline to be an adverse event. “Patients treated with the [placebo formulation] had the expected high frequency of itching, burning, and pain that you see with AD but it was encouraging that the frequency of reporting these events was significantly less in those treated with the active [formulation],” Dr. Gallo said in the interview.

Their report describes a decrease in S. aureus in participants treated with ShA9, and increases in ShA9 DNA. Not all S. aureus strains were directly killed by ShA9, but all strains had reduced expression of mRNA for psm-alpha, an important virulence factor. That reduced expression correlated with ShA9 AIPs and improved EASI scores, the latter of which was observed in a post-hoc analysis. “Participants with S. aureus not killed by ShA9 were still sensitive to inhibition of toxin production, a mechanistic outcome that predicted clinical improvement in mice and may require longer therapy to observe clinical improvement in humans,” the investigators wrote.

Local eczema severity was not significantly different between the bacteriotherapy and control groups. But the post-hoc analysis showed that after 7 days of treatment, and up to 4 days after treatment was discontinued, the patients with S. aureus that was sensitive to killing by ShA9 (21 out of 35 total who received the bacteriotherapy) showed improvement in EASI and SCORAD scores, compared with control patients.

Future research will assess the compound in both S. aureus culture-positive and culture-negative patients, and in patients with mild disease, Dr. Gallo said.

The trial was conducted at USCD and the National Jewish Health General Clinical Research Center in Denver, and was sponsored by the National Institute of Allergy and Infectious Diseases. The ShA9 formulation and related technology are licensed to MatriSys Bioscience, of which Dr. Gallo is the cofounder and an advisory board member. Dr. Gallo holds equity interest in the company.

Skin microbiome therapy to protect against Staphylococcus aureus in patients with atopic dermatitis (AD) proved safe in a phase 1 randomized clinical trial that also demonstrated “encouraging clinical and mechanistic results,” Richard L. Gallo, MD, PhD, and his coinvestigators have reported in Nature Medicine.

Findings from the 1-week, 54-patient trial of a topical formulation containing Staphylococcus hominis A9 (ShA9) offer evidence that the strain directly kills S. aureus, inhibits the production of S. aureus–generated toxins, and enables expansion of a healthy bacterial community, “allowing the rest of the microbiome to start to recover to normal,” Dr. Gallo, professor and chairman of the department of dermatology at the University of California, San Diego, said in an interview.

“And perhaps most exciting,” Dr. Gallo added, is the finding that the subset of patients with AD who were most responsive to the ShA9 compound – approximately two-thirds of the participants who were randomized to receive it – showed improvement in local EASI (Eczema Area and Severity Index) and SCORAD (Scoring Atopic Dermatitis) scores used to assess inflammation. Plans are underway for a larger and longer trial, he said.

S. aureus commonly colonizes patients with AD and exacerbates disease by causing inflammation. In recent years, Dr. Gallo and other investigators have come to believe that AD is a cyclic disease in which the skin’s microbiome affects the host, and the host affects the microbiome. The goal of bacteriotherapy is to break the cycle of S. aureus colonization and improve the skin immune and barrier dysfunction characteristics of AD, Dr. Gallo said.

ShA9, a bacterium isolated from healthy human skin, was chosen as a potential topical therapy for AD based on its capacity both to selectively kill S. aureus and to inhibit toxin production by S. aureus. Dr. Gallo’s team’s preclinical work involved screening thousands of isolates of coagulase-negative staphylococci for gene products that perform these two functions by expressing both antimicrobial peptides (AMPs) and autoinducing peptides (AIPs), the latter of which inhibit the S. aureus quorum-sending system that leads to toxin production. Most patients with AD lack protective strains of coagulase-negative staphylococci, including S. hominis, prior research has found.

The double-blind phase 1 trial randomized 54 adults with moderate-severe AD affecting the ventral forearms in a 2:1 fashion to receive the proprietary lyophilized preparation of ShA9 or an ShA9-free formulation twice daily for 1 week. All participants were culture positive for S. aureus.

Clinical assessments and skin swabs were obtained before and within an hour after the first application of day 1, and swabs were collected on days 4 and 7 within 4 hours of the first application.

Blinded physician assessments and skin swabs were also obtained at 24, 48, and 96 hours after the final dose on day 7.

Based on structured daily diaries, there were no serious adverse events, and significantly fewer adverse events in those treated with ShA9, compared with the vehicle alone; 55.6% versus 83.3%, respectively, were considered to have adverse events.

The adverse event–reporting system captured the normal fluctuation of eczema and considered any report of fluctuation above baseline to be an adverse event. “Patients treated with the [placebo formulation] had the expected high frequency of itching, burning, and pain that you see with AD but it was encouraging that the frequency of reporting these events was significantly less in those treated with the active [formulation],” Dr. Gallo said in the interview.

Their report describes a decrease in S. aureus in participants treated with ShA9, and increases in ShA9 DNA. Not all S. aureus strains were directly killed by ShA9, but all strains had reduced expression of mRNA for psm-alpha, an important virulence factor. That reduced expression correlated with ShA9 AIPs and improved EASI scores, the latter of which was observed in a post-hoc analysis. “Participants with S. aureus not killed by ShA9 were still sensitive to inhibition of toxin production, a mechanistic outcome that predicted clinical improvement in mice and may require longer therapy to observe clinical improvement in humans,” the investigators wrote.

Local eczema severity was not significantly different between the bacteriotherapy and control groups. But the post-hoc analysis showed that after 7 days of treatment, and up to 4 days after treatment was discontinued, the patients with S. aureus that was sensitive to killing by ShA9 (21 out of 35 total who received the bacteriotherapy) showed improvement in EASI and SCORAD scores, compared with control patients.

Future research will assess the compound in both S. aureus culture-positive and culture-negative patients, and in patients with mild disease, Dr. Gallo said.

The trial was conducted at USCD and the National Jewish Health General Clinical Research Center in Denver, and was sponsored by the National Institute of Allergy and Infectious Diseases. The ShA9 formulation and related technology are licensed to MatriSys Bioscience, of which Dr. Gallo is the cofounder and an advisory board member. Dr. Gallo holds equity interest in the company.

Skin microbiome therapy to protect against Staphylococcus aureus in patients with atopic dermatitis (AD) proved safe in a phase 1 randomized clinical trial that also demonstrated “encouraging clinical and mechanistic results,” Richard L. Gallo, MD, PhD, and his coinvestigators have reported in Nature Medicine.

Findings from the 1-week, 54-patient trial of a topical formulation containing Staphylococcus hominis A9 (ShA9) offer evidence that the strain directly kills S. aureus, inhibits the production of S. aureus–generated toxins, and enables expansion of a healthy bacterial community, “allowing the rest of the microbiome to start to recover to normal,” Dr. Gallo, professor and chairman of the department of dermatology at the University of California, San Diego, said in an interview.

“And perhaps most exciting,” Dr. Gallo added, is the finding that the subset of patients with AD who were most responsive to the ShA9 compound – approximately two-thirds of the participants who were randomized to receive it – showed improvement in local EASI (Eczema Area and Severity Index) and SCORAD (Scoring Atopic Dermatitis) scores used to assess inflammation. Plans are underway for a larger and longer trial, he said.

S. aureus commonly colonizes patients with AD and exacerbates disease by causing inflammation. In recent years, Dr. Gallo and other investigators have come to believe that AD is a cyclic disease in which the skin’s microbiome affects the host, and the host affects the microbiome. The goal of bacteriotherapy is to break the cycle of S. aureus colonization and improve the skin immune and barrier dysfunction characteristics of AD, Dr. Gallo said.

ShA9, a bacterium isolated from healthy human skin, was chosen as a potential topical therapy for AD based on its capacity both to selectively kill S. aureus and to inhibit toxin production by S. aureus. Dr. Gallo’s team’s preclinical work involved screening thousands of isolates of coagulase-negative staphylococci for gene products that perform these two functions by expressing both antimicrobial peptides (AMPs) and autoinducing peptides (AIPs), the latter of which inhibit the S. aureus quorum-sending system that leads to toxin production. Most patients with AD lack protective strains of coagulase-negative staphylococci, including S. hominis, prior research has found.

The double-blind phase 1 trial randomized 54 adults with moderate-severe AD affecting the ventral forearms in a 2:1 fashion to receive the proprietary lyophilized preparation of ShA9 or an ShA9-free formulation twice daily for 1 week. All participants were culture positive for S. aureus.

Clinical assessments and skin swabs were obtained before and within an hour after the first application of day 1, and swabs were collected on days 4 and 7 within 4 hours of the first application.

Blinded physician assessments and skin swabs were also obtained at 24, 48, and 96 hours after the final dose on day 7.

Based on structured daily diaries, there were no serious adverse events, and significantly fewer adverse events in those treated with ShA9, compared with the vehicle alone; 55.6% versus 83.3%, respectively, were considered to have adverse events.

The adverse event–reporting system captured the normal fluctuation of eczema and considered any report of fluctuation above baseline to be an adverse event. “Patients treated with the [placebo formulation] had the expected high frequency of itching, burning, and pain that you see with AD but it was encouraging that the frequency of reporting these events was significantly less in those treated with the active [formulation],” Dr. Gallo said in the interview.

Their report describes a decrease in S. aureus in participants treated with ShA9, and increases in ShA9 DNA. Not all S. aureus strains were directly killed by ShA9, but all strains had reduced expression of mRNA for psm-alpha, an important virulence factor. That reduced expression correlated with ShA9 AIPs and improved EASI scores, the latter of which was observed in a post-hoc analysis. “Participants with S. aureus not killed by ShA9 were still sensitive to inhibition of toxin production, a mechanistic outcome that predicted clinical improvement in mice and may require longer therapy to observe clinical improvement in humans,” the investigators wrote.

Local eczema severity was not significantly different between the bacteriotherapy and control groups. But the post-hoc analysis showed that after 7 days of treatment, and up to 4 days after treatment was discontinued, the patients with S. aureus that was sensitive to killing by ShA9 (21 out of 35 total who received the bacteriotherapy) showed improvement in EASI and SCORAD scores, compared with control patients.

Future research will assess the compound in both S. aureus culture-positive and culture-negative patients, and in patients with mild disease, Dr. Gallo said.

The trial was conducted at USCD and the National Jewish Health General Clinical Research Center in Denver, and was sponsored by the National Institute of Allergy and Infectious Diseases. The ShA9 formulation and related technology are licensed to MatriSys Bioscience, of which Dr. Gallo is the cofounder and an advisory board member. Dr. Gallo holds equity interest in the company.