Please note that this is a commentary, an opinion piece: my opinion. The statements here do not necessarily represent those of this news organization or any of the myriad people or institutions that comprise this corner of the human universe.

Some days, speaking as a long-time physician and editor, I wish that there were no such things as race or ethnicity or even geographic origin for that matter. We can’t get away from sex, gender, disability, age, or culture. I’m not sure about religion. I wish people were just people.

But race is deeply embedded in the American experience — an almost invisible but inevitable presence in all of our thoughts and expressions about human activities.

In medical education (for eons it seems) the student has been taught to mention race in the first sentence of a given patient presentation, along with age and sex. In human epidemiologic research, race is almost always a studied variable. In clinical and basic medical research, looking at the impact of race on this, that, or the other is commonplace. “Mixed race not otherwise specified” is ubiquitous in the United States yet blithely ignored by most who tally these statistics. Race is rarely gene-specific. It is more of a social and cultural construct but with plainly visible overt phenotypic markers — an almost infinite mix of daily reality.

Our country, and much of Western civilization in 2024, is based on the principle that all men are created equal, although the originators of that notion were unaware of their own “equity-challenged” situation.

Many organizations, in and out of government, are now understanding, developing, and implementing programs (and thought/language patterns) to socialize diversity, equity, and inclusion (known as DEI) into their culture. It should not be surprising that many who prefer the status quo are not happy with the pressure from this movement and are using whatever methods are available to them to prevent full DEI. Such it always is.

The trusty Copilot from Bing provides these definitions:

• Diversity refers to the presence of variety within the organizational workforce. This includes aspects such as gender, culture, ethnicity, religion, disability, age, and opinion.
• Equity encompasses concepts of fairness and justice. It involves fair compensation, substantive equality, and addressing societal disparities. Equity also considers unique circumstances and adjusts treatment to achieve equal outcomes.
• Inclusion focuses on creating an organizational culture where all employees feel heard, fostering a sense of belonging and integration.

I am more than proud that my old domain of peer-reviewed, primary source, medical (and science) journals is taking a leading role in this noble, necessary, and long overdue movement for medicine.

As the central repository and transmitter of new medical information, including scientific studies, clinical medicine reports, ethics measures, and education, medical journals (including those deemed prestigious) have historically been among the worst offenders in perpetuating non-DEI objectives in their leadership, staffing, focus, instructions for authors, style manuals, and published materials.

This issue came to a head in March 2021 when a JAMA podcast about racism in American medicine was followed by this promotional tweet: “No physician is racist, so how can there be structural racism in health care?”

Reactions and actions were rapid, strong, and decisive. After an interregnum at JAMA, a new editor in chief, Kirsten Bibbins-Domingo, PhD, MD, MAS, was named. She and her large staff of editors and editorial board members from the multijournal JAMA Network joined a worldwide movement of (currently) 56 publishing organizations representing 15,000 journals called the Joint Commitment for Action on Inclusion and Diversity in Publishing.

A recent JAMA editorial with 29 authors describes the entire commitment initiative of publishers-editors. It reports JAMA Network data from 2023 and 2024 from surveys of 455 editors (a 91% response rate) about their own gender (five choices), ethnic origins or geographic ancestry (13 choices), and race (eight choices), demonstrating considerable progress toward DEI goals. The survey’s complex multinational classifications may not jibe with the categorizations used in some countries (too bad that “mixed” is not “mixed in” — a missed opportunity).

This encouraging movement will not fix it all. But when people of certain groups are represented at the table, that point of view is far more likely to make it into the lexicon, language, and omnipresent work products, potentially changing cultural norms. Even the measurement of movement related to disparity in healthcare is marred by frequent variations of data accuracy. More consistency in what to measure can help a lot, and the medical literature can be very influential.

A personal anecdote: When I was a professor at UC Davis in 1978, Allan Bakke, MD, was my student. Some of you will remember the saga of affirmative action on admissions, which was just revisited in the light of a recent decision by the US Supreme Court.

Back in 1978, the dean at UC Davis told me that he kept two file folders on the admission processes in different desk drawers. One categorized all applicants and enrollees by race, and the other did not. Depending on who came to visit and ask questions, he would choose one or the other file to share once he figured out what they were looking for (this is not a joke).

The strength of the current active political pushback against the entire DEI movement has deep roots and should not be underestimated. There will be a lot of to-ing and fro-ing.

French writer Victor Hugo is credited with stating, “There is nothing as powerful as an idea whose time has come.” A majority of Americans, physicians, and other healthcare professionals believe in basic fairness. The time for DEI in all aspects of medicine is now.

Dr. Lundberg, editor in chief of Cancer Commons, disclosed having no relevant financial relationships.

A version of this article appeared on Medscape.com.

Please note that this is a commentary, an opinion piece: my opinion. The statements here do not necessarily represent those of this news organization or any of the myriad people or institutions that comprise this corner of the human universe.

Some days, speaking as a long-time physician and editor, I wish that there were no such things as race or ethnicity or even geographic origin for that matter. We can’t get away from sex, gender, disability, age, or culture. I’m not sure about religion. I wish people were just people.

But race is deeply embedded in the American experience — an almost invisible but inevitable presence in all of our thoughts and expressions about human activities.

In medical education (for eons it seems) the student has been taught to mention race in the first sentence of a given patient presentation, along with age and sex. In human epidemiologic research, race is almost always a studied variable. In clinical and basic medical research, looking at the impact of race on this, that, or the other is commonplace. “Mixed race not otherwise specified” is ubiquitous in the United States yet blithely ignored by most who tally these statistics. Race is rarely gene-specific. It is more of a social and cultural construct but with plainly visible overt phenotypic markers — an almost infinite mix of daily reality.

Our country, and much of Western civilization in 2024, is based on the principle that all men are created equal, although the originators of that notion were unaware of their own “equity-challenged” situation.

Many organizations, in and out of government, are now understanding, developing, and implementing programs (and thought/language patterns) to socialize diversity, equity, and inclusion (known as DEI) into their culture. It should not be surprising that many who prefer the status quo are not happy with the pressure from this movement and are using whatever methods are available to them to prevent full DEI. Such it always is.

The trusty Copilot from Bing provides these definitions:

• Diversity refers to the presence of variety within the organizational workforce. This includes aspects such as gender, culture, ethnicity, religion, disability, age, and opinion.
• Equity encompasses concepts of fairness and justice. It involves fair compensation, substantive equality, and addressing societal disparities. Equity also considers unique circumstances and adjusts treatment to achieve equal outcomes.
• Inclusion focuses on creating an organizational culture where all employees feel heard, fostering a sense of belonging and integration.

I am more than proud that my old domain of peer-reviewed, primary source, medical (and science) journals is taking a leading role in this noble, necessary, and long overdue movement for medicine.

As the central repository and transmitter of new medical information, including scientific studies, clinical medicine reports, ethics measures, and education, medical journals (including those deemed prestigious) have historically been among the worst offenders in perpetuating non-DEI objectives in their leadership, staffing, focus, instructions for authors, style manuals, and published materials.

This issue came to a head in March 2021 when a JAMA podcast about racism in American medicine was followed by this promotional tweet: “No physician is racist, so how can there be structural racism in health care?”

Reactions and actions were rapid, strong, and decisive. After an interregnum at JAMA, a new editor in chief, Kirsten Bibbins-Domingo, PhD, MD, MAS, was named. She and her large staff of editors and editorial board members from the multijournal JAMA Network joined a worldwide movement of (currently) 56 publishing organizations representing 15,000 journals called the Joint Commitment for Action on Inclusion and Diversity in Publishing.

A recent JAMA editorial with 29 authors describes the entire commitment initiative of publishers-editors. It reports JAMA Network data from 2023 and 2024 from surveys of 455 editors (a 91% response rate) about their own gender (five choices), ethnic origins or geographic ancestry (13 choices), and race (eight choices), demonstrating considerable progress toward DEI goals. The survey’s complex multinational classifications may not jibe with the categorizations used in some countries (too bad that “mixed” is not “mixed in” — a missed opportunity).

This encouraging movement will not fix it all. But when people of certain groups are represented at the table, that point of view is far more likely to make it into the lexicon, language, and omnipresent work products, potentially changing cultural norms. Even the measurement of movement related to disparity in healthcare is marred by frequent variations of data accuracy. More consistency in what to measure can help a lot, and the medical literature can be very influential.

A personal anecdote: When I was a professor at UC Davis in 1978, Allan Bakke, MD, was my student. Some of you will remember the saga of affirmative action on admissions, which was just revisited in the light of a recent decision by the US Supreme Court.

Back in 1978, the dean at UC Davis told me that he kept two file folders on the admission processes in different desk drawers. One categorized all applicants and enrollees by race, and the other did not. Depending on who came to visit and ask questions, he would choose one or the other file to share once he figured out what they were looking for (this is not a joke).

The strength of the current active political pushback against the entire DEI movement has deep roots and should not be underestimated. There will be a lot of to-ing and fro-ing.

French writer Victor Hugo is credited with stating, “There is nothing as powerful as an idea whose time has come.” A majority of Americans, physicians, and other healthcare professionals believe in basic fairness. The time for DEI in all aspects of medicine is now.

Dr. Lundberg, editor in chief of Cancer Commons, disclosed having no relevant financial relationships.

A version of this article appeared on Medscape.com.

Please note that this is a commentary, an opinion piece: my opinion. The statements here do not necessarily represent those of this news organization or any of the myriad people or institutions that comprise this corner of the human universe.

Some days, speaking as a long-time physician and editor, I wish that there were no such things as race or ethnicity or even geographic origin for that matter. We can’t get away from sex, gender, disability, age, or culture. I’m not sure about religion. I wish people were just people.

But race is deeply embedded in the American experience — an almost invisible but inevitable presence in all of our thoughts and expressions about human activities.

In medical education (for eons it seems) the student has been taught to mention race in the first sentence of a given patient presentation, along with age and sex. In human epidemiologic research, race is almost always a studied variable. In clinical and basic medical research, looking at the impact of race on this, that, or the other is commonplace. “Mixed race not otherwise specified” is ubiquitous in the United States yet blithely ignored by most who tally these statistics. Race is rarely gene-specific. It is more of a social and cultural construct but with plainly visible overt phenotypic markers — an almost infinite mix of daily reality.

Our country, and much of Western civilization in 2024, is based on the principle that all men are created equal, although the originators of that notion were unaware of their own “equity-challenged” situation.

Many organizations, in and out of government, are now understanding, developing, and implementing programs (and thought/language patterns) to socialize diversity, equity, and inclusion (known as DEI) into their culture. It should not be surprising that many who prefer the status quo are not happy with the pressure from this movement and are using whatever methods are available to them to prevent full DEI. Such it always is.

The trusty Copilot from Bing provides these definitions:

• Diversity refers to the presence of variety within the organizational workforce. This includes aspects such as gender, culture, ethnicity, religion, disability, age, and opinion.
• Equity encompasses concepts of fairness and justice. It involves fair compensation, substantive equality, and addressing societal disparities. Equity also considers unique circumstances and adjusts treatment to achieve equal outcomes.
• Inclusion focuses on creating an organizational culture where all employees feel heard, fostering a sense of belonging and integration.

I am more than proud that my old domain of peer-reviewed, primary source, medical (and science) journals is taking a leading role in this noble, necessary, and long overdue movement for medicine.

As the central repository and transmitter of new medical information, including scientific studies, clinical medicine reports, ethics measures, and education, medical journals (including those deemed prestigious) have historically been among the worst offenders in perpetuating non-DEI objectives in their leadership, staffing, focus, instructions for authors, style manuals, and published materials.

This issue came to a head in March 2021 when a JAMA podcast about racism in American medicine was followed by this promotional tweet: “No physician is racist, so how can there be structural racism in health care?”

Reactions and actions were rapid, strong, and decisive. After an interregnum at JAMA, a new editor in chief, Kirsten Bibbins-Domingo, PhD, MD, MAS, was named. She and her large staff of editors and editorial board members from the multijournal JAMA Network joined a worldwide movement of (currently) 56 publishing organizations representing 15,000 journals called the Joint Commitment for Action on Inclusion and Diversity in Publishing.

A recent JAMA editorial with 29 authors describes the entire commitment initiative of publishers-editors. It reports JAMA Network data from 2023 and 2024 from surveys of 455 editors (a 91% response rate) about their own gender (five choices), ethnic origins or geographic ancestry (13 choices), and race (eight choices), demonstrating considerable progress toward DEI goals. The survey’s complex multinational classifications may not jibe with the categorizations used in some countries (too bad that “mixed” is not “mixed in” — a missed opportunity).

This encouraging movement will not fix it all. But when people of certain groups are represented at the table, that point of view is far more likely to make it into the lexicon, language, and omnipresent work products, potentially changing cultural norms. Even the measurement of movement related to disparity in healthcare is marred by frequent variations of data accuracy. More consistency in what to measure can help a lot, and the medical literature can be very influential.

A personal anecdote: When I was a professor at UC Davis in 1978, Allan Bakke, MD, was my student. Some of you will remember the saga of affirmative action on admissions, which was just revisited in the light of a recent decision by the US Supreme Court.

Back in 1978, the dean at UC Davis told me that he kept two file folders on the admission processes in different desk drawers. One categorized all applicants and enrollees by race, and the other did not. Depending on who came to visit and ask questions, he would choose one or the other file to share once he figured out what they were looking for (this is not a joke).

The strength of the current active political pushback against the entire DEI movement has deep roots and should not be underestimated. There will be a lot of to-ing and fro-ing.

French writer Victor Hugo is credited with stating, “There is nothing as powerful as an idea whose time has come.” A majority of Americans, physicians, and other healthcare professionals believe in basic fairness. The time for DEI in all aspects of medicine is now.

Dr. Lundberg, editor in chief of Cancer Commons, disclosed having no relevant financial relationships.

A version of this article appeared on Medscape.com.

A recent analysis identified significant disparities in survival outcomes as well as clinical and genetic features between Black and White women with a common subtype of endometrial cancer.

In addition to observing differences in clinical and molecular characteristics, the analysis of real-world registries and clinical trials revealed that Black patients with endometrioid endometrial carcinoma had about a twofold higher risk for cancer-related deaths than White patients.

“Even with propensity-score matching, Black patients had a significantly increased risk of death,” Zachary Kopelman, DO, with Walter Reed National Military Medical Center, Bethesda, Maryland, noted in a presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Importantly, Dr. Kopelman added, the analysis also confirmed “dramatic” underrepresentation of Black patients with endometrioid endometrial carcinoma in clinical trials.

Endometrial cancer is one of the most common cancers among women in the United States, with data showing rising incidence and mortality rates. “Worryingly, endometrial cancer is estimated to overtake ovarian cancer as the deadliest gynecologic malignancy this year,” Dr. Kopelman told attendees.

Previous studies have shown that Black patients with endometrial cancer consistently are more likely to have aggressive histologic subtypes, high-grade tumors, and advanced-stage disease and are twice as likely to die from the disease as White patients, he noted.

Within endometrial cancer, the most common histologic subtype is endometrioid, comprising 65%-75% of cases. In other studies examining racial disparities, the endometrioid histology is often combined with other subtypes, such as aggressive uterine serous carcinoma, which may influence study outcomes, Dr. Kopelman explained.

Dr. Kopelman and colleagues focused their analyses on Black and White women with endometrioid endometrial carcinoma, with the goal of identifying disparities in cancer-related and non-cancer deaths, as well as clinical and molecular features in this patient population.

All women included in the analysis had undergone hysterectomy with or without adjuvant treatment. The researchers used a four-pronged approach incorporating data from the SEER program (2004-2016), the National Cancer Database (2004-2017), eight National Cancer Institute-sponsored randomized phase 3 clinical trials, and the Genomics Evidence Neoplasia Information Exchange project.

Dr. Kopelman and colleagues then performed propensity score matching in the National Cancer Database and exact matching in the randomized controlled trials.

When comparing 47,959 White patients with 4397 Black patients in the SEER dataset, Dr. Kopelman and colleagues found that Black patients had more than two times the risk of dying from their cancer (hazard ratio [HR], 2.04) and a 22% greater risk for a non-cancer death compared with White patients (HR, 1.22).

In the overall National Cancer Database cohort comparing 155,706 White and 13,468 Black patients, Black patients had a 52% greater risk of dying from any cause (HR, 1.52). In the propensity score-matched cohort of 13,468 White and 13,468 Black patients, survival among Black patients remained significantly worse, with a 29% greater risk of dying from any cause (HR, 1.29).

When looking at clinical trial data, Black patients were more likely than White patients to have worse performance status and a higher grade or recurrent disease, Dr. Kopelman noted.

Black patients in the clinical trials also had significantly worse progression-free survival in both the original cohort (HR, 2.05) and the matched cohort (adjusted HR [aHR], 1.22), which matched patients for grade, stage, and treatment arm within each trial and balanced age and performance status. Black patients also had worse overall survival in the original cohort (HR, 2.19) and matched cohort (aHR, 1.32).

Looking at molecular features, Black patients had significantly fewer mutations in a handful of cancer-related gene pathways, including PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K pathways.

One caveat, said Dr. Kopelman, is that mutations in PTEN are still present in a high percentage of both Black (62%) and White (72%), which «offers a potential attractive therapeutic opportunity.»

The analysis also revealed a major gap in the number of Black vs White patients enrolled in randomized clinical trials, which is a major “problem,” said Dr. Kopelman.

The study confirms “ongoing disparities in enrollment and underrepresentation of minorities in gynecologic cancer clinical trials, as well as poor outcomes, and should really promote us to enhance research in these areas,” said study discussant Mariam AlHilli, MD, with Cleveland Clinic Lerner College of Medicine and Case Western Reserve University, Cleveland, Ohio.

David M. O’Malley, MD, who gave a separate talk during the same session on practical considerations for implication of clinical trials, encouraged clinicians to “just ask.”

“Just ask the patient in front of you — no matter what their ethnicity, their race, or where they’re coming from — are they interested in participating in a clinical trial?” Or better yet, “I have a clinical trial now which I’m excited about for you,” said Dr. O’Malley, with The Ohio State University, James Comprehensive Cancer Center, Columbus, Ohio.The study had no commercial funding. Dr. Kopelman, Dr. O’Malley, and Dr. AlHilli had no relevant disclosures.

A version of this article appeared on Medscape.com .

A recent analysis identified significant disparities in survival outcomes as well as clinical and genetic features between Black and White women with a common subtype of endometrial cancer.

In addition to observing differences in clinical and molecular characteristics, the analysis of real-world registries and clinical trials revealed that Black patients with endometrioid endometrial carcinoma had about a twofold higher risk for cancer-related deaths than White patients.

“Even with propensity-score matching, Black patients had a significantly increased risk of death,” Zachary Kopelman, DO, with Walter Reed National Military Medical Center, Bethesda, Maryland, noted in a presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Importantly, Dr. Kopelman added, the analysis also confirmed “dramatic” underrepresentation of Black patients with endometrioid endometrial carcinoma in clinical trials.

Endometrial cancer is one of the most common cancers among women in the United States, with data showing rising incidence and mortality rates. “Worryingly, endometrial cancer is estimated to overtake ovarian cancer as the deadliest gynecologic malignancy this year,” Dr. Kopelman told attendees.

Previous studies have shown that Black patients with endometrial cancer consistently are more likely to have aggressive histologic subtypes, high-grade tumors, and advanced-stage disease and are twice as likely to die from the disease as White patients, he noted.

Within endometrial cancer, the most common histologic subtype is endometrioid, comprising 65%-75% of cases. In other studies examining racial disparities, the endometrioid histology is often combined with other subtypes, such as aggressive uterine serous carcinoma, which may influence study outcomes, Dr. Kopelman explained.

Dr. Kopelman and colleagues focused their analyses on Black and White women with endometrioid endometrial carcinoma, with the goal of identifying disparities in cancer-related and non-cancer deaths, as well as clinical and molecular features in this patient population.

All women included in the analysis had undergone hysterectomy with or without adjuvant treatment. The researchers used a four-pronged approach incorporating data from the SEER program (2004-2016), the National Cancer Database (2004-2017), eight National Cancer Institute-sponsored randomized phase 3 clinical trials, and the Genomics Evidence Neoplasia Information Exchange project.

Dr. Kopelman and colleagues then performed propensity score matching in the National Cancer Database and exact matching in the randomized controlled trials.

When comparing 47,959 White patients with 4397 Black patients in the SEER dataset, Dr. Kopelman and colleagues found that Black patients had more than two times the risk of dying from their cancer (hazard ratio [HR], 2.04) and a 22% greater risk for a non-cancer death compared with White patients (HR, 1.22).

In the overall National Cancer Database cohort comparing 155,706 White and 13,468 Black patients, Black patients had a 52% greater risk of dying from any cause (HR, 1.52). In the propensity score-matched cohort of 13,468 White and 13,468 Black patients, survival among Black patients remained significantly worse, with a 29% greater risk of dying from any cause (HR, 1.29).

When looking at clinical trial data, Black patients were more likely than White patients to have worse performance status and a higher grade or recurrent disease, Dr. Kopelman noted.

Black patients in the clinical trials also had significantly worse progression-free survival in both the original cohort (HR, 2.05) and the matched cohort (adjusted HR [aHR], 1.22), which matched patients for grade, stage, and treatment arm within each trial and balanced age and performance status. Black patients also had worse overall survival in the original cohort (HR, 2.19) and matched cohort (aHR, 1.32).

Looking at molecular features, Black patients had significantly fewer mutations in a handful of cancer-related gene pathways, including PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K pathways.

One caveat, said Dr. Kopelman, is that mutations in PTEN are still present in a high percentage of both Black (62%) and White (72%), which «offers a potential attractive therapeutic opportunity.»

The analysis also revealed a major gap in the number of Black vs White patients enrolled in randomized clinical trials, which is a major “problem,” said Dr. Kopelman.

The study confirms “ongoing disparities in enrollment and underrepresentation of minorities in gynecologic cancer clinical trials, as well as poor outcomes, and should really promote us to enhance research in these areas,” said study discussant Mariam AlHilli, MD, with Cleveland Clinic Lerner College of Medicine and Case Western Reserve University, Cleveland, Ohio.

David M. O’Malley, MD, who gave a separate talk during the same session on practical considerations for implication of clinical trials, encouraged clinicians to “just ask.”

“Just ask the patient in front of you — no matter what their ethnicity, their race, or where they’re coming from — are they interested in participating in a clinical trial?” Or better yet, “I have a clinical trial now which I’m excited about for you,” said Dr. O’Malley, with The Ohio State University, James Comprehensive Cancer Center, Columbus, Ohio.The study had no commercial funding. Dr. Kopelman, Dr. O’Malley, and Dr. AlHilli had no relevant disclosures.

A version of this article appeared on Medscape.com .

A recent analysis identified significant disparities in survival outcomes as well as clinical and genetic features between Black and White women with a common subtype of endometrial cancer.

In addition to observing differences in clinical and molecular characteristics, the analysis of real-world registries and clinical trials revealed that Black patients with endometrioid endometrial carcinoma had about a twofold higher risk for cancer-related deaths than White patients.

“Even with propensity-score matching, Black patients had a significantly increased risk of death,” Zachary Kopelman, DO, with Walter Reed National Military Medical Center, Bethesda, Maryland, noted in a presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Importantly, Dr. Kopelman added, the analysis also confirmed “dramatic” underrepresentation of Black patients with endometrioid endometrial carcinoma in clinical trials.

Endometrial cancer is one of the most common cancers among women in the United States, with data showing rising incidence and mortality rates. “Worryingly, endometrial cancer is estimated to overtake ovarian cancer as the deadliest gynecologic malignancy this year,” Dr. Kopelman told attendees.

Previous studies have shown that Black patients with endometrial cancer consistently are more likely to have aggressive histologic subtypes, high-grade tumors, and advanced-stage disease and are twice as likely to die from the disease as White patients, he noted.

Within endometrial cancer, the most common histologic subtype is endometrioid, comprising 65%-75% of cases. In other studies examining racial disparities, the endometrioid histology is often combined with other subtypes, such as aggressive uterine serous carcinoma, which may influence study outcomes, Dr. Kopelman explained.

Dr. Kopelman and colleagues focused their analyses on Black and White women with endometrioid endometrial carcinoma, with the goal of identifying disparities in cancer-related and non-cancer deaths, as well as clinical and molecular features in this patient population.

All women included in the analysis had undergone hysterectomy with or without adjuvant treatment. The researchers used a four-pronged approach incorporating data from the SEER program (2004-2016), the National Cancer Database (2004-2017), eight National Cancer Institute-sponsored randomized phase 3 clinical trials, and the Genomics Evidence Neoplasia Information Exchange project.

Dr. Kopelman and colleagues then performed propensity score matching in the National Cancer Database and exact matching in the randomized controlled trials.

When comparing 47,959 White patients with 4397 Black patients in the SEER dataset, Dr. Kopelman and colleagues found that Black patients had more than two times the risk of dying from their cancer (hazard ratio [HR], 2.04) and a 22% greater risk for a non-cancer death compared with White patients (HR, 1.22).

In the overall National Cancer Database cohort comparing 155,706 White and 13,468 Black patients, Black patients had a 52% greater risk of dying from any cause (HR, 1.52). In the propensity score-matched cohort of 13,468 White and 13,468 Black patients, survival among Black patients remained significantly worse, with a 29% greater risk of dying from any cause (HR, 1.29).

When looking at clinical trial data, Black patients were more likely than White patients to have worse performance status and a higher grade or recurrent disease, Dr. Kopelman noted.

Black patients in the clinical trials also had significantly worse progression-free survival in both the original cohort (HR, 2.05) and the matched cohort (adjusted HR [aHR], 1.22), which matched patients for grade, stage, and treatment arm within each trial and balanced age and performance status. Black patients also had worse overall survival in the original cohort (HR, 2.19) and matched cohort (aHR, 1.32).

Looking at molecular features, Black patients had significantly fewer mutations in a handful of cancer-related gene pathways, including PTEN, PIK3R1, FBXW7, NF1, mTOR, CCND1, and PI3K pathways.

One caveat, said Dr. Kopelman, is that mutations in PTEN are still present in a high percentage of both Black (62%) and White (72%), which «offers a potential attractive therapeutic opportunity.»

The analysis also revealed a major gap in the number of Black vs White patients enrolled in randomized clinical trials, which is a major “problem,” said Dr. Kopelman.

The study confirms “ongoing disparities in enrollment and underrepresentation of minorities in gynecologic cancer clinical trials, as well as poor outcomes, and should really promote us to enhance research in these areas,” said study discussant Mariam AlHilli, MD, with Cleveland Clinic Lerner College of Medicine and Case Western Reserve University, Cleveland, Ohio.

David M. O’Malley, MD, who gave a separate talk during the same session on practical considerations for implication of clinical trials, encouraged clinicians to “just ask.”

“Just ask the patient in front of you — no matter what their ethnicity, their race, or where they’re coming from — are they interested in participating in a clinical trial?” Or better yet, “I have a clinical trial now which I’m excited about for you,” said Dr. O’Malley, with The Ohio State University, James Comprehensive Cancer Center, Columbus, Ohio.The study had no commercial funding. Dr. Kopelman, Dr. O’Malley, and Dr. AlHilli had no relevant disclosures.

A version of this article appeared on Medscape.com .

Regeneron Pharmaceuticals said in an interview that it may be the first company to have an accelerated approval application for its cancer drug rebuffed by the US Food and Drug Administration (FDA) due to concerns about the timing of completion of confirmatory research.

The company once had hoped to win this US clearance for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBCL) by March 31. Last year when Regeneron announced the FDA’s decision to grant priority review for odronextamab, the firm said that the end of this month was the US regulators’ target decision date.

But on March 25, Regeneron said the FDA issued two complete response letters (CRLs) in connection with odronextamab application. It will not approve the experimental medicine at this time.

In the release, Regeneron said the only approvability issue is related to the enrollment status of the confirmatory trials. The letters did not identify issues with the odronextamab clinical efficacy or safety, trial design, labeling, or manufacturing.

“While we acknowledge the general concerns that FDA has about sponsors failing to complete their postmarketing confirmatory trials, the relevant laws and regulatory guidances do not lay out rigid criteria for assessing whether the progress on a confirmatory trial is adequate to allow for an accelerated approval,” Tammy Allen, Regeneron’s director for product and pipeline communications, said in an email. “ And to our knowledge, this is the first time the FDA has issued a CRL for this reason.”

There has been rising concern in recent years about the gap between initial accelerated approvals for medicines and the completion of studies that show whether these promising therapies actually help patients live longer or better. Thus, a serious knowledge gap arises, often for many years, while patients and physicians use drugs with as yet unproven benefit. Recent studies highlighting this knowledge gap include work from Harvard’s Program on Regulation, Therapeutics, and Law (PORTAL) group and researchers at the University of Pennsylvania.

While Congress has long sought to speed approvals of new drugs, in 2022 lawmakers gave the FDA more clout for efforts to shorten the period of uncertainty between accelerated and traditional approval. Congress added a provision to a large spending package that said the federal government could require a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.

“As this is new territory for us and for industry, we’re committed to working closely with them to address and plan on sharing updates on enrollment and regulatory timelines later this year,” Ms. Allen said.

The FDA generally does not comment on applications under review. In response to a question about Regeneron’s statements, an FDA spokeswoman pointed out by email that the 2022 law had made clear how the agency can decline approval if confirmatory clinical trials are not considered underway prior to approval.

Odronextamab is potentially part of a rapidly advancing field of lymphoma treatments, which include autologous chimeric antigen receptor (CAR T-cell) therapy in certain settings. There are severe constraints, though, on CAR-T therapy, including manufacturing delays and treatment-related toxicities. Odronextamab is part of what are called “off-the-shelf” drugs with the same aim as CAR-T. The bispecific antibodies (BsAb) are meant to teach the immune system to fight cancer.

Regeneron said it has been actively enrolling patients in multiple phase 3 trials for odronextamab as part of its OLYMPIA program. The company said this is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes, including in earlier lines of therapy.

Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion should be agreed on prior to resubmission, Regeneron said. The company added that it is working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. The company plans to share updates on enrollment and regulatory timelines later this year.

Regeneron Pharmaceuticals said in an interview that it may be the first company to have an accelerated approval application for its cancer drug rebuffed by the US Food and Drug Administration (FDA) due to concerns about the timing of completion of confirmatory research.

The company once had hoped to win this US clearance for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBCL) by March 31. Last year when Regeneron announced the FDA’s decision to grant priority review for odronextamab, the firm said that the end of this month was the US regulators’ target decision date.

But on March 25, Regeneron said the FDA issued two complete response letters (CRLs) in connection with odronextamab application. It will not approve the experimental medicine at this time.

In the release, Regeneron said the only approvability issue is related to the enrollment status of the confirmatory trials. The letters did not identify issues with the odronextamab clinical efficacy or safety, trial design, labeling, or manufacturing.

“While we acknowledge the general concerns that FDA has about sponsors failing to complete their postmarketing confirmatory trials, the relevant laws and regulatory guidances do not lay out rigid criteria for assessing whether the progress on a confirmatory trial is adequate to allow for an accelerated approval,” Tammy Allen, Regeneron’s director for product and pipeline communications, said in an email. “ And to our knowledge, this is the first time the FDA has issued a CRL for this reason.”

There has been rising concern in recent years about the gap between initial accelerated approvals for medicines and the completion of studies that show whether these promising therapies actually help patients live longer or better. Thus, a serious knowledge gap arises, often for many years, while patients and physicians use drugs with as yet unproven benefit. Recent studies highlighting this knowledge gap include work from Harvard’s Program on Regulation, Therapeutics, and Law (PORTAL) group and researchers at the University of Pennsylvania.

While Congress has long sought to speed approvals of new drugs, in 2022 lawmakers gave the FDA more clout for efforts to shorten the period of uncertainty between accelerated and traditional approval. Congress added a provision to a large spending package that said the federal government could require a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.

“As this is new territory for us and for industry, we’re committed to working closely with them to address and plan on sharing updates on enrollment and regulatory timelines later this year,” Ms. Allen said.

The FDA generally does not comment on applications under review. In response to a question about Regeneron’s statements, an FDA spokeswoman pointed out by email that the 2022 law had made clear how the agency can decline approval if confirmatory clinical trials are not considered underway prior to approval.

Odronextamab is potentially part of a rapidly advancing field of lymphoma treatments, which include autologous chimeric antigen receptor (CAR T-cell) therapy in certain settings. There are severe constraints, though, on CAR-T therapy, including manufacturing delays and treatment-related toxicities. Odronextamab is part of what are called “off-the-shelf” drugs with the same aim as CAR-T. The bispecific antibodies (BsAb) are meant to teach the immune system to fight cancer.

Regeneron said it has been actively enrolling patients in multiple phase 3 trials for odronextamab as part of its OLYMPIA program. The company said this is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes, including in earlier lines of therapy.

Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion should be agreed on prior to resubmission, Regeneron said. The company added that it is working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. The company plans to share updates on enrollment and regulatory timelines later this year.

Regeneron Pharmaceuticals said in an interview that it may be the first company to have an accelerated approval application for its cancer drug rebuffed by the US Food and Drug Administration (FDA) due to concerns about the timing of completion of confirmatory research.

The company once had hoped to win this US clearance for odronextamab in relapsed/refractory (R/R) follicular lymphoma (FL) and in R/R diffuse large B-cell lymphoma (DLBCL) by March 31. Last year when Regeneron announced the FDA’s decision to grant priority review for odronextamab, the firm said that the end of this month was the US regulators’ target decision date.

But on March 25, Regeneron said the FDA issued two complete response letters (CRLs) in connection with odronextamab application. It will not approve the experimental medicine at this time.

In the release, Regeneron said the only approvability issue is related to the enrollment status of the confirmatory trials. The letters did not identify issues with the odronextamab clinical efficacy or safety, trial design, labeling, or manufacturing.

“While we acknowledge the general concerns that FDA has about sponsors failing to complete their postmarketing confirmatory trials, the relevant laws and regulatory guidances do not lay out rigid criteria for assessing whether the progress on a confirmatory trial is adequate to allow for an accelerated approval,” Tammy Allen, Regeneron’s director for product and pipeline communications, said in an email. “ And to our knowledge, this is the first time the FDA has issued a CRL for this reason.”

There has been rising concern in recent years about the gap between initial accelerated approvals for medicines and the completion of studies that show whether these promising therapies actually help patients live longer or better. Thus, a serious knowledge gap arises, often for many years, while patients and physicians use drugs with as yet unproven benefit. Recent studies highlighting this knowledge gap include work from Harvard’s Program on Regulation, Therapeutics, and Law (PORTAL) group and researchers at the University of Pennsylvania.

While Congress has long sought to speed approvals of new drugs, in 2022 lawmakers gave the FDA more clout for efforts to shorten the period of uncertainty between accelerated and traditional approval. Congress added a provision to a large spending package that said the federal government could require a study or studies to be underway prior to approval, or within a specified time period after the date of approval, of the applicable product.

“As this is new territory for us and for industry, we’re committed to working closely with them to address and plan on sharing updates on enrollment and regulatory timelines later this year,” Ms. Allen said.

The FDA generally does not comment on applications under review. In response to a question about Regeneron’s statements, an FDA spokeswoman pointed out by email that the 2022 law had made clear how the agency can decline approval if confirmatory clinical trials are not considered underway prior to approval.

Odronextamab is potentially part of a rapidly advancing field of lymphoma treatments, which include autologous chimeric antigen receptor (CAR T-cell) therapy in certain settings. There are severe constraints, though, on CAR-T therapy, including manufacturing delays and treatment-related toxicities. Odronextamab is part of what are called “off-the-shelf” drugs with the same aim as CAR-T. The bispecific antibodies (BsAb) are meant to teach the immune system to fight cancer.

Regeneron said it has been actively enrolling patients in multiple phase 3 trials for odronextamab as part of its OLYMPIA program. The company said this is intended to change the treatment paradigm of several B-cell non-Hodgkin lymphoma subtypes, including in earlier lines of therapy.

Enrollment in the dose-finding portion has begun, but the CRLs indicate that the confirmatory portions of these trials should be underway and that the timelines to completion should be agreed on prior to resubmission, Regeneron said. The company added that it is working closely with the FDA and investigators to bring odronextamab to patients with R/R FL and R/R DLBCL as quickly as possible. The company plans to share updates on enrollment and regulatory timelines later this year.

TOPLINE:

Age-standardized stroke rates decreased in the United States between 1990 and 2019, while absolute stroke incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates increased, a new study showed. Investigators noted the findings, which also show a significant increase in hemorrhagic stroke and an uptick in stroke among adults under 50 years in the South and Midwest, suggesting a significant shift in the US stroke burden.

METHODOLOGY:

• This in-depth, cross-sectional analysis of the 2019 Global Burden of Disease study included data on all-cause and ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs) between 1990 and 2019 in the United States.
• Researchers focused on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100,000 people.

TAKEAWAY:

• In 2019, the United States recorded 7.09 million prevalent strokes, 83% of which were ischemic and 57% of which occurred in women.
• The absolute numbers of stroke cases, mortality, and DALYs increased from 1990 to 2019, but the age-standardized rates either declined or remained steady.
• Overall incidence increased by 40% for ICH, 51% for SAH, and 13% for , and stroke mortality increased by 56% for ICH, 72% for SAH, and 5.4% for ischemic stroke.
• Age-adjusted analyses showed the results were not uniform across all geographical areas, with older adults (ages, 50-74 years) experiencing decreased incidence in coastal areas and younger individuals (ages, 15-49 years) experiencing an uptick in the South and Midwest United States.

IN PRACTICE:

“As the country prepares for an imminent swell in the aging population, coupled with a noticeable plateau in advancements against stroke mortality, it becomes evident that future directions must focus on a multipronged strategy,” the authors wrote. “This involves both embracing precision medicine’s potential and fortifying widespread public health campaigns.”

SOURCE:

Kevin N. Sheth, MD, of the Yale Center for Brain and Mind Health, Yale School of Medicine, New Haven, Connecticut, was the senior and corresponding author of the study. It was published online in JAMA Neurology.

LIMITATIONS:

The accuracy of stroke ascertainment was limited by the data source, which may be prone to misclassification. The data lacked detailed information on race, ethnicity, and stroke characteristics other than stroke type.

DISCLOSURES:

This work was funded by the Bill and Melinda Gates Foundation, the American Heart Association Medical Student Research Fellowship, grants from the National Institutes of Health, the American Heart Association, the Yale Pepper Scholar Award, and the Neurocritical Care Society Research fellowship. Sheth reported receiving grants from the National Institutes of Health, American Heart Association, and Hyperfine; personal fees/monitoring board fees/equity from Astrocyte, CSL Behring, Zoll, Sense, Bexorg, Rhaeos, and Alva and having a patent for Alva licensed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Age-standardized stroke rates decreased in the United States between 1990 and 2019, while absolute stroke incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates increased, a new study showed. Investigators noted the findings, which also show a significant increase in hemorrhagic stroke and an uptick in stroke among adults under 50 years in the South and Midwest, suggesting a significant shift in the US stroke burden.

METHODOLOGY:

• This in-depth, cross-sectional analysis of the 2019 Global Burden of Disease study included data on all-cause and ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs) between 1990 and 2019 in the United States.
• Researchers focused on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100,000 people.

TAKEAWAY:

• In 2019, the United States recorded 7.09 million prevalent strokes, 83% of which were ischemic and 57% of which occurred in women.
• The absolute numbers of stroke cases, mortality, and DALYs increased from 1990 to 2019, but the age-standardized rates either declined or remained steady.
• Overall incidence increased by 40% for ICH, 51% for SAH, and 13% for , and stroke mortality increased by 56% for ICH, 72% for SAH, and 5.4% for ischemic stroke.
• Age-adjusted analyses showed the results were not uniform across all geographical areas, with older adults (ages, 50-74 years) experiencing decreased incidence in coastal areas and younger individuals (ages, 15-49 years) experiencing an uptick in the South and Midwest United States.

IN PRACTICE:

“As the country prepares for an imminent swell in the aging population, coupled with a noticeable plateau in advancements against stroke mortality, it becomes evident that future directions must focus on a multipronged strategy,” the authors wrote. “This involves both embracing precision medicine’s potential and fortifying widespread public health campaigns.”

SOURCE:

Kevin N. Sheth, MD, of the Yale Center for Brain and Mind Health, Yale School of Medicine, New Haven, Connecticut, was the senior and corresponding author of the study. It was published online in JAMA Neurology.

LIMITATIONS:

The accuracy of stroke ascertainment was limited by the data source, which may be prone to misclassification. The data lacked detailed information on race, ethnicity, and stroke characteristics other than stroke type.

DISCLOSURES:

This work was funded by the Bill and Melinda Gates Foundation, the American Heart Association Medical Student Research Fellowship, grants from the National Institutes of Health, the American Heart Association, the Yale Pepper Scholar Award, and the Neurocritical Care Society Research fellowship. Sheth reported receiving grants from the National Institutes of Health, American Heart Association, and Hyperfine; personal fees/monitoring board fees/equity from Astrocyte, CSL Behring, Zoll, Sense, Bexorg, Rhaeos, and Alva and having a patent for Alva licensed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Age-standardized stroke rates decreased in the United States between 1990 and 2019, while absolute stroke incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates increased, a new study showed. Investigators noted the findings, which also show a significant increase in hemorrhagic stroke and an uptick in stroke among adults under 50 years in the South and Midwest, suggesting a significant shift in the US stroke burden.

METHODOLOGY:

• This in-depth, cross-sectional analysis of the 2019 Global Burden of Disease study included data on all-cause and ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs) between 1990 and 2019 in the United States.
• Researchers focused on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100,000 people.

TAKEAWAY:

• In 2019, the United States recorded 7.09 million prevalent strokes, 83% of which were ischemic and 57% of which occurred in women.
• The absolute numbers of stroke cases, mortality, and DALYs increased from 1990 to 2019, but the age-standardized rates either declined or remained steady.
• Overall incidence increased by 40% for ICH, 51% for SAH, and 13% for , and stroke mortality increased by 56% for ICH, 72% for SAH, and 5.4% for ischemic stroke.
• Age-adjusted analyses showed the results were not uniform across all geographical areas, with older adults (ages, 50-74 years) experiencing decreased incidence in coastal areas and younger individuals (ages, 15-49 years) experiencing an uptick in the South and Midwest United States.

IN PRACTICE:

“As the country prepares for an imminent swell in the aging population, coupled with a noticeable plateau in advancements against stroke mortality, it becomes evident that future directions must focus on a multipronged strategy,” the authors wrote. “This involves both embracing precision medicine’s potential and fortifying widespread public health campaigns.”

SOURCE:

Kevin N. Sheth, MD, of the Yale Center for Brain and Mind Health, Yale School of Medicine, New Haven, Connecticut, was the senior and corresponding author of the study. It was published online in JAMA Neurology.

LIMITATIONS:

The accuracy of stroke ascertainment was limited by the data source, which may be prone to misclassification. The data lacked detailed information on race, ethnicity, and stroke characteristics other than stroke type.

DISCLOSURES:

This work was funded by the Bill and Melinda Gates Foundation, the American Heart Association Medical Student Research Fellowship, grants from the National Institutes of Health, the American Heart Association, the Yale Pepper Scholar Award, and the Neurocritical Care Society Research fellowship. Sheth reported receiving grants from the National Institutes of Health, American Heart Association, and Hyperfine; personal fees/monitoring board fees/equity from Astrocyte, CSL Behring, Zoll, Sense, Bexorg, Rhaeos, and Alva and having a patent for Alva licensed. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

In most Western countries, professional standards dictate that physicians should practice medicine with compassion. Patients also expect compassionate care from physicians because it represents a model capable of providing greater patient satisfaction, fostering better doctor-patient relationships, and enabling better psychological states among patients.

The etymology of the term “compassion” derives from the Latin roots “com,” meaning “together with,” and “pati,” meaning “to endure or suffer.” When discussing compassion, it is necessary to distinguish it from empathy, a term generally used to refer to cognitive or emotional processes in which the perspective of the other (in this case, the patient) is taken. Compassion implies or requires empathy and includes the desire to help or alleviate the suffering of others. Compassion in the medical context is likely a specific instance of a more complex adaptive system that has evolved, not only among humans, to motivate recognition and assistance when others suffer.
 

Compassion Fatigue

Physicians’ compassion is expected by patients and the profession. It is fundamental for effective clinical practice. Although compassion is central to medical practice, most research related to the topic has focused on “compassion fatigue,” which is understood as a specific type of professional burnout, as if physicians had a limited reserve of compassion that dwindles or becomes exhausted with use or overuse. This is one aspect of a much more complex problem, in which compassion represents the endpoint of a dynamic process that encompasses the influences of the physician, the patient, the clinic, and the institution.

Compassion Capacity: Conditioning Factors

Chronic exposure of physicians to conflicting work demands may be associated with the depletion of their psychological resources and, consequently, emotional and cognitive fatigue that can contribute to poorer work outcomes, including the ability to express compassion.

Rates of professional burnout in medicine are increasing. The driving factors of this phenomenon are largely rooted in organizations and healthcare systems and include excessive workloads, inefficient work processes, administrative burdens, and lack of input or control by physicians regarding issues concerning their work life. The outcome often is early retirement of physicians, a current, increasingly widespread phenomenon and a critical issue not only for the Italian National Health Service but also for other healthcare systems worldwide.
 

Organizational and Personal Values

There is no clear empirical evidence supporting the hypothesis that working in healthcare environments experienced as discrepant with one’s own values has negative effects on key professional outcomes. However, a study published in the Journal of Internal Medicine highlighted the overall negative effect of misalignment between system values and physicians’ personal values, including impaired ability to provide compassionate care, as well as reduced job satisfaction, burnout, absenteeism, and considering the possibility of early retirement. Results from 1000 surveyed professionals indicate that physicians’ subjective competence in providing compassionate care may remain high, but their ability to express it is compromised. From data analysis, the authors hypothesize that when working in environments with discrepant values, occupational contingencies may repeatedly require physicians to set aside their personal values, which can lead them to refrain from using available skills to keep their performance in line with organizational requirements.

These results and hypotheses are not consistent with the notion of compassion fatigue as a reflection of the cost of care resulting from exposure to repeated suffering. Previous evidence shows that expressing compassion in healthcare facilitates greater understanding, suggesting that providing compassion does not impoverish physicians but rather supports them in the effectiveness of interventions and in their satisfaction.

In summary, this study suggests that what prevents compassion is the inability to provide it when hindered by factors related to the situation in which the physician operates. Improving compassion does not simply depend on motivating individual professionals to be more compassionate or on promoting fundamental skills, but probably on the creation of organizational and clinical conditions in which physician compassion can thrive.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

In most Western countries, professional standards dictate that physicians should practice medicine with compassion. Patients also expect compassionate care from physicians because it represents a model capable of providing greater patient satisfaction, fostering better doctor-patient relationships, and enabling better psychological states among patients.

The etymology of the term “compassion” derives from the Latin roots “com,” meaning “together with,” and “pati,” meaning “to endure or suffer.” When discussing compassion, it is necessary to distinguish it from empathy, a term generally used to refer to cognitive or emotional processes in which the perspective of the other (in this case, the patient) is taken. Compassion implies or requires empathy and includes the desire to help or alleviate the suffering of others. Compassion in the medical context is likely a specific instance of a more complex adaptive system that has evolved, not only among humans, to motivate recognition and assistance when others suffer.
 

Compassion Fatigue

Physicians’ compassion is expected by patients and the profession. It is fundamental for effective clinical practice. Although compassion is central to medical practice, most research related to the topic has focused on “compassion fatigue,” which is understood as a specific type of professional burnout, as if physicians had a limited reserve of compassion that dwindles or becomes exhausted with use or overuse. This is one aspect of a much more complex problem, in which compassion represents the endpoint of a dynamic process that encompasses the influences of the physician, the patient, the clinic, and the institution.

Compassion Capacity: Conditioning Factors

Chronic exposure of physicians to conflicting work demands may be associated with the depletion of their psychological resources and, consequently, emotional and cognitive fatigue that can contribute to poorer work outcomes, including the ability to express compassion.

Rates of professional burnout in medicine are increasing. The driving factors of this phenomenon are largely rooted in organizations and healthcare systems and include excessive workloads, inefficient work processes, administrative burdens, and lack of input or control by physicians regarding issues concerning their work life. The outcome often is early retirement of physicians, a current, increasingly widespread phenomenon and a critical issue not only for the Italian National Health Service but also for other healthcare systems worldwide.
 

Organizational and Personal Values

There is no clear empirical evidence supporting the hypothesis that working in healthcare environments experienced as discrepant with one’s own values has negative effects on key professional outcomes. However, a study published in the Journal of Internal Medicine highlighted the overall negative effect of misalignment between system values and physicians’ personal values, including impaired ability to provide compassionate care, as well as reduced job satisfaction, burnout, absenteeism, and considering the possibility of early retirement. Results from 1000 surveyed professionals indicate that physicians’ subjective competence in providing compassionate care may remain high, but their ability to express it is compromised. From data analysis, the authors hypothesize that when working in environments with discrepant values, occupational contingencies may repeatedly require physicians to set aside their personal values, which can lead them to refrain from using available skills to keep their performance in line with organizational requirements.

These results and hypotheses are not consistent with the notion of compassion fatigue as a reflection of the cost of care resulting from exposure to repeated suffering. Previous evidence shows that expressing compassion in healthcare facilitates greater understanding, suggesting that providing compassion does not impoverish physicians but rather supports them in the effectiveness of interventions and in their satisfaction.

In summary, this study suggests that what prevents compassion is the inability to provide it when hindered by factors related to the situation in which the physician operates. Improving compassion does not simply depend on motivating individual professionals to be more compassionate or on promoting fundamental skills, but probably on the creation of organizational and clinical conditions in which physician compassion can thrive.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

In most Western countries, professional standards dictate that physicians should practice medicine with compassion. Patients also expect compassionate care from physicians because it represents a model capable of providing greater patient satisfaction, fostering better doctor-patient relationships, and enabling better psychological states among patients.

The etymology of the term “compassion” derives from the Latin roots “com,” meaning “together with,” and “pati,” meaning “to endure or suffer.” When discussing compassion, it is necessary to distinguish it from empathy, a term generally used to refer to cognitive or emotional processes in which the perspective of the other (in this case, the patient) is taken. Compassion implies or requires empathy and includes the desire to help or alleviate the suffering of others. Compassion in the medical context is likely a specific instance of a more complex adaptive system that has evolved, not only among humans, to motivate recognition and assistance when others suffer.
 

Compassion Fatigue

Physicians’ compassion is expected by patients and the profession. It is fundamental for effective clinical practice. Although compassion is central to medical practice, most research related to the topic has focused on “compassion fatigue,” which is understood as a specific type of professional burnout, as if physicians had a limited reserve of compassion that dwindles or becomes exhausted with use or overuse. This is one aspect of a much more complex problem, in which compassion represents the endpoint of a dynamic process that encompasses the influences of the physician, the patient, the clinic, and the institution.

Compassion Capacity: Conditioning Factors

Chronic exposure of physicians to conflicting work demands may be associated with the depletion of their psychological resources and, consequently, emotional and cognitive fatigue that can contribute to poorer work outcomes, including the ability to express compassion.

Rates of professional burnout in medicine are increasing. The driving factors of this phenomenon are largely rooted in organizations and healthcare systems and include excessive workloads, inefficient work processes, administrative burdens, and lack of input or control by physicians regarding issues concerning their work life. The outcome often is early retirement of physicians, a current, increasingly widespread phenomenon and a critical issue not only for the Italian National Health Service but also for other healthcare systems worldwide.
 

Organizational and Personal Values

There is no clear empirical evidence supporting the hypothesis that working in healthcare environments experienced as discrepant with one’s own values has negative effects on key professional outcomes. However, a study published in the Journal of Internal Medicine highlighted the overall negative effect of misalignment between system values and physicians’ personal values, including impaired ability to provide compassionate care, as well as reduced job satisfaction, burnout, absenteeism, and considering the possibility of early retirement. Results from 1000 surveyed professionals indicate that physicians’ subjective competence in providing compassionate care may remain high, but their ability to express it is compromised. From data analysis, the authors hypothesize that when working in environments with discrepant values, occupational contingencies may repeatedly require physicians to set aside their personal values, which can lead them to refrain from using available skills to keep their performance in line with organizational requirements.

These results and hypotheses are not consistent with the notion of compassion fatigue as a reflection of the cost of care resulting from exposure to repeated suffering. Previous evidence shows that expressing compassion in healthcare facilitates greater understanding, suggesting that providing compassion does not impoverish physicians but rather supports them in the effectiveness of interventions and in their satisfaction.

In summary, this study suggests that what prevents compassion is the inability to provide it when hindered by factors related to the situation in which the physician operates. Improving compassion does not simply depend on motivating individual professionals to be more compassionate or on promoting fundamental skills, but probably on the creation of organizational and clinical conditions in which physician compassion can thrive.

This story was translated from Univadis Italy, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Whether you have totally bought into the “obesity is a disease” paradigm or are still in denial, you must admit that the development of a suite of effective weight loss medications has created a tsunami of interest and economic activity in this country on a scale not seen since the Beanie Baby craze of the mid-1990s. But, obesity management is serious business. While most of those soft cuddly toys are gathering dust in shoeboxes across this country, weight loss medications are likely to be the vanguard of rapidly evolving revolution in healthcare management that will be with us for the foreseeable future.

Most thoughtful folks who purchased Beanie Babies in 1994 had no illusions and knew that in a few short years this bubble of soft cuddly toys was going to burst. However, do those of us on the front line of medical care know what the future holds for the patients who are being prescribed or are scavenging those too-good-to-be-true medications?

My guess is that in the long run we will need a combination of some serious tinkering by the pharmaceutical industry and a trek up some steep learning curves before we eventually arrive at a safe and effective chemical management for obese patients. I recently read an article by an obesity management specialist at Harvard Medical School who voiced her concerns that we are missing an opportunity to make this explosion of popularity in GLP-1 drugs into an important learning experience.

In an opinion piece in JAMA Internal Medicine, Dr. Fatima Cody Stanford and her coauthors argue that we, actually the US Food and Drug Administration (FDA), is over-focused on weight loss in determining the efficacy of anti-obesity medications. Dr. Stanford and colleagues point out that when a patient loses weight it isn’t just fat — it is complex process that may include muscle and bone mineralization as well. She has consulted for at least one obesity-drug manufacturer and says that these companies have the resources to produce data on body composition that could help clinicians create management plans that would address the patients’ overall health. However, the FDA has not demanded this broader and deeper assessment of general health when reviewing the drug trials.

I don’t think we can blame the patients for not asking whether they will healthier while taking these medications. They have already spent a lifetime, even if it is just a decade, of suffering as the “fat one.” A new outfit and a look in the mirror can’t help but make them feel better ... in the short term anyway. We as physicians must shoulder some of the blame for focusing on weight. Our spoken or unspoken message has been “Lose weight and you will be healthier.” We may make our message sound more professional by tossing around terms like “BMI,” but as Dr. Stanford points out, “we have known BMI is a flawed metric for a long time.”

There is the notion that obese people have had to build more muscle to help them carry around the extra weight, so that we should expect them to lose that extra muscle along with the fat. However, in older adults there is an entity called sarcopenic obesity, in which the patient doesn’t have that extra muscle to lose.

In a brief Internet research venture, I could find little on the subject of muscle loss and GLP-1s, other than “it can happen.” And, nothing on the effect in adolescents. And that is one of Dr. Stanford’s points. We just don’t know. She said that looking at body composition can be costly and not something that the clinician can do. However, as far as muscle mass is concerned, we need to be alert to the potential for loss. Simple assessments of strength can help us tailor our management to the specific patient’s need.

The bottom line is this ... now that we have effective medications for “weight loss,” we need to redefine the relationship between weight and health. “We” means us as clinicians. It means the folks at FDA. And, if we can improve our messaging, it will osmose to the rest of the population. Just because you’ve dropped two dress sizes doesn’t mean you’re healthy.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Whether you have totally bought into the “obesity is a disease” paradigm or are still in denial, you must admit that the development of a suite of effective weight loss medications has created a tsunami of interest and economic activity in this country on a scale not seen since the Beanie Baby craze of the mid-1990s. But, obesity management is serious business. While most of those soft cuddly toys are gathering dust in shoeboxes across this country, weight loss medications are likely to be the vanguard of rapidly evolving revolution in healthcare management that will be with us for the foreseeable future.

Most thoughtful folks who purchased Beanie Babies in 1994 had no illusions and knew that in a few short years this bubble of soft cuddly toys was going to burst. However, do those of us on the front line of medical care know what the future holds for the patients who are being prescribed or are scavenging those too-good-to-be-true medications?

My guess is that in the long run we will need a combination of some serious tinkering by the pharmaceutical industry and a trek up some steep learning curves before we eventually arrive at a safe and effective chemical management for obese patients. I recently read an article by an obesity management specialist at Harvard Medical School who voiced her concerns that we are missing an opportunity to make this explosion of popularity in GLP-1 drugs into an important learning experience.

In an opinion piece in JAMA Internal Medicine, Dr. Fatima Cody Stanford and her coauthors argue that we, actually the US Food and Drug Administration (FDA), is over-focused on weight loss in determining the efficacy of anti-obesity medications. Dr. Stanford and colleagues point out that when a patient loses weight it isn’t just fat — it is complex process that may include muscle and bone mineralization as well. She has consulted for at least one obesity-drug manufacturer and says that these companies have the resources to produce data on body composition that could help clinicians create management plans that would address the patients’ overall health. However, the FDA has not demanded this broader and deeper assessment of general health when reviewing the drug trials.

I don’t think we can blame the patients for not asking whether they will healthier while taking these medications. They have already spent a lifetime, even if it is just a decade, of suffering as the “fat one.” A new outfit and a look in the mirror can’t help but make them feel better ... in the short term anyway. We as physicians must shoulder some of the blame for focusing on weight. Our spoken or unspoken message has been “Lose weight and you will be healthier.” We may make our message sound more professional by tossing around terms like “BMI,” but as Dr. Stanford points out, “we have known BMI is a flawed metric for a long time.”

There is the notion that obese people have had to build more muscle to help them carry around the extra weight, so that we should expect them to lose that extra muscle along with the fat. However, in older adults there is an entity called sarcopenic obesity, in which the patient doesn’t have that extra muscle to lose.

In a brief Internet research venture, I could find little on the subject of muscle loss and GLP-1s, other than “it can happen.” And, nothing on the effect in adolescents. And that is one of Dr. Stanford’s points. We just don’t know. She said that looking at body composition can be costly and not something that the clinician can do. However, as far as muscle mass is concerned, we need to be alert to the potential for loss. Simple assessments of strength can help us tailor our management to the specific patient’s need.

The bottom line is this ... now that we have effective medications for “weight loss,” we need to redefine the relationship between weight and health. “We” means us as clinicians. It means the folks at FDA. And, if we can improve our messaging, it will osmose to the rest of the population. Just because you’ve dropped two dress sizes doesn’t mean you’re healthy.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Whether you have totally bought into the “obesity is a disease” paradigm or are still in denial, you must admit that the development of a suite of effective weight loss medications has created a tsunami of interest and economic activity in this country on a scale not seen since the Beanie Baby craze of the mid-1990s. But, obesity management is serious business. While most of those soft cuddly toys are gathering dust in shoeboxes across this country, weight loss medications are likely to be the vanguard of rapidly evolving revolution in healthcare management that will be with us for the foreseeable future.

Most thoughtful folks who purchased Beanie Babies in 1994 had no illusions and knew that in a few short years this bubble of soft cuddly toys was going to burst. However, do those of us on the front line of medical care know what the future holds for the patients who are being prescribed or are scavenging those too-good-to-be-true medications?

My guess is that in the long run we will need a combination of some serious tinkering by the pharmaceutical industry and a trek up some steep learning curves before we eventually arrive at a safe and effective chemical management for obese patients. I recently read an article by an obesity management specialist at Harvard Medical School who voiced her concerns that we are missing an opportunity to make this explosion of popularity in GLP-1 drugs into an important learning experience.

In an opinion piece in JAMA Internal Medicine, Dr. Fatima Cody Stanford and her coauthors argue that we, actually the US Food and Drug Administration (FDA), is over-focused on weight loss in determining the efficacy of anti-obesity medications. Dr. Stanford and colleagues point out that when a patient loses weight it isn’t just fat — it is complex process that may include muscle and bone mineralization as well. She has consulted for at least one obesity-drug manufacturer and says that these companies have the resources to produce data on body composition that could help clinicians create management plans that would address the patients’ overall health. However, the FDA has not demanded this broader and deeper assessment of general health when reviewing the drug trials.

I don’t think we can blame the patients for not asking whether they will healthier while taking these medications. They have already spent a lifetime, even if it is just a decade, of suffering as the “fat one.” A new outfit and a look in the mirror can’t help but make them feel better ... in the short term anyway. We as physicians must shoulder some of the blame for focusing on weight. Our spoken or unspoken message has been “Lose weight and you will be healthier.” We may make our message sound more professional by tossing around terms like “BMI,” but as Dr. Stanford points out, “we have known BMI is a flawed metric for a long time.”

There is the notion that obese people have had to build more muscle to help them carry around the extra weight, so that we should expect them to lose that extra muscle along with the fat. However, in older adults there is an entity called sarcopenic obesity, in which the patient doesn’t have that extra muscle to lose.

In a brief Internet research venture, I could find little on the subject of muscle loss and GLP-1s, other than “it can happen.” And, nothing on the effect in adolescents. And that is one of Dr. Stanford’s points. We just don’t know. She said that looking at body composition can be costly and not something that the clinician can do. However, as far as muscle mass is concerned, we need to be alert to the potential for loss. Simple assessments of strength can help us tailor our management to the specific patient’s need.

The bottom line is this ... now that we have effective medications for “weight loss,” we need to redefine the relationship between weight and health. “We” means us as clinicians. It means the folks at FDA. And, if we can improve our messaging, it will osmose to the rest of the population. Just because you’ve dropped two dress sizes doesn’t mean you’re healthy.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

The size of the human brain has increased over time, a new finding that may help explain a previously reported decline in incident dementia.

A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.

“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.

The study was published online in JAMA Neurology.
 

Dementia Protection?

An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.

“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.

The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.

Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm² vs 1933 cm²).

Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area. 

“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.

Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.

“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.

While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.

Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference. 
 

Exciting Work 

“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial. 

“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.

“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.

The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.

Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added. 

“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.

Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.

A version of this article appeared on Medscape.com.

The size of the human brain has increased over time, a new finding that may help explain a previously reported decline in incident dementia.

A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.

“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.

The study was published online in JAMA Neurology.
 

Dementia Protection?

An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.

“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.

The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.

Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm² vs 1933 cm²).

Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area. 

“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.

Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.

“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.

While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.

Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference. 
 

Exciting Work 

“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial. 

“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.

“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.

The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.

Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added. 

“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.

Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.

A version of this article appeared on Medscape.com.

The size of the human brain has increased over time, a new finding that may help explain a previously reported decline in incident dementia.

A secular trends analysis using brain imaging data from the long-running Framingham Heart Study revealed an increase in intracranial volume (ICV), cortical gray matter, white matter, and hippocampal volumes, as well as cortical surface area in people born in the 1970s versus those born in the 1930s.

“We hypothesize that the increased size of the brain will lead to increased ‘reserve’ against the diseases of aging, consequently reducing overall risk of dementia,” said Charles DeCarli, MD, director of the Alzheimer’s Disease Research Center and Imaging of Dementia and Aging Laboratory, Department of Neurology and Center for Neuroscience, University of California at Davis.

The study was published online in JAMA Neurology.
 

Dementia Protection?

An earlier report from the Framingham Heart Study suggested that dementia incidence is declining.

“This difference occurred among persons with at least a high school education and was not affected by differences in vascular risk. Our work was stimulated by this finding and the possibility that differences in brain size might be occurring over the three generations of the Framingham Heart Study which might explain an increased resilience to dementia,” said Dr. DeCarli.

The cross-sectional study used data from 3226 Framingham participants (53% women) born in the decades 1930–1970. None had dementia or a history of stroke. At a mean age of 57.7 years, they underwent brain MRI.

Compared with the 1930s birth decade, the 1970s birth decade had a 6.6% greater ICV (1321 mL vs 1234 mL), 7.7% greater white matter volume (476.3 mL vs 441.9 mL), 5.7% greater hippocampal volume (6.69 mL vs 6.51 mL), and 14.9% greater cortical surface area (2222 cm² vs 1933 cm²).

Cortical thickness was thinner by 21% over the same period, coinciding with larger intracranial volume, cerebral white matter volume, and cortical surface area. 

“We were surprised to find that the brain is getting larger, but the cortex is thinning very slightly. The apparent thinning of the cortex is related to the increased need for expansion of the cortical ribbon. This is based on hypotheses related to the effects of evolution and cortical development designed to make neuronal integration most efficient,” said Dr. DeCarli.

Repeat analysis applied to a subgroup of 1145 individuals of similar age range born in the 1940s (mean age, 60 years) and 1950s (mean age, 59 years) resulted in similar findings.

“These findings likely reflect both secular improvements in early life environmental influences through health, social-cultural, and educational factors, as well as secular improvements in modifiable dementia risk factors leading to better brain health and reserve,” the authors wrote.

While the effects observed are “likely to be small at the level of the individual, they are likely to be substantial at the population level, adding to growing literature that suggests optimized brain development and ideal health through modification of risk factors could substantially modify the effect of common neurodegenerative diseases such as stroke and Alzheiemer’s disease on dementia incidence,” they added.

Limitations included the predominately non-Hispanic White, healthy, and well-educated population that is the Framingham cohort, which is not representative of the broader US population. The cross-sectional nature of the study also limited causal inference. 
 

Exciting Work 

“If these results are confirmed by others and the observed differences by decade are as large as those reported, it has important implications for aging and dementia studies,” Prashanthi Lemuria, PhD, with Mayo Clinic, Rochester, Minnesota, wrote in an accompanying editorial. 

“First, studies that use brain charts for the human life span to understand the mechanisms of aging, by stitching together data from individuals across the decades, are significantly overestimating the degree of brain health decline using volumes across the life span because the baseline brain health in individuals who are in their older decades is likely lower to begin with,” Dr. Lemuria noted.

“Second, cortical thickness measurements, often used in dementia studies as a cross-sectional marker for neurodegeneration, showed greatest decline due to secular trends and are not scaled for ICV. Therefore, these should be traded in favor of gray matter volumes after consideration of ICV to estimate the true degree of neurodegeneration,” Dr. Vemuri added.

The data also suggest that longitudinal imaging study designs should be preferred when testing hypotheses on brain health, Dr. Vemuri wrote.

Although this work is “exciting and will bring attention to secular trends in brain health, much work is yet to be done to validate and replicate these findings and, more importantly, understand the mechanistic basis of these trends,” she added. 

“Do these secular trends in improvement of brain health underlie the decrease in dementia risk? The jury may be still out, but the authors are commended for investigating new avenues,” Dr. Vemuri concluded.

Support for this research was provided by the National Institute on Aging and the National Institute on Neurological Disorders and Stroke and the National Institutes of Health. Dr. DeCarli reported serving as a consultant to Novartis on a safety study of heart failure during the conduct of the study and receiving consultant fees from Eisai and Novo Nordisk outside the submitted work. Dr. Lemuria had no disclosures.

A version of this article appeared on Medscape.com.

Black people, men, older adults, and those living in rural communities are less likely to receive thrombolytic therapy after ischemic stroke, early research shows.

“The findings should serve as an eye-opener that social determinants of health seem to be playing a role in who receives thrombolytic therapy, said study investigator Chanaka Kahathuduwa, MD, PhD, resident physician, Department of Neurology, School of Medicine, Texas Tech University Health Sciences Center, Lubbock. 

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Contributor to Poor Outcomes

Social determinants of health are important contributors to poor stroke-related outcomes, the investigators noted. They pointed out that previous research has yielded conflicting results as to the cause.

Whereas some studies suggest poor social determinants of health drive increased stroke incidence, others raise the question of whether there are disparities in acute stroke care. 

To investigate, the researchers used a publicly available database and diagnostic and procedure codes to identify patients presenting at emergency departments in Texas from 2016 to 2019 with ischemic stroke who did and did not receive thrombolytic therapy.

“We focused on Texas, which has a very large area but few places where people have easy access to health care, which is a problem,” said study co-investigator Chathurika Dhanasekara, MD, PhD, research assistant professor in the Department of Surgery, School of Medicine, Texas Tech University Health Sciences Center.

The study included 63,983 stroke patients, of whom 51.6% were female, 66.6% were White, and 17.7% were Black. Of these, 7198 (11.2%) received thrombolytic therapy; such therapies include the tissue plasminogen activators (tPAs) alteplase and tenecteplace.

Researchers collected information on social determinants of health such as age, race, gender, insurance type, and residence based on zip codes. They computed risk ratios (RRs) of administering thrombolysis on the basis of these variables.

Results showed that Black patients were less likely than their White counterparts to receive thrombolysis (RR, 0.90; 95% CI, 0.85-0.96). In addition, patients older than 65 years were less likely those aged 18-45 years to receive thrombolysis (RR, 0.47; 95% CI, 0.44-0.51), and rural residents were less likely than urban dwellers to receive the intervention (RR, 0.60; 95% CI, 0.55-0.65).

It makes some sense, the researchers said, that rural stroke patients would be less likely to get thrombolysis because there’s a limited time window — within 4.5 hours — during which this therapy can be given, and such patients may live a long distance from a hospital.

Two other groups less likely to receive thrombolysis were Hispanic persons versus non-Hispanic persons (RR, 0.93; 95% CI, 0.87-0.98) and Medicare/Medicaid/Veterans Administration patients (RR, 0.77; 95% CI, 0.73-0.81) or uninsured patients (RR, 0.90; 95% CI, 0.94-0.87) vs those with private insurance.

Interestingly, male patients were less likely than female patients to receive thrombolysis (RR, 0.95; 95% CI, 0.90-0.99).
 

Surprising Findings

With the exception of the discrepancy in thrombolysis rates between rural versus urban dwellers, the study’s findings were surprising, said Dr. Kahathuduwa. 

Researchers divided participants into quartiles, from least to most disadvantaged, based on the Social Vulnerability Index (SVI), created by the Centers for Disease Control and Prevention to determine social vulnerability or factors that can negatively affect a community’s health. 

Among the 7930 individuals in the least disadvantaged group, 1037 received thrombolysis. In comparison, among the 7966 persons in the most disadvantaged group, 964 received thrombolysis.

After adjusting for age, sex, and education, investigators found that patients in the first quartile based on SVI were more likely to be associated with thrombolysis vs those in the second and third quartiles (RR, 1.13; 95% CI, 1.04-1.22).

The researchers also examined the impact of comorbidities using the Charlson Comorbidity Index. Patients with diabetes, hypertension, and high cholesterol in addition to signs of stroke would rouse a higher degree of suspicion and be more likely to be treated with tPA or tenecteplase, said Dr. Kahathuduwa.

“But even when we controlled for those comorbidities, the relationships we identified between health disparities and the likelihood of receiving thrombolysis remained the same,” said Dr. Kahathuduwa.

It’s not clear from this study what factors contribute to the disparities in stroke treatment. “All we know is these relationships exist,” said Dr. Kahathuduwa. “We should use this as a foundation to understand what’s really going on at the grassroots level.”

However, he added, it’s possible that accessibility plays a role. He noted that Lubbock has the only Level 1 stroke center in west Texas; most stroke centers in the state are concentrated in cities in east and central Texas.

The investigators are embarking on further research to assess the impact of determinants of health on receipt of endovascular therapy and the role of stroke severity.

“In an ideal world, all patients who need thrombolytic therapy would get thrombolytic therapy within the recommended time window because the benefits are very clear,” said Dr. Kahathuduwa.

The findings may not be generalizable because they come from a single database. “Our findings need to be validated in another independent dataset before we can confidently determine what’s going on,” said Dr. Kahathuduwa.

A limitation of the study was that it is unknown how many of the participants were seen at the hospital within the recommended time frame and would thus be eligible to receive the treatment.

Commenting on the research, Martinson Arnan, MD , a vascular neurologist at Bronson Neuroscience Center, Kalamazoo, Michigan, said the study’s “exploratory finding” is important and “illuminates the potential impact of social determinants of health on disparities in acute stroke treatment.”

Neurologists consistently emphasize the principle that “time is brain” — that timely restoration of blood flow is crucial for minimizing morbidity associated with ischemic stroke. This study offers a potential opportunity to investigate how social determinants of health may affect stroke care, said Dr. Arnan.

However, he added, further research is needed “to understand whether the differences in outcomes observed here are influenced by levels of health education, concordance between patients and their treating providers, or other issues related to access barriers.” 

The investigators and Dr. Arnan report no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Black people, men, older adults, and those living in rural communities are less likely to receive thrombolytic therapy after ischemic stroke, early research shows.

“The findings should serve as an eye-opener that social determinants of health seem to be playing a role in who receives thrombolytic therapy, said study investigator Chanaka Kahathuduwa, MD, PhD, resident physician, Department of Neurology, School of Medicine, Texas Tech University Health Sciences Center, Lubbock. 

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Contributor to Poor Outcomes

Social determinants of health are important contributors to poor stroke-related outcomes, the investigators noted. They pointed out that previous research has yielded conflicting results as to the cause.

Whereas some studies suggest poor social determinants of health drive increased stroke incidence, others raise the question of whether there are disparities in acute stroke care. 

To investigate, the researchers used a publicly available database and diagnostic and procedure codes to identify patients presenting at emergency departments in Texas from 2016 to 2019 with ischemic stroke who did and did not receive thrombolytic therapy.

“We focused on Texas, which has a very large area but few places where people have easy access to health care, which is a problem,” said study co-investigator Chathurika Dhanasekara, MD, PhD, research assistant professor in the Department of Surgery, School of Medicine, Texas Tech University Health Sciences Center.

The study included 63,983 stroke patients, of whom 51.6% were female, 66.6% were White, and 17.7% were Black. Of these, 7198 (11.2%) received thrombolytic therapy; such therapies include the tissue plasminogen activators (tPAs) alteplase and tenecteplace.

Researchers collected information on social determinants of health such as age, race, gender, insurance type, and residence based on zip codes. They computed risk ratios (RRs) of administering thrombolysis on the basis of these variables.

Results showed that Black patients were less likely than their White counterparts to receive thrombolysis (RR, 0.90; 95% CI, 0.85-0.96). In addition, patients older than 65 years were less likely those aged 18-45 years to receive thrombolysis (RR, 0.47; 95% CI, 0.44-0.51), and rural residents were less likely than urban dwellers to receive the intervention (RR, 0.60; 95% CI, 0.55-0.65).

It makes some sense, the researchers said, that rural stroke patients would be less likely to get thrombolysis because there’s a limited time window — within 4.5 hours — during which this therapy can be given, and such patients may live a long distance from a hospital.

Two other groups less likely to receive thrombolysis were Hispanic persons versus non-Hispanic persons (RR, 0.93; 95% CI, 0.87-0.98) and Medicare/Medicaid/Veterans Administration patients (RR, 0.77; 95% CI, 0.73-0.81) or uninsured patients (RR, 0.90; 95% CI, 0.94-0.87) vs those with private insurance.

Interestingly, male patients were less likely than female patients to receive thrombolysis (RR, 0.95; 95% CI, 0.90-0.99).
 

Surprising Findings

With the exception of the discrepancy in thrombolysis rates between rural versus urban dwellers, the study’s findings were surprising, said Dr. Kahathuduwa. 

Researchers divided participants into quartiles, from least to most disadvantaged, based on the Social Vulnerability Index (SVI), created by the Centers for Disease Control and Prevention to determine social vulnerability or factors that can negatively affect a community’s health. 

Among the 7930 individuals in the least disadvantaged group, 1037 received thrombolysis. In comparison, among the 7966 persons in the most disadvantaged group, 964 received thrombolysis.

After adjusting for age, sex, and education, investigators found that patients in the first quartile based on SVI were more likely to be associated with thrombolysis vs those in the second and third quartiles (RR, 1.13; 95% CI, 1.04-1.22).

The researchers also examined the impact of comorbidities using the Charlson Comorbidity Index. Patients with diabetes, hypertension, and high cholesterol in addition to signs of stroke would rouse a higher degree of suspicion and be more likely to be treated with tPA or tenecteplase, said Dr. Kahathuduwa.

“But even when we controlled for those comorbidities, the relationships we identified between health disparities and the likelihood of receiving thrombolysis remained the same,” said Dr. Kahathuduwa.

It’s not clear from this study what factors contribute to the disparities in stroke treatment. “All we know is these relationships exist,” said Dr. Kahathuduwa. “We should use this as a foundation to understand what’s really going on at the grassroots level.”

However, he added, it’s possible that accessibility plays a role. He noted that Lubbock has the only Level 1 stroke center in west Texas; most stroke centers in the state are concentrated in cities in east and central Texas.

The investigators are embarking on further research to assess the impact of determinants of health on receipt of endovascular therapy and the role of stroke severity.

“In an ideal world, all patients who need thrombolytic therapy would get thrombolytic therapy within the recommended time window because the benefits are very clear,” said Dr. Kahathuduwa.

The findings may not be generalizable because they come from a single database. “Our findings need to be validated in another independent dataset before we can confidently determine what’s going on,” said Dr. Kahathuduwa.

A limitation of the study was that it is unknown how many of the participants were seen at the hospital within the recommended time frame and would thus be eligible to receive the treatment.

Commenting on the research, Martinson Arnan, MD , a vascular neurologist at Bronson Neuroscience Center, Kalamazoo, Michigan, said the study’s “exploratory finding” is important and “illuminates the potential impact of social determinants of health on disparities in acute stroke treatment.”

Neurologists consistently emphasize the principle that “time is brain” — that timely restoration of blood flow is crucial for minimizing morbidity associated with ischemic stroke. This study offers a potential opportunity to investigate how social determinants of health may affect stroke care, said Dr. Arnan.

However, he added, further research is needed “to understand whether the differences in outcomes observed here are influenced by levels of health education, concordance between patients and their treating providers, or other issues related to access barriers.” 

The investigators and Dr. Arnan report no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Black people, men, older adults, and those living in rural communities are less likely to receive thrombolytic therapy after ischemic stroke, early research shows.

“The findings should serve as an eye-opener that social determinants of health seem to be playing a role in who receives thrombolytic therapy, said study investigator Chanaka Kahathuduwa, MD, PhD, resident physician, Department of Neurology, School of Medicine, Texas Tech University Health Sciences Center, Lubbock. 

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Contributor to Poor Outcomes

Social determinants of health are important contributors to poor stroke-related outcomes, the investigators noted. They pointed out that previous research has yielded conflicting results as to the cause.

Whereas some studies suggest poor social determinants of health drive increased stroke incidence, others raise the question of whether there are disparities in acute stroke care. 

To investigate, the researchers used a publicly available database and diagnostic and procedure codes to identify patients presenting at emergency departments in Texas from 2016 to 2019 with ischemic stroke who did and did not receive thrombolytic therapy.

“We focused on Texas, which has a very large area but few places where people have easy access to health care, which is a problem,” said study co-investigator Chathurika Dhanasekara, MD, PhD, research assistant professor in the Department of Surgery, School of Medicine, Texas Tech University Health Sciences Center.

The study included 63,983 stroke patients, of whom 51.6% were female, 66.6% were White, and 17.7% were Black. Of these, 7198 (11.2%) received thrombolytic therapy; such therapies include the tissue plasminogen activators (tPAs) alteplase and tenecteplace.

Researchers collected information on social determinants of health such as age, race, gender, insurance type, and residence based on zip codes. They computed risk ratios (RRs) of administering thrombolysis on the basis of these variables.

Results showed that Black patients were less likely than their White counterparts to receive thrombolysis (RR, 0.90; 95% CI, 0.85-0.96). In addition, patients older than 65 years were less likely those aged 18-45 years to receive thrombolysis (RR, 0.47; 95% CI, 0.44-0.51), and rural residents were less likely than urban dwellers to receive the intervention (RR, 0.60; 95% CI, 0.55-0.65).

It makes some sense, the researchers said, that rural stroke patients would be less likely to get thrombolysis because there’s a limited time window — within 4.5 hours — during which this therapy can be given, and such patients may live a long distance from a hospital.

Two other groups less likely to receive thrombolysis were Hispanic persons versus non-Hispanic persons (RR, 0.93; 95% CI, 0.87-0.98) and Medicare/Medicaid/Veterans Administration patients (RR, 0.77; 95% CI, 0.73-0.81) or uninsured patients (RR, 0.90; 95% CI, 0.94-0.87) vs those with private insurance.

Interestingly, male patients were less likely than female patients to receive thrombolysis (RR, 0.95; 95% CI, 0.90-0.99).
 

Surprising Findings

With the exception of the discrepancy in thrombolysis rates between rural versus urban dwellers, the study’s findings were surprising, said Dr. Kahathuduwa. 

Researchers divided participants into quartiles, from least to most disadvantaged, based on the Social Vulnerability Index (SVI), created by the Centers for Disease Control and Prevention to determine social vulnerability or factors that can negatively affect a community’s health. 

Among the 7930 individuals in the least disadvantaged group, 1037 received thrombolysis. In comparison, among the 7966 persons in the most disadvantaged group, 964 received thrombolysis.

After adjusting for age, sex, and education, investigators found that patients in the first quartile based on SVI were more likely to be associated with thrombolysis vs those in the second and third quartiles (RR, 1.13; 95% CI, 1.04-1.22).

The researchers also examined the impact of comorbidities using the Charlson Comorbidity Index. Patients with diabetes, hypertension, and high cholesterol in addition to signs of stroke would rouse a higher degree of suspicion and be more likely to be treated with tPA or tenecteplase, said Dr. Kahathuduwa.

“But even when we controlled for those comorbidities, the relationships we identified between health disparities and the likelihood of receiving thrombolysis remained the same,” said Dr. Kahathuduwa.

It’s not clear from this study what factors contribute to the disparities in stroke treatment. “All we know is these relationships exist,” said Dr. Kahathuduwa. “We should use this as a foundation to understand what’s really going on at the grassroots level.”

However, he added, it’s possible that accessibility plays a role. He noted that Lubbock has the only Level 1 stroke center in west Texas; most stroke centers in the state are concentrated in cities in east and central Texas.

The investigators are embarking on further research to assess the impact of determinants of health on receipt of endovascular therapy and the role of stroke severity.

“In an ideal world, all patients who need thrombolytic therapy would get thrombolytic therapy within the recommended time window because the benefits are very clear,” said Dr. Kahathuduwa.

The findings may not be generalizable because they come from a single database. “Our findings need to be validated in another independent dataset before we can confidently determine what’s going on,” said Dr. Kahathuduwa.

A limitation of the study was that it is unknown how many of the participants were seen at the hospital within the recommended time frame and would thus be eligible to receive the treatment.

Commenting on the research, Martinson Arnan, MD , a vascular neurologist at Bronson Neuroscience Center, Kalamazoo, Michigan, said the study’s “exploratory finding” is important and “illuminates the potential impact of social determinants of health on disparities in acute stroke treatment.”

Neurologists consistently emphasize the principle that “time is brain” — that timely restoration of blood flow is crucial for minimizing morbidity associated with ischemic stroke. This study offers a potential opportunity to investigate how social determinants of health may affect stroke care, said Dr. Arnan.

However, he added, further research is needed “to understand whether the differences in outcomes observed here are influenced by levels of health education, concordance between patients and their treating providers, or other issues related to access barriers.” 

The investigators and Dr. Arnan report no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Breastfeeding by women with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) who are taking monoclonal antibodies (mAbs) appears to be safe for infants, new research confirmed.

Registry data showed no differences in health or development in the first 3 years of life among infants exposed to natalizumab, ocrelizumab, rituximab, or ofatumumab, compared with unexposed infants.

“Most monoclonal antibody medications for multiple sclerosis are not currently approved for use while a mother is breastfeeding,” even though the disease can develop during a person’s reproductive years, study investigator Kerstin Hellwig, MD, with Ruhr University in Bochum, Germany, said in a news release.

“Our data show infants exposed to these medications through breastfeeding experienced no negative effects on health or development within the first 3 years of life,” Dr. Hellwig said.

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Registry Data and Analysis

Using the German MS and Pregnancy Registry, researchers identified 183 infants born to mothers taking mAbs while breastfeeding — 180 with a diagnosis of MS and three with a diagnosis of NMOSD. The infants were matched to 183 unexposed infants (control group).

Exposure to mAbs during lactation started a median of 19 days postpartum and lasted for a median of 172 days. The most commonly used mAb during lactation was natalizumab (125 women), followed by ocrelizumab (34 women), rituximab (11 women), and ofatumumab (10 women).

Among the entire infant cohort, two were first exposed to natalizumab and then ocrelizumab; one was exposed to rituximab and then ocrelizumab; three had been previously breastfed on glatiramer acetate and two on interferons.

The primary outcomes were hospitalizations, antibiotic use, developmental delay, and weight during the first 3 years of life in mAb-exposed versus unexposed infants.

In adjusted regression analyses, mAb exposure during breastfeeding was not significantly associated with annual hospitalization (rate ratio [RR], 1.23; P = .473), annual systemic antibiotic use (RR, 1.55; P = .093), developmental delay (odds ratio, 1.16; P = .716), or weight.

A limitation of the study was that only about a third of the infants were followed for the full 3 years. Therefore, Dr. Hellwig said, the results for the third year of life are less meaningful than for years 1 and 2.
 

‘Reassuring’ Data

Reached for comment, Edith L. Graham, MD, Department of Neurology, Multiple Sclerosis and Neuroimmunology, Northwestern University, Chicago, Illinois, noted that this is the largest group of breastfed infants exposed to mAbs used to treat MS and said the data provide “reassuring infant outcomes with no increase in hospitalization, antibiotic use, or developmental delay.”

Dr. Graham noted that recent publications have reported more on the use of anti-CD20 mAbs (ocrelizumab/rituximab/ofatumumab) while breastfeeding, “and this study adds data for patients on natalizumab.”

“It will be important to know how infusion timing after birth impacts transfer of monoclonal antibodies depending on the milk stage as it transitions from colostrum to mature milk in the first month postpartum,” Dr. Graham said.

“While infection rates of infants are reassuring, data on allergies in the exposed infants would be interesting to look at as well,” she added. “While these infusions are not orally bioavailable, we do not know the full extent of impact on the neonatal gut microbiome.”

In addition, Dr. Graham said it would be important to know whether drugs administered monthly, such as natalizumab and ofatumumab, accumulate in the breast milk at higher levels than medications such as ocrelizumab and rituximab, which are administered twice a year.

The German MS and pregnancy registry was partly supported by the Innovation Fund of the Federal Joint Committee, Almirall Hermal GmbH, Biogen GmbH Germany, Hexal AG, Merck Serono GmbH, Novartis Pharma GmbH, Roche Deutschland GmbH, Sanofi Genzyme, and Teva GmbH. Dr. Hellwig and Dr. Graham had no relevant disclosures.

A version of this article appeared on Medscape.com.

Breastfeeding by women with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) who are taking monoclonal antibodies (mAbs) appears to be safe for infants, new research confirmed.

Registry data showed no differences in health or development in the first 3 years of life among infants exposed to natalizumab, ocrelizumab, rituximab, or ofatumumab, compared with unexposed infants.

“Most monoclonal antibody medications for multiple sclerosis are not currently approved for use while a mother is breastfeeding,” even though the disease can develop during a person’s reproductive years, study investigator Kerstin Hellwig, MD, with Ruhr University in Bochum, Germany, said in a news release.

“Our data show infants exposed to these medications through breastfeeding experienced no negative effects on health or development within the first 3 years of life,” Dr. Hellwig said.

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Registry Data and Analysis

Using the German MS and Pregnancy Registry, researchers identified 183 infants born to mothers taking mAbs while breastfeeding — 180 with a diagnosis of MS and three with a diagnosis of NMOSD. The infants were matched to 183 unexposed infants (control group).

Exposure to mAbs during lactation started a median of 19 days postpartum and lasted for a median of 172 days. The most commonly used mAb during lactation was natalizumab (125 women), followed by ocrelizumab (34 women), rituximab (11 women), and ofatumumab (10 women).

Among the entire infant cohort, two were first exposed to natalizumab and then ocrelizumab; one was exposed to rituximab and then ocrelizumab; three had been previously breastfed on glatiramer acetate and two on interferons.

The primary outcomes were hospitalizations, antibiotic use, developmental delay, and weight during the first 3 years of life in mAb-exposed versus unexposed infants.

In adjusted regression analyses, mAb exposure during breastfeeding was not significantly associated with annual hospitalization (rate ratio [RR], 1.23; P = .473), annual systemic antibiotic use (RR, 1.55; P = .093), developmental delay (odds ratio, 1.16; P = .716), or weight.

A limitation of the study was that only about a third of the infants were followed for the full 3 years. Therefore, Dr. Hellwig said, the results for the third year of life are less meaningful than for years 1 and 2.
 

‘Reassuring’ Data

Reached for comment, Edith L. Graham, MD, Department of Neurology, Multiple Sclerosis and Neuroimmunology, Northwestern University, Chicago, Illinois, noted that this is the largest group of breastfed infants exposed to mAbs used to treat MS and said the data provide “reassuring infant outcomes with no increase in hospitalization, antibiotic use, or developmental delay.”

Dr. Graham noted that recent publications have reported more on the use of anti-CD20 mAbs (ocrelizumab/rituximab/ofatumumab) while breastfeeding, “and this study adds data for patients on natalizumab.”

“It will be important to know how infusion timing after birth impacts transfer of monoclonal antibodies depending on the milk stage as it transitions from colostrum to mature milk in the first month postpartum,” Dr. Graham said.

“While infection rates of infants are reassuring, data on allergies in the exposed infants would be interesting to look at as well,” she added. “While these infusions are not orally bioavailable, we do not know the full extent of impact on the neonatal gut microbiome.”

In addition, Dr. Graham said it would be important to know whether drugs administered monthly, such as natalizumab and ofatumumab, accumulate in the breast milk at higher levels than medications such as ocrelizumab and rituximab, which are administered twice a year.

The German MS and pregnancy registry was partly supported by the Innovation Fund of the Federal Joint Committee, Almirall Hermal GmbH, Biogen GmbH Germany, Hexal AG, Merck Serono GmbH, Novartis Pharma GmbH, Roche Deutschland GmbH, Sanofi Genzyme, and Teva GmbH. Dr. Hellwig and Dr. Graham had no relevant disclosures.

A version of this article appeared on Medscape.com.

Breastfeeding by women with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) who are taking monoclonal antibodies (mAbs) appears to be safe for infants, new research confirmed.

Registry data showed no differences in health or development in the first 3 years of life among infants exposed to natalizumab, ocrelizumab, rituximab, or ofatumumab, compared with unexposed infants.

“Most monoclonal antibody medications for multiple sclerosis are not currently approved for use while a mother is breastfeeding,” even though the disease can develop during a person’s reproductive years, study investigator Kerstin Hellwig, MD, with Ruhr University in Bochum, Germany, said in a news release.

“Our data show infants exposed to these medications through breastfeeding experienced no negative effects on health or development within the first 3 years of life,” Dr. Hellwig said.

The findings were released ahead of the study’s scheduled presentation at the annual meeting of the American Academy of Neurology.
 

Registry Data and Analysis

Using the German MS and Pregnancy Registry, researchers identified 183 infants born to mothers taking mAbs while breastfeeding — 180 with a diagnosis of MS and three with a diagnosis of NMOSD. The infants were matched to 183 unexposed infants (control group).

Exposure to mAbs during lactation started a median of 19 days postpartum and lasted for a median of 172 days. The most commonly used mAb during lactation was natalizumab (125 women), followed by ocrelizumab (34 women), rituximab (11 women), and ofatumumab (10 women).

Among the entire infant cohort, two were first exposed to natalizumab and then ocrelizumab; one was exposed to rituximab and then ocrelizumab; three had been previously breastfed on glatiramer acetate and two on interferons.

The primary outcomes were hospitalizations, antibiotic use, developmental delay, and weight during the first 3 years of life in mAb-exposed versus unexposed infants.

In adjusted regression analyses, mAb exposure during breastfeeding was not significantly associated with annual hospitalization (rate ratio [RR], 1.23; P = .473), annual systemic antibiotic use (RR, 1.55; P = .093), developmental delay (odds ratio, 1.16; P = .716), or weight.

A limitation of the study was that only about a third of the infants were followed for the full 3 years. Therefore, Dr. Hellwig said, the results for the third year of life are less meaningful than for years 1 and 2.
 

‘Reassuring’ Data

Reached for comment, Edith L. Graham, MD, Department of Neurology, Multiple Sclerosis and Neuroimmunology, Northwestern University, Chicago, Illinois, noted that this is the largest group of breastfed infants exposed to mAbs used to treat MS and said the data provide “reassuring infant outcomes with no increase in hospitalization, antibiotic use, or developmental delay.”

Dr. Graham noted that recent publications have reported more on the use of anti-CD20 mAbs (ocrelizumab/rituximab/ofatumumab) while breastfeeding, “and this study adds data for patients on natalizumab.”

“It will be important to know how infusion timing after birth impacts transfer of monoclonal antibodies depending on the milk stage as it transitions from colostrum to mature milk in the first month postpartum,” Dr. Graham said.

“While infection rates of infants are reassuring, data on allergies in the exposed infants would be interesting to look at as well,” she added. “While these infusions are not orally bioavailable, we do not know the full extent of impact on the neonatal gut microbiome.”

In addition, Dr. Graham said it would be important to know whether drugs administered monthly, such as natalizumab and ofatumumab, accumulate in the breast milk at higher levels than medications such as ocrelizumab and rituximab, which are administered twice a year.

The German MS and pregnancy registry was partly supported by the Innovation Fund of the Federal Joint Committee, Almirall Hermal GmbH, Biogen GmbH Germany, Hexal AG, Merck Serono GmbH, Novartis Pharma GmbH, Roche Deutschland GmbH, Sanofi Genzyme, and Teva GmbH. Dr. Hellwig and Dr. Graham had no relevant disclosures.

A version of this article appeared on Medscape.com.

Patients with cancer receiving chemotherapeutics may develop diarrhea, which can be highly distressing. In a recent journal article, oncologist Marcus Hentrich, MD, and gastroenterologist Volker Penndorf, MD, PhD, both of Rotkreuzklinikum in Munich, Germany, explained how affected patients should be treated.

As Dr. Hentrich and Dr. Penndorf explained, classical cytostatic drugs can induce diarrhea through direct damage to the intestinal mucosa. The pathomechanisms of monoclonal antibodies and oral targeted substances are not yet fully understood. According to the authors, the risk for toxic mucosal damage (toxic enteritis) increases with the severity and duration of neutropenia. Up to two thirds of patients with neutropenia develop diarrhea, and an infectious cause is rarely identified.

The cytostatic drug irinotecan, which can lead to an acute cholinergic syndrome within 24 hours, is a special case. This syndrome is characterized by watery diarrhea, abdominal cramps, vomiting, sweating, and bradycardia. Additionally, the development of late-onset diarrhea, occurring approximately 3 days after administration, is frequent.

According to the authors, risk factors for toxic enteritis with diarrhea include advanced age, poor performance and nutritional status, simultaneous radiotherapy of the abdomen and pelvis, and preexisting intestinal conditions.

Medication prophylaxis for chemotherapy-induced diarrhea has not been established. An exception is atropine for prophylaxis and treatment of irinotecan-induced cholinergic syndrome.

Indications for diagnostic procedures are outlined in the current German guideline for supportive therapy in patients with cancer.

For diarrhea accompanied by fever, blood cultures are mandatory. A complete blood count provides information on various aspects (leukocytosis as an inflammatory reaction, neutropenia as a marker for infection risk, hemoglobin as a marker for possible hemoconcentration or existing bleeding, and thrombocytopenia as a marker for bleeding tendency). Disproportionate thrombocytopenia may warrant assessment of fragmented cells and enterohemorrhagic Escherichia coli diagnostics.

To assess electrolyte and fluid loss, electrolytes, albumin, and total protein should be measured. The C-reactive protein value may help identify inflammatory conditions. It may also be elevated, however, because of tumor-related factors. Measuring urea and creatinine allows for estimating whether there is already a prerenal impairment of kidney function. Liver function parameters are mandatory for critically ill patients. In patients with hypotension or tachycardia, blood gas analysis and lactate determination are advisable. Among imaging techniques, ultrasound may be helpful. Indications for conventional abdominal x-ray are rare. In the presence of clinical signs of peritoneal irritation (such as guarding and rebound tenderness), a CT scan should be considered to detect further complications (perforation, ileus, enterocolitis, etc.) promptly.

Endoscopic examinations are recommended only in cases of persistent, worsening symptoms, according to the guideline. Colonoscopy is contraindicated in suspected neutropenic enterocolitis (NEC) because of the risk for perforation.

According to Dr. Hentrich and Dr. Penndorf, diarrhea therapy is carried out in stages and depends on the severity and response to each therapy. The Common Terminology Criteria for Adverse Events distinguishes the following severity grades:

• Grade 1: < four stools per day above baseline
• Grade 2: Four to six stools per day above baseline
• Grade 3: ≥ seven stools per day above baseline; fecal incontinence, hospitalization indicated; limited activities of daily living
• Grade 4: Life-threatening consequences, urgent intervention indicated

Therapy for Grades 1-2

The standard therapeutic after excluding infectious causes is loperamide (initially 4 mg orally, followed by 2 mg every 2-4 hours). A daily dose should not exceed 16 mg.

For irinotecan-associated diarrhea, adjunctive administration of budesonide (3 mg orally three times per day) with loperamide was shown to be effective in a small, randomized study (off-label). Another randomized study demonstrated the efficacy of combining loperamide with racecadotril (100 mg orally three times per day for 48 hours).
 

Therapy for Grade 3 Diarrhea

In severe diarrhea persisting despite loperamide therapy for 24-48 hours, octreotide (100-150 μg subcutaneously three times per day) may be administered (maximum three times 500 μg). Although octreotide is often used successfully for chemotherapy-induced diarrhea, it is not approved for this indication (off-label use).

According to the authors, other therapy options for loperamide-refractory diarrhea include codeine, tincture of opium, budesonide, and racecadotril. Psyllium husk or diphenoxylate plus atropine may also be attempted. In patients with prolonged neutropenia, overdosing of motility inhibitors should be avoided because of the risk for ileus.

The use of probiotics for chemotherapy-induced diarrhea cannot be generally recommended because of insufficient evidence, and cases of probiotic-associated bacteremia and fungemia have been described.

A particularly serious complication of intensive chemotherapy associated with diarrhea is NEC. It is characterized by fever, abdominal pain, and diarrhea during severe neutropenia (neutrophil count < 500/μL), the authors explained. NEC occurs predominantly, but not exclusively, after intensive chemotherapy for hematologic malignancies, especially acute leukemias.

More common than NEC and often preceding it is the so-called chemotherapy-associated bowel syndrome. It is characterized by fever ≥ 37.8 °C and abdominal pain or absence of stool for at least 72 hours.

Therapy consists of conservative symptomatic measures such as diet, adequate hydration with electrolyte balance, and analgesia. Due to the high risk for bacteremia, antibiotic therapy is indicated after blood cultures are obtained (piperacillin-tazobactam or a carbapenem). According to the authors, NEC improves in most patients with neutrophil regeneration. Granulocyte colony-stimulating factor therapy appears reasonable in this context, although conclusive studies are lacking. Surgical intervention with removal of necrotic bowel segments may be considered in exceptional cases.

This story was translated from Univadis Germany, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Patients with cancer receiving chemotherapeutics may develop diarrhea, which can be highly distressing. In a recent journal article, oncologist Marcus Hentrich, MD, and gastroenterologist Volker Penndorf, MD, PhD, both of Rotkreuzklinikum in Munich, Germany, explained how affected patients should be treated.

As Dr. Hentrich and Dr. Penndorf explained, classical cytostatic drugs can induce diarrhea through direct damage to the intestinal mucosa. The pathomechanisms of monoclonal antibodies and oral targeted substances are not yet fully understood. According to the authors, the risk for toxic mucosal damage (toxic enteritis) increases with the severity and duration of neutropenia. Up to two thirds of patients with neutropenia develop diarrhea, and an infectious cause is rarely identified.

The cytostatic drug irinotecan, which can lead to an acute cholinergic syndrome within 24 hours, is a special case. This syndrome is characterized by watery diarrhea, abdominal cramps, vomiting, sweating, and bradycardia. Additionally, the development of late-onset diarrhea, occurring approximately 3 days after administration, is frequent.

According to the authors, risk factors for toxic enteritis with diarrhea include advanced age, poor performance and nutritional status, simultaneous radiotherapy of the abdomen and pelvis, and preexisting intestinal conditions.

Medication prophylaxis for chemotherapy-induced diarrhea has not been established. An exception is atropine for prophylaxis and treatment of irinotecan-induced cholinergic syndrome.

Indications for diagnostic procedures are outlined in the current German guideline for supportive therapy in patients with cancer.

For diarrhea accompanied by fever, blood cultures are mandatory. A complete blood count provides information on various aspects (leukocytosis as an inflammatory reaction, neutropenia as a marker for infection risk, hemoglobin as a marker for possible hemoconcentration or existing bleeding, and thrombocytopenia as a marker for bleeding tendency). Disproportionate thrombocytopenia may warrant assessment of fragmented cells and enterohemorrhagic Escherichia coli diagnostics.

To assess electrolyte and fluid loss, electrolytes, albumin, and total protein should be measured. The C-reactive protein value may help identify inflammatory conditions. It may also be elevated, however, because of tumor-related factors. Measuring urea and creatinine allows for estimating whether there is already a prerenal impairment of kidney function. Liver function parameters are mandatory for critically ill patients. In patients with hypotension or tachycardia, blood gas analysis and lactate determination are advisable. Among imaging techniques, ultrasound may be helpful. Indications for conventional abdominal x-ray are rare. In the presence of clinical signs of peritoneal irritation (such as guarding and rebound tenderness), a CT scan should be considered to detect further complications (perforation, ileus, enterocolitis, etc.) promptly.

Endoscopic examinations are recommended only in cases of persistent, worsening symptoms, according to the guideline. Colonoscopy is contraindicated in suspected neutropenic enterocolitis (NEC) because of the risk for perforation.

According to Dr. Hentrich and Dr. Penndorf, diarrhea therapy is carried out in stages and depends on the severity and response to each therapy. The Common Terminology Criteria for Adverse Events distinguishes the following severity grades:

• Grade 1: < four stools per day above baseline
• Grade 2: Four to six stools per day above baseline
• Grade 3: ≥ seven stools per day above baseline; fecal incontinence, hospitalization indicated; limited activities of daily living
• Grade 4: Life-threatening consequences, urgent intervention indicated

Therapy for Grades 1-2

The standard therapeutic after excluding infectious causes is loperamide (initially 4 mg orally, followed by 2 mg every 2-4 hours). A daily dose should not exceed 16 mg.

For irinotecan-associated diarrhea, adjunctive administration of budesonide (3 mg orally three times per day) with loperamide was shown to be effective in a small, randomized study (off-label). Another randomized study demonstrated the efficacy of combining loperamide with racecadotril (100 mg orally three times per day for 48 hours).
 

Therapy for Grade 3 Diarrhea

In severe diarrhea persisting despite loperamide therapy for 24-48 hours, octreotide (100-150 μg subcutaneously three times per day) may be administered (maximum three times 500 μg). Although octreotide is often used successfully for chemotherapy-induced diarrhea, it is not approved for this indication (off-label use).

According to the authors, other therapy options for loperamide-refractory diarrhea include codeine, tincture of opium, budesonide, and racecadotril. Psyllium husk or diphenoxylate plus atropine may also be attempted. In patients with prolonged neutropenia, overdosing of motility inhibitors should be avoided because of the risk for ileus.

The use of probiotics for chemotherapy-induced diarrhea cannot be generally recommended because of insufficient evidence, and cases of probiotic-associated bacteremia and fungemia have been described.

A particularly serious complication of intensive chemotherapy associated with diarrhea is NEC. It is characterized by fever, abdominal pain, and diarrhea during severe neutropenia (neutrophil count < 500/μL), the authors explained. NEC occurs predominantly, but not exclusively, after intensive chemotherapy for hematologic malignancies, especially acute leukemias.

More common than NEC and often preceding it is the so-called chemotherapy-associated bowel syndrome. It is characterized by fever ≥ 37.8 °C and abdominal pain or absence of stool for at least 72 hours.

Therapy consists of conservative symptomatic measures such as diet, adequate hydration with electrolyte balance, and analgesia. Due to the high risk for bacteremia, antibiotic therapy is indicated after blood cultures are obtained (piperacillin-tazobactam or a carbapenem). According to the authors, NEC improves in most patients with neutrophil regeneration. Granulocyte colony-stimulating factor therapy appears reasonable in this context, although conclusive studies are lacking. Surgical intervention with removal of necrotic bowel segments may be considered in exceptional cases.

This story was translated from Univadis Germany, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Patients with cancer receiving chemotherapeutics may develop diarrhea, which can be highly distressing. In a recent journal article, oncologist Marcus Hentrich, MD, and gastroenterologist Volker Penndorf, MD, PhD, both of Rotkreuzklinikum in Munich, Germany, explained how affected patients should be treated.

As Dr. Hentrich and Dr. Penndorf explained, classical cytostatic drugs can induce diarrhea through direct damage to the intestinal mucosa. The pathomechanisms of monoclonal antibodies and oral targeted substances are not yet fully understood. According to the authors, the risk for toxic mucosal damage (toxic enteritis) increases with the severity and duration of neutropenia. Up to two thirds of patients with neutropenia develop diarrhea, and an infectious cause is rarely identified.

The cytostatic drug irinotecan, which can lead to an acute cholinergic syndrome within 24 hours, is a special case. This syndrome is characterized by watery diarrhea, abdominal cramps, vomiting, sweating, and bradycardia. Additionally, the development of late-onset diarrhea, occurring approximately 3 days after administration, is frequent.

According to the authors, risk factors for toxic enteritis with diarrhea include advanced age, poor performance and nutritional status, simultaneous radiotherapy of the abdomen and pelvis, and preexisting intestinal conditions.

Medication prophylaxis for chemotherapy-induced diarrhea has not been established. An exception is atropine for prophylaxis and treatment of irinotecan-induced cholinergic syndrome.

Indications for diagnostic procedures are outlined in the current German guideline for supportive therapy in patients with cancer.

For diarrhea accompanied by fever, blood cultures are mandatory. A complete blood count provides information on various aspects (leukocytosis as an inflammatory reaction, neutropenia as a marker for infection risk, hemoglobin as a marker for possible hemoconcentration or existing bleeding, and thrombocytopenia as a marker for bleeding tendency). Disproportionate thrombocytopenia may warrant assessment of fragmented cells and enterohemorrhagic Escherichia coli diagnostics.

To assess electrolyte and fluid loss, electrolytes, albumin, and total protein should be measured. The C-reactive protein value may help identify inflammatory conditions. It may also be elevated, however, because of tumor-related factors. Measuring urea and creatinine allows for estimating whether there is already a prerenal impairment of kidney function. Liver function parameters are mandatory for critically ill patients. In patients with hypotension or tachycardia, blood gas analysis and lactate determination are advisable. Among imaging techniques, ultrasound may be helpful. Indications for conventional abdominal x-ray are rare. In the presence of clinical signs of peritoneal irritation (such as guarding and rebound tenderness), a CT scan should be considered to detect further complications (perforation, ileus, enterocolitis, etc.) promptly.

Endoscopic examinations are recommended only in cases of persistent, worsening symptoms, according to the guideline. Colonoscopy is contraindicated in suspected neutropenic enterocolitis (NEC) because of the risk for perforation.

According to Dr. Hentrich and Dr. Penndorf, diarrhea therapy is carried out in stages and depends on the severity and response to each therapy. The Common Terminology Criteria for Adverse Events distinguishes the following severity grades:

• Grade 1: < four stools per day above baseline
• Grade 2: Four to six stools per day above baseline
• Grade 3: ≥ seven stools per day above baseline; fecal incontinence, hospitalization indicated; limited activities of daily living
• Grade 4: Life-threatening consequences, urgent intervention indicated

Therapy for Grades 1-2

The standard therapeutic after excluding infectious causes is loperamide (initially 4 mg orally, followed by 2 mg every 2-4 hours). A daily dose should not exceed 16 mg.

For irinotecan-associated diarrhea, adjunctive administration of budesonide (3 mg orally three times per day) with loperamide was shown to be effective in a small, randomized study (off-label). Another randomized study demonstrated the efficacy of combining loperamide with racecadotril (100 mg orally three times per day for 48 hours).
 

Therapy for Grade 3 Diarrhea

In severe diarrhea persisting despite loperamide therapy for 24-48 hours, octreotide (100-150 μg subcutaneously three times per day) may be administered (maximum three times 500 μg). Although octreotide is often used successfully for chemotherapy-induced diarrhea, it is not approved for this indication (off-label use).

According to the authors, other therapy options for loperamide-refractory diarrhea include codeine, tincture of opium, budesonide, and racecadotril. Psyllium husk or diphenoxylate plus atropine may also be attempted. In patients with prolonged neutropenia, overdosing of motility inhibitors should be avoided because of the risk for ileus.

The use of probiotics for chemotherapy-induced diarrhea cannot be generally recommended because of insufficient evidence, and cases of probiotic-associated bacteremia and fungemia have been described.

A particularly serious complication of intensive chemotherapy associated with diarrhea is NEC. It is characterized by fever, abdominal pain, and diarrhea during severe neutropenia (neutrophil count < 500/μL), the authors explained. NEC occurs predominantly, but not exclusively, after intensive chemotherapy for hematologic malignancies, especially acute leukemias.

More common than NEC and often preceding it is the so-called chemotherapy-associated bowel syndrome. It is characterized by fever ≥ 37.8 °C and abdominal pain or absence of stool for at least 72 hours.

Therapy consists of conservative symptomatic measures such as diet, adequate hydration with electrolyte balance, and analgesia. Due to the high risk for bacteremia, antibiotic therapy is indicated after blood cultures are obtained (piperacillin-tazobactam or a carbapenem). According to the authors, NEC improves in most patients with neutrophil regeneration. Granulocyte colony-stimulating factor therapy appears reasonable in this context, although conclusive studies are lacking. Surgical intervention with removal of necrotic bowel segments may be considered in exceptional cases.

This story was translated from Univadis Germany, which is part of the Medscape professional network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.