Ob.Gyn. News

The US Food and Drug Administration (FDA) has expanded the approval of dostarlimab-gxly (Jemperli, GSK) in conjunction with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for adults with primary advanced or recurrent endometrial cancer.

Prior FDA approval of the combination was granted for adults with primary advanced or recurrent endometrial cancer that was mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H).

The expanded approval, granted following a priority review, was based on efficacy and safety demonstrated in the randomized, controlled, multicenter RUBY trial, which included 494 patients who were randomized to receive the dostarlimab-gxly regimen or placebo plus carboplatin and paclitaxel, followed by placebo.

Researchers observed a significant improvement in median overall survival with treatment vs placebo in the overall population — 44.6 vs 28.2 months, respectively (hazard ratio [HR], 0.69). Median progression-free survival was also significantly better in the treatment vs placebo group — 11.8 vs 7.9 months, respectively (HR, 0.64).

“Today’s expanded approval will offer even more patients the opportunity for improved outcomes,” Matthew Powell, MD, of Washington University School of Medicine, and principal investigator on the RUBY trial, said in a press release. “This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer.”

Adverse reactions occurring in at least 20% of patients receiving dostarlimab-gxly include anemia, increased creatinine levels, peripheral neuropathy, decreased white blood cell counts, fatigue, nausea, alopecia, low platelet counts, increased glucose levels, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin levels, abdominal pain, dyspnea, decreased appetite, increased amylase levels, urinary tract infection, and vomiting. Immune-mediated adverse reactions with dostarlimab-gxly were similar to those previously reported.

The recommended dostarlimab-gxly dose, according to the full prescribing information, is 500 mg every 3 weeks for six cycles administered before carboplatin and paclitaxel if given on the same day, followed by 1000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.
 

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

The US Food and Drug Administration (FDA) has expanded the approval of dostarlimab-gxly (Jemperli, GSK) in conjunction with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for adults with primary advanced or recurrent endometrial cancer.

Prior FDA approval of the combination was granted for adults with primary advanced or recurrent endometrial cancer that was mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H).

The expanded approval, granted following a priority review, was based on efficacy and safety demonstrated in the randomized, controlled, multicenter RUBY trial, which included 494 patients who were randomized to receive the dostarlimab-gxly regimen or placebo plus carboplatin and paclitaxel, followed by placebo.

Researchers observed a significant improvement in median overall survival with treatment vs placebo in the overall population — 44.6 vs 28.2 months, respectively (hazard ratio [HR], 0.69). Median progression-free survival was also significantly better in the treatment vs placebo group — 11.8 vs 7.9 months, respectively (HR, 0.64).

“Today’s expanded approval will offer even more patients the opportunity for improved outcomes,” Matthew Powell, MD, of Washington University School of Medicine, and principal investigator on the RUBY trial, said in a press release. “This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer.”

Adverse reactions occurring in at least 20% of patients receiving dostarlimab-gxly include anemia, increased creatinine levels, peripheral neuropathy, decreased white blood cell counts, fatigue, nausea, alopecia, low platelet counts, increased glucose levels, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin levels, abdominal pain, dyspnea, decreased appetite, increased amylase levels, urinary tract infection, and vomiting. Immune-mediated adverse reactions with dostarlimab-gxly were similar to those previously reported.

The recommended dostarlimab-gxly dose, according to the full prescribing information, is 500 mg every 3 weeks for six cycles administered before carboplatin and paclitaxel if given on the same day, followed by 1000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.
 

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

The US Food and Drug Administration (FDA) has expanded the approval of dostarlimab-gxly (Jemperli, GSK) in conjunction with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for adults with primary advanced or recurrent endometrial cancer.

Prior FDA approval of the combination was granted for adults with primary advanced or recurrent endometrial cancer that was mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H).

The expanded approval, granted following a priority review, was based on efficacy and safety demonstrated in the randomized, controlled, multicenter RUBY trial, which included 494 patients who were randomized to receive the dostarlimab-gxly regimen or placebo plus carboplatin and paclitaxel, followed by placebo.

Researchers observed a significant improvement in median overall survival with treatment vs placebo in the overall population — 44.6 vs 28.2 months, respectively (hazard ratio [HR], 0.69). Median progression-free survival was also significantly better in the treatment vs placebo group — 11.8 vs 7.9 months, respectively (HR, 0.64).

“Today’s expanded approval will offer even more patients the opportunity for improved outcomes,” Matthew Powell, MD, of Washington University School of Medicine, and principal investigator on the RUBY trial, said in a press release. “This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer.”

Adverse reactions occurring in at least 20% of patients receiving dostarlimab-gxly include anemia, increased creatinine levels, peripheral neuropathy, decreased white blood cell counts, fatigue, nausea, alopecia, low platelet counts, increased glucose levels, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin levels, abdominal pain, dyspnea, decreased appetite, increased amylase levels, urinary tract infection, and vomiting. Immune-mediated adverse reactions with dostarlimab-gxly were similar to those previously reported.

The recommended dostarlimab-gxly dose, according to the full prescribing information, is 500 mg every 3 weeks for six cycles administered before carboplatin and paclitaxel if given on the same day, followed by 1000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.
 

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

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created 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.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created 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.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created 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.

More than 5% of cases of sudden infant death may be linked to maternal obesity, new research showed.

“When a parent has a child that dies of sudden unexplained infant death [SUID], it’s extremely devastating,” said Jan-Marino Ramirez, PhD, the Zain Nadella Endowed Chair in Pediatric Neurosciences at the University of Washington, Seattle, and director of the Center for Integrative Brain Research at Seattle Children’s Hospital. “And the most devastating problem is that there’s no clear answer. Understanding the mechanisms will help parents understand.”

The study was published online in JAMA Pediatrics.

In the United States, approximately 3500 cases of SUID are reported yearly. After educational campaigns in the 1990s demonstrating safe infant sleep positions, rates of these fatalities dropped but have since plateaued.
 

Maternal Obesity During Pregnancy

Rates of maternal obesity are increasing globally, and more than half of women of reproductive age are overweight or obese.

“Maternal obesity before pregnancy affects placental development, gene expression, and has long-term implications,” said Patrick Catalano, MD, a professor in residence at the Departments of Reproductive Endocrinology and Obstetrics and Gynecology at Massachusetts General Hospital and Harvard Medical School in Boston.

Maternal obesity is a well-documented risk factor for adverse outcomes of pregnancy including stillbirth, preterm birth, and admission to the neonatal intensive care unit. Swedish researchers in 2014 reported maternal obesity was linked to an increase in infant mortality that increased with body mass index (BMI), but that study did not look specifically at SUID.

For their new study, Dr. Ramirez and colleagues looked at data from all live births in the United States from 2015 to 2019 recorded by the Centers for Disease Control and Prevention and the National Center for Health Statistics. Of the 18,857,694 live births occurring at 28 weeks of gestation or later, 16,545 infants died of a sudden, unexplained cause.

Rates of SUID in babies born to mothers with obesity increased in a statistically significant, dose-dependent manner relative to normal weight mothers. The unadjusted absolute risks for SUID were 0.74 cases per 1000 births for normal weight mothers, 0.99 cases at BMIs between 30 and 35, 1.17 cases at BMIs between 35 and 40, and 1.47 instances at BMI ≥ 40.

After adjustment for maternal age, race, ethnicity, and level of education, the adjusted odds ratio for a case of SUID was 1.39 among women with the highest levels of obesity (95% CI, 1.31-1.47), according to the researchers.

While the study revealed an association between maternal obesity and SUID, the basis for this connection remains unknown, the investigators noted. One possibility for the link is that obesity increases the risk for obstructive sleep apnea, which can result in intermittent hypoxia. That, in turn, causes oxidative stress, which may possibly have effects on the fetus causing effects that eventually lead to SUID in the infant.

An accompanying editorial by Jacqueline Maya, MD; Marie-France Hivert, MD, MMSc; and Lydia Shook, MD, from the Massachusetts General Hospital and Harvard Medical School, suggested that the SUID is unlikely directly influenced by high maternal BMI but rather by the metabolic concerns related to obesity such as inflammation, insulin resistance, and abnormal lipid metabolism. Epigenetics may also play a role.

“We believe the evidence for this study of an association between prepregnancy obesity and SUID is a call to action for the scientific and medical community to better understand the complex interplay of biological, social, and behavioral factors that may lead to SUID, a devastating complication that no family should experience,” the authors of the editorial wrote.

Dr. Ramirez stressed the importance of not initiating guilt because there are many factors in SUID such as genetics that cannot be controlled.

“We are far from saying a baby died because you were obese; that’s an important message to parents,” he said. What he sees as important, rather, is using this new research to elucidate further mechanisms that may allow for more targeted interventions: “If we discover that it’s due to, for example, sleep apnea, that’s something we can prevent.”

The researchers reported no conflicts of interest.

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

More than 5% of cases of sudden infant death may be linked to maternal obesity, new research showed.

“When a parent has a child that dies of sudden unexplained infant death [SUID], it’s extremely devastating,” said Jan-Marino Ramirez, PhD, the Zain Nadella Endowed Chair in Pediatric Neurosciences at the University of Washington, Seattle, and director of the Center for Integrative Brain Research at Seattle Children’s Hospital. “And the most devastating problem is that there’s no clear answer. Understanding the mechanisms will help parents understand.”

The study was published online in JAMA Pediatrics.

In the United States, approximately 3500 cases of SUID are reported yearly. After educational campaigns in the 1990s demonstrating safe infant sleep positions, rates of these fatalities dropped but have since plateaued.
 

Maternal Obesity During Pregnancy

Rates of maternal obesity are increasing globally, and more than half of women of reproductive age are overweight or obese.

“Maternal obesity before pregnancy affects placental development, gene expression, and has long-term implications,” said Patrick Catalano, MD, a professor in residence at the Departments of Reproductive Endocrinology and Obstetrics and Gynecology at Massachusetts General Hospital and Harvard Medical School in Boston.

Maternal obesity is a well-documented risk factor for adverse outcomes of pregnancy including stillbirth, preterm birth, and admission to the neonatal intensive care unit. Swedish researchers in 2014 reported maternal obesity was linked to an increase in infant mortality that increased with body mass index (BMI), but that study did not look specifically at SUID.

For their new study, Dr. Ramirez and colleagues looked at data from all live births in the United States from 2015 to 2019 recorded by the Centers for Disease Control and Prevention and the National Center for Health Statistics. Of the 18,857,694 live births occurring at 28 weeks of gestation or later, 16,545 infants died of a sudden, unexplained cause.

Rates of SUID in babies born to mothers with obesity increased in a statistically significant, dose-dependent manner relative to normal weight mothers. The unadjusted absolute risks for SUID were 0.74 cases per 1000 births for normal weight mothers, 0.99 cases at BMIs between 30 and 35, 1.17 cases at BMIs between 35 and 40, and 1.47 instances at BMI ≥ 40.

After adjustment for maternal age, race, ethnicity, and level of education, the adjusted odds ratio for a case of SUID was 1.39 among women with the highest levels of obesity (95% CI, 1.31-1.47), according to the researchers.

While the study revealed an association between maternal obesity and SUID, the basis for this connection remains unknown, the investigators noted. One possibility for the link is that obesity increases the risk for obstructive sleep apnea, which can result in intermittent hypoxia. That, in turn, causes oxidative stress, which may possibly have effects on the fetus causing effects that eventually lead to SUID in the infant.

An accompanying editorial by Jacqueline Maya, MD; Marie-France Hivert, MD, MMSc; and Lydia Shook, MD, from the Massachusetts General Hospital and Harvard Medical School, suggested that the SUID is unlikely directly influenced by high maternal BMI but rather by the metabolic concerns related to obesity such as inflammation, insulin resistance, and abnormal lipid metabolism. Epigenetics may also play a role.

“We believe the evidence for this study of an association between prepregnancy obesity and SUID is a call to action for the scientific and medical community to better understand the complex interplay of biological, social, and behavioral factors that may lead to SUID, a devastating complication that no family should experience,” the authors of the editorial wrote.

Dr. Ramirez stressed the importance of not initiating guilt because there are many factors in SUID such as genetics that cannot be controlled.

“We are far from saying a baby died because you were obese; that’s an important message to parents,” he said. What he sees as important, rather, is using this new research to elucidate further mechanisms that may allow for more targeted interventions: “If we discover that it’s due to, for example, sleep apnea, that’s something we can prevent.”

The researchers reported no conflicts of interest.

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

More than 5% of cases of sudden infant death may be linked to maternal obesity, new research showed.

“When a parent has a child that dies of sudden unexplained infant death [SUID], it’s extremely devastating,” said Jan-Marino Ramirez, PhD, the Zain Nadella Endowed Chair in Pediatric Neurosciences at the University of Washington, Seattle, and director of the Center for Integrative Brain Research at Seattle Children’s Hospital. “And the most devastating problem is that there’s no clear answer. Understanding the mechanisms will help parents understand.”

The study was published online in JAMA Pediatrics.

In the United States, approximately 3500 cases of SUID are reported yearly. After educational campaigns in the 1990s demonstrating safe infant sleep positions, rates of these fatalities dropped but have since plateaued.
 

Maternal Obesity During Pregnancy

Rates of maternal obesity are increasing globally, and more than half of women of reproductive age are overweight or obese.

“Maternal obesity before pregnancy affects placental development, gene expression, and has long-term implications,” said Patrick Catalano, MD, a professor in residence at the Departments of Reproductive Endocrinology and Obstetrics and Gynecology at Massachusetts General Hospital and Harvard Medical School in Boston.

Maternal obesity is a well-documented risk factor for adverse outcomes of pregnancy including stillbirth, preterm birth, and admission to the neonatal intensive care unit. Swedish researchers in 2014 reported maternal obesity was linked to an increase in infant mortality that increased with body mass index (BMI), but that study did not look specifically at SUID.

For their new study, Dr. Ramirez and colleagues looked at data from all live births in the United States from 2015 to 2019 recorded by the Centers for Disease Control and Prevention and the National Center for Health Statistics. Of the 18,857,694 live births occurring at 28 weeks of gestation or later, 16,545 infants died of a sudden, unexplained cause.

Rates of SUID in babies born to mothers with obesity increased in a statistically significant, dose-dependent manner relative to normal weight mothers. The unadjusted absolute risks for SUID were 0.74 cases per 1000 births for normal weight mothers, 0.99 cases at BMIs between 30 and 35, 1.17 cases at BMIs between 35 and 40, and 1.47 instances at BMI ≥ 40.

After adjustment for maternal age, race, ethnicity, and level of education, the adjusted odds ratio for a case of SUID was 1.39 among women with the highest levels of obesity (95% CI, 1.31-1.47), according to the researchers.

While the study revealed an association between maternal obesity and SUID, the basis for this connection remains unknown, the investigators noted. One possibility for the link is that obesity increases the risk for obstructive sleep apnea, which can result in intermittent hypoxia. That, in turn, causes oxidative stress, which may possibly have effects on the fetus causing effects that eventually lead to SUID in the infant.

An accompanying editorial by Jacqueline Maya, MD; Marie-France Hivert, MD, MMSc; and Lydia Shook, MD, from the Massachusetts General Hospital and Harvard Medical School, suggested that the SUID is unlikely directly influenced by high maternal BMI but rather by the metabolic concerns related to obesity such as inflammation, insulin resistance, and abnormal lipid metabolism. Epigenetics may also play a role.

“We believe the evidence for this study of an association between prepregnancy obesity and SUID is a call to action for the scientific and medical community to better understand the complex interplay of biological, social, and behavioral factors that may lead to SUID, a devastating complication that no family should experience,” the authors of the editorial wrote.

Dr. Ramirez stressed the importance of not initiating guilt because there are many factors in SUID such as genetics that cannot be controlled.

“We are far from saying a baby died because you were obese; that’s an important message to parents,” he said. What he sees as important, rather, is using this new research to elucidate further mechanisms that may allow for more targeted interventions: “If we discover that it’s due to, for example, sleep apnea, that’s something we can prevent.”

The researchers reported no conflicts of interest.

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

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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

An ancient virus that infected our ancestors tens of millions of years ago may be helping to fuel cancer today, according to a fascinating new study in Science Advances. Targeting these viral remnants still lingering in our DNA could lead to more effective cancer treatment with fewer side effects, the researchers said.

The study “gives a better understanding of how gene regulation can be impacted by these ancient retroviral sequences,” said Dixie Mager, PhD, scientist emeritus at the Terry Fox Laboratory at the British Columbia Cancer Research Institute, Vancouver, British Columbia, Canada. (Mager was not involved in the study.)

Long thought to be “junk” DNA with no biologic function, “endogenous retroviruses,” which have mutated over time and lost their ability to create the virus, are now known to regulate genes — allowing some genes to turn on and off. Research in recent years suggests they may play a role in diseases like cancer.

But scientists weren’t exactly sure what that role was, said senior study author Edward Chuong, PhD, a genome biologist at the University of Colorado Boulder.

Most studies have looked at whether endogenous retroviruses code for proteins that influence cancer. But these ancient viral strands usually don’t code for proteins at all.

Dr. Chuong took a different approach. Inspired by scientists who’ve studied how viral remnants regulate positive processes (immunity, brain development, or placenta development), he and his team explored whether some might regulate genes that, once activated, help cancer thrive.

Borrowing from epigenomic analysis data (data on molecules that alter gene expression) for 21 cancers mapped by the Cancer Genome Atlas, the researchers identified 19 virus-derived DNA sequences that bind to regulatory proteins more in cancer cells than in healthy cells. All of these could potentially act as gene regulators that promote cancer.

The researchers homed in on one sequence, called LTR10, because it showed especially high activity in several cancers, including lung and colorectal cancer. This DNA segment comes from a virus that entered our ancestors’ genome 30 million years ago, and it’s activated in a third of colorectal cancers.

Using the gene editing technology clustered regularly interspaced short palindromic repeats (CRISPR), Dr. Chuong’s team silenced LTR10 in colorectal cancer cells, altering the gene sequence so it couldn’t bind to regulatory proteins. Doing so dampened the activity of nearby cancer-promoting genes.

“They still behaved like cancer cells,” Dr. Chuong said. But “it made the cancer cells more susceptible to radiation. That would imply that the presence of that viral ‘switch’ actually helped those cancer cells survive radiation therapy.”

Previously, two studies had found that viral regulators play a role in promoting two types of cancer: Leukemia and prostate cancer. The new study shows these two cases weren’t flukes. All 21 cancers they looked at had at least one of those 19 viral elements, presumably working as cancer enhancers.

The study also identified what activates LTR10 to make it promote cancer. The culprit is a regulator protein called mitogen-activated protein (MAP) kinase, which is overactivated in about 40% of all human cancers.

Some cancer drugs — MAP kinase inhibitors — already target MAP kinase, and they’re often the first ones prescribed when a patient is diagnosed with cancer, Dr. Chuong said. As with many cancer treatments, doctors don’t know why they work, just that they do.

“By understanding the mechanisms in the cell, we might be able to make them work better or further optimize their treatment,” he said.

“MAP kinase inhibitors are really like a sledgehammer to the cell,” Dr. Chuong said — meaning they affect many cellular processes, not just those related to cancer.

“If we’re able to say that these viral switches are what’s important, then that could potentially help us develop a more targeted therapy that uses something like CRISPR to silence these viral elements,” he said. Or it could help providers choose a MAP kinase inhibitor from among the dozens available best suited to treat an individual patient and avoid side effects.  

Still, whether the findings translate to real cancer patients remains to be seen. “It’s very, very hard to go the final step of showing in a patient that these actually make a difference in the cancer,” Dr. Mager said.

More lab research, human trials, and at least a few years will be needed before this discovery could help treat cancer. “Directly targeting these elements as a therapy would be at least 5 years out,” Dr. Chuong said, “partly because that application would rely on CRISPR epigenome editing technology that is still being developed for clinical use.”
 

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

This transcript has been edited for clarity. 

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University Grossman School of Medicine in New York City. 

There are many things screwy with our healthcare system. Many of you [reading] this are dealing with bureaucracy, paperwork, all sorts of constraints, restraints, and requirements that sometimes make the practice of medicine, or even nursing, difficult.

I don’t think I’ve seen anything screwier, from a moral point of view, than the system we have that allows for preauthorization by third-party payers, or insurers, in order to give care to patients. It’s pretty clear that a third-party payer has a conflict of interest. It’s simple: They don’t want to spend money.

Their goal as profit-making companies is to reduce what it is that they’re going to authorize. That clearly is driving how the preauthorization process works. We’re not getting a neutral review by third parties of the appropriateness of treatment recommendations or somebody saying, this is the standard of care and this is what ought to happen.

We’re letting the people who have the pocketbooks and the wallets have prior approval of what the doctor thinks is correct. That is really not the way to practice medicine. 

We now have more evidence about what really is going on. A doctor was recently interviewed by ProPublica and said that she had worked for Cigna as a reviewer. Basically, the message she got from that insurer was to speed it up, go fast, and basically “deny, deny, deny” when she got requests. Those are her words, not mine.

We get a peek under the tent of how this works, and Dr. Day is basically saying she had to leave because she just didn’t feel that it was evidence-driven. It was driven by concerns about who’s going to lose money or make money.

If you want to check to see whether something is appropriate, the question becomes, who ought to do prior review? 

Who does it now? Sometimes doctors. Sometimes nurses who aren’t in the specialty where the request is coming in for preapproval. I’ve even seen situations where some companies use nurses in other countries, such as the Philippines, to do preapproval. They send them information, like a clip, to use to deny things that basically is boilerplate language, whatever the request is.

Looming up now, some insurers are starting to think, well, maybe artificial intelligence could do it. Just review the written request, trigger certain responses on the part of the artificial intelligence — it can deny the claims just as well as a human — and maybe it’s even cheaper to set up that system for the insurer.

This is ethically nuts. We need to have a system where doctors’ judgments drive what patients get. You listen to doctors, as I do, about preapproval access and they say patients sometimes give up trying to get what they think is needed. Continuity of care is interrupted if they have to keep making requests all the time.

There are adverse events when the thing that the doctor thought was most appropriate isn’t approved and something else is used that is less safe or less efficacious. It isn’t in patient interest to have the person with the wallet saying, this is what we think you need, and then having unqualified people or even automated intelligence with no accountability and no transparency get involved in preauthorization.

This system costs us money because middlemen are doing all this work. It basically becomes one of the huge scandals, in my view, of our health system, that doctors don’t ultimately decide what the patient needs. A preauthorizing third party or robot, without transparency, without accountability, and behind closed doors second-guesses what’s going on.

I’m Art Caplan at the Division of Medical Ethics at the New York University Grossman School of Medicine.

Arthur L. Caplan, Director, Division of Medical Ethics, New York University Langone Medical Center, New York, New York, has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape.

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

This transcript has been edited for clarity. 

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University Grossman School of Medicine in New York City. 

There are many things screwy with our healthcare system. Many of you [reading] this are dealing with bureaucracy, paperwork, all sorts of constraints, restraints, and requirements that sometimes make the practice of medicine, or even nursing, difficult.

I don’t think I’ve seen anything screwier, from a moral point of view, than the system we have that allows for preauthorization by third-party payers, or insurers, in order to give care to patients. It’s pretty clear that a third-party payer has a conflict of interest. It’s simple: They don’t want to spend money.

Their goal as profit-making companies is to reduce what it is that they’re going to authorize. That clearly is driving how the preauthorization process works. We’re not getting a neutral review by third parties of the appropriateness of treatment recommendations or somebody saying, this is the standard of care and this is what ought to happen.

We’re letting the people who have the pocketbooks and the wallets have prior approval of what the doctor thinks is correct. That is really not the way to practice medicine. 

We now have more evidence about what really is going on. A doctor was recently interviewed by ProPublica and said that she had worked for Cigna as a reviewer. Basically, the message she got from that insurer was to speed it up, go fast, and basically “deny, deny, deny” when she got requests. Those are her words, not mine.

We get a peek under the tent of how this works, and Dr. Day is basically saying she had to leave because she just didn’t feel that it was evidence-driven. It was driven by concerns about who’s going to lose money or make money.

If you want to check to see whether something is appropriate, the question becomes, who ought to do prior review? 

Who does it now? Sometimes doctors. Sometimes nurses who aren’t in the specialty where the request is coming in for preapproval. I’ve even seen situations where some companies use nurses in other countries, such as the Philippines, to do preapproval. They send them information, like a clip, to use to deny things that basically is boilerplate language, whatever the request is.

Looming up now, some insurers are starting to think, well, maybe artificial intelligence could do it. Just review the written request, trigger certain responses on the part of the artificial intelligence — it can deny the claims just as well as a human — and maybe it’s even cheaper to set up that system for the insurer.

This is ethically nuts. We need to have a system where doctors’ judgments drive what patients get. You listen to doctors, as I do, about preapproval access and they say patients sometimes give up trying to get what they think is needed. Continuity of care is interrupted if they have to keep making requests all the time.

There are adverse events when the thing that the doctor thought was most appropriate isn’t approved and something else is used that is less safe or less efficacious. It isn’t in patient interest to have the person with the wallet saying, this is what we think you need, and then having unqualified people or even automated intelligence with no accountability and no transparency get involved in preauthorization.

This system costs us money because middlemen are doing all this work. It basically becomes one of the huge scandals, in my view, of our health system, that doctors don’t ultimately decide what the patient needs. A preauthorizing third party or robot, without transparency, without accountability, and behind closed doors second-guesses what’s going on.

I’m Art Caplan at the Division of Medical Ethics at the New York University Grossman School of Medicine.

Arthur L. Caplan, Director, Division of Medical Ethics, New York University Langone Medical Center, New York, New York, has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape.

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

This transcript has been edited for clarity. 

Hi. I’m Art Caplan. I’m at the Division of Medical Ethics at New York University Grossman School of Medicine in New York City. 

There are many things screwy with our healthcare system. Many of you [reading] this are dealing with bureaucracy, paperwork, all sorts of constraints, restraints, and requirements that sometimes make the practice of medicine, or even nursing, difficult.

I don’t think I’ve seen anything screwier, from a moral point of view, than the system we have that allows for preauthorization by third-party payers, or insurers, in order to give care to patients. It’s pretty clear that a third-party payer has a conflict of interest. It’s simple: They don’t want to spend money.

Their goal as profit-making companies is to reduce what it is that they’re going to authorize. That clearly is driving how the preauthorization process works. We’re not getting a neutral review by third parties of the appropriateness of treatment recommendations or somebody saying, this is the standard of care and this is what ought to happen.

We’re letting the people who have the pocketbooks and the wallets have prior approval of what the doctor thinks is correct. That is really not the way to practice medicine. 

We now have more evidence about what really is going on. A doctor was recently interviewed by ProPublica and said that she had worked for Cigna as a reviewer. Basically, the message she got from that insurer was to speed it up, go fast, and basically “deny, deny, deny” when she got requests. Those are her words, not mine.

We get a peek under the tent of how this works, and Dr. Day is basically saying she had to leave because she just didn’t feel that it was evidence-driven. It was driven by concerns about who’s going to lose money or make money.

If you want to check to see whether something is appropriate, the question becomes, who ought to do prior review? 

Who does it now? Sometimes doctors. Sometimes nurses who aren’t in the specialty where the request is coming in for preapproval. I’ve even seen situations where some companies use nurses in other countries, such as the Philippines, to do preapproval. They send them information, like a clip, to use to deny things that basically is boilerplate language, whatever the request is.

Looming up now, some insurers are starting to think, well, maybe artificial intelligence could do it. Just review the written request, trigger certain responses on the part of the artificial intelligence — it can deny the claims just as well as a human — and maybe it’s even cheaper to set up that system for the insurer.

This is ethically nuts. We need to have a system where doctors’ judgments drive what patients get. You listen to doctors, as I do, about preapproval access and they say patients sometimes give up trying to get what they think is needed. Continuity of care is interrupted if they have to keep making requests all the time.

There are adverse events when the thing that the doctor thought was most appropriate isn’t approved and something else is used that is less safe or less efficacious. It isn’t in patient interest to have the person with the wallet saying, this is what we think you need, and then having unqualified people or even automated intelligence with no accountability and no transparency get involved in preauthorization.

This system costs us money because middlemen are doing all this work. It basically becomes one of the huge scandals, in my view, of our health system, that doctors don’t ultimately decide what the patient needs. A preauthorizing third party or robot, without transparency, without accountability, and behind closed doors second-guesses what’s going on.

I’m Art Caplan at the Division of Medical Ethics at the New York University Grossman School of Medicine.

Arthur L. Caplan, Director, Division of Medical Ethics, New York University Langone Medical Center, New York, New York, has disclosed the following relevant financial relationships: Served as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). Serves as a contributing author and advisor for Medscape.

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

Federal officials intend to compel US hospitals to improve obstetrical services, with a plan that could result in a potential loss of Medicare and Medicaid funds for institutions that fail to comply with the demands.

The Centers for Medicare and Medicaid Services (CMS) on July 10 announced this proposal, tucking its plan for new conditions of participation (COP) for obstetrician services into the draft 2025 rule on Medicare payments for outpatient hospital services.

The COP requirements are considered the most powerful tool CMS has for trying to improve the quality of medical care. With the new obstetric COP requirement, CMS said it intends to address what it sees as potential shortfalls in training, staffing, transfer protocols, and emergency services readiness.

In practice, hospitals, CMS, and accrediting bodies such as the Joint Commission usually try to address deficiencies to prevent what would be a devastating financial loss for a hospital.

“CMS is using all of our tools to improve the safety, quality, and timeliness of the care that hospitals provide to pregnant women,” Dora Hughes, MD, MPH, acting chief medical officer of the agency, said in a press release about the proposal.

CMS estimated the proposal may add new annual expenses of $70,671 per hospital. For comparison, this figure would represent far less than 1% of the total $1.4 trillion spent on hospital care in the United States in 2022.

CMS said it is trying to address the reasons women in the United States face more risk in giving birth than those in other nations. There were 22 maternal deaths for every 100,000 live births in this country in 2022, compared with 8.6 deaths per 100,000 live births or lower that year in Canada, France, the United Kingdom, Germany, and Japan, CMS said.

But CMS is seeking to impose this new requirement at a time amid growing concerns about “maternity care deserts.”
 

Reasonable Asks?

Between 2011 and 2021, one out of every four rural hospitals in America stopped providing obstetrics services, Senate Finance Chairman Ron Wyden (D-Ore.) said at a May hearing. Mr. Wyden last year was part of a fight to try to prevent the closure of a birthing center in Baker City in rural eastern Oregon.

The federal government should focus first on helping hospitals keep obstetrical facilities open, said Elizabeth Powers, MD, MHA, the health services officer of the Winding Waters Clinic in Enterprise, Oregon.

“Until we can ensure access to services, we can’t even work on quality,” Dr. Powers told this news organization. “If you’re thinking about a Maslow’s hierarchy of achieving health outcomes, access is your foundation, and without a shift in payment, that foundation is eroded.”

In the draft rule, CMS sketched broad mandates about staffing and training. For example, the agency proposes requiring if a hospital offers obstetrical services, “the services must be well organized and provided in accordance with nationally recognized acceptable standards of practice.”

That means CMS likely will need to provide further guidance for hospitals if it proceeds with this plan for obstetric COP requirements, said Soumi Saha, PharmD, JD, senior vice president of government affairs at Premier Inc., a healthcare consultancy and purchasing organization.

Premier is among the many groups, including the American Hospital Association, that oppose the COP proposal.

Dr. Saha said a better approach would be to consolidate the work being done through the US Department of Health and Human Services (HHS), including earlier CMS projects, to address maternal health in a cohesive way. The Centers for Disease Control and Prevention has programs, as does the HHS Office on Women’s Health.

“How do we really get to a holistic, national, unified approach to addressing this issue that is led by HHS at the top level as the top agency and trickles down consistently versus having all of these kinds of disparate programs in place?” she said.

In recent years, the federal and state governments have taken many steps to try to improve maternal healthcare.

These include the extension of Medicaid benefits to new mothers out to 12 months following delivery in most states. CMS also has encouraged hospitals to participate in voluntary statewide or national programs to improve the quality of perinatal care. Last year the agency launched a “Birthing-Friendly” designation icon for qualifying hospitals on its Care Compare online tool.
 

Support and Opposition

CMS is accepting comments on the draft 2025 hospital outpatient rule, which includes the obstetric COP proposal, through September 9.

Supporters of the obstetric COP approach included the American Nurses Association (ANA), which urged CMS to consider how staffing shortages can undermine patient care in creating COP requirements.

“Nurses are professionals providing critical healthcare services to patients; they should not have to fight for allotted breaks and other challenges created by antiquated views of the profession and payment policies that disincentivize adequate nurse staffing,” Debbie Hatmaker, PhD, RN, ANA’s chief nursing officer, wrote in a June 7 comment to CMS.

The American College of Obstetricians and Gynecologists (ACOG) and the Association of American Medical Colleges (AAMC) also objected to the prospect of new COP for maternal healthcare. They detailed their concerns in separate comments submitted in June 2024.

ACOG said it feared many hospitals might opt to close labor and delivery (L&D) units due to new CMS COP requirements, especially if these take effect “without important and direct stakeholder engagement and buy-in.” More than 200 rural hospitals across the United States stopped providing L&D services in the last decade, Christopher M. Zahn, MD, ACOG’s interim chief executive officer, wrote in a comment to CMS.

“The reason for these closures is varied. Many rural hospitals that still have L&D units continue to lose money on patient services overall, and their ability to continue to deliver maternity care is at risk,” Dr. Zahn wrote.

The AAMC urged CMS to focus on using other strategies such as quality measures to try to improve maternal health and to drop the COP approach. CMS must consider how many clinicians play a role in successful births, including those who see patients during their pregnancies, Jonathan Jaffery, MD, MS, AAMC’s chief healthcare officer, wrote in a comment to the agency.

“Hospitals do have a critical role in improving maternal healthcare equity, especially for labor and delivery outcomes,” he wrote, “but cannot be held solely responsible for implementing much-needed improvements and solutions.”
 

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

Federal officials intend to compel US hospitals to improve obstetrical services, with a plan that could result in a potential loss of Medicare and Medicaid funds for institutions that fail to comply with the demands.

The Centers for Medicare and Medicaid Services (CMS) on July 10 announced this proposal, tucking its plan for new conditions of participation (COP) for obstetrician services into the draft 2025 rule on Medicare payments for outpatient hospital services.

The COP requirements are considered the most powerful tool CMS has for trying to improve the quality of medical care. With the new obstetric COP requirement, CMS said it intends to address what it sees as potential shortfalls in training, staffing, transfer protocols, and emergency services readiness.

In practice, hospitals, CMS, and accrediting bodies such as the Joint Commission usually try to address deficiencies to prevent what would be a devastating financial loss for a hospital.

“CMS is using all of our tools to improve the safety, quality, and timeliness of the care that hospitals provide to pregnant women,” Dora Hughes, MD, MPH, acting chief medical officer of the agency, said in a press release about the proposal.

CMS estimated the proposal may add new annual expenses of $70,671 per hospital. For comparison, this figure would represent far less than 1% of the total $1.4 trillion spent on hospital care in the United States in 2022.

CMS said it is trying to address the reasons women in the United States face more risk in giving birth than those in other nations. There were 22 maternal deaths for every 100,000 live births in this country in 2022, compared with 8.6 deaths per 100,000 live births or lower that year in Canada, France, the United Kingdom, Germany, and Japan, CMS said.

But CMS is seeking to impose this new requirement at a time amid growing concerns about “maternity care deserts.”
 

Reasonable Asks?

Between 2011 and 2021, one out of every four rural hospitals in America stopped providing obstetrics services, Senate Finance Chairman Ron Wyden (D-Ore.) said at a May hearing. Mr. Wyden last year was part of a fight to try to prevent the closure of a birthing center in Baker City in rural eastern Oregon.

The federal government should focus first on helping hospitals keep obstetrical facilities open, said Elizabeth Powers, MD, MHA, the health services officer of the Winding Waters Clinic in Enterprise, Oregon.

“Until we can ensure access to services, we can’t even work on quality,” Dr. Powers told this news organization. “If you’re thinking about a Maslow’s hierarchy of achieving health outcomes, access is your foundation, and without a shift in payment, that foundation is eroded.”

In the draft rule, CMS sketched broad mandates about staffing and training. For example, the agency proposes requiring if a hospital offers obstetrical services, “the services must be well organized and provided in accordance with nationally recognized acceptable standards of practice.”

That means CMS likely will need to provide further guidance for hospitals if it proceeds with this plan for obstetric COP requirements, said Soumi Saha, PharmD, JD, senior vice president of government affairs at Premier Inc., a healthcare consultancy and purchasing organization.

Premier is among the many groups, including the American Hospital Association, that oppose the COP proposal.

Dr. Saha said a better approach would be to consolidate the work being done through the US Department of Health and Human Services (HHS), including earlier CMS projects, to address maternal health in a cohesive way. The Centers for Disease Control and Prevention has programs, as does the HHS Office on Women’s Health.

“How do we really get to a holistic, national, unified approach to addressing this issue that is led by HHS at the top level as the top agency and trickles down consistently versus having all of these kinds of disparate programs in place?” she said.

In recent years, the federal and state governments have taken many steps to try to improve maternal healthcare.

These include the extension of Medicaid benefits to new mothers out to 12 months following delivery in most states. CMS also has encouraged hospitals to participate in voluntary statewide or national programs to improve the quality of perinatal care. Last year the agency launched a “Birthing-Friendly” designation icon for qualifying hospitals on its Care Compare online tool.
 

Support and Opposition

CMS is accepting comments on the draft 2025 hospital outpatient rule, which includes the obstetric COP proposal, through September 9.

Supporters of the obstetric COP approach included the American Nurses Association (ANA), which urged CMS to consider how staffing shortages can undermine patient care in creating COP requirements.

“Nurses are professionals providing critical healthcare services to patients; they should not have to fight for allotted breaks and other challenges created by antiquated views of the profession and payment policies that disincentivize adequate nurse staffing,” Debbie Hatmaker, PhD, RN, ANA’s chief nursing officer, wrote in a June 7 comment to CMS.

The American College of Obstetricians and Gynecologists (ACOG) and the Association of American Medical Colleges (AAMC) also objected to the prospect of new COP for maternal healthcare. They detailed their concerns in separate comments submitted in June 2024.

ACOG said it feared many hospitals might opt to close labor and delivery (L&D) units due to new CMS COP requirements, especially if these take effect “without important and direct stakeholder engagement and buy-in.” More than 200 rural hospitals across the United States stopped providing L&D services in the last decade, Christopher M. Zahn, MD, ACOG’s interim chief executive officer, wrote in a comment to CMS.

“The reason for these closures is varied. Many rural hospitals that still have L&D units continue to lose money on patient services overall, and their ability to continue to deliver maternity care is at risk,” Dr. Zahn wrote.

The AAMC urged CMS to focus on using other strategies such as quality measures to try to improve maternal health and to drop the COP approach. CMS must consider how many clinicians play a role in successful births, including those who see patients during their pregnancies, Jonathan Jaffery, MD, MS, AAMC’s chief healthcare officer, wrote in a comment to the agency.

“Hospitals do have a critical role in improving maternal healthcare equity, especially for labor and delivery outcomes,” he wrote, “but cannot be held solely responsible for implementing much-needed improvements and solutions.”
 

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

Federal officials intend to compel US hospitals to improve obstetrical services, with a plan that could result in a potential loss of Medicare and Medicaid funds for institutions that fail to comply with the demands.

The Centers for Medicare and Medicaid Services (CMS) on July 10 announced this proposal, tucking its plan for new conditions of participation (COP) for obstetrician services into the draft 2025 rule on Medicare payments for outpatient hospital services.

The COP requirements are considered the most powerful tool CMS has for trying to improve the quality of medical care. With the new obstetric COP requirement, CMS said it intends to address what it sees as potential shortfalls in training, staffing, transfer protocols, and emergency services readiness.

In practice, hospitals, CMS, and accrediting bodies such as the Joint Commission usually try to address deficiencies to prevent what would be a devastating financial loss for a hospital.

“CMS is using all of our tools to improve the safety, quality, and timeliness of the care that hospitals provide to pregnant women,” Dora Hughes, MD, MPH, acting chief medical officer of the agency, said in a press release about the proposal.

CMS estimated the proposal may add new annual expenses of $70,671 per hospital. For comparison, this figure would represent far less than 1% of the total $1.4 trillion spent on hospital care in the United States in 2022.

CMS said it is trying to address the reasons women in the United States face more risk in giving birth than those in other nations. There were 22 maternal deaths for every 100,000 live births in this country in 2022, compared with 8.6 deaths per 100,000 live births or lower that year in Canada, France, the United Kingdom, Germany, and Japan, CMS said.

But CMS is seeking to impose this new requirement at a time amid growing concerns about “maternity care deserts.”
 

Reasonable Asks?

Between 2011 and 2021, one out of every four rural hospitals in America stopped providing obstetrics services, Senate Finance Chairman Ron Wyden (D-Ore.) said at a May hearing. Mr. Wyden last year was part of a fight to try to prevent the closure of a birthing center in Baker City in rural eastern Oregon.

The federal government should focus first on helping hospitals keep obstetrical facilities open, said Elizabeth Powers, MD, MHA, the health services officer of the Winding Waters Clinic in Enterprise, Oregon.

“Until we can ensure access to services, we can’t even work on quality,” Dr. Powers told this news organization. “If you’re thinking about a Maslow’s hierarchy of achieving health outcomes, access is your foundation, and without a shift in payment, that foundation is eroded.”

In the draft rule, CMS sketched broad mandates about staffing and training. For example, the agency proposes requiring if a hospital offers obstetrical services, “the services must be well organized and provided in accordance with nationally recognized acceptable standards of practice.”

That means CMS likely will need to provide further guidance for hospitals if it proceeds with this plan for obstetric COP requirements, said Soumi Saha, PharmD, JD, senior vice president of government affairs at Premier Inc., a healthcare consultancy and purchasing organization.

Premier is among the many groups, including the American Hospital Association, that oppose the COP proposal.

Dr. Saha said a better approach would be to consolidate the work being done through the US Department of Health and Human Services (HHS), including earlier CMS projects, to address maternal health in a cohesive way. The Centers for Disease Control and Prevention has programs, as does the HHS Office on Women’s Health.

“How do we really get to a holistic, national, unified approach to addressing this issue that is led by HHS at the top level as the top agency and trickles down consistently versus having all of these kinds of disparate programs in place?” she said.

In recent years, the federal and state governments have taken many steps to try to improve maternal healthcare.

These include the extension of Medicaid benefits to new mothers out to 12 months following delivery in most states. CMS also has encouraged hospitals to participate in voluntary statewide or national programs to improve the quality of perinatal care. Last year the agency launched a “Birthing-Friendly” designation icon for qualifying hospitals on its Care Compare online tool.
 

Support and Opposition

CMS is accepting comments on the draft 2025 hospital outpatient rule, which includes the obstetric COP proposal, through September 9.

Supporters of the obstetric COP approach included the American Nurses Association (ANA), which urged CMS to consider how staffing shortages can undermine patient care in creating COP requirements.

“Nurses are professionals providing critical healthcare services to patients; they should not have to fight for allotted breaks and other challenges created by antiquated views of the profession and payment policies that disincentivize adequate nurse staffing,” Debbie Hatmaker, PhD, RN, ANA’s chief nursing officer, wrote in a June 7 comment to CMS.

The American College of Obstetricians and Gynecologists (ACOG) and the Association of American Medical Colleges (AAMC) also objected to the prospect of new COP for maternal healthcare. They detailed their concerns in separate comments submitted in June 2024.

ACOG said it feared many hospitals might opt to close labor and delivery (L&D) units due to new CMS COP requirements, especially if these take effect “without important and direct stakeholder engagement and buy-in.” More than 200 rural hospitals across the United States stopped providing L&D services in the last decade, Christopher M. Zahn, MD, ACOG’s interim chief executive officer, wrote in a comment to CMS.

“The reason for these closures is varied. Many rural hospitals that still have L&D units continue to lose money on patient services overall, and their ability to continue to deliver maternity care is at risk,” Dr. Zahn wrote.

The AAMC urged CMS to focus on using other strategies such as quality measures to try to improve maternal health and to drop the COP approach. CMS must consider how many clinicians play a role in successful births, including those who see patients during their pregnancies, Jonathan Jaffery, MD, MS, AAMC’s chief healthcare officer, wrote in a comment to the agency.

“Hospitals do have a critical role in improving maternal healthcare equity, especially for labor and delivery outcomes,” he wrote, “but cannot be held solely responsible for implementing much-needed improvements and solutions.”
 

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

TOPLINE:

Elevated blood levels of estradiol are associated with an increased risk for corneal ectasia, characterized by thinning and outward bulging of the tissue, in premenopausal women.

METHODOLOGY:

• Researchers conducted an observational case-control study of premenopausal women with naturally occurring corneal ectasia, named keratoconus (n = 36), or those who developed ectasia after refractive surgery (n = 29) from an eye clinic in Israel between 2019 and 2022, and healthy women from hospital staff (n = 31).
• The median age of the participants was 29, 33, and 31 years, respectively.
• Levels of estradiol in the study participants were measured on the second day of their menstrual cycles.

TAKEAWAY:

• The mean levels of estradiol were 38.0 pg/mL in patients with keratoconus, 43.4 pg/mL in those who developed ectasia after surgery, and 28.6 pg/mL in the healthy controls (all P = .001).
• Increased levels of estradiol were associated with corneal ectasia (adjusted odds ratio, 2.44; P < .001).
• Age and use of oral contraceptives were not associated with the risk for corneal ectasia.

IN PRACTICE:

“Our results could have an impact on patient selection for refractive surgery and on better management of patients with keratoconus,” the authors wrote.

SOURCE:

The study was led by Nir Stanescu, MD, of the Department of Ophthalmology at Assuta Samson Hospital, in Ashdod, Israel. It was published online in the European Journal of Ophthalmology.

LIMITATIONS:

The sample size of the study was relatively small. Causality could not be established due to cross-sectional design. The control group consisting of hospital staff may have led to selection bias. The study did not account for factors such as body mass index, diet, smoking status, alcohol consumption, and exercise, which may affect the circulating levels of estradiol.

DISCLOSURES:

The study did not receive any financial support. The authors declared no conflicts of interests.

This article was created 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.

TOPLINE:

Elevated blood levels of estradiol are associated with an increased risk for corneal ectasia, characterized by thinning and outward bulging of the tissue, in premenopausal women.

METHODOLOGY:

• Researchers conducted an observational case-control study of premenopausal women with naturally occurring corneal ectasia, named keratoconus (n = 36), or those who developed ectasia after refractive surgery (n = 29) from an eye clinic in Israel between 2019 and 2022, and healthy women from hospital staff (n = 31).
• The median age of the participants was 29, 33, and 31 years, respectively.
• Levels of estradiol in the study participants were measured on the second day of their menstrual cycles.

TAKEAWAY:

• The mean levels of estradiol were 38.0 pg/mL in patients with keratoconus, 43.4 pg/mL in those who developed ectasia after surgery, and 28.6 pg/mL in the healthy controls (all P = .001).
• Increased levels of estradiol were associated with corneal ectasia (adjusted odds ratio, 2.44; P < .001).
• Age and use of oral contraceptives were not associated with the risk for corneal ectasia.

IN PRACTICE:

“Our results could have an impact on patient selection for refractive surgery and on better management of patients with keratoconus,” the authors wrote.

SOURCE:

The study was led by Nir Stanescu, MD, of the Department of Ophthalmology at Assuta Samson Hospital, in Ashdod, Israel. It was published online in the European Journal of Ophthalmology.

LIMITATIONS:

The sample size of the study was relatively small. Causality could not be established due to cross-sectional design. The control group consisting of hospital staff may have led to selection bias. The study did not account for factors such as body mass index, diet, smoking status, alcohol consumption, and exercise, which may affect the circulating levels of estradiol.

DISCLOSURES:

The study did not receive any financial support. The authors declared no conflicts of interests.

This article was created 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.

TOPLINE:

Elevated blood levels of estradiol are associated with an increased risk for corneal ectasia, characterized by thinning and outward bulging of the tissue, in premenopausal women.

METHODOLOGY:

• Researchers conducted an observational case-control study of premenopausal women with naturally occurring corneal ectasia, named keratoconus (n = 36), or those who developed ectasia after refractive surgery (n = 29) from an eye clinic in Israel between 2019 and 2022, and healthy women from hospital staff (n = 31).
• The median age of the participants was 29, 33, and 31 years, respectively.
• Levels of estradiol in the study participants were measured on the second day of their menstrual cycles.

TAKEAWAY:

• The mean levels of estradiol were 38.0 pg/mL in patients with keratoconus, 43.4 pg/mL in those who developed ectasia after surgery, and 28.6 pg/mL in the healthy controls (all P = .001).
• Increased levels of estradiol were associated with corneal ectasia (adjusted odds ratio, 2.44; P < .001).
• Age and use of oral contraceptives were not associated with the risk for corneal ectasia.

IN PRACTICE:

“Our results could have an impact on patient selection for refractive surgery and on better management of patients with keratoconus,” the authors wrote.

SOURCE:

The study was led by Nir Stanescu, MD, of the Department of Ophthalmology at Assuta Samson Hospital, in Ashdod, Israel. It was published online in the European Journal of Ophthalmology.

LIMITATIONS:

The sample size of the study was relatively small. Causality could not be established due to cross-sectional design. The control group consisting of hospital staff may have led to selection bias. The study did not account for factors such as body mass index, diet, smoking status, alcohol consumption, and exercise, which may affect the circulating levels of estradiol.

DISCLOSURES:

The study did not receive any financial support. The authors declared no conflicts of interests.

This article was created 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.

When Bristeria Clark went into labor with her son in 2015, her contractions were steady at first. Then, they stalled. Her cervix stopped dilating. After a few hours, doctors at Phoebe Putney Memorial Hospital in Albany, Georgia, prepped Ms. Clark for an emergency cesarean section.

It wasn’t the vaginal birth Ms. Clark had hoped for during her pregnancy.

“I was freaking out. That was my first child. Like, of course you don’t plan that,” she said. “I just remember the gas pulling up to my face and I ended up going to sleep.”

She remembered feeling a rush of relief when she woke to see that her baby boy was healthy.

Ms. Clark, a 33-year-old nursing student who also works full-time in county government, had another C-section when her second child was born in 2020. This time, the cesarean was planned.

Ms. Clark said she’s grateful the physicians and nurses who delivered both her babies were kind and caring during her labor and delivery. But looking back, she said, she wishes she had had a doula for one-on-one support through pregnancy, childbirth, and the postpartum period. Now she wants to give other women the option she didn’t have.

Ms. Clark is a member of Morehouse School of Medicine’s first class of rural doulas, called Perinatal Patient Navigators.

The program recently graduated a dozen participants, all Black women from southwestern Georgia. They have completed more than 5 months of training and are scheduled to begin working with pregnant and postpartum patients this year.

“We’re developing a workforce that’s going to be providing the support that Black women and birthing people need,” Natalie Hernandez-Green, an associate professor of obstetrics and gynecology at Morehouse School of Medicine, Atlanta, Georgia, said at the doula commencement ceremony in Albany, Georgia.

Albany is Morehouse School of Medicine’s second Perinatal Patient Navigator program site. The first has been up and running in Atlanta since training began in the fall of 2022.

Georgia has one of the highest rates of maternal mortality in the country, according to an analysis by KFF, a health information nonprofit that includes KFF Health News. And Black Georgians are more than twice as likely as White Georgians to die of causes related to pregnancy.

“It doesn’t matter whether you’re rich or poor. Black women are dying at [an] alarming rate from pregnancy-related complications,” said Dr. Hernandez-Green, who is also executive director of the Center for Maternal Health Equity at Morehouse School of Medicine. “And we’re about to change that, one person at a time.”

The presence of a doula, along with regular nursing care, is associated with improved labor and delivery outcomes, reduced stress, and higher rates of patient satisfaction, according to the American College of Obstetricians and Gynecologists.

Multiple studies also link doulas to fewer expensive childbirth interventions, including cesarean births.

Doulas are not medical professionals. They are trained to offer education about the pregnancy and postpartum periods, to guide patients through the healthcare system, and to provide emotional and physical support before, during, and after childbirth.

Morehouse School of Medicine’s program is among a growing number of similar efforts being introduced across the country as more communities look to doulas to help address maternal mortality and poor maternal health outcomes, particularly for Black women and other women of color.

Now that she has graduated, Ms. Clark said she’s looking forward to helping other women in her community as a doula. “To be that person that would be there for my clients, treat them like a sister or like a mother, in a sense of just treating them with utmost respect,” she said. “The ultimate goal is to make them feel comfortable and let them know ‘I’m here to support you.’ ” Her training has inspired her to become an advocate for maternal health issues in southwestern Georgia.

Grants fund Morehouse School of Medicine’s doula program, which costs $350,000 a year to operate. Graduates are given a $2,000 training stipend and the program places five graduates with healthcare providers in southwestern Georgia. Grant money also pays the doulas’ salaries for 1 year. 

“It’s not sustainable if you’re chasing the next grant to fund it,” said Rachel Hardeman, a professor of health and racial equity at the University of Minnesota School of Public Health.

Thirteen states cover doulas through Medicaid, according to the Georgetown University Center for Children and Families.

Dr. Hardeman and others have found that when Medicaid programs cover doula care, states save millions of dollars in healthcare costs. “We were able to calculate the return on investment if Medicaid decided to reimburse doulas for pregnant people who are Medicaid beneficiaries,” she said.

That’s because doulas can help reduce the number of expensive medical interventions during and after birth, and improving delivery outcomes, including reduced cesarean sections.

Doulas can even reduce the likelihood of preterm birth. 

“An infant that is born at a very, very early gestational age is going to require a great deal of resources and interventions to ensure that they survive and then continue to thrive,” Dr. Hardeman said.

There is growing demand for doula services in Georgia, said Fowzio Jama, director of research for Healthy Mothers, Healthy Babies Coalition of Georgia. Her group recently completed a pilot study that offered doula services to about 170 Georgians covered under Medicaid. “We had a wait-list of over 200 clients and we wanted to give them the support that they needed, but we just couldn’t with the given resources that we had,” Ms. Jama said.

Doula services can cost hundreds or thousands of dollars out-of-pocket, making it too expensive for many low-income people, rural communities, and communities of color, many of which suffer from shortages in maternity care, according to the March of Dimes.

The Healthy Mothers, Healthy Babies study found that matching high-risk patients with doulas — particularly doulas from similar racial and ethnic backgrounds — had a positive effect on patients. 

“There was a reduced use of pitocin to induce labor. We saw fewer requests for pain medication. And with our infants, only 6% were low birth weight,” Ms. Jama said.

Still, she and others acknowledge that doulas alone can’t fix the problem of high maternal mortality and morbidity rates.

States, including Georgia, need to do more to bring comprehensive maternity care to communities that need more options, Dr. Hardeman said.

“I think it’s important to understand that doulas are not going to save us, and we should not put that expectation on them. Doulas are a tool,” she said. “They are a piece of the puzzle that is helping to impact a really, really complex issue.”

In the meantime, Joan Anderson, 55, said she’s excited to get to work supporting patients, especially from rural areas around Albany.

“I feel like I’m equipped to go out and be that voice, be that person that our community needs so bad,” said Ms. Anderson, a graduate of the Morehouse School of Medicine doula program. “I am encouraged to know that I will be joining in that mission, that fight for us, as far as maternal health is concerned.”

Ms. Anderson said that someday she wants to open a birthing center to provide maternity care. “We do not have one here in southwest Georgia at all,” Ms. Anderson said.

In addition to providing support during and after childbirth, Ms. Anderson and her fellow graduates are trained to assess their patients’ needs and connect them to services such as food assistance, mental health care, transportation to prenatal appointments, and breastfeeding assistance.

Their work is likely to have ripple effects across a largely rural corner of Georgia, said Sherrell Byrd, who co-founded and directs SOWEGA Rising, a nonprofit organization in southwestern Georgia.

“So many of the graduates are part of church networks, they are part of community organizations, some of them are our government workers. They’re very connected,” Ms. Byrd said. “And I think that connectedness is what’s going to help them be successful moving forward.”

This reporting is part of a fellowship with the Association of Health Care Journalists supported by The Commonwealth Fund. It comes from a partnership that includes WABE, NPR, and KFF Health News.

A version of this article first appeared on KFF Health News.

When Bristeria Clark went into labor with her son in 2015, her contractions were steady at first. Then, they stalled. Her cervix stopped dilating. After a few hours, doctors at Phoebe Putney Memorial Hospital in Albany, Georgia, prepped Ms. Clark for an emergency cesarean section.

It wasn’t the vaginal birth Ms. Clark had hoped for during her pregnancy.

“I was freaking out. That was my first child. Like, of course you don’t plan that,” she said. “I just remember the gas pulling up to my face and I ended up going to sleep.”

She remembered feeling a rush of relief when she woke to see that her baby boy was healthy.

Ms. Clark, a 33-year-old nursing student who also works full-time in county government, had another C-section when her second child was born in 2020. This time, the cesarean was planned.

Ms. Clark said she’s grateful the physicians and nurses who delivered both her babies were kind and caring during her labor and delivery. But looking back, she said, she wishes she had had a doula for one-on-one support through pregnancy, childbirth, and the postpartum period. Now she wants to give other women the option she didn’t have.

Ms. Clark is a member of Morehouse School of Medicine’s first class of rural doulas, called Perinatal Patient Navigators.

The program recently graduated a dozen participants, all Black women from southwestern Georgia. They have completed more than 5 months of training and are scheduled to begin working with pregnant and postpartum patients this year.

“We’re developing a workforce that’s going to be providing the support that Black women and birthing people need,” Natalie Hernandez-Green, an associate professor of obstetrics and gynecology at Morehouse School of Medicine, Atlanta, Georgia, said at the doula commencement ceremony in Albany, Georgia.

Albany is Morehouse School of Medicine’s second Perinatal Patient Navigator program site. The first has been up and running in Atlanta since training began in the fall of 2022.

Georgia has one of the highest rates of maternal mortality in the country, according to an analysis by KFF, a health information nonprofit that includes KFF Health News. And Black Georgians are more than twice as likely as White Georgians to die of causes related to pregnancy.

“It doesn’t matter whether you’re rich or poor. Black women are dying at [an] alarming rate from pregnancy-related complications,” said Dr. Hernandez-Green, who is also executive director of the Center for Maternal Health Equity at Morehouse School of Medicine. “And we’re about to change that, one person at a time.”

The presence of a doula, along with regular nursing care, is associated with improved labor and delivery outcomes, reduced stress, and higher rates of patient satisfaction, according to the American College of Obstetricians and Gynecologists.

Multiple studies also link doulas to fewer expensive childbirth interventions, including cesarean births.

Doulas are not medical professionals. They are trained to offer education about the pregnancy and postpartum periods, to guide patients through the healthcare system, and to provide emotional and physical support before, during, and after childbirth.

Morehouse School of Medicine’s program is among a growing number of similar efforts being introduced across the country as more communities look to doulas to help address maternal mortality and poor maternal health outcomes, particularly for Black women and other women of color.

Now that she has graduated, Ms. Clark said she’s looking forward to helping other women in her community as a doula. “To be that person that would be there for my clients, treat them like a sister or like a mother, in a sense of just treating them with utmost respect,” she said. “The ultimate goal is to make them feel comfortable and let them know ‘I’m here to support you.’ ” Her training has inspired her to become an advocate for maternal health issues in southwestern Georgia.

Grants fund Morehouse School of Medicine’s doula program, which costs $350,000 a year to operate. Graduates are given a $2,000 training stipend and the program places five graduates with healthcare providers in southwestern Georgia. Grant money also pays the doulas’ salaries for 1 year. 

“It’s not sustainable if you’re chasing the next grant to fund it,” said Rachel Hardeman, a professor of health and racial equity at the University of Minnesota School of Public Health.

Thirteen states cover doulas through Medicaid, according to the Georgetown University Center for Children and Families.

Dr. Hardeman and others have found that when Medicaid programs cover doula care, states save millions of dollars in healthcare costs. “We were able to calculate the return on investment if Medicaid decided to reimburse doulas for pregnant people who are Medicaid beneficiaries,” she said.

That’s because doulas can help reduce the number of expensive medical interventions during and after birth, and improving delivery outcomes, including reduced cesarean sections.

Doulas can even reduce the likelihood of preterm birth. 

“An infant that is born at a very, very early gestational age is going to require a great deal of resources and interventions to ensure that they survive and then continue to thrive,” Dr. Hardeman said.

There is growing demand for doula services in Georgia, said Fowzio Jama, director of research for Healthy Mothers, Healthy Babies Coalition of Georgia. Her group recently completed a pilot study that offered doula services to about 170 Georgians covered under Medicaid. “We had a wait-list of over 200 clients and we wanted to give them the support that they needed, but we just couldn’t with the given resources that we had,” Ms. Jama said.

Doula services can cost hundreds or thousands of dollars out-of-pocket, making it too expensive for many low-income people, rural communities, and communities of color, many of which suffer from shortages in maternity care, according to the March of Dimes.

The Healthy Mothers, Healthy Babies study found that matching high-risk patients with doulas — particularly doulas from similar racial and ethnic backgrounds — had a positive effect on patients. 

“There was a reduced use of pitocin to induce labor. We saw fewer requests for pain medication. And with our infants, only 6% were low birth weight,” Ms. Jama said.

Still, she and others acknowledge that doulas alone can’t fix the problem of high maternal mortality and morbidity rates.

States, including Georgia, need to do more to bring comprehensive maternity care to communities that need more options, Dr. Hardeman said.

“I think it’s important to understand that doulas are not going to save us, and we should not put that expectation on them. Doulas are a tool,” she said. “They are a piece of the puzzle that is helping to impact a really, really complex issue.”

In the meantime, Joan Anderson, 55, said she’s excited to get to work supporting patients, especially from rural areas around Albany.

“I feel like I’m equipped to go out and be that voice, be that person that our community needs so bad,” said Ms. Anderson, a graduate of the Morehouse School of Medicine doula program. “I am encouraged to know that I will be joining in that mission, that fight for us, as far as maternal health is concerned.”

Ms. Anderson said that someday she wants to open a birthing center to provide maternity care. “We do not have one here in southwest Georgia at all,” Ms. Anderson said.

In addition to providing support during and after childbirth, Ms. Anderson and her fellow graduates are trained to assess their patients’ needs and connect them to services such as food assistance, mental health care, transportation to prenatal appointments, and breastfeeding assistance.

Their work is likely to have ripple effects across a largely rural corner of Georgia, said Sherrell Byrd, who co-founded and directs SOWEGA Rising, a nonprofit organization in southwestern Georgia.

“So many of the graduates are part of church networks, they are part of community organizations, some of them are our government workers. They’re very connected,” Ms. Byrd said. “And I think that connectedness is what’s going to help them be successful moving forward.”

This reporting is part of a fellowship with the Association of Health Care Journalists supported by The Commonwealth Fund. It comes from a partnership that includes WABE, NPR, and KFF Health News.

A version of this article first appeared on KFF Health News.

When Bristeria Clark went into labor with her son in 2015, her contractions were steady at first. Then, they stalled. Her cervix stopped dilating. After a few hours, doctors at Phoebe Putney Memorial Hospital in Albany, Georgia, prepped Ms. Clark for an emergency cesarean section.

It wasn’t the vaginal birth Ms. Clark had hoped for during her pregnancy.

“I was freaking out. That was my first child. Like, of course you don’t plan that,” she said. “I just remember the gas pulling up to my face and I ended up going to sleep.”

She remembered feeling a rush of relief when she woke to see that her baby boy was healthy.

Ms. Clark, a 33-year-old nursing student who also works full-time in county government, had another C-section when her second child was born in 2020. This time, the cesarean was planned.

Ms. Clark said she’s grateful the physicians and nurses who delivered both her babies were kind and caring during her labor and delivery. But looking back, she said, she wishes she had had a doula for one-on-one support through pregnancy, childbirth, and the postpartum period. Now she wants to give other women the option she didn’t have.

Ms. Clark is a member of Morehouse School of Medicine’s first class of rural doulas, called Perinatal Patient Navigators.

The program recently graduated a dozen participants, all Black women from southwestern Georgia. They have completed more than 5 months of training and are scheduled to begin working with pregnant and postpartum patients this year.

“We’re developing a workforce that’s going to be providing the support that Black women and birthing people need,” Natalie Hernandez-Green, an associate professor of obstetrics and gynecology at Morehouse School of Medicine, Atlanta, Georgia, said at the doula commencement ceremony in Albany, Georgia.

Albany is Morehouse School of Medicine’s second Perinatal Patient Navigator program site. The first has been up and running in Atlanta since training began in the fall of 2022.

Georgia has one of the highest rates of maternal mortality in the country, according to an analysis by KFF, a health information nonprofit that includes KFF Health News. And Black Georgians are more than twice as likely as White Georgians to die of causes related to pregnancy.

“It doesn’t matter whether you’re rich or poor. Black women are dying at [an] alarming rate from pregnancy-related complications,” said Dr. Hernandez-Green, who is also executive director of the Center for Maternal Health Equity at Morehouse School of Medicine. “And we’re about to change that, one person at a time.”

The presence of a doula, along with regular nursing care, is associated with improved labor and delivery outcomes, reduced stress, and higher rates of patient satisfaction, according to the American College of Obstetricians and Gynecologists.

Multiple studies also link doulas to fewer expensive childbirth interventions, including cesarean births.

Doulas are not medical professionals. They are trained to offer education about the pregnancy and postpartum periods, to guide patients through the healthcare system, and to provide emotional and physical support before, during, and after childbirth.

Morehouse School of Medicine’s program is among a growing number of similar efforts being introduced across the country as more communities look to doulas to help address maternal mortality and poor maternal health outcomes, particularly for Black women and other women of color.

Now that she has graduated, Ms. Clark said she’s looking forward to helping other women in her community as a doula. “To be that person that would be there for my clients, treat them like a sister or like a mother, in a sense of just treating them with utmost respect,” she said. “The ultimate goal is to make them feel comfortable and let them know ‘I’m here to support you.’ ” Her training has inspired her to become an advocate for maternal health issues in southwestern Georgia.

Grants fund Morehouse School of Medicine’s doula program, which costs $350,000 a year to operate. Graduates are given a $2,000 training stipend and the program places five graduates with healthcare providers in southwestern Georgia. Grant money also pays the doulas’ salaries for 1 year. 

“It’s not sustainable if you’re chasing the next grant to fund it,” said Rachel Hardeman, a professor of health and racial equity at the University of Minnesota School of Public Health.

Thirteen states cover doulas through Medicaid, according to the Georgetown University Center for Children and Families.

Dr. Hardeman and others have found that when Medicaid programs cover doula care, states save millions of dollars in healthcare costs. “We were able to calculate the return on investment if Medicaid decided to reimburse doulas for pregnant people who are Medicaid beneficiaries,” she said.

That’s because doulas can help reduce the number of expensive medical interventions during and after birth, and improving delivery outcomes, including reduced cesarean sections.

Doulas can even reduce the likelihood of preterm birth. 

“An infant that is born at a very, very early gestational age is going to require a great deal of resources and interventions to ensure that they survive and then continue to thrive,” Dr. Hardeman said.

There is growing demand for doula services in Georgia, said Fowzio Jama, director of research for Healthy Mothers, Healthy Babies Coalition of Georgia. Her group recently completed a pilot study that offered doula services to about 170 Georgians covered under Medicaid. “We had a wait-list of over 200 clients and we wanted to give them the support that they needed, but we just couldn’t with the given resources that we had,” Ms. Jama said.

Doula services can cost hundreds or thousands of dollars out-of-pocket, making it too expensive for many low-income people, rural communities, and communities of color, many of which suffer from shortages in maternity care, according to the March of Dimes.

The Healthy Mothers, Healthy Babies study found that matching high-risk patients with doulas — particularly doulas from similar racial and ethnic backgrounds — had a positive effect on patients. 

“There was a reduced use of pitocin to induce labor. We saw fewer requests for pain medication. And with our infants, only 6% were low birth weight,” Ms. Jama said.

Still, she and others acknowledge that doulas alone can’t fix the problem of high maternal mortality and morbidity rates.

States, including Georgia, need to do more to bring comprehensive maternity care to communities that need more options, Dr. Hardeman said.

“I think it’s important to understand that doulas are not going to save us, and we should not put that expectation on them. Doulas are a tool,” she said. “They are a piece of the puzzle that is helping to impact a really, really complex issue.”

In the meantime, Joan Anderson, 55, said she’s excited to get to work supporting patients, especially from rural areas around Albany.

“I feel like I’m equipped to go out and be that voice, be that person that our community needs so bad,” said Ms. Anderson, a graduate of the Morehouse School of Medicine doula program. “I am encouraged to know that I will be joining in that mission, that fight for us, as far as maternal health is concerned.”

Ms. Anderson said that someday she wants to open a birthing center to provide maternity care. “We do not have one here in southwest Georgia at all,” Ms. Anderson said.

In addition to providing support during and after childbirth, Ms. Anderson and her fellow graduates are trained to assess their patients’ needs and connect them to services such as food assistance, mental health care, transportation to prenatal appointments, and breastfeeding assistance.

Their work is likely to have ripple effects across a largely rural corner of Georgia, said Sherrell Byrd, who co-founded and directs SOWEGA Rising, a nonprofit organization in southwestern Georgia.

“So many of the graduates are part of church networks, they are part of community organizations, some of them are our government workers. They’re very connected,” Ms. Byrd said. “And I think that connectedness is what’s going to help them be successful moving forward.”

This reporting is part of a fellowship with the Association of Health Care Journalists supported by The Commonwealth Fund. It comes from a partnership that includes WABE, NPR, and KFF Health News.

A version of this article first appeared on KFF Health News.

The CDK4/6 inhibitors abemaciclib and ribociclib were independently associated with better progression-free survival (PFS) when compared with palbociclib in a real-world comparison of the agents as first line treatment, along with endocrine therapy (ET), for patients with hormone receptor–positive, HER2-negative advanced breast cancer.

Lead investigator Claudio Vernieri, MD, PhD, presented these findings of the PALMARES-2 study at the annual meeting of the American Society of Clinical Oncology.

“Along with different safety profiles, drug-drug interactions, and costs of the three available CDK4/6 inhibitor molecules, our efficacy data may help clinicians and patients in choosing the most appropriate CDK4/6 inhibitor in specific clinical contexts,” Dr. Vernieri, who is from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, said during the meeting.

CDK4/6 inhibitors combined with ET, are the standard of care as first line treatment for this population, noted Dr. Vernieri. However, their efficacy has never been directly compared in a large clinical trial.

“Since these compounds have different pharmacokinetics, pharmacodynamics, safety profiles, costs, and drug-drug interactions, identifying which of the three CDK4/6 inhibitors may be more effective in specific clinical contexts is a highly clinically relevant issue,” he said. “Real-world data represent a key source to perform direct comparisons.”

The PALMARES-2 study was a retrospective, multicenter, population-based study, in 18 Italian cancer centers. Its two main objectives were to compare the real-world PFS of abemaciclib versus ribociclib versus palbociclib, in combination with ET, in the whole study cohort, as well as in various subgroups including patients with endocrine-resistant disease, luminal B-like disease, or in premenopausal women.

A total of 1,850 patients (median age, 63 years) were enrolled between January 1, 2016 and September 1, 2023, with 750 (40.6%) receiving palbociclib, and 676 (36.5%) and 424 (22.9%) receiving ribociclib and abemaciclib, respectively.
 

Baseline imbalance

Importantly, there were significant imbalances in baseline characteristics of the patients, with those receiving abemaciclib being more likely to have endocrine-resistant disease, low progesterone receptor expression, and liver metastasis, and less likely to have de novo metastatic disease, compared with other patients, said Dr. Vernieri.

The analysis showed that across the entire cohort, the median real-world PFS and overall survival (OS) were 34.7 months and 66.6 months, respectively, by a January 1, 2024, data cutoff date. “I believe that the overall survival data are still immature to make a definitive conclusion,” he commented, noting that at enrollment only about half of patients had undergone disease progression, and at the close of the study only about 25% had died.

After adjusting for clinically relevant patient- and tumor-related covariates, “we found that both abemaciclib and ribociclib were more effective than palbociclib, whereas we did not find statistically significant differences between abemaciclib and ribociclib,” he reported.

Specifically, the adjusted hazard ratio (aHR) for PFS was 0.71 for abemaciclib versus palbociclib (95% CI, 0.56-0.90; P = .005), 0.81 for ribociclib versus palbociclib (95% CI, 0.65-0.99; P = .048), and 0.91 for abemaciclib versus ribociclib (95% CI, 0.70-1.19; P = .505).

“Regarding subgroup analysis, we found that abemaciclib and ribociclib were more effective than palbociclib in patients with endocrine-resistant or luminal B-like disease, as well as in premenopausal women. Abemaciclib was superior to palbociclib in patients with poorer ECOG [Eastern Cooperative Oncology Group] performance status and to both palbociclib and ribociclib in patients with de novo metastatic disease. Both ribociclib and abemaciclib showed a trend toward higher efficacy in patients with liver metastases. However, this difference only reached statistical significance in patients treated with ribociclib. And finally, the three CDK4/6 inhibitors were similarly effective in patients who were older or at bone-only disease,” he concluded.
 

Justifying adjustment

Speaking during the audience question period Giuseppe Del Priore, MD, from Morehouse School of Medicine in Atlanta, Georgia, said he preferred unadjusted results when examining real-world data, “because that’s the benefit,” and he questioned why the researchers had adjusted their numbers.

Dr. Vernieri explained that the adjustments were made to account for the important imbalances in the baseline characteristics of the patients.

“When we plotted unadjusted curves, we did not find statistically significant differences between these three drugs, only a trend toward the direction that I showed you today,” he said. “However, as you saw from the tables showing the characteristics of patients, there were important imbalances in terms of important prognostic factors in the three patient cohorts. So, I think that, for this kind of data and based on this level of imbalance, adjustment is necessary.

“To reinforce our conclusions, what we did was also to perform a propensity score match–based analysis,” Dr. Vernieri continued. “I did not have the time to show the results today, but these data were fully in line with the study conclusions. And we also performed a backward selection of variables. So, we basically selected variables more likely to be associated with patient prognosis. And also those models confirm the study conclusion. So I think the conclusions are quite solid.”

Dr. Del Priore, an adjunct professor of obstetrics and gynecology with a specialty in oncology, on the other hand, said he was not convinced that any of the drugs might be better or worse in the actual population treated.

“I still maintain that unadjusted real-world data should be presented and then only a limited adjusted analysis performed using the most unbalanced variables,” he said. “To do more elaborate adjustments may falsely imply a difference in drug choice and outcomes which never should be the conclusion with observational studies. Instead, the conclusions should be that, with typical use, the following similarities in PFS and OS were observed. Then point out how drug choice and important prognostic variables might be linked, thus limiting the generalizable conclusions even further.

“I would conclude that prospective studies should balance for the variables used in the PALMARES-2 analyses, which actually may have been chosen for adjustment post hoc,” Dr. Del Priore said.

The study was funded by the Italian Association for Cancer Research, the European Research Council, the Ministero della Salute, the Scientific Directorate of Fondazione IRCCS Istituto Nazionale dei Tumori, Giuliani’s Foundation and Roche. Dr. Vernieri reported consulting or advisory roles with Daiichi Sankyo/Astra Zeneca, Novartis, and Pfizer; speakers’ bureau roles with Accademia Nazionale Di Medicina (ACCMED), Istituto Gentili, Lilly and Novartis; and research funding from Roche. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

The CDK4/6 inhibitors abemaciclib and ribociclib were independently associated with better progression-free survival (PFS) when compared with palbociclib in a real-world comparison of the agents as first line treatment, along with endocrine therapy (ET), for patients with hormone receptor–positive, HER2-negative advanced breast cancer.

Lead investigator Claudio Vernieri, MD, PhD, presented these findings of the PALMARES-2 study at the annual meeting of the American Society of Clinical Oncology.

“Along with different safety profiles, drug-drug interactions, and costs of the three available CDK4/6 inhibitor molecules, our efficacy data may help clinicians and patients in choosing the most appropriate CDK4/6 inhibitor in specific clinical contexts,” Dr. Vernieri, who is from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, said during the meeting.

CDK4/6 inhibitors combined with ET, are the standard of care as first line treatment for this population, noted Dr. Vernieri. However, their efficacy has never been directly compared in a large clinical trial.

“Since these compounds have different pharmacokinetics, pharmacodynamics, safety profiles, costs, and drug-drug interactions, identifying which of the three CDK4/6 inhibitors may be more effective in specific clinical contexts is a highly clinically relevant issue,” he said. “Real-world data represent a key source to perform direct comparisons.”

The PALMARES-2 study was a retrospective, multicenter, population-based study, in 18 Italian cancer centers. Its two main objectives were to compare the real-world PFS of abemaciclib versus ribociclib versus palbociclib, in combination with ET, in the whole study cohort, as well as in various subgroups including patients with endocrine-resistant disease, luminal B-like disease, or in premenopausal women.

A total of 1,850 patients (median age, 63 years) were enrolled between January 1, 2016 and September 1, 2023, with 750 (40.6%) receiving palbociclib, and 676 (36.5%) and 424 (22.9%) receiving ribociclib and abemaciclib, respectively.
 

Baseline imbalance

Importantly, there were significant imbalances in baseline characteristics of the patients, with those receiving abemaciclib being more likely to have endocrine-resistant disease, low progesterone receptor expression, and liver metastasis, and less likely to have de novo metastatic disease, compared with other patients, said Dr. Vernieri.

The analysis showed that across the entire cohort, the median real-world PFS and overall survival (OS) were 34.7 months and 66.6 months, respectively, by a January 1, 2024, data cutoff date. “I believe that the overall survival data are still immature to make a definitive conclusion,” he commented, noting that at enrollment only about half of patients had undergone disease progression, and at the close of the study only about 25% had died.

After adjusting for clinically relevant patient- and tumor-related covariates, “we found that both abemaciclib and ribociclib were more effective than palbociclib, whereas we did not find statistically significant differences between abemaciclib and ribociclib,” he reported.

Specifically, the adjusted hazard ratio (aHR) for PFS was 0.71 for abemaciclib versus palbociclib (95% CI, 0.56-0.90; P = .005), 0.81 for ribociclib versus palbociclib (95% CI, 0.65-0.99; P = .048), and 0.91 for abemaciclib versus ribociclib (95% CI, 0.70-1.19; P = .505).

“Regarding subgroup analysis, we found that abemaciclib and ribociclib were more effective than palbociclib in patients with endocrine-resistant or luminal B-like disease, as well as in premenopausal women. Abemaciclib was superior to palbociclib in patients with poorer ECOG [Eastern Cooperative Oncology Group] performance status and to both palbociclib and ribociclib in patients with de novo metastatic disease. Both ribociclib and abemaciclib showed a trend toward higher efficacy in patients with liver metastases. However, this difference only reached statistical significance in patients treated with ribociclib. And finally, the three CDK4/6 inhibitors were similarly effective in patients who were older or at bone-only disease,” he concluded.
 

Justifying adjustment

Speaking during the audience question period Giuseppe Del Priore, MD, from Morehouse School of Medicine in Atlanta, Georgia, said he preferred unadjusted results when examining real-world data, “because that’s the benefit,” and he questioned why the researchers had adjusted their numbers.

Dr. Vernieri explained that the adjustments were made to account for the important imbalances in the baseline characteristics of the patients.

“When we plotted unadjusted curves, we did not find statistically significant differences between these three drugs, only a trend toward the direction that I showed you today,” he said. “However, as you saw from the tables showing the characteristics of patients, there were important imbalances in terms of important prognostic factors in the three patient cohorts. So, I think that, for this kind of data and based on this level of imbalance, adjustment is necessary.

“To reinforce our conclusions, what we did was also to perform a propensity score match–based analysis,” Dr. Vernieri continued. “I did not have the time to show the results today, but these data were fully in line with the study conclusions. And we also performed a backward selection of variables. So, we basically selected variables more likely to be associated with patient prognosis. And also those models confirm the study conclusion. So I think the conclusions are quite solid.”

Dr. Del Priore, an adjunct professor of obstetrics and gynecology with a specialty in oncology, on the other hand, said he was not convinced that any of the drugs might be better or worse in the actual population treated.

“I still maintain that unadjusted real-world data should be presented and then only a limited adjusted analysis performed using the most unbalanced variables,” he said. “To do more elaborate adjustments may falsely imply a difference in drug choice and outcomes which never should be the conclusion with observational studies. Instead, the conclusions should be that, with typical use, the following similarities in PFS and OS were observed. Then point out how drug choice and important prognostic variables might be linked, thus limiting the generalizable conclusions even further.

“I would conclude that prospective studies should balance for the variables used in the PALMARES-2 analyses, which actually may have been chosen for adjustment post hoc,” Dr. Del Priore said.

The study was funded by the Italian Association for Cancer Research, the European Research Council, the Ministero della Salute, the Scientific Directorate of Fondazione IRCCS Istituto Nazionale dei Tumori, Giuliani’s Foundation and Roche. Dr. Vernieri reported consulting or advisory roles with Daiichi Sankyo/Astra Zeneca, Novartis, and Pfizer; speakers’ bureau roles with Accademia Nazionale Di Medicina (ACCMED), Istituto Gentili, Lilly and Novartis; and research funding from Roche. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

The CDK4/6 inhibitors abemaciclib and ribociclib were independently associated with better progression-free survival (PFS) when compared with palbociclib in a real-world comparison of the agents as first line treatment, along with endocrine therapy (ET), for patients with hormone receptor–positive, HER2-negative advanced breast cancer.

Lead investigator Claudio Vernieri, MD, PhD, presented these findings of the PALMARES-2 study at the annual meeting of the American Society of Clinical Oncology.

“Along with different safety profiles, drug-drug interactions, and costs of the three available CDK4/6 inhibitor molecules, our efficacy data may help clinicians and patients in choosing the most appropriate CDK4/6 inhibitor in specific clinical contexts,” Dr. Vernieri, who is from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, said during the meeting.

CDK4/6 inhibitors combined with ET, are the standard of care as first line treatment for this population, noted Dr. Vernieri. However, their efficacy has never been directly compared in a large clinical trial.

“Since these compounds have different pharmacokinetics, pharmacodynamics, safety profiles, costs, and drug-drug interactions, identifying which of the three CDK4/6 inhibitors may be more effective in specific clinical contexts is a highly clinically relevant issue,” he said. “Real-world data represent a key source to perform direct comparisons.”

The PALMARES-2 study was a retrospective, multicenter, population-based study, in 18 Italian cancer centers. Its two main objectives were to compare the real-world PFS of abemaciclib versus ribociclib versus palbociclib, in combination with ET, in the whole study cohort, as well as in various subgroups including patients with endocrine-resistant disease, luminal B-like disease, or in premenopausal women.

A total of 1,850 patients (median age, 63 years) were enrolled between January 1, 2016 and September 1, 2023, with 750 (40.6%) receiving palbociclib, and 676 (36.5%) and 424 (22.9%) receiving ribociclib and abemaciclib, respectively.
 

Baseline imbalance

Importantly, there were significant imbalances in baseline characteristics of the patients, with those receiving abemaciclib being more likely to have endocrine-resistant disease, low progesterone receptor expression, and liver metastasis, and less likely to have de novo metastatic disease, compared with other patients, said Dr. Vernieri.

The analysis showed that across the entire cohort, the median real-world PFS and overall survival (OS) were 34.7 months and 66.6 months, respectively, by a January 1, 2024, data cutoff date. “I believe that the overall survival data are still immature to make a definitive conclusion,” he commented, noting that at enrollment only about half of patients had undergone disease progression, and at the close of the study only about 25% had died.

After adjusting for clinically relevant patient- and tumor-related covariates, “we found that both abemaciclib and ribociclib were more effective than palbociclib, whereas we did not find statistically significant differences between abemaciclib and ribociclib,” he reported.

Specifically, the adjusted hazard ratio (aHR) for PFS was 0.71 for abemaciclib versus palbociclib (95% CI, 0.56-0.90; P = .005), 0.81 for ribociclib versus palbociclib (95% CI, 0.65-0.99; P = .048), and 0.91 for abemaciclib versus ribociclib (95% CI, 0.70-1.19; P = .505).

“Regarding subgroup analysis, we found that abemaciclib and ribociclib were more effective than palbociclib in patients with endocrine-resistant or luminal B-like disease, as well as in premenopausal women. Abemaciclib was superior to palbociclib in patients with poorer ECOG [Eastern Cooperative Oncology Group] performance status and to both palbociclib and ribociclib in patients with de novo metastatic disease. Both ribociclib and abemaciclib showed a trend toward higher efficacy in patients with liver metastases. However, this difference only reached statistical significance in patients treated with ribociclib. And finally, the three CDK4/6 inhibitors were similarly effective in patients who were older or at bone-only disease,” he concluded.
 

Justifying adjustment

Speaking during the audience question period Giuseppe Del Priore, MD, from Morehouse School of Medicine in Atlanta, Georgia, said he preferred unadjusted results when examining real-world data, “because that’s the benefit,” and he questioned why the researchers had adjusted their numbers.

Dr. Vernieri explained that the adjustments were made to account for the important imbalances in the baseline characteristics of the patients.

“When we plotted unadjusted curves, we did not find statistically significant differences between these three drugs, only a trend toward the direction that I showed you today,” he said. “However, as you saw from the tables showing the characteristics of patients, there were important imbalances in terms of important prognostic factors in the three patient cohorts. So, I think that, for this kind of data and based on this level of imbalance, adjustment is necessary.

“To reinforce our conclusions, what we did was also to perform a propensity score match–based analysis,” Dr. Vernieri continued. “I did not have the time to show the results today, but these data were fully in line with the study conclusions. And we also performed a backward selection of variables. So, we basically selected variables more likely to be associated with patient prognosis. And also those models confirm the study conclusion. So I think the conclusions are quite solid.”

Dr. Del Priore, an adjunct professor of obstetrics and gynecology with a specialty in oncology, on the other hand, said he was not convinced that any of the drugs might be better or worse in the actual population treated.

“I still maintain that unadjusted real-world data should be presented and then only a limited adjusted analysis performed using the most unbalanced variables,” he said. “To do more elaborate adjustments may falsely imply a difference in drug choice and outcomes which never should be the conclusion with observational studies. Instead, the conclusions should be that, with typical use, the following similarities in PFS and OS were observed. Then point out how drug choice and important prognostic variables might be linked, thus limiting the generalizable conclusions even further.

“I would conclude that prospective studies should balance for the variables used in the PALMARES-2 analyses, which actually may have been chosen for adjustment post hoc,” Dr. Del Priore said.

The study was funded by the Italian Association for Cancer Research, the European Research Council, the Ministero della Salute, the Scientific Directorate of Fondazione IRCCS Istituto Nazionale dei Tumori, Giuliani’s Foundation and Roche. Dr. Vernieri reported consulting or advisory roles with Daiichi Sankyo/Astra Zeneca, Novartis, and Pfizer; speakers’ bureau roles with Accademia Nazionale Di Medicina (ACCMED), Istituto Gentili, Lilly and Novartis; and research funding from Roche. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

TOPLINE:

Patients with stage I triple-negative breast cancer (TNBC) who have higher levels of stromal tumor-infiltrating lymphocytes (TILs) demonstrate “excellent” 10-year breast cancer–specific survival without chemotherapy, according to new findings, which suggest that stromal TILs could be a useful biomarker to optimize treatment decisions in this patient population.

METHODOLOGY:

• The absolute benefit of chemotherapy remains unclear among patients with stage I TNBC. High levels of stromal TILs, a promising biomarker, have been linked to better survival in patients with TNBC, but data focused on stage I disease are lacking.
• In the current analysis, researchers identified a cohort of 1041 women (mean age at diagnosis, 64.4 years) from the Netherlands Cancer Registry with stage I TNBC who had an available TIL score and had undergone a lumpectomy or a mastectomy but had not received neoadjuvant or adjuvant chemotherapy.
• Patients’ clinical data were matched to their corresponding pathologic data provided by the Dutch Pathology Registry, and a pathologist blinded to outcomes scored stromal TIL levels according to the International Immuno-Oncology Biomarker Working Group guidelines.
• The primary endpoint was breast cancer–specific survival at prespecified stromal TIL cutoffs of 30%, 50%, and 75%. Secondary outcomes included specific survival by pathologic tumor stage and overall survival.

TAKEAWAY:

• Overall, 8.6% of women had a pT1a tumor, 38.7% had a pT1b tumor, and 52.6% had a pT1c tumor. In the cohort, 25.6% of patients had stromal TIL levels of 30% or higher, 19.5% had levels of 50% or higher, and 13.5% had levels of 75% or higher.
• Over a median follow-up of 11.4 years, 335 patients died, 107 (32%) of whom died from breast cancer. Patients with smaller tumors (pT1abNO) had better survival outcomes than those with larger tumors (pT1cNO) — a 10-year breast cancer–specific survival of 92% vs 86%, respectively.
• In the overall cohort, stromal TIL levels of 30% or higher were associated with better breast cancer–specific survival than those with stromal TIL levels below 30% (96% vs 87%; hazard ratio [HR], 0.45). Stromal TIL levels of 50% or greater were also associated with better 10-year breast cancer–specific survival than those with levels below 50% (92% vs 88%; HR, 0.59). A similar pattern was observed for stromal TIL levels and overall survival.
• In patients with pT1c tumors, the 10-year breast cancer–specific survival among those with stromal TIL levels of 30% or higher was 95% vs 83% for levels below the 30% cutoff (HR, 0.24). Similarly, the 10-year breast cancer–specific survival for those in the 50% or higher group was 95% vs 84% for levels below that cutoff (HR, 0.27). The 10-year breast cancer–specific survival improved to 98% among patients with stromal TIL levels of 75% or higher (HR, 0.09).