User login
Sexual assault in women tied to increased stroke, dementia risk
Traumatic experiences, especially sexual assault, may put women at greater risk for poor brain health.
In the Ms Brain study, middle-aged women with trauma exposure had a greater volume of white matter hyperintensities (WMHs) than those without trauma. In addition, the differences persisted even after adjusting for depressive or post-traumatic stress symptoms.
WMHs are “an important indicator of small vessel disease in the brain and have been linked to future stroke risk, dementia risk, and mortality,” lead investigator Rebecca Thurston, PhD, from the University of Pittsburgh, told this news organization.
“What I take from this is, really, that sexual assault has implications for women’s health, far beyond exclusively mental health outcomes, but also for their cardiovascular health, as we have shown in other work and for their stroke and dementia risk as we are seeing in the present work,” Dr. Thurston added.
The study was presented at the North American Menopause Society (NAMS) Annual Meeting in Washington, D.C., and has been accepted for publication in the journal Brain Imaging and Behavior.
Beyond the usual suspects
As part of the study, 145 women (mean age, 59 years) free of clinical cardiovascular disease, stroke, or dementia provided their medical history, including history of traumatic experiences, depression, and post-traumatic stress disorder and underwent magnetic resonance brain imaging for WMHs.
More than two-thirds (68%) of the women reported at least one trauma, most commonly sexual assault (23%).
In multivariate analysis, women with trauma exposure had greater WMH volume than women without trauma (P = .01), with sexual assault most strongly associated with greater WMH volume (P = .02).
The associations persisted after adjusting for depressive or post-traumatic stress symptoms.
“A history of sexual assault was particularly related to white matter hyperintensities in the parietal lobe, and these kinds of white matter hyperintensities have been linked to Alzheimer’s disease in a fairly pronounced way,” Dr. Thurston said.
“When we think about risk factors for stroke, dementia, we need to think beyond exclusively our usual suspects and also think about women [who experienced] psychological trauma and experienced sexual assault in particular. So ask about it and consider it part of your screening regimen,” she added.
‘Burgeoning’ literature
Commenting on the findings, Charles Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, Dell Medical School, University of Texas at Austin, and director of its Institute for Early Life Adversity Research, said the research adds to the “burgeoning literature on the long term neurobiological consequences of trauma and more specifically, sexual abuse, on brain imaging measures.”
“Our group and others reported several years ago that patients with mood disorders, more specifically bipolar disorder and major depression, had higher rates of WMH than matched controls. Those older studies did not control for a history of early life adversity such as childhood maltreatment,” Dr. Nemeroff said.
“In addition to this finding of increased WMH in subjects exposed to trauma is a very large literature documenting other central nervous system (CNS) changes in this population, including cortical thinning in certain brain areas and clearly an emerging finding that different forms of childhood maltreatment are associated with quite distinct structural brain alterations in adulthood,” he noted.
The study was supported by grants from the National Institutes of Health. Dr. Thurston and Dr. Nemeroff have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Traumatic experiences, especially sexual assault, may put women at greater risk for poor brain health.
In the Ms Brain study, middle-aged women with trauma exposure had a greater volume of white matter hyperintensities (WMHs) than those without trauma. In addition, the differences persisted even after adjusting for depressive or post-traumatic stress symptoms.
WMHs are “an important indicator of small vessel disease in the brain and have been linked to future stroke risk, dementia risk, and mortality,” lead investigator Rebecca Thurston, PhD, from the University of Pittsburgh, told this news organization.
“What I take from this is, really, that sexual assault has implications for women’s health, far beyond exclusively mental health outcomes, but also for their cardiovascular health, as we have shown in other work and for their stroke and dementia risk as we are seeing in the present work,” Dr. Thurston added.
The study was presented at the North American Menopause Society (NAMS) Annual Meeting in Washington, D.C., and has been accepted for publication in the journal Brain Imaging and Behavior.
Beyond the usual suspects
As part of the study, 145 women (mean age, 59 years) free of clinical cardiovascular disease, stroke, or dementia provided their medical history, including history of traumatic experiences, depression, and post-traumatic stress disorder and underwent magnetic resonance brain imaging for WMHs.
More than two-thirds (68%) of the women reported at least one trauma, most commonly sexual assault (23%).
In multivariate analysis, women with trauma exposure had greater WMH volume than women without trauma (P = .01), with sexual assault most strongly associated with greater WMH volume (P = .02).
The associations persisted after adjusting for depressive or post-traumatic stress symptoms.
“A history of sexual assault was particularly related to white matter hyperintensities in the parietal lobe, and these kinds of white matter hyperintensities have been linked to Alzheimer’s disease in a fairly pronounced way,” Dr. Thurston said.
“When we think about risk factors for stroke, dementia, we need to think beyond exclusively our usual suspects and also think about women [who experienced] psychological trauma and experienced sexual assault in particular. So ask about it and consider it part of your screening regimen,” she added.
‘Burgeoning’ literature
Commenting on the findings, Charles Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, Dell Medical School, University of Texas at Austin, and director of its Institute for Early Life Adversity Research, said the research adds to the “burgeoning literature on the long term neurobiological consequences of trauma and more specifically, sexual abuse, on brain imaging measures.”
“Our group and others reported several years ago that patients with mood disorders, more specifically bipolar disorder and major depression, had higher rates of WMH than matched controls. Those older studies did not control for a history of early life adversity such as childhood maltreatment,” Dr. Nemeroff said.
“In addition to this finding of increased WMH in subjects exposed to trauma is a very large literature documenting other central nervous system (CNS) changes in this population, including cortical thinning in certain brain areas and clearly an emerging finding that different forms of childhood maltreatment are associated with quite distinct structural brain alterations in adulthood,” he noted.
The study was supported by grants from the National Institutes of Health. Dr. Thurston and Dr. Nemeroff have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Traumatic experiences, especially sexual assault, may put women at greater risk for poor brain health.
In the Ms Brain study, middle-aged women with trauma exposure had a greater volume of white matter hyperintensities (WMHs) than those without trauma. In addition, the differences persisted even after adjusting for depressive or post-traumatic stress symptoms.
WMHs are “an important indicator of small vessel disease in the brain and have been linked to future stroke risk, dementia risk, and mortality,” lead investigator Rebecca Thurston, PhD, from the University of Pittsburgh, told this news organization.
“What I take from this is, really, that sexual assault has implications for women’s health, far beyond exclusively mental health outcomes, but also for their cardiovascular health, as we have shown in other work and for their stroke and dementia risk as we are seeing in the present work,” Dr. Thurston added.
The study was presented at the North American Menopause Society (NAMS) Annual Meeting in Washington, D.C., and has been accepted for publication in the journal Brain Imaging and Behavior.
Beyond the usual suspects
As part of the study, 145 women (mean age, 59 years) free of clinical cardiovascular disease, stroke, or dementia provided their medical history, including history of traumatic experiences, depression, and post-traumatic stress disorder and underwent magnetic resonance brain imaging for WMHs.
More than two-thirds (68%) of the women reported at least one trauma, most commonly sexual assault (23%).
In multivariate analysis, women with trauma exposure had greater WMH volume than women without trauma (P = .01), with sexual assault most strongly associated with greater WMH volume (P = .02).
The associations persisted after adjusting for depressive or post-traumatic stress symptoms.
“A history of sexual assault was particularly related to white matter hyperintensities in the parietal lobe, and these kinds of white matter hyperintensities have been linked to Alzheimer’s disease in a fairly pronounced way,” Dr. Thurston said.
“When we think about risk factors for stroke, dementia, we need to think beyond exclusively our usual suspects and also think about women [who experienced] psychological trauma and experienced sexual assault in particular. So ask about it and consider it part of your screening regimen,” she added.
‘Burgeoning’ literature
Commenting on the findings, Charles Nemeroff, MD, PhD, professor and chair, department of psychiatry and behavioral sciences, Dell Medical School, University of Texas at Austin, and director of its Institute for Early Life Adversity Research, said the research adds to the “burgeoning literature on the long term neurobiological consequences of trauma and more specifically, sexual abuse, on brain imaging measures.”
“Our group and others reported several years ago that patients with mood disorders, more specifically bipolar disorder and major depression, had higher rates of WMH than matched controls. Those older studies did not control for a history of early life adversity such as childhood maltreatment,” Dr. Nemeroff said.
“In addition to this finding of increased WMH in subjects exposed to trauma is a very large literature documenting other central nervous system (CNS) changes in this population, including cortical thinning in certain brain areas and clearly an emerging finding that different forms of childhood maltreatment are associated with quite distinct structural brain alterations in adulthood,” he noted.
The study was supported by grants from the National Institutes of Health. Dr. Thurston and Dr. Nemeroff have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COVID-19 vaccines in pregnancy may protect baby, too
Women who receive COVID-19 vaccines during pregnancy pass antibodies to their babies, which could protect newborns from the disease, research has shown.
.
Researchers with New York University Langone Health conducted a study that included pregnant women who had received at least one dose of an mRNA COVID-19 vaccine (Pfizer/BioNTech or Moderna) by June 4.
All neonates had antibodies to the spike protein at high titers, the researchers found.
Unlike similar prior studies, the researchers also looked for antibodies to the nucleocapsid protein, which would have indicated the presence of antibodies from natural COVID-19 infection. They did not detect antibodies to the nucleocapsid protein, and the lack of these antibodies suggests that the antibodies to the spike protein resulted from vaccination and not from prior infection, the researchers said.
The participants had a median time from completion of the vaccine series to delivery of 13 weeks. The study was published online in the American Journal of Obstetrics & Gynecology MFM.
“The presence of these anti-spike antibodies in the cord blood should, at least in theory, offer these newborns some degree of protection,” said study investigator Ashley S. Roman, MD, director of the division of maternal-fetal medicine at NYU Langone Health. “While the primary rationale for vaccination during pregnancy is to keep moms healthy and keep moms out of the hospital, the outstanding question to us was whether there is any fetal or neonatal benefit conferred by receiving the vaccine during pregnancy.”
Questions remain about the degree and durability of protection for newborns from these antibodies. An ongoing study, MOMI-VAX, aims to systematically measure antibody levels in mothers who receive COVID-19 vaccines during pregnancy and in their babies over time.
The present study contributes welcome preliminary evidence suggesting a benefit to infants, said Emily Adhikari, MD, of the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study.
Still, “the main concern and our priority as obstetricians is to vaccinate pregnant women to protect them from severe or critical illness,” she said.
Although most individuals infected with SARS-CoV-2 recover, a significant portion of pregnant women get seriously sick, Dr. Adhikari said. “With this recent Delta surge, we are seeing more pregnant patients who are sicker,” said Dr. Adhikari, who has published research from one hospital describing this trend.
When weighing whether patients should receive COVID-19 vaccines in pregnancy, the risks from infection have outweighed any risk from vaccination to such an extent that there is “not a comparison to make,” Dr. Adhikari said. “The risks of the infection are so much higher.
“For me, it is a matter of making sure that my patient understands that we have really good safety data on these vaccines and there is no reason to think that a pregnant person would be harmed by them. On the contrary, the benefit is to protect and maybe even save your life,” Dr. Adhikari said. “And now we have more evidence that the fetus may also benefit.”
The rationale for vaccinations during pregnancy can vary, Dr. Roman said. Flu shots in pregnancy mainly are intended to protect the mother, though they confer protection for newborns as well. With the whooping cough vaccine given in the third trimester, however, the primary aim is to protect the baby from whooping cough in the first months of life, Dr. Roman said.
“I think it is really important for pregnant women to understand that antibodies crossing the placenta is a good thing,” she added.
As patients who already have received COVID-19 vaccines become pregnant and may become eligible for a booster dose, Dr. Adhikari will offer it, she said, though she has confidence in the protection provided by the initial immune response.
Dr. Roman and Dr. Adhikari had no disclosures.
Women who receive COVID-19 vaccines during pregnancy pass antibodies to their babies, which could protect newborns from the disease, research has shown.
.
Researchers with New York University Langone Health conducted a study that included pregnant women who had received at least one dose of an mRNA COVID-19 vaccine (Pfizer/BioNTech or Moderna) by June 4.
All neonates had antibodies to the spike protein at high titers, the researchers found.
Unlike similar prior studies, the researchers also looked for antibodies to the nucleocapsid protein, which would have indicated the presence of antibodies from natural COVID-19 infection. They did not detect antibodies to the nucleocapsid protein, and the lack of these antibodies suggests that the antibodies to the spike protein resulted from vaccination and not from prior infection, the researchers said.
The participants had a median time from completion of the vaccine series to delivery of 13 weeks. The study was published online in the American Journal of Obstetrics & Gynecology MFM.
“The presence of these anti-spike antibodies in the cord blood should, at least in theory, offer these newborns some degree of protection,” said study investigator Ashley S. Roman, MD, director of the division of maternal-fetal medicine at NYU Langone Health. “While the primary rationale for vaccination during pregnancy is to keep moms healthy and keep moms out of the hospital, the outstanding question to us was whether there is any fetal or neonatal benefit conferred by receiving the vaccine during pregnancy.”
Questions remain about the degree and durability of protection for newborns from these antibodies. An ongoing study, MOMI-VAX, aims to systematically measure antibody levels in mothers who receive COVID-19 vaccines during pregnancy and in their babies over time.
The present study contributes welcome preliminary evidence suggesting a benefit to infants, said Emily Adhikari, MD, of the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study.
Still, “the main concern and our priority as obstetricians is to vaccinate pregnant women to protect them from severe or critical illness,” she said.
Although most individuals infected with SARS-CoV-2 recover, a significant portion of pregnant women get seriously sick, Dr. Adhikari said. “With this recent Delta surge, we are seeing more pregnant patients who are sicker,” said Dr. Adhikari, who has published research from one hospital describing this trend.
When weighing whether patients should receive COVID-19 vaccines in pregnancy, the risks from infection have outweighed any risk from vaccination to such an extent that there is “not a comparison to make,” Dr. Adhikari said. “The risks of the infection are so much higher.
“For me, it is a matter of making sure that my patient understands that we have really good safety data on these vaccines and there is no reason to think that a pregnant person would be harmed by them. On the contrary, the benefit is to protect and maybe even save your life,” Dr. Adhikari said. “And now we have more evidence that the fetus may also benefit.”
The rationale for vaccinations during pregnancy can vary, Dr. Roman said. Flu shots in pregnancy mainly are intended to protect the mother, though they confer protection for newborns as well. With the whooping cough vaccine given in the third trimester, however, the primary aim is to protect the baby from whooping cough in the first months of life, Dr. Roman said.
“I think it is really important for pregnant women to understand that antibodies crossing the placenta is a good thing,” she added.
As patients who already have received COVID-19 vaccines become pregnant and may become eligible for a booster dose, Dr. Adhikari will offer it, she said, though she has confidence in the protection provided by the initial immune response.
Dr. Roman and Dr. Adhikari had no disclosures.
Women who receive COVID-19 vaccines during pregnancy pass antibodies to their babies, which could protect newborns from the disease, research has shown.
.
Researchers with New York University Langone Health conducted a study that included pregnant women who had received at least one dose of an mRNA COVID-19 vaccine (Pfizer/BioNTech or Moderna) by June 4.
All neonates had antibodies to the spike protein at high titers, the researchers found.
Unlike similar prior studies, the researchers also looked for antibodies to the nucleocapsid protein, which would have indicated the presence of antibodies from natural COVID-19 infection. They did not detect antibodies to the nucleocapsid protein, and the lack of these antibodies suggests that the antibodies to the spike protein resulted from vaccination and not from prior infection, the researchers said.
The participants had a median time from completion of the vaccine series to delivery of 13 weeks. The study was published online in the American Journal of Obstetrics & Gynecology MFM.
“The presence of these anti-spike antibodies in the cord blood should, at least in theory, offer these newborns some degree of protection,” said study investigator Ashley S. Roman, MD, director of the division of maternal-fetal medicine at NYU Langone Health. “While the primary rationale for vaccination during pregnancy is to keep moms healthy and keep moms out of the hospital, the outstanding question to us was whether there is any fetal or neonatal benefit conferred by receiving the vaccine during pregnancy.”
Questions remain about the degree and durability of protection for newborns from these antibodies. An ongoing study, MOMI-VAX, aims to systematically measure antibody levels in mothers who receive COVID-19 vaccines during pregnancy and in their babies over time.
The present study contributes welcome preliminary evidence suggesting a benefit to infants, said Emily Adhikari, MD, of the University of Texas Southwestern Medical Center in Dallas, who was not involved in the study.
Still, “the main concern and our priority as obstetricians is to vaccinate pregnant women to protect them from severe or critical illness,” she said.
Although most individuals infected with SARS-CoV-2 recover, a significant portion of pregnant women get seriously sick, Dr. Adhikari said. “With this recent Delta surge, we are seeing more pregnant patients who are sicker,” said Dr. Adhikari, who has published research from one hospital describing this trend.
When weighing whether patients should receive COVID-19 vaccines in pregnancy, the risks from infection have outweighed any risk from vaccination to such an extent that there is “not a comparison to make,” Dr. Adhikari said. “The risks of the infection are so much higher.
“For me, it is a matter of making sure that my patient understands that we have really good safety data on these vaccines and there is no reason to think that a pregnant person would be harmed by them. On the contrary, the benefit is to protect and maybe even save your life,” Dr. Adhikari said. “And now we have more evidence that the fetus may also benefit.”
The rationale for vaccinations during pregnancy can vary, Dr. Roman said. Flu shots in pregnancy mainly are intended to protect the mother, though they confer protection for newborns as well. With the whooping cough vaccine given in the third trimester, however, the primary aim is to protect the baby from whooping cough in the first months of life, Dr. Roman said.
“I think it is really important for pregnant women to understand that antibodies crossing the placenta is a good thing,” she added.
As patients who already have received COVID-19 vaccines become pregnant and may become eligible for a booster dose, Dr. Adhikari will offer it, she said, though she has confidence in the protection provided by the initial immune response.
Dr. Roman and Dr. Adhikari had no disclosures.
FROM AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY MFM
Consensus statement warns against acetaminophen use during pregnancy
Pregnant women should use paracetamol/acetaminophen only with a medical indication and at the lowest effective dose for the shortest possible time, according to an international consensus statement published online Sept. 23 in Nature Reviews Endocrinology.
With global rates of use high and risks considered negligible, the expert panel of 13 U.S. and European authors call for focused research into how this analgesic and febrifuge may impair fetal development and lead to adverse outcomes in children. They outline several precautionary measures to be taken in the meantime.
According to first author and epidemiologist Ann Z. Bauer, ScD, a postdoctoral research fellow at the University of Massachusetts in Lowell, and colleagues, this drug is used by an estimated 65% of pregnant women in the United States, and more than 50% worldwide. It is currently the active ingredient in more than 600 prescription and nonprescription medications, including Tylenol, which historically has been deemed safe in all trimesters of pregnancy.
But a growing body of experimental and epidemiological evidence suggests prenatal exposure to paracetamol (N-acetyl-p-aminophenol, or APAP) might alter fetal development and elevate the risks of neurodevelopmental, reproductive and urogenital disorders in both sexes. Exposure in utero has been linked, for example, to potential behavioral problems in children.
The new recommendations are based on a review of experimental animal and cell-based research as well as human epidemiological data published from January 1995 to October 2020. The authors include clinicians, epidemiologists, and scientists specializing in toxicology, endocrinology, reproductive medicine and neurodevelopment.
Recommendations
Although the new guidance does not differ markedly from current advice, the authors believe stronger communication and greater awareness of risks are needed. In addition to restricting use of this medication to low doses for short periods when medically necessary, expectant mothers should receive counseling before conception or early in pregnancy. If uncertain about its use, they should consult their physicians or pharmacists.
In other recommendations, the panel said:
- The 2015 FDA Drug Safety Communication recommendations should be updated based on evaluation of all available scientific evidence.
- The European Medicines Agency Pharmacovigilance Risk Assessment Committee should review the most recent epidemiologic and experimental research and issue an updated Drug Safety Communication.
- Obstetric and gynecological associations should update their guidance after reviewing all available research.
- The Acetaminophen Awareness Coalition (“Know Your Dose” Campaign) should add standardized warnings and specifically advise pregnant women to forgo APAP unless it’s medically indicated.
- All sales of APAP-containing medications should be accompanied by recommendations specifically for use in pregnancy. This information should include warning labels on packaging, and if possible, APAP should be sold only in pharmacies (as in France).
Mechanism of action
APAP is an endocrine disruptor (Neuroscientist. 2020 Sep 11. doi: 10.1177/1073858420952046). “Chemicals that disrupt the endocrine system are concerning because they can interfere with the activity of endogenous hormones that are essential for healthy neurological, urogenital, and reproductive development,” researchers wrote.
“The precise mechanism is not clear but its toxicity is thought to be due mainly to hormone disruption,” Dr. Bauer said in an interview.
Moreover, APAP readily crosses the placenta and blood–brain barrier, and changes in APAP metabolism during pregnancy might make women and their fetuses more vulnerable to its toxic effects. For instance, the molar dose fraction of APAP converted to the oxidative metabolite N-acetyl-p-benzoquinone imine increases during pregnancy. In addition to its hepatotoxicity, this poisonous byproduct is thought to be a genotoxin that increases DNA cleavage by acting on the enzyme topoisomerase II.
Asked for her perspective on the statement, Kjersti Aagaard, MD, PhD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, called the expert panel’s statement thoughtful and comprehensive, but she urged caution in interpreting the role of acetaminophen.
The challenge in linking any commonly used medication to adverse effects and congenital defects, she said, is “teasing out an association from causation. Given the commonality of the use of acetaminophen with the relative rarity of the outcomes, it is clear that not all cases of exposure result in adverse outcomes.”
As for judicious use, she said, one would be to reduce a high fever, which can cause miscarriage, neural tube defects, and potential heart disease in adulthood. Acetaminophen is the drug of choice in this case since nonsteroidal anti-inflammatory drugs such as ibuprofen are not recommended owing to their known risks to the fetal heart.
Dr. Aagaard emphasized that while acetaminophen use is temporally associated with learning and behavioral problems, and urogenital disorders at birth in male infants such as like hypospadias, so is exposure to multiple environmental chemicals and pollutants, as well as climate change. “It would be a real mistake with real life implications if we associated any congenital disease or disorder with a commonly used medication with known benefits if the true causal link lies elsewhere.”
She said the precautionary statements fall into the time-honored therapeutic principle of first do no harm. “However, the call for research action must be undertaken earnestly and sincerely.”
According to Dr. Bauer, the statement’s essential take-home message is that “physicians should educate themselves and educate women about what we’re learning about the risks of acetaminophen in pregnancy.” Risk can be minimized by using the lowest effective dose for the shortest time and only when medically indicated. “Pregnant women should speak to their physicians about acetaminophen. It’s about empowerment and making smart decisions,” she said.
This study received no specific funding. Coauthor Dr. R.T. Mitchell is supported by a UK Research Institute fellowship.
Pregnant women should use paracetamol/acetaminophen only with a medical indication and at the lowest effective dose for the shortest possible time, according to an international consensus statement published online Sept. 23 in Nature Reviews Endocrinology.
With global rates of use high and risks considered negligible, the expert panel of 13 U.S. and European authors call for focused research into how this analgesic and febrifuge may impair fetal development and lead to adverse outcomes in children. They outline several precautionary measures to be taken in the meantime.
According to first author and epidemiologist Ann Z. Bauer, ScD, a postdoctoral research fellow at the University of Massachusetts in Lowell, and colleagues, this drug is used by an estimated 65% of pregnant women in the United States, and more than 50% worldwide. It is currently the active ingredient in more than 600 prescription and nonprescription medications, including Tylenol, which historically has been deemed safe in all trimesters of pregnancy.
But a growing body of experimental and epidemiological evidence suggests prenatal exposure to paracetamol (N-acetyl-p-aminophenol, or APAP) might alter fetal development and elevate the risks of neurodevelopmental, reproductive and urogenital disorders in both sexes. Exposure in utero has been linked, for example, to potential behavioral problems in children.
The new recommendations are based on a review of experimental animal and cell-based research as well as human epidemiological data published from January 1995 to October 2020. The authors include clinicians, epidemiologists, and scientists specializing in toxicology, endocrinology, reproductive medicine and neurodevelopment.
Recommendations
Although the new guidance does not differ markedly from current advice, the authors believe stronger communication and greater awareness of risks are needed. In addition to restricting use of this medication to low doses for short periods when medically necessary, expectant mothers should receive counseling before conception or early in pregnancy. If uncertain about its use, they should consult their physicians or pharmacists.
In other recommendations, the panel said:
- The 2015 FDA Drug Safety Communication recommendations should be updated based on evaluation of all available scientific evidence.
- The European Medicines Agency Pharmacovigilance Risk Assessment Committee should review the most recent epidemiologic and experimental research and issue an updated Drug Safety Communication.
- Obstetric and gynecological associations should update their guidance after reviewing all available research.
- The Acetaminophen Awareness Coalition (“Know Your Dose” Campaign) should add standardized warnings and specifically advise pregnant women to forgo APAP unless it’s medically indicated.
- All sales of APAP-containing medications should be accompanied by recommendations specifically for use in pregnancy. This information should include warning labels on packaging, and if possible, APAP should be sold only in pharmacies (as in France).
Mechanism of action
APAP is an endocrine disruptor (Neuroscientist. 2020 Sep 11. doi: 10.1177/1073858420952046). “Chemicals that disrupt the endocrine system are concerning because they can interfere with the activity of endogenous hormones that are essential for healthy neurological, urogenital, and reproductive development,” researchers wrote.
“The precise mechanism is not clear but its toxicity is thought to be due mainly to hormone disruption,” Dr. Bauer said in an interview.
Moreover, APAP readily crosses the placenta and blood–brain barrier, and changes in APAP metabolism during pregnancy might make women and their fetuses more vulnerable to its toxic effects. For instance, the molar dose fraction of APAP converted to the oxidative metabolite N-acetyl-p-benzoquinone imine increases during pregnancy. In addition to its hepatotoxicity, this poisonous byproduct is thought to be a genotoxin that increases DNA cleavage by acting on the enzyme topoisomerase II.
Asked for her perspective on the statement, Kjersti Aagaard, MD, PhD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, called the expert panel’s statement thoughtful and comprehensive, but she urged caution in interpreting the role of acetaminophen.
The challenge in linking any commonly used medication to adverse effects and congenital defects, she said, is “teasing out an association from causation. Given the commonality of the use of acetaminophen with the relative rarity of the outcomes, it is clear that not all cases of exposure result in adverse outcomes.”
As for judicious use, she said, one would be to reduce a high fever, which can cause miscarriage, neural tube defects, and potential heart disease in adulthood. Acetaminophen is the drug of choice in this case since nonsteroidal anti-inflammatory drugs such as ibuprofen are not recommended owing to their known risks to the fetal heart.
Dr. Aagaard emphasized that while acetaminophen use is temporally associated with learning and behavioral problems, and urogenital disorders at birth in male infants such as like hypospadias, so is exposure to multiple environmental chemicals and pollutants, as well as climate change. “It would be a real mistake with real life implications if we associated any congenital disease or disorder with a commonly used medication with known benefits if the true causal link lies elsewhere.”
She said the precautionary statements fall into the time-honored therapeutic principle of first do no harm. “However, the call for research action must be undertaken earnestly and sincerely.”
According to Dr. Bauer, the statement’s essential take-home message is that “physicians should educate themselves and educate women about what we’re learning about the risks of acetaminophen in pregnancy.” Risk can be minimized by using the lowest effective dose for the shortest time and only when medically indicated. “Pregnant women should speak to their physicians about acetaminophen. It’s about empowerment and making smart decisions,” she said.
This study received no specific funding. Coauthor Dr. R.T. Mitchell is supported by a UK Research Institute fellowship.
Pregnant women should use paracetamol/acetaminophen only with a medical indication and at the lowest effective dose for the shortest possible time, according to an international consensus statement published online Sept. 23 in Nature Reviews Endocrinology.
With global rates of use high and risks considered negligible, the expert panel of 13 U.S. and European authors call for focused research into how this analgesic and febrifuge may impair fetal development and lead to adverse outcomes in children. They outline several precautionary measures to be taken in the meantime.
According to first author and epidemiologist Ann Z. Bauer, ScD, a postdoctoral research fellow at the University of Massachusetts in Lowell, and colleagues, this drug is used by an estimated 65% of pregnant women in the United States, and more than 50% worldwide. It is currently the active ingredient in more than 600 prescription and nonprescription medications, including Tylenol, which historically has been deemed safe in all trimesters of pregnancy.
But a growing body of experimental and epidemiological evidence suggests prenatal exposure to paracetamol (N-acetyl-p-aminophenol, or APAP) might alter fetal development and elevate the risks of neurodevelopmental, reproductive and urogenital disorders in both sexes. Exposure in utero has been linked, for example, to potential behavioral problems in children.
The new recommendations are based on a review of experimental animal and cell-based research as well as human epidemiological data published from January 1995 to October 2020. The authors include clinicians, epidemiologists, and scientists specializing in toxicology, endocrinology, reproductive medicine and neurodevelopment.
Recommendations
Although the new guidance does not differ markedly from current advice, the authors believe stronger communication and greater awareness of risks are needed. In addition to restricting use of this medication to low doses for short periods when medically necessary, expectant mothers should receive counseling before conception or early in pregnancy. If uncertain about its use, they should consult their physicians or pharmacists.
In other recommendations, the panel said:
- The 2015 FDA Drug Safety Communication recommendations should be updated based on evaluation of all available scientific evidence.
- The European Medicines Agency Pharmacovigilance Risk Assessment Committee should review the most recent epidemiologic and experimental research and issue an updated Drug Safety Communication.
- Obstetric and gynecological associations should update their guidance after reviewing all available research.
- The Acetaminophen Awareness Coalition (“Know Your Dose” Campaign) should add standardized warnings and specifically advise pregnant women to forgo APAP unless it’s medically indicated.
- All sales of APAP-containing medications should be accompanied by recommendations specifically for use in pregnancy. This information should include warning labels on packaging, and if possible, APAP should be sold only in pharmacies (as in France).
Mechanism of action
APAP is an endocrine disruptor (Neuroscientist. 2020 Sep 11. doi: 10.1177/1073858420952046). “Chemicals that disrupt the endocrine system are concerning because they can interfere with the activity of endogenous hormones that are essential for healthy neurological, urogenital, and reproductive development,” researchers wrote.
“The precise mechanism is not clear but its toxicity is thought to be due mainly to hormone disruption,” Dr. Bauer said in an interview.
Moreover, APAP readily crosses the placenta and blood–brain barrier, and changes in APAP metabolism during pregnancy might make women and their fetuses more vulnerable to its toxic effects. For instance, the molar dose fraction of APAP converted to the oxidative metabolite N-acetyl-p-benzoquinone imine increases during pregnancy. In addition to its hepatotoxicity, this poisonous byproduct is thought to be a genotoxin that increases DNA cleavage by acting on the enzyme topoisomerase II.
Asked for her perspective on the statement, Kjersti Aagaard, MD, PhD, a professor of obstetrics and gynecology at Baylor College of Medicine and Texas Children’s Hospital in Houston, called the expert panel’s statement thoughtful and comprehensive, but she urged caution in interpreting the role of acetaminophen.
The challenge in linking any commonly used medication to adverse effects and congenital defects, she said, is “teasing out an association from causation. Given the commonality of the use of acetaminophen with the relative rarity of the outcomes, it is clear that not all cases of exposure result in adverse outcomes.”
As for judicious use, she said, one would be to reduce a high fever, which can cause miscarriage, neural tube defects, and potential heart disease in adulthood. Acetaminophen is the drug of choice in this case since nonsteroidal anti-inflammatory drugs such as ibuprofen are not recommended owing to their known risks to the fetal heart.
Dr. Aagaard emphasized that while acetaminophen use is temporally associated with learning and behavioral problems, and urogenital disorders at birth in male infants such as like hypospadias, so is exposure to multiple environmental chemicals and pollutants, as well as climate change. “It would be a real mistake with real life implications if we associated any congenital disease or disorder with a commonly used medication with known benefits if the true causal link lies elsewhere.”
She said the precautionary statements fall into the time-honored therapeutic principle of first do no harm. “However, the call for research action must be undertaken earnestly and sincerely.”
According to Dr. Bauer, the statement’s essential take-home message is that “physicians should educate themselves and educate women about what we’re learning about the risks of acetaminophen in pregnancy.” Risk can be minimized by using the lowest effective dose for the shortest time and only when medically indicated. “Pregnant women should speak to their physicians about acetaminophen. It’s about empowerment and making smart decisions,” she said.
This study received no specific funding. Coauthor Dr. R.T. Mitchell is supported by a UK Research Institute fellowship.
Pandemic affected home life of nearly 70% of female physicians with children
The survey, conducted by the Robert Graham Center and the American Board of Family Medicine from May to June 2020, examined the professional and personal experiences of being a mother and a primary care physician during the pandemic.
“The pandemic was hard for everyone, but for women who had children in the home, and it didn’t really matter what age, it seemed like the emotional impact was much harder,” study author Yalda Jabbarpour, MD, said in an interview.
The results of the survey of 89 female physicians who worked in the primary care specialty were published in the Journal of Mother Studies.
Dr. Jabbapour and her colleagues found that 67% of female physicians with children said the pandemic had a great “impact” on their home life compared with 25% of those without children. Furthermore, 41% of physician moms said COVID-19 greatly affected their work life, as opposed to 17% of their counterparts without children.
“Women are going into medicine at much higher rates. In primary care, it’s becoming close to the majority,” said Dr. Jabbarpour, a family physician and medical director of the Robert Graham Center for Policy Studies. “That has important workforce implications. If we’re not supporting our female physicians and they are greater than 50% of the physician workforce and they’re burning out, who’s going to have a doctor anymore?”
Child care challenges
Researchers found that the emotional toll female physicians experienced early on in the pandemic was indicative of the challenges they were facing. Some of those challenges included managing anxiety, increased stress from both work and home, and social isolation from friends and family.
Another challenge physician mothers had to deal with was fulfilling child care and homeschooling needs, as many women didn’t know what to do with their children and didn’t have external support from their employers.
Child care options vanished for many people during the pandemic, Emily Kaye, MD, MPH, who was not involved in the study, said in an interview.
“I think it was incredibly challenging for everyone and uniquely challenging for women who were young mothers, specifically with respect to child care” said Dr. Kaye, assistant professor in the department of oncology at St. Jude Children’s Research Hospital. “Many women were expected to just continue plugging on in the absence of any reasonable or safe form of child care.”
Some of the changes physician-mothers said they were required to make at home or in their personal lives included physical changes related to their family safety, such as decontaminating themselves in their garages before heading home after a shift. Some also reported that they had to find new ways to maintain emotional and mental health because of social isolation from family and friends.
The survey results, which were taken early on in the pandemic, highlight the need for health policies that support physician mothers and families, as women shoulder the burden of parenting and domestic responsibilities in heterosexual relationships, the researchers said.
“I’m hoping that people pay attention and start to implement more family friendly policies within their workplaces,” Dr. Jabbarpour said. “But during a pandemic, it was essential for [female health care workers] to go in, and they had nowhere to put their kids. [Therefore], the choice became leaving young children alone at home, putting them into daycare facilities that did remain open without knowing if they were [safe], or quitting their jobs. None of those choices are good.”
Community support as a potential solution
Dr. Kaye said she believes that there should be a “long overdue investment” in community support, affordable and accessible child care, flexible spending, paid family leave, and other forms of caregiving support.
“In order to keep women physicians in the workforce, we need to have a significant increase in investment in the social safety net in this country,” Dr. Kaye said.
Researchers said more studies should evaluate the role the COVID-19 pandemic had on the primary care workforce in the U.S., “with a specific emphasis on how the pandemic impacted mothers, and should more intentionally consider the further intersections of race and ethnicity in the experiences of physician-mothers.”
“I think people are burning out and then there’s all this anti-science, anti-health sentiment out there, which makes it harder,” Dr. Jabbarpour said. “If we did repeat this study now, I think things would be even more dire in the voices of the women that we heard.”
Dr. Jabbarpour and Dr. Kaye reported no disclosures.
The survey, conducted by the Robert Graham Center and the American Board of Family Medicine from May to June 2020, examined the professional and personal experiences of being a mother and a primary care physician during the pandemic.
“The pandemic was hard for everyone, but for women who had children in the home, and it didn’t really matter what age, it seemed like the emotional impact was much harder,” study author Yalda Jabbarpour, MD, said in an interview.
The results of the survey of 89 female physicians who worked in the primary care specialty were published in the Journal of Mother Studies.
Dr. Jabbapour and her colleagues found that 67% of female physicians with children said the pandemic had a great “impact” on their home life compared with 25% of those without children. Furthermore, 41% of physician moms said COVID-19 greatly affected their work life, as opposed to 17% of their counterparts without children.
“Women are going into medicine at much higher rates. In primary care, it’s becoming close to the majority,” said Dr. Jabbarpour, a family physician and medical director of the Robert Graham Center for Policy Studies. “That has important workforce implications. If we’re not supporting our female physicians and they are greater than 50% of the physician workforce and they’re burning out, who’s going to have a doctor anymore?”
Child care challenges
Researchers found that the emotional toll female physicians experienced early on in the pandemic was indicative of the challenges they were facing. Some of those challenges included managing anxiety, increased stress from both work and home, and social isolation from friends and family.
Another challenge physician mothers had to deal with was fulfilling child care and homeschooling needs, as many women didn’t know what to do with their children and didn’t have external support from their employers.
Child care options vanished for many people during the pandemic, Emily Kaye, MD, MPH, who was not involved in the study, said in an interview.
“I think it was incredibly challenging for everyone and uniquely challenging for women who were young mothers, specifically with respect to child care” said Dr. Kaye, assistant professor in the department of oncology at St. Jude Children’s Research Hospital. “Many women were expected to just continue plugging on in the absence of any reasonable or safe form of child care.”
Some of the changes physician-mothers said they were required to make at home or in their personal lives included physical changes related to their family safety, such as decontaminating themselves in their garages before heading home after a shift. Some also reported that they had to find new ways to maintain emotional and mental health because of social isolation from family and friends.
The survey results, which were taken early on in the pandemic, highlight the need for health policies that support physician mothers and families, as women shoulder the burden of parenting and domestic responsibilities in heterosexual relationships, the researchers said.
“I’m hoping that people pay attention and start to implement more family friendly policies within their workplaces,” Dr. Jabbarpour said. “But during a pandemic, it was essential for [female health care workers] to go in, and they had nowhere to put their kids. [Therefore], the choice became leaving young children alone at home, putting them into daycare facilities that did remain open without knowing if they were [safe], or quitting their jobs. None of those choices are good.”
Community support as a potential solution
Dr. Kaye said she believes that there should be a “long overdue investment” in community support, affordable and accessible child care, flexible spending, paid family leave, and other forms of caregiving support.
“In order to keep women physicians in the workforce, we need to have a significant increase in investment in the social safety net in this country,” Dr. Kaye said.
Researchers said more studies should evaluate the role the COVID-19 pandemic had on the primary care workforce in the U.S., “with a specific emphasis on how the pandemic impacted mothers, and should more intentionally consider the further intersections of race and ethnicity in the experiences of physician-mothers.”
“I think people are burning out and then there’s all this anti-science, anti-health sentiment out there, which makes it harder,” Dr. Jabbarpour said. “If we did repeat this study now, I think things would be even more dire in the voices of the women that we heard.”
Dr. Jabbarpour and Dr. Kaye reported no disclosures.
The survey, conducted by the Robert Graham Center and the American Board of Family Medicine from May to June 2020, examined the professional and personal experiences of being a mother and a primary care physician during the pandemic.
“The pandemic was hard for everyone, but for women who had children in the home, and it didn’t really matter what age, it seemed like the emotional impact was much harder,” study author Yalda Jabbarpour, MD, said in an interview.
The results of the survey of 89 female physicians who worked in the primary care specialty were published in the Journal of Mother Studies.
Dr. Jabbapour and her colleagues found that 67% of female physicians with children said the pandemic had a great “impact” on their home life compared with 25% of those without children. Furthermore, 41% of physician moms said COVID-19 greatly affected their work life, as opposed to 17% of their counterparts without children.
“Women are going into medicine at much higher rates. In primary care, it’s becoming close to the majority,” said Dr. Jabbarpour, a family physician and medical director of the Robert Graham Center for Policy Studies. “That has important workforce implications. If we’re not supporting our female physicians and they are greater than 50% of the physician workforce and they’re burning out, who’s going to have a doctor anymore?”
Child care challenges
Researchers found that the emotional toll female physicians experienced early on in the pandemic was indicative of the challenges they were facing. Some of those challenges included managing anxiety, increased stress from both work and home, and social isolation from friends and family.
Another challenge physician mothers had to deal with was fulfilling child care and homeschooling needs, as many women didn’t know what to do with their children and didn’t have external support from their employers.
Child care options vanished for many people during the pandemic, Emily Kaye, MD, MPH, who was not involved in the study, said in an interview.
“I think it was incredibly challenging for everyone and uniquely challenging for women who were young mothers, specifically with respect to child care” said Dr. Kaye, assistant professor in the department of oncology at St. Jude Children’s Research Hospital. “Many women were expected to just continue plugging on in the absence of any reasonable or safe form of child care.”
Some of the changes physician-mothers said they were required to make at home or in their personal lives included physical changes related to their family safety, such as decontaminating themselves in their garages before heading home after a shift. Some also reported that they had to find new ways to maintain emotional and mental health because of social isolation from family and friends.
The survey results, which were taken early on in the pandemic, highlight the need for health policies that support physician mothers and families, as women shoulder the burden of parenting and domestic responsibilities in heterosexual relationships, the researchers said.
“I’m hoping that people pay attention and start to implement more family friendly policies within their workplaces,” Dr. Jabbarpour said. “But during a pandemic, it was essential for [female health care workers] to go in, and they had nowhere to put their kids. [Therefore], the choice became leaving young children alone at home, putting them into daycare facilities that did remain open without knowing if they were [safe], or quitting their jobs. None of those choices are good.”
Community support as a potential solution
Dr. Kaye said she believes that there should be a “long overdue investment” in community support, affordable and accessible child care, flexible spending, paid family leave, and other forms of caregiving support.
“In order to keep women physicians in the workforce, we need to have a significant increase in investment in the social safety net in this country,” Dr. Kaye said.
Researchers said more studies should evaluate the role the COVID-19 pandemic had on the primary care workforce in the U.S., “with a specific emphasis on how the pandemic impacted mothers, and should more intentionally consider the further intersections of race and ethnicity in the experiences of physician-mothers.”
“I think people are burning out and then there’s all this anti-science, anti-health sentiment out there, which makes it harder,” Dr. Jabbarpour said. “If we did repeat this study now, I think things would be even more dire in the voices of the women that we heard.”
Dr. Jabbarpour and Dr. Kaye reported no disclosures.
FROM JOURNAL OF MOTHER STUDIES
Supreme Court sets date for case that challenges Roe v. Wade
The Supreme Court will hear arguments in a major Mississippi abortion case on Dec. 1, which could challenge the landmark Roe v. Wade decision that guarantees a woman’s right to an abortion.
On Sept. 20, the court issued its calendar for arguments that will be heard in late November and early December, The Associated Press reported.
The Mississippi case, Dobbs v. Jackson Women’s Health Organization, is seeking to overturn Roe v. Wade by asking the Supreme Court to uphold a ban on most abortions after the 15th week of pregnancy. The state also said the court should overrule the 1992 decision in Planned Parenthood v. Casey that prevents states from banning abortion before viability, which is around 24 weeks of pregnancy.
Earlier in September, the Supreme Court allowed a Texas law to take effect that bans abortions after cardiac activity can be detected, which is around 6 weeks of pregnancy and often before many women know they’re pregnant. The court, which was split 5-4, didn’t rule on the constitutional nature of the law, instead declining to block its enforcement.
Hundreds of legal briefs have been filed on both sides of the case, the AP reported. On Sept. 20, more than 500 women athletes, including members of the Women’s National Basketball Players Association, the National Women’s Soccer League Players Association, and Olympic medalists, filed a brief that said an abortion ban would be devastating for female athletes.
The Mississippi law was enacted in 2018 but was blocked after a challenge at the federal court level. The state’s only abortion clinic, Jackson Women’s Health Organization, remains open and offers abortions up to 16 weeks of pregnancy, the AP reported. About 100 abortions a year are completed after 15 weeks, the organization said.
More than 90% of abortions in the United States occur in the first 13 weeks of pregnancy, the AP said.
The Supreme Court justices will return to the courtroom in October to hear arguments now that all of them have been vaccinated, the AP reported. The justices had been hearing cases by phone during the pandemic.
The public won’t be able to attend sessions, but the court will allow live audio of the session.
A version of this article first appeared on WebMD.com.
The Supreme Court will hear arguments in a major Mississippi abortion case on Dec. 1, which could challenge the landmark Roe v. Wade decision that guarantees a woman’s right to an abortion.
On Sept. 20, the court issued its calendar for arguments that will be heard in late November and early December, The Associated Press reported.
The Mississippi case, Dobbs v. Jackson Women’s Health Organization, is seeking to overturn Roe v. Wade by asking the Supreme Court to uphold a ban on most abortions after the 15th week of pregnancy. The state also said the court should overrule the 1992 decision in Planned Parenthood v. Casey that prevents states from banning abortion before viability, which is around 24 weeks of pregnancy.
Earlier in September, the Supreme Court allowed a Texas law to take effect that bans abortions after cardiac activity can be detected, which is around 6 weeks of pregnancy and often before many women know they’re pregnant. The court, which was split 5-4, didn’t rule on the constitutional nature of the law, instead declining to block its enforcement.
Hundreds of legal briefs have been filed on both sides of the case, the AP reported. On Sept. 20, more than 500 women athletes, including members of the Women’s National Basketball Players Association, the National Women’s Soccer League Players Association, and Olympic medalists, filed a brief that said an abortion ban would be devastating for female athletes.
The Mississippi law was enacted in 2018 but was blocked after a challenge at the federal court level. The state’s only abortion clinic, Jackson Women’s Health Organization, remains open and offers abortions up to 16 weeks of pregnancy, the AP reported. About 100 abortions a year are completed after 15 weeks, the organization said.
More than 90% of abortions in the United States occur in the first 13 weeks of pregnancy, the AP said.
The Supreme Court justices will return to the courtroom in October to hear arguments now that all of them have been vaccinated, the AP reported. The justices had been hearing cases by phone during the pandemic.
The public won’t be able to attend sessions, but the court will allow live audio of the session.
A version of this article first appeared on WebMD.com.
The Supreme Court will hear arguments in a major Mississippi abortion case on Dec. 1, which could challenge the landmark Roe v. Wade decision that guarantees a woman’s right to an abortion.
On Sept. 20, the court issued its calendar for arguments that will be heard in late November and early December, The Associated Press reported.
The Mississippi case, Dobbs v. Jackson Women’s Health Organization, is seeking to overturn Roe v. Wade by asking the Supreme Court to uphold a ban on most abortions after the 15th week of pregnancy. The state also said the court should overrule the 1992 decision in Planned Parenthood v. Casey that prevents states from banning abortion before viability, which is around 24 weeks of pregnancy.
Earlier in September, the Supreme Court allowed a Texas law to take effect that bans abortions after cardiac activity can be detected, which is around 6 weeks of pregnancy and often before many women know they’re pregnant. The court, which was split 5-4, didn’t rule on the constitutional nature of the law, instead declining to block its enforcement.
Hundreds of legal briefs have been filed on both sides of the case, the AP reported. On Sept. 20, more than 500 women athletes, including members of the Women’s National Basketball Players Association, the National Women’s Soccer League Players Association, and Olympic medalists, filed a brief that said an abortion ban would be devastating for female athletes.
The Mississippi law was enacted in 2018 but was blocked after a challenge at the federal court level. The state’s only abortion clinic, Jackson Women’s Health Organization, remains open and offers abortions up to 16 weeks of pregnancy, the AP reported. About 100 abortions a year are completed after 15 weeks, the organization said.
More than 90% of abortions in the United States occur in the first 13 weeks of pregnancy, the AP said.
The Supreme Court justices will return to the courtroom in October to hear arguments now that all of them have been vaccinated, the AP reported. The justices had been hearing cases by phone during the pandemic.
The public won’t be able to attend sessions, but the court will allow live audio of the session.
A version of this article first appeared on WebMD.com.
Texas doctor admits to violating abortion ban
A Texas doctor revealed in a Washington Post op-ed Sept. 18 that he violated the state ban on abortions performed beyond 6 weeks -- a move he knows could come with legal consequences.
San Antonio doctor Alan Braid, MD, said the new statewide restrictions reminded him of darker days during his 1972 obstetrics and gynecology residency, when he saw three teenagers die from illegal abortions.
“For me, it is 1972 all over again,” he wrote. “And that is why, on the morning of Sept. 6, I provided an abortion to a woman who, though still in her first trimester, was beyond the state’s new limit. I acted because I had a duty of care to this patient, as I do for all patients, and because she has a fundamental right to receive this care.”
“I fully understood that there could be legal consequences -- but I wanted to make sure that Texas didn’t get away with its bid to prevent this blatantly unconstitutional law from being tested,” he continued.
According to The Washington Post, Dr. Braid’s wish may come true. Two lawsuits against were filed Sept. 20. In one, a prisoner in Arkansas said he filed the suit in part because he could receive $10,000 if successful, according to the Post. The second was filed by a man in Chicago who wants the law struck down.
Dr. Braid’s op-ed is the first public admission to violating a Texas state law that took effect Sept. 1 banning abortion once a fetal heartbeat is detected. The controversial policy gives private citizens the right to bring civil litigation -- resulting in at least $10,000 in damages -- against providers and anyone else involved in the process.
Since the law went into effect, most patients seeking abortions are too far along to qualify, Dr. Braid wrote.
“I tell them that we can offer services only if we cannot see the presence of cardiac activity on an ultrasound, which usually occurs at about six weeks, before most people know they are pregnant. The tension is unbearable as they lie there, waiting to hear their fate,” he wrote.
“I understand that by providing an abortion beyond the new legal limit, I am taking a personal risk, but it’s something I believe in strongly,” he continued. “Represented by the Center for Reproductive Rights, my clinics are among the plaintiffs in an ongoing federal lawsuit to stop S.B. 8.”
A version of this article first appeared on WebMD.com .
A Texas doctor revealed in a Washington Post op-ed Sept. 18 that he violated the state ban on abortions performed beyond 6 weeks -- a move he knows could come with legal consequences.
San Antonio doctor Alan Braid, MD, said the new statewide restrictions reminded him of darker days during his 1972 obstetrics and gynecology residency, when he saw three teenagers die from illegal abortions.
“For me, it is 1972 all over again,” he wrote. “And that is why, on the morning of Sept. 6, I provided an abortion to a woman who, though still in her first trimester, was beyond the state’s new limit. I acted because I had a duty of care to this patient, as I do for all patients, and because she has a fundamental right to receive this care.”
“I fully understood that there could be legal consequences -- but I wanted to make sure that Texas didn’t get away with its bid to prevent this blatantly unconstitutional law from being tested,” he continued.
According to The Washington Post, Dr. Braid’s wish may come true. Two lawsuits against were filed Sept. 20. In one, a prisoner in Arkansas said he filed the suit in part because he could receive $10,000 if successful, according to the Post. The second was filed by a man in Chicago who wants the law struck down.
Dr. Braid’s op-ed is the first public admission to violating a Texas state law that took effect Sept. 1 banning abortion once a fetal heartbeat is detected. The controversial policy gives private citizens the right to bring civil litigation -- resulting in at least $10,000 in damages -- against providers and anyone else involved in the process.
Since the law went into effect, most patients seeking abortions are too far along to qualify, Dr. Braid wrote.
“I tell them that we can offer services only if we cannot see the presence of cardiac activity on an ultrasound, which usually occurs at about six weeks, before most people know they are pregnant. The tension is unbearable as they lie there, waiting to hear their fate,” he wrote.
“I understand that by providing an abortion beyond the new legal limit, I am taking a personal risk, but it’s something I believe in strongly,” he continued. “Represented by the Center for Reproductive Rights, my clinics are among the plaintiffs in an ongoing federal lawsuit to stop S.B. 8.”
A version of this article first appeared on WebMD.com .
A Texas doctor revealed in a Washington Post op-ed Sept. 18 that he violated the state ban on abortions performed beyond 6 weeks -- a move he knows could come with legal consequences.
San Antonio doctor Alan Braid, MD, said the new statewide restrictions reminded him of darker days during his 1972 obstetrics and gynecology residency, when he saw three teenagers die from illegal abortions.
“For me, it is 1972 all over again,” he wrote. “And that is why, on the morning of Sept. 6, I provided an abortion to a woman who, though still in her first trimester, was beyond the state’s new limit. I acted because I had a duty of care to this patient, as I do for all patients, and because she has a fundamental right to receive this care.”
“I fully understood that there could be legal consequences -- but I wanted to make sure that Texas didn’t get away with its bid to prevent this blatantly unconstitutional law from being tested,” he continued.
According to The Washington Post, Dr. Braid’s wish may come true. Two lawsuits against were filed Sept. 20. In one, a prisoner in Arkansas said he filed the suit in part because he could receive $10,000 if successful, according to the Post. The second was filed by a man in Chicago who wants the law struck down.
Dr. Braid’s op-ed is the first public admission to violating a Texas state law that took effect Sept. 1 banning abortion once a fetal heartbeat is detected. The controversial policy gives private citizens the right to bring civil litigation -- resulting in at least $10,000 in damages -- against providers and anyone else involved in the process.
Since the law went into effect, most patients seeking abortions are too far along to qualify, Dr. Braid wrote.
“I tell them that we can offer services only if we cannot see the presence of cardiac activity on an ultrasound, which usually occurs at about six weeks, before most people know they are pregnant. The tension is unbearable as they lie there, waiting to hear their fate,” he wrote.
“I understand that by providing an abortion beyond the new legal limit, I am taking a personal risk, but it’s something I believe in strongly,” he continued. “Represented by the Center for Reproductive Rights, my clinics are among the plaintiffs in an ongoing federal lawsuit to stop S.B. 8.”
A version of this article first appeared on WebMD.com .
Moderate alcohol intake may curb subsequent diabetes after gestational diabetes
Among women with a history of gestational diabetes, alcohol intake of half a drink to one drink daily was associated with a 55% lower risk for subsequent type 2 diabetes, based on data from approximately 4,700 women in the Nurses’ Health Study II cohort.
However, the findings must be considered in the context of other risks and benefits of alcohol consumption before making statements or clinical recommendations, wrote Stefanie N. Hinkle, PhD, of the National Institutes of Health, Bethesda, Md., and colleagues.
Women with a history of gestational diabetes remain at increased risk for developing type 2 diabetes, so modifiable diet and lifestyle factors deserve further study, the researchers noted. Previous research has shown an association between light to moderate alcohol consumption and reduced risk of type 2 diabetes among women in the general population, but data on a similar risk reduction for women with a history of gestational diabetes are lacking, they added.
In a study published in JAMA Network Open, the researchers reviewed data from 4,740 women enrolled in the Nurses’ Health Study II who reported a history of gestational diabetes. These women were followed from Jan. 1, 1991, to Dec. 31, 2017, as part of the Diabetes & Women’s Health Study; dietary intake, including alcohol intake, was assessed every 4 years via validated food frequency questionnaires.
The average age at baseline was 38 years, and the median follow-up time was 24 years, yielding a total of 78,328 person-years of follow-up. Alcohol consumption was divided into four categories: none; 0.1 g/day to 4.9 g/day; 5.0 to 14.9 g/day, and 15.0 g/day or higher.
A total of 897 incident cases of type 2 diabetes were reported during the study period. After adjustment for multiple dietary and lifestyle variables, including diet and physical activity, only alcohol consumption of 5.0-14.9 g/day (approximately half a drink to one drink) was associated with a significantly decreased risk for incident type 2 diabetes (hazard ratio, 0.45) compared with women who reported no alcohol consumption.
On further adjustment for body mass index, women who reported alcohol consumption in the 5.0-14.9 g/day range had a 41% lower risk for developing incident type 2 diabetes (HR, 0.59); alcohol consumption in the other ranges remained unassociated with type 2 diabetes risk, although the researchers noted that these estimates were attenuated.
The median daily intake for women who consumed alcohol was 2.3 g/day, approximately one drink per week. Beer was the most frequently consumed type of alcohol.
When the researchers analyzed the data by alcohol type, notably, “only beer consumption of 1 or more servings a week was associated with a lower risk for type 2 diabetes,” although previous studies have suggested a stronger association in diabetes risk reduction with wine consumption vs. beer, the researchers noted.
The study findings were the potential for confounding factors not included in the adjustment, potential underreporting of alcohol intake, and potential screening bias toward women who were more health conscious, the researchers noted. Other limitations were lack of generalizability given that most of the study participants were white women, and a lack of data on binge drinking and whether alcohol was consumed with meals, they added. The study strengths included the prospective design, large size, long-term follow-up, and use of validated questionnaires, they said.
The researchers cautioned that the results should not be interpreted without considering other health outcomes. “Consistent with the 2020 Dietary Guidelines for Americans, which recommend that adults who do not consume alcohol do not initiate drinking, it may not be prudent for those with a history of gestational diabetes who do not consume alcohol to initiate drinking alcohol solely to reduce their risk for type 2 diabetes,” they emphasized.
Risk/benefit ratio for alcohol includes many factors
“There is a relative paucity of data regarding women’s long-term health as it may relate to pregnancy and pregnancy outcomes,” Angela Bianco, MD, of Mount Sinai Hospital, New York, said in an interview.
Dr. Bianco said she was surprised by some of the study findings.
“Generally speaking, I consider alcohol to be of little to no nutritional value, and to have a high sugar content/glycemic index,” she said. “However, a reduced incidence of adult-onset diabetes has been observed among moderate drinkers in other large prospective studies as well,” she noted. “In contrast, some studies have shown an increased risk of diabetes among a proportion of subjects in the top alcohol consumption category, while other studies have found no association. Possible inconsistencies may be due to differences in drinking patterns and the types of beverages consumed,” Dr. Bianco explained.
A key point for clinicians to keep in mind is that “the study may be flawed based on the different criteria used to make a diagnosis of history of gestational diabetes, the fact that they excluded patients that did not return the questionnaires, and the fact that respondents may not have answered correctly due to recall bias” or other reasons, Dr. Bianco said. “Additionally, those who responded obviously had access to health care, which in and of itself is a confounder,” she noted.
Another key point is that “the effect of alcohol being consumed with or without a meal was not examined,” said Dr. Bianco. “Alcohol concentration is reduced if consumed with meals. Alcohol can lead to hypoglycemia (from reduced gluconeogenesis) during fasting states, but after meals (postprandial states) it can result in lower glucose disposal and higher blood glucose levels,” she said. “The available literature suggests that alcohol may improve insulin sensitivity and reduce resistance, but there is likely a U-shaped association between alcohol consumption and the risk of diabetes,” Dr. Bianco noted. “There is likely a delicate balance between benefits and risks of alcohol intake. The inherent benefit/risk ratio must take into account with other potential comorbidities including BMI, activity level, stress, and preexisting conditions,” she said.
“Additional long-term studies engaging patients with diverse ethnic and socioeconomic backgrounds with detailed information regarding the role of nutrition, alcohol intake, tobacco and drug use, environmental exposures, and medical comorbidities need to be performed,” Dr. Bianco concluded.
The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of General Medical Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases; the Nurses’ Health Study II was supported by the National Institutes of Health. Lead author Dr. Hinkle and coauthor Cuilin Zhang, MD, are employees of the U.S. federal government. The researchers and Dr. Bianco had no financial conflicts to disclose.
Among women with a history of gestational diabetes, alcohol intake of half a drink to one drink daily was associated with a 55% lower risk for subsequent type 2 diabetes, based on data from approximately 4,700 women in the Nurses’ Health Study II cohort.
However, the findings must be considered in the context of other risks and benefits of alcohol consumption before making statements or clinical recommendations, wrote Stefanie N. Hinkle, PhD, of the National Institutes of Health, Bethesda, Md., and colleagues.
Women with a history of gestational diabetes remain at increased risk for developing type 2 diabetes, so modifiable diet and lifestyle factors deserve further study, the researchers noted. Previous research has shown an association between light to moderate alcohol consumption and reduced risk of type 2 diabetes among women in the general population, but data on a similar risk reduction for women with a history of gestational diabetes are lacking, they added.
In a study published in JAMA Network Open, the researchers reviewed data from 4,740 women enrolled in the Nurses’ Health Study II who reported a history of gestational diabetes. These women were followed from Jan. 1, 1991, to Dec. 31, 2017, as part of the Diabetes & Women’s Health Study; dietary intake, including alcohol intake, was assessed every 4 years via validated food frequency questionnaires.
The average age at baseline was 38 years, and the median follow-up time was 24 years, yielding a total of 78,328 person-years of follow-up. Alcohol consumption was divided into four categories: none; 0.1 g/day to 4.9 g/day; 5.0 to 14.9 g/day, and 15.0 g/day or higher.
A total of 897 incident cases of type 2 diabetes were reported during the study period. After adjustment for multiple dietary and lifestyle variables, including diet and physical activity, only alcohol consumption of 5.0-14.9 g/day (approximately half a drink to one drink) was associated with a significantly decreased risk for incident type 2 diabetes (hazard ratio, 0.45) compared with women who reported no alcohol consumption.
On further adjustment for body mass index, women who reported alcohol consumption in the 5.0-14.9 g/day range had a 41% lower risk for developing incident type 2 diabetes (HR, 0.59); alcohol consumption in the other ranges remained unassociated with type 2 diabetes risk, although the researchers noted that these estimates were attenuated.
The median daily intake for women who consumed alcohol was 2.3 g/day, approximately one drink per week. Beer was the most frequently consumed type of alcohol.
When the researchers analyzed the data by alcohol type, notably, “only beer consumption of 1 or more servings a week was associated with a lower risk for type 2 diabetes,” although previous studies have suggested a stronger association in diabetes risk reduction with wine consumption vs. beer, the researchers noted.
The study findings were the potential for confounding factors not included in the adjustment, potential underreporting of alcohol intake, and potential screening bias toward women who were more health conscious, the researchers noted. Other limitations were lack of generalizability given that most of the study participants were white women, and a lack of data on binge drinking and whether alcohol was consumed with meals, they added. The study strengths included the prospective design, large size, long-term follow-up, and use of validated questionnaires, they said.
The researchers cautioned that the results should not be interpreted without considering other health outcomes. “Consistent with the 2020 Dietary Guidelines for Americans, which recommend that adults who do not consume alcohol do not initiate drinking, it may not be prudent for those with a history of gestational diabetes who do not consume alcohol to initiate drinking alcohol solely to reduce their risk for type 2 diabetes,” they emphasized.
Risk/benefit ratio for alcohol includes many factors
“There is a relative paucity of data regarding women’s long-term health as it may relate to pregnancy and pregnancy outcomes,” Angela Bianco, MD, of Mount Sinai Hospital, New York, said in an interview.
Dr. Bianco said she was surprised by some of the study findings.
“Generally speaking, I consider alcohol to be of little to no nutritional value, and to have a high sugar content/glycemic index,” she said. “However, a reduced incidence of adult-onset diabetes has been observed among moderate drinkers in other large prospective studies as well,” she noted. “In contrast, some studies have shown an increased risk of diabetes among a proportion of subjects in the top alcohol consumption category, while other studies have found no association. Possible inconsistencies may be due to differences in drinking patterns and the types of beverages consumed,” Dr. Bianco explained.
A key point for clinicians to keep in mind is that “the study may be flawed based on the different criteria used to make a diagnosis of history of gestational diabetes, the fact that they excluded patients that did not return the questionnaires, and the fact that respondents may not have answered correctly due to recall bias” or other reasons, Dr. Bianco said. “Additionally, those who responded obviously had access to health care, which in and of itself is a confounder,” she noted.
Another key point is that “the effect of alcohol being consumed with or without a meal was not examined,” said Dr. Bianco. “Alcohol concentration is reduced if consumed with meals. Alcohol can lead to hypoglycemia (from reduced gluconeogenesis) during fasting states, but after meals (postprandial states) it can result in lower glucose disposal and higher blood glucose levels,” she said. “The available literature suggests that alcohol may improve insulin sensitivity and reduce resistance, but there is likely a U-shaped association between alcohol consumption and the risk of diabetes,” Dr. Bianco noted. “There is likely a delicate balance between benefits and risks of alcohol intake. The inherent benefit/risk ratio must take into account with other potential comorbidities including BMI, activity level, stress, and preexisting conditions,” she said.
“Additional long-term studies engaging patients with diverse ethnic and socioeconomic backgrounds with detailed information regarding the role of nutrition, alcohol intake, tobacco and drug use, environmental exposures, and medical comorbidities need to be performed,” Dr. Bianco concluded.
The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of General Medical Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases; the Nurses’ Health Study II was supported by the National Institutes of Health. Lead author Dr. Hinkle and coauthor Cuilin Zhang, MD, are employees of the U.S. federal government. The researchers and Dr. Bianco had no financial conflicts to disclose.
Among women with a history of gestational diabetes, alcohol intake of half a drink to one drink daily was associated with a 55% lower risk for subsequent type 2 diabetes, based on data from approximately 4,700 women in the Nurses’ Health Study II cohort.
However, the findings must be considered in the context of other risks and benefits of alcohol consumption before making statements or clinical recommendations, wrote Stefanie N. Hinkle, PhD, of the National Institutes of Health, Bethesda, Md., and colleagues.
Women with a history of gestational diabetes remain at increased risk for developing type 2 diabetes, so modifiable diet and lifestyle factors deserve further study, the researchers noted. Previous research has shown an association between light to moderate alcohol consumption and reduced risk of type 2 diabetes among women in the general population, but data on a similar risk reduction for women with a history of gestational diabetes are lacking, they added.
In a study published in JAMA Network Open, the researchers reviewed data from 4,740 women enrolled in the Nurses’ Health Study II who reported a history of gestational diabetes. These women were followed from Jan. 1, 1991, to Dec. 31, 2017, as part of the Diabetes & Women’s Health Study; dietary intake, including alcohol intake, was assessed every 4 years via validated food frequency questionnaires.
The average age at baseline was 38 years, and the median follow-up time was 24 years, yielding a total of 78,328 person-years of follow-up. Alcohol consumption was divided into four categories: none; 0.1 g/day to 4.9 g/day; 5.0 to 14.9 g/day, and 15.0 g/day or higher.
A total of 897 incident cases of type 2 diabetes were reported during the study period. After adjustment for multiple dietary and lifestyle variables, including diet and physical activity, only alcohol consumption of 5.0-14.9 g/day (approximately half a drink to one drink) was associated with a significantly decreased risk for incident type 2 diabetes (hazard ratio, 0.45) compared with women who reported no alcohol consumption.
On further adjustment for body mass index, women who reported alcohol consumption in the 5.0-14.9 g/day range had a 41% lower risk for developing incident type 2 diabetes (HR, 0.59); alcohol consumption in the other ranges remained unassociated with type 2 diabetes risk, although the researchers noted that these estimates were attenuated.
The median daily intake for women who consumed alcohol was 2.3 g/day, approximately one drink per week. Beer was the most frequently consumed type of alcohol.
When the researchers analyzed the data by alcohol type, notably, “only beer consumption of 1 or more servings a week was associated with a lower risk for type 2 diabetes,” although previous studies have suggested a stronger association in diabetes risk reduction with wine consumption vs. beer, the researchers noted.
The study findings were the potential for confounding factors not included in the adjustment, potential underreporting of alcohol intake, and potential screening bias toward women who were more health conscious, the researchers noted. Other limitations were lack of generalizability given that most of the study participants were white women, and a lack of data on binge drinking and whether alcohol was consumed with meals, they added. The study strengths included the prospective design, large size, long-term follow-up, and use of validated questionnaires, they said.
The researchers cautioned that the results should not be interpreted without considering other health outcomes. “Consistent with the 2020 Dietary Guidelines for Americans, which recommend that adults who do not consume alcohol do not initiate drinking, it may not be prudent for those with a history of gestational diabetes who do not consume alcohol to initiate drinking alcohol solely to reduce their risk for type 2 diabetes,” they emphasized.
Risk/benefit ratio for alcohol includes many factors
“There is a relative paucity of data regarding women’s long-term health as it may relate to pregnancy and pregnancy outcomes,” Angela Bianco, MD, of Mount Sinai Hospital, New York, said in an interview.
Dr. Bianco said she was surprised by some of the study findings.
“Generally speaking, I consider alcohol to be of little to no nutritional value, and to have a high sugar content/glycemic index,” she said. “However, a reduced incidence of adult-onset diabetes has been observed among moderate drinkers in other large prospective studies as well,” she noted. “In contrast, some studies have shown an increased risk of diabetes among a proportion of subjects in the top alcohol consumption category, while other studies have found no association. Possible inconsistencies may be due to differences in drinking patterns and the types of beverages consumed,” Dr. Bianco explained.
A key point for clinicians to keep in mind is that “the study may be flawed based on the different criteria used to make a diagnosis of history of gestational diabetes, the fact that they excluded patients that did not return the questionnaires, and the fact that respondents may not have answered correctly due to recall bias” or other reasons, Dr. Bianco said. “Additionally, those who responded obviously had access to health care, which in and of itself is a confounder,” she noted.
Another key point is that “the effect of alcohol being consumed with or without a meal was not examined,” said Dr. Bianco. “Alcohol concentration is reduced if consumed with meals. Alcohol can lead to hypoglycemia (from reduced gluconeogenesis) during fasting states, but after meals (postprandial states) it can result in lower glucose disposal and higher blood glucose levels,” she said. “The available literature suggests that alcohol may improve insulin sensitivity and reduce resistance, but there is likely a U-shaped association between alcohol consumption and the risk of diabetes,” Dr. Bianco noted. “There is likely a delicate balance between benefits and risks of alcohol intake. The inherent benefit/risk ratio must take into account with other potential comorbidities including BMI, activity level, stress, and preexisting conditions,” she said.
“Additional long-term studies engaging patients with diverse ethnic and socioeconomic backgrounds with detailed information regarding the role of nutrition, alcohol intake, tobacco and drug use, environmental exposures, and medical comorbidities need to be performed,” Dr. Bianco concluded.
The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of General Medical Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases; the Nurses’ Health Study II was supported by the National Institutes of Health. Lead author Dr. Hinkle and coauthor Cuilin Zhang, MD, are employees of the U.S. federal government. The researchers and Dr. Bianco had no financial conflicts to disclose.
FROM JAMA NETWORK OPEN
Survey: Nursing shortages affect safety during labor and delivery
Just over 58% of the 1,130 respondents put nursing shortages ahead of physician support and backup (39.0%), inconsistent standards of care (38.5%), and nursing education (31.1%) as the most important challenge to patient safety, the Ob Hospitalist Group (OBHG) said in a new report.
“The survey reveals some startling gaps in physician and patient support all along the care continuum in obstetrics and OB hospitalist programs filling them,” said Lenny Castiglione, the CEO of OBHG, a national network of over 1,000 obstetric hospitalists. “As pressure builds on ob. units to improve care and reduce costs, and as clinical resources are stretched in the continuing battle against COVID-19 and its variants, health systems need to take serious measures to fill these gaps through staff recruitment, retention, and training.”
The national shortage of nurses is expected to get worse over the coming years as Baby Boomers’ need for health care increases and the large population (over 1 million) of older registered nurses retires by 2030, the OBHG said based on projections from the American Association of Colleges of Nursing.
Ob. hospitalists were somewhat more likely to see the nursing shortage as a major problem, compared with community-based Obs (58% vs. 48%), but the biggest difference in perception of safety risk between the two groups (53% for hospitalists vs. 22% for community physicians) involved inconsistent standards of care. “This is likely due to the ob. hospitalists’ 24/7 presence on the unit, and their visibility into the care provided across the unit,” the report noted.
Priorities for the future
Participants also were asked to rank each of seven focus areas on a scale of 0 (lowest priority) to 3 (highest) by its importance in the next 5 years. Maternal mortality was identified as the highest priority by 59.2% of physicians, followed by gaps in access to care between patient populations (38.0%), rural health care (26.5%), and ob.gyn. shortage (26.4%), the OBHG said.
A number of respondents noted the increase in high-risk patients, many of whom are obese and/or older and have comorbidities. “We know that the risk of C-sections increases relative to maternal weight. We need to focus on maternal morbidity and mortality,” one physician wrote in the open-ended response section.
When compared with the community obs., the hospitalists were much more likely to assign top priority over the next 5 years to maternal mortality (73% vs. 50%) and to gaps in access between patient populations (51% vs. 30%), according to the OBHG survey, which was conducted in January of 2021.
How will practice change in 5 years?
As for changes coming to obstetrical care over the next 5 years, respondents gave their strongest prediction to increased use of telemedicine, with 81.2% saying it would increase and just 14.4% predicting no change. The focus on subspecialization is expected to increase by 79.4% of participants (16.5% said no change), and 75.7% said that use of mid-level providers would rise (20.6% said no change), the survey data show.
The move toward mid-level providers was noted in many of the open-ended responses. “There is nothing mid-level about the midwifery care my colleagues provide our patients. They are experts in their field,” one physician wrote, but another said, “just because I foresee a shift toward increasing utilization of mid-levels and primary care practitioners for women’s health does not mean I endorse this trend.”
Just over 58% of the 1,130 respondents put nursing shortages ahead of physician support and backup (39.0%), inconsistent standards of care (38.5%), and nursing education (31.1%) as the most important challenge to patient safety, the Ob Hospitalist Group (OBHG) said in a new report.
“The survey reveals some startling gaps in physician and patient support all along the care continuum in obstetrics and OB hospitalist programs filling them,” said Lenny Castiglione, the CEO of OBHG, a national network of over 1,000 obstetric hospitalists. “As pressure builds on ob. units to improve care and reduce costs, and as clinical resources are stretched in the continuing battle against COVID-19 and its variants, health systems need to take serious measures to fill these gaps through staff recruitment, retention, and training.”
The national shortage of nurses is expected to get worse over the coming years as Baby Boomers’ need for health care increases and the large population (over 1 million) of older registered nurses retires by 2030, the OBHG said based on projections from the American Association of Colleges of Nursing.
Ob. hospitalists were somewhat more likely to see the nursing shortage as a major problem, compared with community-based Obs (58% vs. 48%), but the biggest difference in perception of safety risk between the two groups (53% for hospitalists vs. 22% for community physicians) involved inconsistent standards of care. “This is likely due to the ob. hospitalists’ 24/7 presence on the unit, and their visibility into the care provided across the unit,” the report noted.
Priorities for the future
Participants also were asked to rank each of seven focus areas on a scale of 0 (lowest priority) to 3 (highest) by its importance in the next 5 years. Maternal mortality was identified as the highest priority by 59.2% of physicians, followed by gaps in access to care between patient populations (38.0%), rural health care (26.5%), and ob.gyn. shortage (26.4%), the OBHG said.
A number of respondents noted the increase in high-risk patients, many of whom are obese and/or older and have comorbidities. “We know that the risk of C-sections increases relative to maternal weight. We need to focus on maternal morbidity and mortality,” one physician wrote in the open-ended response section.
When compared with the community obs., the hospitalists were much more likely to assign top priority over the next 5 years to maternal mortality (73% vs. 50%) and to gaps in access between patient populations (51% vs. 30%), according to the OBHG survey, which was conducted in January of 2021.
How will practice change in 5 years?
As for changes coming to obstetrical care over the next 5 years, respondents gave their strongest prediction to increased use of telemedicine, with 81.2% saying it would increase and just 14.4% predicting no change. The focus on subspecialization is expected to increase by 79.4% of participants (16.5% said no change), and 75.7% said that use of mid-level providers would rise (20.6% said no change), the survey data show.
The move toward mid-level providers was noted in many of the open-ended responses. “There is nothing mid-level about the midwifery care my colleagues provide our patients. They are experts in their field,” one physician wrote, but another said, “just because I foresee a shift toward increasing utilization of mid-levels and primary care practitioners for women’s health does not mean I endorse this trend.”
Just over 58% of the 1,130 respondents put nursing shortages ahead of physician support and backup (39.0%), inconsistent standards of care (38.5%), and nursing education (31.1%) as the most important challenge to patient safety, the Ob Hospitalist Group (OBHG) said in a new report.
“The survey reveals some startling gaps in physician and patient support all along the care continuum in obstetrics and OB hospitalist programs filling them,” said Lenny Castiglione, the CEO of OBHG, a national network of over 1,000 obstetric hospitalists. “As pressure builds on ob. units to improve care and reduce costs, and as clinical resources are stretched in the continuing battle against COVID-19 and its variants, health systems need to take serious measures to fill these gaps through staff recruitment, retention, and training.”
The national shortage of nurses is expected to get worse over the coming years as Baby Boomers’ need for health care increases and the large population (over 1 million) of older registered nurses retires by 2030, the OBHG said based on projections from the American Association of Colleges of Nursing.
Ob. hospitalists were somewhat more likely to see the nursing shortage as a major problem, compared with community-based Obs (58% vs. 48%), but the biggest difference in perception of safety risk between the two groups (53% for hospitalists vs. 22% for community physicians) involved inconsistent standards of care. “This is likely due to the ob. hospitalists’ 24/7 presence on the unit, and their visibility into the care provided across the unit,” the report noted.
Priorities for the future
Participants also were asked to rank each of seven focus areas on a scale of 0 (lowest priority) to 3 (highest) by its importance in the next 5 years. Maternal mortality was identified as the highest priority by 59.2% of physicians, followed by gaps in access to care between patient populations (38.0%), rural health care (26.5%), and ob.gyn. shortage (26.4%), the OBHG said.
A number of respondents noted the increase in high-risk patients, many of whom are obese and/or older and have comorbidities. “We know that the risk of C-sections increases relative to maternal weight. We need to focus on maternal morbidity and mortality,” one physician wrote in the open-ended response section.
When compared with the community obs., the hospitalists were much more likely to assign top priority over the next 5 years to maternal mortality (73% vs. 50%) and to gaps in access between patient populations (51% vs. 30%), according to the OBHG survey, which was conducted in January of 2021.
How will practice change in 5 years?
As for changes coming to obstetrical care over the next 5 years, respondents gave their strongest prediction to increased use of telemedicine, with 81.2% saying it would increase and just 14.4% predicting no change. The focus on subspecialization is expected to increase by 79.4% of participants (16.5% said no change), and 75.7% said that use of mid-level providers would rise (20.6% said no change), the survey data show.
The move toward mid-level providers was noted in many of the open-ended responses. “There is nothing mid-level about the midwifery care my colleagues provide our patients. They are experts in their field,” one physician wrote, but another said, “just because I foresee a shift toward increasing utilization of mid-levels and primary care practitioners for women’s health does not mean I endorse this trend.”
Maryland reduces cesarean delivery rates
A statewide educational initiative in Maryland was associated with a significant reduction in cesarean delivery rates over 30 months, although program implementation was widely variable across participating hospitals, according to investigators.
Cesarean deliveries dropped 1.6% among nulliparous, term, singleton, vertex births, falling short of the 3.2% reduction recently achieved by a similar program in California, reported lead author Jennifer A. Callaghan-Koru, PhD, of the University of Maryland, Baltimore County, and colleagues.
“Although cesarean delivery can be lifesaving, evidence suggests that there is no benefit to maternal health when national cesarean delivery rates are higher than 20 per 100 live births,” the investigators wrote in Obstetrics & Gynecology.
They noted that cesarean delivery rates in the United States rose dramatically between 1996 and 2006, from 20.7% to 32.9%, before falling back to 31.7% in 2019.
According to the investigators, high cesarean delivery rates have drawn action from a roster of stakeholders, including the American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM), the Department of Health and Human Services, the Joint Commission, and the Council on Patient Safety in Women’s Health Care.
The latter group created an evidence-based obstetric patient safety bundle that was used in the present study. The investigators recruited 31 out of 32 birthing hospitals in Maryland, and over the course of 30 months, educated the participating hospitals on the practices recommended by the bundle, via in-person and remote training.
To measure implementation and associated outcomes, the investigators used a data portal provided by the ACOG Alliance for Innovation in Maternal Health (AIM) program, which supports adoption of the council’s safety bundle nationwide. Data included number of births; number of cesarean births; overall cesarean delivery rates; cesarean rates among nulliparous, term, singleton, vertex births; cesarean rates among nulliparous, term, singleton, vertex inductions; as well as severe maternal morbidity rates.
Among the 26 safety practices in the bundle, hospitals reported current use of 7 (median) before the program began, with a range from 0 to 23. During the 30-month collaboration, hospitals added a median of 4 practices, ranging from 0 to 17.
Concurrently, cesarean delivery rates for nulliparous, term, singleton, vertex births dropped from 26.9% to 28.5% (P = .011), while rates for inductions dropped to a greater degree, from 36.1% to 31.3% (P less than .001). Further analysis showed that greater reductions in rates of cesarean delivery were associated with adoption of practices in the “Response” domain.
“The Response domain has the largest number of practices that standardize clinical care, including induction scheduling, diagnosis and treatment of labor dystocia and failed induction, and interpretation of fetal heart rate patterns,” the investigators wrote. “The important role of standardizing care is consistent with a Cochrane review that found moderately strong evidence that the implementation of clinical practice guidelines, alongside feedback to clinicians (e.g., second opinions, audit and feedback of rates), can reduce cesarean delivery.”
Dr. Callaghan-Koru and colleagues noted the high variability of implementation among hospitals, which could explain why statewide reductions weren’t more dramatic.
“Other evaluations of perinatal quality improvement collaboratives have also found that some hospitals get left behind in these efforts, without making considerable progress and improving outcomes,” they wrote. “Given that work by state perinatal quality improvement collaboratives represents a primary national strategy for reducing maternal morbidity and mortality, it is critically important to conduct further implementation research to identify determinants of success and strategies to support all participating hospitals to make improvements.”
According to Iris Krishna, MD, of Emory University, Atlanta, each state’s starting point may predict how successful similar programs will be.
“The safe reduction in the cesarean delivery rate will vary by state,” Dr. Krishna said in a written comment. “States that have a well-established perinatal quality collaborative that have the support on the provider, hospital, and statewide level are more likely to successfully implement strategies and see a statistically significant decrease.”
She went on to emphasize the importance of collaboration across multiple levels of organization, and across a variety of health care providers and administrators.
“Successful implementation requires a multidisciplinary team (physicians, nurses, quality improvement officers) and a multifaceted approach (statewide policies),” Dr. Krishna said. “Key stakeholders will need to ‘buy in’ or be willing to support the policy and practice change to ensure its success. To address obstacles, initiatives to support vaginal birth are important, such as provider training on labor and support techniques, criteria for diagnosis of and management of labor dystocia and arrest disorders, standard responses to abnormal fetal heart rate patterns, and availability of expertise to lessen the need for cesarean delivery, such as breech version, instrumented delivery, and twin delivery protocols. It is also important for hospitals to a have a mentor model of quality improvement and shared learning strategies that work.”
Dr. Krishna agreed with the investigators that more work is necessary to determine best strategies for future intervention.
“Research is needed in identifying determinants of success and sustainment,” she said.
Dr. Burke received funding from her employer, Trinity Health, to conduct a pilot study concerning blood loss.
A statewide educational initiative in Maryland was associated with a significant reduction in cesarean delivery rates over 30 months, although program implementation was widely variable across participating hospitals, according to investigators.
Cesarean deliveries dropped 1.6% among nulliparous, term, singleton, vertex births, falling short of the 3.2% reduction recently achieved by a similar program in California, reported lead author Jennifer A. Callaghan-Koru, PhD, of the University of Maryland, Baltimore County, and colleagues.
“Although cesarean delivery can be lifesaving, evidence suggests that there is no benefit to maternal health when national cesarean delivery rates are higher than 20 per 100 live births,” the investigators wrote in Obstetrics & Gynecology.
They noted that cesarean delivery rates in the United States rose dramatically between 1996 and 2006, from 20.7% to 32.9%, before falling back to 31.7% in 2019.
According to the investigators, high cesarean delivery rates have drawn action from a roster of stakeholders, including the American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM), the Department of Health and Human Services, the Joint Commission, and the Council on Patient Safety in Women’s Health Care.
The latter group created an evidence-based obstetric patient safety bundle that was used in the present study. The investigators recruited 31 out of 32 birthing hospitals in Maryland, and over the course of 30 months, educated the participating hospitals on the practices recommended by the bundle, via in-person and remote training.
To measure implementation and associated outcomes, the investigators used a data portal provided by the ACOG Alliance for Innovation in Maternal Health (AIM) program, which supports adoption of the council’s safety bundle nationwide. Data included number of births; number of cesarean births; overall cesarean delivery rates; cesarean rates among nulliparous, term, singleton, vertex births; cesarean rates among nulliparous, term, singleton, vertex inductions; as well as severe maternal morbidity rates.
Among the 26 safety practices in the bundle, hospitals reported current use of 7 (median) before the program began, with a range from 0 to 23. During the 30-month collaboration, hospitals added a median of 4 practices, ranging from 0 to 17.
Concurrently, cesarean delivery rates for nulliparous, term, singleton, vertex births dropped from 26.9% to 28.5% (P = .011), while rates for inductions dropped to a greater degree, from 36.1% to 31.3% (P less than .001). Further analysis showed that greater reductions in rates of cesarean delivery were associated with adoption of practices in the “Response” domain.
“The Response domain has the largest number of practices that standardize clinical care, including induction scheduling, diagnosis and treatment of labor dystocia and failed induction, and interpretation of fetal heart rate patterns,” the investigators wrote. “The important role of standardizing care is consistent with a Cochrane review that found moderately strong evidence that the implementation of clinical practice guidelines, alongside feedback to clinicians (e.g., second opinions, audit and feedback of rates), can reduce cesarean delivery.”
Dr. Callaghan-Koru and colleagues noted the high variability of implementation among hospitals, which could explain why statewide reductions weren’t more dramatic.
“Other evaluations of perinatal quality improvement collaboratives have also found that some hospitals get left behind in these efforts, without making considerable progress and improving outcomes,” they wrote. “Given that work by state perinatal quality improvement collaboratives represents a primary national strategy for reducing maternal morbidity and mortality, it is critically important to conduct further implementation research to identify determinants of success and strategies to support all participating hospitals to make improvements.”
According to Iris Krishna, MD, of Emory University, Atlanta, each state’s starting point may predict how successful similar programs will be.
“The safe reduction in the cesarean delivery rate will vary by state,” Dr. Krishna said in a written comment. “States that have a well-established perinatal quality collaborative that have the support on the provider, hospital, and statewide level are more likely to successfully implement strategies and see a statistically significant decrease.”
She went on to emphasize the importance of collaboration across multiple levels of organization, and across a variety of health care providers and administrators.
“Successful implementation requires a multidisciplinary team (physicians, nurses, quality improvement officers) and a multifaceted approach (statewide policies),” Dr. Krishna said. “Key stakeholders will need to ‘buy in’ or be willing to support the policy and practice change to ensure its success. To address obstacles, initiatives to support vaginal birth are important, such as provider training on labor and support techniques, criteria for diagnosis of and management of labor dystocia and arrest disorders, standard responses to abnormal fetal heart rate patterns, and availability of expertise to lessen the need for cesarean delivery, such as breech version, instrumented delivery, and twin delivery protocols. It is also important for hospitals to a have a mentor model of quality improvement and shared learning strategies that work.”
Dr. Krishna agreed with the investigators that more work is necessary to determine best strategies for future intervention.
“Research is needed in identifying determinants of success and sustainment,” she said.
Dr. Burke received funding from her employer, Trinity Health, to conduct a pilot study concerning blood loss.
A statewide educational initiative in Maryland was associated with a significant reduction in cesarean delivery rates over 30 months, although program implementation was widely variable across participating hospitals, according to investigators.
Cesarean deliveries dropped 1.6% among nulliparous, term, singleton, vertex births, falling short of the 3.2% reduction recently achieved by a similar program in California, reported lead author Jennifer A. Callaghan-Koru, PhD, of the University of Maryland, Baltimore County, and colleagues.
“Although cesarean delivery can be lifesaving, evidence suggests that there is no benefit to maternal health when national cesarean delivery rates are higher than 20 per 100 live births,” the investigators wrote in Obstetrics & Gynecology.
They noted that cesarean delivery rates in the United States rose dramatically between 1996 and 2006, from 20.7% to 32.9%, before falling back to 31.7% in 2019.
According to the investigators, high cesarean delivery rates have drawn action from a roster of stakeholders, including the American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM), the Department of Health and Human Services, the Joint Commission, and the Council on Patient Safety in Women’s Health Care.
The latter group created an evidence-based obstetric patient safety bundle that was used in the present study. The investigators recruited 31 out of 32 birthing hospitals in Maryland, and over the course of 30 months, educated the participating hospitals on the practices recommended by the bundle, via in-person and remote training.
To measure implementation and associated outcomes, the investigators used a data portal provided by the ACOG Alliance for Innovation in Maternal Health (AIM) program, which supports adoption of the council’s safety bundle nationwide. Data included number of births; number of cesarean births; overall cesarean delivery rates; cesarean rates among nulliparous, term, singleton, vertex births; cesarean rates among nulliparous, term, singleton, vertex inductions; as well as severe maternal morbidity rates.
Among the 26 safety practices in the bundle, hospitals reported current use of 7 (median) before the program began, with a range from 0 to 23. During the 30-month collaboration, hospitals added a median of 4 practices, ranging from 0 to 17.
Concurrently, cesarean delivery rates for nulliparous, term, singleton, vertex births dropped from 26.9% to 28.5% (P = .011), while rates for inductions dropped to a greater degree, from 36.1% to 31.3% (P less than .001). Further analysis showed that greater reductions in rates of cesarean delivery were associated with adoption of practices in the “Response” domain.
“The Response domain has the largest number of practices that standardize clinical care, including induction scheduling, diagnosis and treatment of labor dystocia and failed induction, and interpretation of fetal heart rate patterns,” the investigators wrote. “The important role of standardizing care is consistent with a Cochrane review that found moderately strong evidence that the implementation of clinical practice guidelines, alongside feedback to clinicians (e.g., second opinions, audit and feedback of rates), can reduce cesarean delivery.”
Dr. Callaghan-Koru and colleagues noted the high variability of implementation among hospitals, which could explain why statewide reductions weren’t more dramatic.
“Other evaluations of perinatal quality improvement collaboratives have also found that some hospitals get left behind in these efforts, without making considerable progress and improving outcomes,” they wrote. “Given that work by state perinatal quality improvement collaboratives represents a primary national strategy for reducing maternal morbidity and mortality, it is critically important to conduct further implementation research to identify determinants of success and strategies to support all participating hospitals to make improvements.”
According to Iris Krishna, MD, of Emory University, Atlanta, each state’s starting point may predict how successful similar programs will be.
“The safe reduction in the cesarean delivery rate will vary by state,” Dr. Krishna said in a written comment. “States that have a well-established perinatal quality collaborative that have the support on the provider, hospital, and statewide level are more likely to successfully implement strategies and see a statistically significant decrease.”
She went on to emphasize the importance of collaboration across multiple levels of organization, and across a variety of health care providers and administrators.
“Successful implementation requires a multidisciplinary team (physicians, nurses, quality improvement officers) and a multifaceted approach (statewide policies),” Dr. Krishna said. “Key stakeholders will need to ‘buy in’ or be willing to support the policy and practice change to ensure its success. To address obstacles, initiatives to support vaginal birth are important, such as provider training on labor and support techniques, criteria for diagnosis of and management of labor dystocia and arrest disorders, standard responses to abnormal fetal heart rate patterns, and availability of expertise to lessen the need for cesarean delivery, such as breech version, instrumented delivery, and twin delivery protocols. It is also important for hospitals to a have a mentor model of quality improvement and shared learning strategies that work.”
Dr. Krishna agreed with the investigators that more work is necessary to determine best strategies for future intervention.
“Research is needed in identifying determinants of success and sustainment,” she said.
Dr. Burke received funding from her employer, Trinity Health, to conduct a pilot study concerning blood loss.
FROM OBSTETRICS & GYNECOLOGY
‘New first-line standard of care’ in cervical cancer
That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.
The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.
The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.
“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.
Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.
Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.
Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.
“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”
KEYNOTE-826 details
This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.
The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.
Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).
PFS and OS results
The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.
After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).
The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.
In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).
OS rates were also significantly improved, he noted.
The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).
In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).
Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).
Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.
The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.
Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.
He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.
KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.
A version of this article was first published on Medscape.com.
That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.
The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.
The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.
“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.
Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.
Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.
Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.
“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”
KEYNOTE-826 details
This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.
The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.
Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).
PFS and OS results
The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.
After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).
The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.
In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).
OS rates were also significantly improved, he noted.
The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).
In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).
Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).
Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.
The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.
Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.
He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.
KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.
A version of this article was first published on Medscape.com.
That declaration was made by Raza Mirza, MD, chief oncologist at Copenhagen University Hospital in Denmark, who was invited to discuss the pros and cons of the KEYNOTE-826 trial at the European Society for Medical Oncology (ESMO) Congress 2021.
The trial showed that adding the checkpoint inhibitor pembrolizumab (Keytruda) to standard chemotherapy — with or without bevacizumab — resulted in about a one third reduction in the risk for both disease progression and death compared with chemotherapy alone.
The benefit of adding pembrolizumab was seen both in the overall study population and in patients with higher levels of programmed death ligand-1 (PD-L1), but not in those with biomarker-negative tumors, reported investigator Nicoletta Colombo, MD, PhD, from the University of Milan-Bicocca, Italy.
“Overall, data from KEYNOTE-826 suggest that pembrolizumab plus platinum-based chemotherapy with or without bevacizumab may be a new first-line standard of care,” she said in a late-breaking oral abstract presentation. The study was also simultaneously published online in The New England Journal of Medicine.
Since 2014, the standard of care for treating patients with recurrent, persistent, or metastatic cervical cancer has been chemotherapy with a platinum compound, paclitaxel, plus bevacizumab, based on the results of the GOG 240 study.
Immunotherapy with PD-1 inhibitors have shown efficacy as monotherapy in second- or later-line therapy for women with cervical cancer, but until now no data about the addition of these agents to chemotherapy were available, Dr. Colombo noted.
Dr. Mirza noted that there is sound rationale for using checkpoint inhibitors targeted against PD-1 in patients with cervical cancer, because PD-L1 has been shown to be a consistent biomarker for infection of the cervix with human papillomavirus (HPV), which is responsible for more than 90% of cervical cancers.
“PD-L1 is significantly upregulated in cervical cancer and detectable by immunohistochemistry,” he said. “PD-L1 expression reduces the immune response since it is able to bind to PD-1 on T-cell lymphocytes, thereby inhibiting their function. These findings suggest that targeting the PD-1/PD-L1 pathway may be therapeutically effective and should be considered in the treatment of cervical cancer.”
KEYNOTE-826 details
This was a double-blind trial conducted in 617 patients stratified by metastatic disease status at diagnosis; PD-L1 combined positive score (CPS) either < 1, 1 to < 10, or ≥ 10. They were randomized in a 1:1 ratio to receive pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus platinum-based chemotherapy, with bevacizumab added at the investigator’s discretion.
The dual primary endpoints of progression-free survival (PFS) and overall survival (OS) were each tested sequentially in patients with a PD-L1 CPS ≥ 1 in both the intention-to-treat (ITT) or “all-comers” population, and in patients with a PD-L1 CPS ≥ 10.
Patient characteristics were generally well balanced between the treatment groups, except for a slightly higher proportion of patients with squamous cell histology in the pembrolizumab versus the placebo group (76.3% vs 68.3%).
PFS and OS results
The addition of pembrolizumab was associated with improved PFS across most protocol-specified subgroups, Dr. Colombo and colleagues noted.
After a median follow-up of 22 months, the 12-month PFS rate in the biomarker-selected population (all patients with a PD-L1 CPS ≥ 1) was 45.5% for patients in the pembrolizumab group versus 34.1% in the placebo group. This translated into a hazard ratio (HR) for progression on pembrolizumab of 0.62 (P < .001).
The respective PFS rates in the ITT population were 44.7% and 33.5%, with an HR for progression of 0.65 (P < .001) with the checkpoint inhibitor.
In patients with PD-L1 CPS ≥ 10, the respective rates of PFS and the HR were 44.6%, 33.5%, and 0.58 (P < .001).
OS rates were also significantly improved, he noted.
The 12-month and 24-month OS rates in all patients with PD-L1 CPS ≥ 1 were 75.3% and 53%, respectively, for patients assigned to pembrolizumab versus 63.1% and 41.7% in patients assigned to placebo, translating to an HR for death with pembrolizumab in this group of 0.64 (P < .001).
In the all-comers (ITT) population, respective 12- and 24-month OS rates were 74.8% and 50.4% with pembrolizumab versus 63.6% and 40.4% with placebo. This difference translated into an HR for death with anti-PD-1 of 0.67 (P < .001).
Among patients with the higher PD-L1 levels (≥ CPS 10), the respective OS rates were 75.7% and 54.4% with pembrolizumab versus 61.5% and 44.6% with placebo (HR 0.61, P < .001).
Dr. Mirza emphasized that “we did not see any efficacy of pembrolizumab in the biomarker-negative population,” with an HR for PFS of 0.94 and HR for OS of 1.0 in this subgroup.
The most common grade ≥ 3 adverse events were anemia, which occurred in 30.3% of patients assigned to pembrolizumab compared with 26.9% in the placebo group, and neutropenias, which occurred in 12.4% and 9.7% of patients, respectively. One patient in the pembrolizumab group died from an immune-related event, encephalitis.
Despite his enthusiasm for the regimen, Dr. Mirza tempered it by pointing out that there was an imbalance in the sample sizes regarding histology, and a potential bias introduced by the failure to stratify by tumor histology.
He noted that in other studies checkpoint inhibitors have had only modest activity against adenocarcinomas, which were more frequent in the placebo group in KEYNOTE-826, resulting in a potential positive bias in favor of pembrolizumab.
KEYNOTE-826 is funded by MSD. Dr. Colombo has disclosed consultant, research, and promotional speaking activities for multiple companies. Dr. Mirza has disclosed personal financial interests with Merck and other companies.
A version of this article was first published on Medscape.com.