Women's Health

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.

Nursing shortages are the biggest safety risk for patients in labor and delivery units, according to a recent survey of obstetricians.

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.”

rfranki@mdedge.com

Nursing shortages are the biggest safety risk for patients in labor and delivery units, according to a recent survey of obstetricians.

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.”

rfranki@mdedge.com

Nursing shortages are the biggest safety risk for patients in labor and delivery units, according to a recent survey of obstetricians.

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.”

rfranki@mdedge.com

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.

The new standard of care for women with persistent, recurrent, or perhaps primary metastatic cervical cancer should be pembrolizumab added to chemotherapy with bevacizumab in [the] biomarker-positive population.

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.

The new standard of care for women with persistent, recurrent, or perhaps primary metastatic cervical cancer should be pembrolizumab added to chemotherapy with bevacizumab in [the] biomarker-positive population.

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.

The new standard of care for women with persistent, recurrent, or perhaps primary metastatic cervical cancer should be pembrolizumab added to chemotherapy with bevacizumab in [the] biomarker-positive population.

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.

For patients with endometriosis-related dysmenorrhea, it is cost effective to use medical therapy before surgery, according to investigators.

A stepwise strategy involving two medications, then surgery, was associated with the lowest cost per quality-adjusted life-years (QALYs), reported lead author, Jacqueline A. Bohn, MD, of Oregon Health & Science University, Portland, and colleagues.

“In 2009, the medical costs associated with endometriosis in the United States were estimated at $69.4 billion annually,” the investigators wrote in Obstetrics and Gynecology. “Despite the recognized cost burden of this disease, cost-effectiveness data on the various treatment strategies is limited. Previous studies have investigated the direct and indirect costs regarding endometriosis; however, there are no prior studies that evaluate the cost-effectiveness of a stepwise regimen to guide management.”

To fill this knowledge gap, Dr. Bohn and colleagues created a cost-effectiveness model comparing four treatment strategies:

NSAIDs, then surgery

NSAIDs, then short-acting reversible contraceptives or long-acting reversible contraceptives (LARCs), then surgery

NSAIDs, then a short-acting reversible contraceptive or a LARC, then a LARC or gonadotropin-releasing hormone (GnRH) modulator, then surgery

Surgery alone

The analysis, which compared costs, QALYs, and incremental cost-effectiveness ratios, involved a theoretical cohort of 4,817,894 women aged 18-45 years, representing the estimated number of reproductive-age women in the United States with endometriosis-related dysmenorrhea. Costs were determined from published literature and inflated to 2019 dollars. Medical treatments were theoretically given for 6 months each, and the cost of laparoscopic surgery incorporated 12 months of postoperative care.

Of the four strategies, the two-medication approach was most cost effective, with a cost per QALY of $1,158. This was followed closely by the three-medication regimen, at $1,158, the single-medication regimen, at $2,108, and finally, surgery alone, at $4,338.

“We found that, although cost effective, requiring trial of a third medication offered little comparative advantage before proceeding directly to surgery after the second therapy fails,” the investigators wrote. “Yet, for the woman who is anxious about surgical intervention, or when a prolonged wait for a surgical specialist occurs, trial of a GnRH modulator may be worthwhile.”

Compared with surgery alone, each regimen starting with medical therapy remained below the standard willingness-to-pay threshold of $100,000 per QALY; however, the investigators recommend against trying more than three medications.

“Delaying surgical management in a woman with pain refractory to more than three medications may decrease quality of life and further increase cost,” they wrote.

To make surgery alone the most cost-effective option, surgery success would need to exceed 83%, Dr. Bohn and colleagues concluded.

According to Hugh Taylor, MD, of Yale University, New Haven, Conn., it’s unlikely that this surgery success threshold will be met, since surgery alone typically leads to recurrence.

“We know there’s a very high relapse rate after surgery,” Dr. Taylor said in an interview. “Even if the surgery may be initially successful, there’s roughly a 50% recurrence rate after about 2 years. So, finding the right medical therapy will give you more chance for long-term success.”

Dr. Taylor said it’s “really nice” that Dr. Bohn and colleagues conducted a sequential analysis because the findings support the most common approach in real-world practice.

“It confirms that starting with a medical therapy prior to surgery is an appropriate, successful treatment for endometriosis, which is something that many, many people in the community do, but we haven’t had a real trial to show that,” he said.

Dr. Taylor offered two areas of improvement for similar studies in the future: First, he suggested separating LARCs from oral contraceptives because LARCs may be less effective for some patients with endometriosis; and second, he suggested that limiting the third medication to a GnRH antagonist would be more applicable to real-world practice than using the broader category of GnRH modulators.

Although the three-medication approach involving a GnRH modulator was slightly more expensive than the two-medication approach, Dr. Taylor said the costs were so similar that a three-medication approach is “still reasonable,” particularly because it could spare patients from surgery.

Dr. Taylor also speculated that trying a GnRH antagonist could become more cost effective soon. Although only one GnRH antagonist is currently on the market, he noted that a second agent is poised for Food and Drug Administration approval, while a third is in the pipeline, and this competition may decrease drug prices.

The investigators disclosed support from the National Institutes of Health, Arnold Ventures, the World Health Organization, Merck, and others. Dr. Taylor reported that Yale University receives funding for endometriosis biomarker research from AbbVie.

For patients with endometriosis-related dysmenorrhea, it is cost effective to use medical therapy before surgery, according to investigators.

A stepwise strategy involving two medications, then surgery, was associated with the lowest cost per quality-adjusted life-years (QALYs), reported lead author, Jacqueline A. Bohn, MD, of Oregon Health & Science University, Portland, and colleagues.

“In 2009, the medical costs associated with endometriosis in the United States were estimated at $69.4 billion annually,” the investigators wrote in Obstetrics and Gynecology. “Despite the recognized cost burden of this disease, cost-effectiveness data on the various treatment strategies is limited. Previous studies have investigated the direct and indirect costs regarding endometriosis; however, there are no prior studies that evaluate the cost-effectiveness of a stepwise regimen to guide management.”

To fill this knowledge gap, Dr. Bohn and colleagues created a cost-effectiveness model comparing four treatment strategies:

NSAIDs, then surgery

NSAIDs, then short-acting reversible contraceptives or long-acting reversible contraceptives (LARCs), then surgery

NSAIDs, then a short-acting reversible contraceptive or a LARC, then a LARC or gonadotropin-releasing hormone (GnRH) modulator, then surgery

Surgery alone

The analysis, which compared costs, QALYs, and incremental cost-effectiveness ratios, involved a theoretical cohort of 4,817,894 women aged 18-45 years, representing the estimated number of reproductive-age women in the United States with endometriosis-related dysmenorrhea. Costs were determined from published literature and inflated to 2019 dollars. Medical treatments were theoretically given for 6 months each, and the cost of laparoscopic surgery incorporated 12 months of postoperative care.

Of the four strategies, the two-medication approach was most cost effective, with a cost per QALY of $1,158. This was followed closely by the three-medication regimen, at $1,158, the single-medication regimen, at $2,108, and finally, surgery alone, at $4,338.

“We found that, although cost effective, requiring trial of a third medication offered little comparative advantage before proceeding directly to surgery after the second therapy fails,” the investigators wrote. “Yet, for the woman who is anxious about surgical intervention, or when a prolonged wait for a surgical specialist occurs, trial of a GnRH modulator may be worthwhile.”

Compared with surgery alone, each regimen starting with medical therapy remained below the standard willingness-to-pay threshold of $100,000 per QALY; however, the investigators recommend against trying more than three medications.

“Delaying surgical management in a woman with pain refractory to more than three medications may decrease quality of life and further increase cost,” they wrote.

To make surgery alone the most cost-effective option, surgery success would need to exceed 83%, Dr. Bohn and colleagues concluded.

According to Hugh Taylor, MD, of Yale University, New Haven, Conn., it’s unlikely that this surgery success threshold will be met, since surgery alone typically leads to recurrence.

“We know there’s a very high relapse rate after surgery,” Dr. Taylor said in an interview. “Even if the surgery may be initially successful, there’s roughly a 50% recurrence rate after about 2 years. So, finding the right medical therapy will give you more chance for long-term success.”

Dr. Taylor said it’s “really nice” that Dr. Bohn and colleagues conducted a sequential analysis because the findings support the most common approach in real-world practice.

“It confirms that starting with a medical therapy prior to surgery is an appropriate, successful treatment for endometriosis, which is something that many, many people in the community do, but we haven’t had a real trial to show that,” he said.

Dr. Taylor offered two areas of improvement for similar studies in the future: First, he suggested separating LARCs from oral contraceptives because LARCs may be less effective for some patients with endometriosis; and second, he suggested that limiting the third medication to a GnRH antagonist would be more applicable to real-world practice than using the broader category of GnRH modulators.

Although the three-medication approach involving a GnRH modulator was slightly more expensive than the two-medication approach, Dr. Taylor said the costs were so similar that a three-medication approach is “still reasonable,” particularly because it could spare patients from surgery.

Dr. Taylor also speculated that trying a GnRH antagonist could become more cost effective soon. Although only one GnRH antagonist is currently on the market, he noted that a second agent is poised for Food and Drug Administration approval, while a third is in the pipeline, and this competition may decrease drug prices.

The investigators disclosed support from the National Institutes of Health, Arnold Ventures, the World Health Organization, Merck, and others. Dr. Taylor reported that Yale University receives funding for endometriosis biomarker research from AbbVie.

For patients with endometriosis-related dysmenorrhea, it is cost effective to use medical therapy before surgery, according to investigators.

A stepwise strategy involving two medications, then surgery, was associated with the lowest cost per quality-adjusted life-years (QALYs), reported lead author, Jacqueline A. Bohn, MD, of Oregon Health & Science University, Portland, and colleagues.

“In 2009, the medical costs associated with endometriosis in the United States were estimated at $69.4 billion annually,” the investigators wrote in Obstetrics and Gynecology. “Despite the recognized cost burden of this disease, cost-effectiveness data on the various treatment strategies is limited. Previous studies have investigated the direct and indirect costs regarding endometriosis; however, there are no prior studies that evaluate the cost-effectiveness of a stepwise regimen to guide management.”

To fill this knowledge gap, Dr. Bohn and colleagues created a cost-effectiveness model comparing four treatment strategies:

NSAIDs, then surgery

NSAIDs, then short-acting reversible contraceptives or long-acting reversible contraceptives (LARCs), then surgery

NSAIDs, then a short-acting reversible contraceptive or a LARC, then a LARC or gonadotropin-releasing hormone (GnRH) modulator, then surgery

Surgery alone

The analysis, which compared costs, QALYs, and incremental cost-effectiveness ratios, involved a theoretical cohort of 4,817,894 women aged 18-45 years, representing the estimated number of reproductive-age women in the United States with endometriosis-related dysmenorrhea. Costs were determined from published literature and inflated to 2019 dollars. Medical treatments were theoretically given for 6 months each, and the cost of laparoscopic surgery incorporated 12 months of postoperative care.

Of the four strategies, the two-medication approach was most cost effective, with a cost per QALY of $1,158. This was followed closely by the three-medication regimen, at $1,158, the single-medication regimen, at $2,108, and finally, surgery alone, at $4,338.

“We found that, although cost effective, requiring trial of a third medication offered little comparative advantage before proceeding directly to surgery after the second therapy fails,” the investigators wrote. “Yet, for the woman who is anxious about surgical intervention, or when a prolonged wait for a surgical specialist occurs, trial of a GnRH modulator may be worthwhile.”

Compared with surgery alone, each regimen starting with medical therapy remained below the standard willingness-to-pay threshold of $100,000 per QALY; however, the investigators recommend against trying more than three medications.

“Delaying surgical management in a woman with pain refractory to more than three medications may decrease quality of life and further increase cost,” they wrote.

To make surgery alone the most cost-effective option, surgery success would need to exceed 83%, Dr. Bohn and colleagues concluded.

According to Hugh Taylor, MD, of Yale University, New Haven, Conn., it’s unlikely that this surgery success threshold will be met, since surgery alone typically leads to recurrence.

“We know there’s a very high relapse rate after surgery,” Dr. Taylor said in an interview. “Even if the surgery may be initially successful, there’s roughly a 50% recurrence rate after about 2 years. So, finding the right medical therapy will give you more chance for long-term success.”

Dr. Taylor said it’s “really nice” that Dr. Bohn and colleagues conducted a sequential analysis because the findings support the most common approach in real-world practice.

“It confirms that starting with a medical therapy prior to surgery is an appropriate, successful treatment for endometriosis, which is something that many, many people in the community do, but we haven’t had a real trial to show that,” he said.

Dr. Taylor offered two areas of improvement for similar studies in the future: First, he suggested separating LARCs from oral contraceptives because LARCs may be less effective for some patients with endometriosis; and second, he suggested that limiting the third medication to a GnRH antagonist would be more applicable to real-world practice than using the broader category of GnRH modulators.

Although the three-medication approach involving a GnRH modulator was slightly more expensive than the two-medication approach, Dr. Taylor said the costs were so similar that a three-medication approach is “still reasonable,” particularly because it could spare patients from surgery.

Dr. Taylor also speculated that trying a GnRH antagonist could become more cost effective soon. Although only one GnRH antagonist is currently on the market, he noted that a second agent is poised for Food and Drug Administration approval, while a third is in the pipeline, and this competition may decrease drug prices.

The investigators disclosed support from the National Institutes of Health, Arnold Ventures, the World Health Organization, Merck, and others. Dr. Taylor reported that Yale University receives funding for endometriosis biomarker research from AbbVie.

Persistent human papillomavirus (HPV) 16 and HPV 18 during a pregnancy may be associated with an increased risk of premature birth.

Findings published online in JAMA Network Open found that 15.9% of individuals who had a persistent HPV 16 or 18 infection during the first and third trimesters of their pregnancy gave birth prematurely, compared with 5.6% of those who did not have an HPV infection at all.

The findings prompted the question of “the pathophysiology of HPV in pregnancy and how the virus is affecting the placenta,” said Lisette Davidson Tanner, MD, MPH, FACOG, who was not involved in the study.

Researchers said the findings are the first to show the association between preterm birth and HPV, which is an incurable virus that most sexually active individuals will get at some point in their lives, according to the Centers for Disease Control and Prevention.

“The results of this study are very important in helping us understand the burden caused by HPV in pregnancy,” study author Helen Trottier, MSc, PhD, researcher at the Centre Hospitalier Universitaire Sainte-Justine, said in an interview. “We may have just pinpointed an important cause of preterm birth that has so far been unexplained.”

Dr. Trottier and colleagues examined data from 1,052 pregnant women from three university-affiliated health care centers in Montreal between Nov. 8, 2010, and Oct. 16, 2016.

Only 5.6% of those who did not have an HPV infection had a premature birth, compared with 6.9% of those who tested positive for any HPV infection in the first trimester.

When looking at the first trimester, researchers found 12% of those diagnosed with HPV 16 and 18 had a preterm birth, compared to 4.9% of those who had a high-risk HPV infection other than HPV 16/18. When looking at the third trimester, researchers found that 15.9% of those with HPV 16/18 had an increased risk of giving birth prematurely, compared to those who had other high-risk HPV infections.

When researchers looked at the persistence of these HPV infections, they found that most HPV infections detected in the first trimester persist to the third trimester. The findings also revealed that persistent vaginal HPV 16/18 detection was significantly associated with all preterm births and spontaneous preterm births. This association was also found among those who had HPV infections detected in their placentas.

Meanwhile, 5.8% of those who had an HPV infection only during the first trimester experienced a preterm birth.

The researchers also found that HPV infections were frequent in pregnancy even among populations “considered to be at low risk based on sociodemographic and sexual history characteristics,” they wrote. Dr. Trottier said she hopes the findings will strengthen support for HPV vaccination.

Dr. Trottier’s study adds to a growing body of research regarding the adverse effects of HPV, according to Dr. Tanner, assistant professor of gynecology and obstetrics at Emory University, Atlanta. “It is already well known that HPV is associated with a number of anogenital and oropharyngeal cancers,” Dr. Tanner said in an interview. “The potential association with preterm birth only adds weight to the recommendations to screen for and prevent HPV infection.”

HPV 16 and 18 are high-risk types that cause about 70% of cervical cancers and precancerous cervical lesions, according to the World Health Organization. However, there are three HPV vaccines – 9-valent HPV vaccine (Gardasil), quadrivalent HPV vaccine (Gardasil®, 4vHPV), and bivalent HPV vaccine (Cervarix) – that help protect against HPV 16/18.

The findings strengthen the benefits of HPV vaccination, Dr. Trottier explained. “There is no cure when the HPV infection is present,” Dr. Trottier said. “If the link [between preterm birth and HPV infections] is indeed causal, we can expect a greater risk of preterm delivery in these women. The effective tool we have is the HPV vaccination, but it should ideally be received before the start of sexual activity in order to prevent future infections that could occur in women.”

The American College of Obstetricians and Gynecologists recommends HPV vaccination for girls and women between the ages of 11 and 26 years old. However, Dr. Tanner said, women aged 27-45 who were previously unvaccinated may still receive benefit from the vaccine. 

“Despite the known efficacy of the vaccine, only 50% of patients are up to date with their HPV vaccination,” Dr. Tanner explained. “This study further highlights the need to educate and encourage patients to be vaccinated.”

The researchers said future studies should investigate the association of HPV vaccination and vaccination programs with the risk of preterm birth.

The experts disclosed no conflicts of interest.

Persistent human papillomavirus (HPV) 16 and HPV 18 during a pregnancy may be associated with an increased risk of premature birth.

Findings published online in JAMA Network Open found that 15.9% of individuals who had a persistent HPV 16 or 18 infection during the first and third trimesters of their pregnancy gave birth prematurely, compared with 5.6% of those who did not have an HPV infection at all.

The findings prompted the question of “the pathophysiology of HPV in pregnancy and how the virus is affecting the placenta,” said Lisette Davidson Tanner, MD, MPH, FACOG, who was not involved in the study.

Researchers said the findings are the first to show the association between preterm birth and HPV, which is an incurable virus that most sexually active individuals will get at some point in their lives, according to the Centers for Disease Control and Prevention.

“The results of this study are very important in helping us understand the burden caused by HPV in pregnancy,” study author Helen Trottier, MSc, PhD, researcher at the Centre Hospitalier Universitaire Sainte-Justine, said in an interview. “We may have just pinpointed an important cause of preterm birth that has so far been unexplained.”

Dr. Trottier and colleagues examined data from 1,052 pregnant women from three university-affiliated health care centers in Montreal between Nov. 8, 2010, and Oct. 16, 2016.

Only 5.6% of those who did not have an HPV infection had a premature birth, compared with 6.9% of those who tested positive for any HPV infection in the first trimester.

When looking at the first trimester, researchers found 12% of those diagnosed with HPV 16 and 18 had a preterm birth, compared to 4.9% of those who had a high-risk HPV infection other than HPV 16/18. When looking at the third trimester, researchers found that 15.9% of those with HPV 16/18 had an increased risk of giving birth prematurely, compared to those who had other high-risk HPV infections.

When researchers looked at the persistence of these HPV infections, they found that most HPV infections detected in the first trimester persist to the third trimester. The findings also revealed that persistent vaginal HPV 16/18 detection was significantly associated with all preterm births and spontaneous preterm births. This association was also found among those who had HPV infections detected in their placentas.

Meanwhile, 5.8% of those who had an HPV infection only during the first trimester experienced a preterm birth.

The researchers also found that HPV infections were frequent in pregnancy even among populations “considered to be at low risk based on sociodemographic and sexual history characteristics,” they wrote. Dr. Trottier said she hopes the findings will strengthen support for HPV vaccination.

Dr. Trottier’s study adds to a growing body of research regarding the adverse effects of HPV, according to Dr. Tanner, assistant professor of gynecology and obstetrics at Emory University, Atlanta. “It is already well known that HPV is associated with a number of anogenital and oropharyngeal cancers,” Dr. Tanner said in an interview. “The potential association with preterm birth only adds weight to the recommendations to screen for and prevent HPV infection.”

HPV 16 and 18 are high-risk types that cause about 70% of cervical cancers and precancerous cervical lesions, according to the World Health Organization. However, there are three HPV vaccines – 9-valent HPV vaccine (Gardasil), quadrivalent HPV vaccine (Gardasil®, 4vHPV), and bivalent HPV vaccine (Cervarix) – that help protect against HPV 16/18.

The findings strengthen the benefits of HPV vaccination, Dr. Trottier explained. “There is no cure when the HPV infection is present,” Dr. Trottier said. “If the link [between preterm birth and HPV infections] is indeed causal, we can expect a greater risk of preterm delivery in these women. The effective tool we have is the HPV vaccination, but it should ideally be received before the start of sexual activity in order to prevent future infections that could occur in women.”

The American College of Obstetricians and Gynecologists recommends HPV vaccination for girls and women between the ages of 11 and 26 years old. However, Dr. Tanner said, women aged 27-45 who were previously unvaccinated may still receive benefit from the vaccine. 

“Despite the known efficacy of the vaccine, only 50% of patients are up to date with their HPV vaccination,” Dr. Tanner explained. “This study further highlights the need to educate and encourage patients to be vaccinated.”

The researchers said future studies should investigate the association of HPV vaccination and vaccination programs with the risk of preterm birth.

The experts disclosed no conflicts of interest.

Persistent human papillomavirus (HPV) 16 and HPV 18 during a pregnancy may be associated with an increased risk of premature birth.

Findings published online in JAMA Network Open found that 15.9% of individuals who had a persistent HPV 16 or 18 infection during the first and third trimesters of their pregnancy gave birth prematurely, compared with 5.6% of those who did not have an HPV infection at all.

The findings prompted the question of “the pathophysiology of HPV in pregnancy and how the virus is affecting the placenta,” said Lisette Davidson Tanner, MD, MPH, FACOG, who was not involved in the study.

Researchers said the findings are the first to show the association between preterm birth and HPV, which is an incurable virus that most sexually active individuals will get at some point in their lives, according to the Centers for Disease Control and Prevention.

“The results of this study are very important in helping us understand the burden caused by HPV in pregnancy,” study author Helen Trottier, MSc, PhD, researcher at the Centre Hospitalier Universitaire Sainte-Justine, said in an interview. “We may have just pinpointed an important cause of preterm birth that has so far been unexplained.”

Dr. Trottier and colleagues examined data from 1,052 pregnant women from three university-affiliated health care centers in Montreal between Nov. 8, 2010, and Oct. 16, 2016.

Only 5.6% of those who did not have an HPV infection had a premature birth, compared with 6.9% of those who tested positive for any HPV infection in the first trimester.

When looking at the first trimester, researchers found 12% of those diagnosed with HPV 16 and 18 had a preterm birth, compared to 4.9% of those who had a high-risk HPV infection other than HPV 16/18. When looking at the third trimester, researchers found that 15.9% of those with HPV 16/18 had an increased risk of giving birth prematurely, compared to those who had other high-risk HPV infections.

When researchers looked at the persistence of these HPV infections, they found that most HPV infections detected in the first trimester persist to the third trimester. The findings also revealed that persistent vaginal HPV 16/18 detection was significantly associated with all preterm births and spontaneous preterm births. This association was also found among those who had HPV infections detected in their placentas.

Meanwhile, 5.8% of those who had an HPV infection only during the first trimester experienced a preterm birth.

The researchers also found that HPV infections were frequent in pregnancy even among populations “considered to be at low risk based on sociodemographic and sexual history characteristics,” they wrote. Dr. Trottier said she hopes the findings will strengthen support for HPV vaccination.

Dr. Trottier’s study adds to a growing body of research regarding the adverse effects of HPV, according to Dr. Tanner, assistant professor of gynecology and obstetrics at Emory University, Atlanta. “It is already well known that HPV is associated with a number of anogenital and oropharyngeal cancers,” Dr. Tanner said in an interview. “The potential association with preterm birth only adds weight to the recommendations to screen for and prevent HPV infection.”

HPV 16 and 18 are high-risk types that cause about 70% of cervical cancers and precancerous cervical lesions, according to the World Health Organization. However, there are three HPV vaccines – 9-valent HPV vaccine (Gardasil), quadrivalent HPV vaccine (Gardasil®, 4vHPV), and bivalent HPV vaccine (Cervarix) – that help protect against HPV 16/18.

The findings strengthen the benefits of HPV vaccination, Dr. Trottier explained. “There is no cure when the HPV infection is present,” Dr. Trottier said. “If the link [between preterm birth and HPV infections] is indeed causal, we can expect a greater risk of preterm delivery in these women. The effective tool we have is the HPV vaccination, but it should ideally be received before the start of sexual activity in order to prevent future infections that could occur in women.”

The American College of Obstetricians and Gynecologists recommends HPV vaccination for girls and women between the ages of 11 and 26 years old. However, Dr. Tanner said, women aged 27-45 who were previously unvaccinated may still receive benefit from the vaccine. 

“Despite the known efficacy of the vaccine, only 50% of patients are up to date with their HPV vaccination,” Dr. Tanner explained. “This study further highlights the need to educate and encourage patients to be vaccinated.”

The researchers said future studies should investigate the association of HPV vaccination and vaccination programs with the risk of preterm birth.

The experts disclosed no conflicts of interest.

Premature menopause is well known to be linked to cardiovascular disease in women, but it may not carry as much weight as more traditional cardiovascular risk factors in determining a patient’s 10-year risk of having a heart attack or stroke in this population, a cohort study that evaluated the veracity of premature menopause found.

Premature menopause can serve as a “marker or warning sign” that cardiologists should pay closer attention to traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, lead study author Sadiya S. Khan, MD, MS, said in an interview. “When we looked at the addition of premature menopause into the risk-prediction equation, we did not see that it meaningfully improved the ability of the risk predictions of pooled cohort equations [PCEs] to identify who developed cardiovascular disease,” said Dr. Khan, a cardiologist at Northwestern University, Chicago.

The cohort study included 5,466 Black women and 10,584 White women from seven U.S. population-based cohorts, including the Women’s Health Initiative, of whom 951 and 1,039, respectively, self-reported early menopause. The cohort study researchers noted that the 2019 American College of Cardiology/American Heart Association guideline for prevention of CVD acknowledged premature menopause as risk-enhancing factor in the CVD assessment in women younger than 40.

The cohort study found that Black women had almost twice the rate of premature menopause than White women, 17.4% and 9.8%, respectively. And it found that premature menopause was significantly linked with ASCVD in both populations independent of traditional risk factors – a 24% greater risk for Black women and 28% greater risk for White women.
 

‘Surprising’ finding

However, when premature menopause was added to the pooled cohort equations per the 2013 ACC/AHA guideline, the researchers found no incremental benefit, a finding Dr. Khan called “really surprising to us.”

She added, “If we look at the differences in the characteristics of women who have premature menopause, compared with those who didn’t, there were slight differences in terms of higher blood pressure, higher body mass index, and slightly higher glucose. So maybe what we’re seeing – and this is more speculative – is that risk factors are developing after early menopause, and the focus should be earlier in the patient’s life course to try to prevent hypertension, diabetes, and obesity.”

Dr. Khan emphasized that the findings don’t obviate the value of premature menopause in assessing ASCVD risk in women. “We still know that this is an important marker for women and their risk for heart disease, and it should be a warning sign to pay close attention to those other risk factors and what other preventive measures can be taken,” she said.

Christie Ballantyne, MD, said it’s important to note that the study did not dismiss the relevance of premature menopause in shared decision-making for postmenopausal women. “It certainly doesn’t mean that premature menopause is not a risk,” Dr. Ballantyne said in an interview. “Premature menopause may cause a worsening of traditional CVD risk factors, so that’s one possible explanation for it. The other possible explanation is that women with worse ASCVD risk factors – who are more overweight, have higher blood pressure, and have more diabetes and insulin resistance – are more likely to have earlier menopause.” Dr. Ballantyne is chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston.

“You should still look very carefully at the patient’s risk factors, calculate the pooled cohort equations, and make sure you get a recommendation,” he said. “If their risks are up, give recommendations on how to improve diet and exercise. Consider if you need to treat lipids or treat blood pressure with more than diet and exercise because there’s nothing magical about 7.5%”, the threshold for lipid-lowering therapy in the ASCVD risk calculator.

Dr. Khan and coauthors disclosed receiving grants from the National Institutes of Health and the American Heart Association. One coauthor reported a financial relationship with HGM Biopharmaceuticals. Dr. Ballantyne is a lead investigator of the Atherosclerosis Risk in Communities study, one of the population-based cohorts used in the cohort study. He has no other relevant relationships to disclose.

Premature menopause is well known to be linked to cardiovascular disease in women, but it may not carry as much weight as more traditional cardiovascular risk factors in determining a patient’s 10-year risk of having a heart attack or stroke in this population, a cohort study that evaluated the veracity of premature menopause found.

Premature menopause can serve as a “marker or warning sign” that cardiologists should pay closer attention to traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, lead study author Sadiya S. Khan, MD, MS, said in an interview. “When we looked at the addition of premature menopause into the risk-prediction equation, we did not see that it meaningfully improved the ability of the risk predictions of pooled cohort equations [PCEs] to identify who developed cardiovascular disease,” said Dr. Khan, a cardiologist at Northwestern University, Chicago.

The cohort study included 5,466 Black women and 10,584 White women from seven U.S. population-based cohorts, including the Women’s Health Initiative, of whom 951 and 1,039, respectively, self-reported early menopause. The cohort study researchers noted that the 2019 American College of Cardiology/American Heart Association guideline for prevention of CVD acknowledged premature menopause as risk-enhancing factor in the CVD assessment in women younger than 40.

The cohort study found that Black women had almost twice the rate of premature menopause than White women, 17.4% and 9.8%, respectively. And it found that premature menopause was significantly linked with ASCVD in both populations independent of traditional risk factors – a 24% greater risk for Black women and 28% greater risk for White women.
 

‘Surprising’ finding

However, when premature menopause was added to the pooled cohort equations per the 2013 ACC/AHA guideline, the researchers found no incremental benefit, a finding Dr. Khan called “really surprising to us.”

She added, “If we look at the differences in the characteristics of women who have premature menopause, compared with those who didn’t, there were slight differences in terms of higher blood pressure, higher body mass index, and slightly higher glucose. So maybe what we’re seeing – and this is more speculative – is that risk factors are developing after early menopause, and the focus should be earlier in the patient’s life course to try to prevent hypertension, diabetes, and obesity.”

Dr. Khan emphasized that the findings don’t obviate the value of premature menopause in assessing ASCVD risk in women. “We still know that this is an important marker for women and their risk for heart disease, and it should be a warning sign to pay close attention to those other risk factors and what other preventive measures can be taken,” she said.

Christie Ballantyne, MD, said it’s important to note that the study did not dismiss the relevance of premature menopause in shared decision-making for postmenopausal women. “It certainly doesn’t mean that premature menopause is not a risk,” Dr. Ballantyne said in an interview. “Premature menopause may cause a worsening of traditional CVD risk factors, so that’s one possible explanation for it. The other possible explanation is that women with worse ASCVD risk factors – who are more overweight, have higher blood pressure, and have more diabetes and insulin resistance – are more likely to have earlier menopause.” Dr. Ballantyne is chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston.

“You should still look very carefully at the patient’s risk factors, calculate the pooled cohort equations, and make sure you get a recommendation,” he said. “If their risks are up, give recommendations on how to improve diet and exercise. Consider if you need to treat lipids or treat blood pressure with more than diet and exercise because there’s nothing magical about 7.5%”, the threshold for lipid-lowering therapy in the ASCVD risk calculator.

Dr. Khan and coauthors disclosed receiving grants from the National Institutes of Health and the American Heart Association. One coauthor reported a financial relationship with HGM Biopharmaceuticals. Dr. Ballantyne is a lead investigator of the Atherosclerosis Risk in Communities study, one of the population-based cohorts used in the cohort study. He has no other relevant relationships to disclose.

Premature menopause is well known to be linked to cardiovascular disease in women, but it may not carry as much weight as more traditional cardiovascular risk factors in determining a patient’s 10-year risk of having a heart attack or stroke in this population, a cohort study that evaluated the veracity of premature menopause found.

Premature menopause can serve as a “marker or warning sign” that cardiologists should pay closer attention to traditional atherosclerotic cardiovascular disease (ASCVD) risk factors, lead study author Sadiya S. Khan, MD, MS, said in an interview. “When we looked at the addition of premature menopause into the risk-prediction equation, we did not see that it meaningfully improved the ability of the risk predictions of pooled cohort equations [PCEs] to identify who developed cardiovascular disease,” said Dr. Khan, a cardiologist at Northwestern University, Chicago.

The cohort study included 5,466 Black women and 10,584 White women from seven U.S. population-based cohorts, including the Women’s Health Initiative, of whom 951 and 1,039, respectively, self-reported early menopause. The cohort study researchers noted that the 2019 American College of Cardiology/American Heart Association guideline for prevention of CVD acknowledged premature menopause as risk-enhancing factor in the CVD assessment in women younger than 40.

The cohort study found that Black women had almost twice the rate of premature menopause than White women, 17.4% and 9.8%, respectively. And it found that premature menopause was significantly linked with ASCVD in both populations independent of traditional risk factors – a 24% greater risk for Black women and 28% greater risk for White women.
 

‘Surprising’ finding

However, when premature menopause was added to the pooled cohort equations per the 2013 ACC/AHA guideline, the researchers found no incremental benefit, a finding Dr. Khan called “really surprising to us.”

She added, “If we look at the differences in the characteristics of women who have premature menopause, compared with those who didn’t, there were slight differences in terms of higher blood pressure, higher body mass index, and slightly higher glucose. So maybe what we’re seeing – and this is more speculative – is that risk factors are developing after early menopause, and the focus should be earlier in the patient’s life course to try to prevent hypertension, diabetes, and obesity.”

Dr. Khan emphasized that the findings don’t obviate the value of premature menopause in assessing ASCVD risk in women. “We still know that this is an important marker for women and their risk for heart disease, and it should be a warning sign to pay close attention to those other risk factors and what other preventive measures can be taken,” she said.

Christie Ballantyne, MD, said it’s important to note that the study did not dismiss the relevance of premature menopause in shared decision-making for postmenopausal women. “It certainly doesn’t mean that premature menopause is not a risk,” Dr. Ballantyne said in an interview. “Premature menopause may cause a worsening of traditional CVD risk factors, so that’s one possible explanation for it. The other possible explanation is that women with worse ASCVD risk factors – who are more overweight, have higher blood pressure, and have more diabetes and insulin resistance – are more likely to have earlier menopause.” Dr. Ballantyne is chief of cardiology at Baylor College of Medicine and director of cardiovascular disease prevention at Methodist DeBakey Heart Center, both in Houston.

“You should still look very carefully at the patient’s risk factors, calculate the pooled cohort equations, and make sure you get a recommendation,” he said. “If their risks are up, give recommendations on how to improve diet and exercise. Consider if you need to treat lipids or treat blood pressure with more than diet and exercise because there’s nothing magical about 7.5%”, the threshold for lipid-lowering therapy in the ASCVD risk calculator.

Dr. Khan and coauthors disclosed receiving grants from the National Institutes of Health and the American Heart Association. One coauthor reported a financial relationship with HGM Biopharmaceuticals. Dr. Ballantyne is a lead investigator of the Atherosclerosis Risk in Communities study, one of the population-based cohorts used in the cohort study. He has no other relevant relationships to disclose.

In the first revision to its guidance on the management of osteoporosis in a decade, the North American Menopause Society has issued an updated position statement addressing evolving evidence on osteoporosis issues ranging from screening and risk assessment to appropriate use of preventive therapy in postmenopausal women.

“Since the 2010 statement, there have been important new developments in our field, including better delineation of risk factors for fracture, resulting in better strategies for assessing fracture risk,” Michael R. McClung, MD, who is a NAMS board member and colead of the editorial panel for the 2021 position statement, told this news organization. Dr. McClung is also director emeritus of the Oregon Osteoporosis Center in Portland.

“There is much more information about the long-term safety of therapies,” he added. Dr. McClung also noted “the availability of four new drugs for the prevention and treatment of osteoporosis and clinical experience informing us of the effects of using different treatments in various sequences.”
 

Osteoporosis is substantially underdiagnosed and undertreated

A basis for the update, recently published in Menopause: The Journal of the North American Menopause Society, is the need to tackle the troubling fact that approximately half of postmenopausal women will experience a fracture related to osteoporosis in their lifetime, yet the condition is “substantially underdiagnosed and undertreated,” NAMS underscores.

With that in mind, osteoporosis should be considered by practitioners treating menopausal and postmenopausal women at all levels of care.

“All physicians and advanced care providers caring for postmenopausal women should be comfortable assessing and managing their patients with, or at risk for, fractures,” Dr. McClung added.
 

Osteoporosis prevention in young menopausal women

The NAMS statement covers a broad range of issues, and while most recommendations generally follow those of other societies’ guidelines, a unique aspect is the emphasis on preventing osteoporosis in young menopausal women with estrogen or other drugs.

While underscoring that all menopausal women should be encouraged to adopt healthy lifestyles, with good diets and physical activity to reduce the risk of bone loss and fractures, pharmacologic interventions also have a role, NAMS says.

Though long an issue of debate, NAMS voices support for estrogen therapy as having an important role in osteoporosis prevention, as estrogen deficiency is the principal cause of bone loss in postmenopausal women.

“Hormone therapy is the most appropriate choice to prevent bone loss at the time of menopause for healthy women, particularly those who have menopause symptoms,” the group states. Drug interventions are specifically supported in women with premature menopause, at least until the average age of natural menopause, in addition to those with low bone mineral density (BMD) (T-score < –1.0) and those experiencing relatively rapid bone loss related to acute estrogen deficiency in the menopause transition or on discontinuing estrogen therapy.

“Although using drugs to prevent osteoporosis is not included in national osteoporosis guidelines, a strong clinical argument can be made for doing so, especially in women who come to menopause with low bone mass,” the report states.

And therapy is also recommended if patients have a low BMD and other risk factors for fracture, such as family history, but do not meet the criteria for osteoporosis treatment.

Ultimately, clinicians should work with patients when deciding the options, Dr. McClung said. 

“After carefully weighing the small risks associated with hormone therapy or other therapies begun at the time of menopause, menopause practitioners and their patients can and should make informed decisions about the use of Food and Drug Administration–approved medications to prevent osteoporosis in women who are at risk for developing that condition,” he noted, adding that his view on the matter is his own and not necessarily that of NAMS.
 

New treatments endorsed for high-risk patients to avoid ‘bone attack’

While most patients are treated for osteoporosis with antiremodeling drugs such as bisphosphonates and denosumab, NAMS endorses “a new paradigm of beginning treatment with a bone-building agent followed by an antiremodeling agent” for women at very high risk of fracture.

“Consider osteoanabolic therapies for patients at very high risk of fracture, including older women with recent fractures, T-scores –3.0 and lower, or multiple other risk factors,” the statement suggests.

Among those at highest risk are women who have sustained a first fracture.

“A recent fracture in a postmenopausal woman is the strongest risk factor for another fracture,” Dr. McClung said.

In fact, “having a fracture should be thought of and assessed as a ‘bone attack,’ ” he asserted.

Therapy is recommended in such cases to rapidly increase bone density and reduce their subsequent fracture risk.

“For these patients, osteoanabolic or bone-building agents are more effective than bisphosphonates and are recommended as initial therapy,” Dr. McClung noted.

Treatment discontinuation?

On the issue of drug holidays and when or whether to stop therapy, as no therapies cure osteoporosis, medications should not be permanently stopped, even if bone density increases, NAMS recommends.

“By analogy, we do not stop diabetes therapy when A1c levels become normal,” Dr. McClung noted.

“Because the benefits of therapy on bone density and fracture protection wane, quickly for nonbisphosphonates and more slowly with bisphosphonates, short-term therapy, for instance 5 years, is not optimal treatment,” he said.

While the short-term interruption of bisphosphonate therapy may be considered in some patients, “the concept of ‘drug holidays’ does not pertain to nonbisphosphonate drugs,” Dr. McClung said.

NAMS adds that management of therapeutic choices should instead be ongoing.

“During therapy, reevaluate the treatment goals and the choice of medication on an ongoing basis through periodic medical examination and follow-up BMD testing,” NAMS recommends.

In terms of assessment, the measurement of bone mineral density while on treatment can gauge the current risk of fracture, and NAMS supports the use of the T-score at the hip as an appropriate clinical target in guiding choices of therapy.

Ultimately, “effective tools for diagnosing osteoporosis and assessing fracture risk are available, and well-studied strategies exist for managing bone health in women at both low and high risk of fracture,” NAMS concludes.

“By individualizing treatment approaches and monitoring and adjusting those approaches if the clinical picture changes, the consequences of osteoporosis on a menopausal woman’s activity and well-being can be minimized.”

Dr. McClung has reported receiving consulting fees from Amgen and Myovant, and honorarium for speaking from Amgen and Alexon. He serves on the boards of NAMS and the International Osteoporosis Foundation.

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

In the first revision to its guidance on the management of osteoporosis in a decade, the North American Menopause Society has issued an updated position statement addressing evolving evidence on osteoporosis issues ranging from screening and risk assessment to appropriate use of preventive therapy in postmenopausal women.

“Since the 2010 statement, there have been important new developments in our field, including better delineation of risk factors for fracture, resulting in better strategies for assessing fracture risk,” Michael R. McClung, MD, who is a NAMS board member and colead of the editorial panel for the 2021 position statement, told this news organization. Dr. McClung is also director emeritus of the Oregon Osteoporosis Center in Portland.

“There is much more information about the long-term safety of therapies,” he added. Dr. McClung also noted “the availability of four new drugs for the prevention and treatment of osteoporosis and clinical experience informing us of the effects of using different treatments in various sequences.”
 

Osteoporosis is substantially underdiagnosed and undertreated

A basis for the update, recently published in Menopause: The Journal of the North American Menopause Society, is the need to tackle the troubling fact that approximately half of postmenopausal women will experience a fracture related to osteoporosis in their lifetime, yet the condition is “substantially underdiagnosed and undertreated,” NAMS underscores.

With that in mind, osteoporosis should be considered by practitioners treating menopausal and postmenopausal women at all levels of care.

“All physicians and advanced care providers caring for postmenopausal women should be comfortable assessing and managing their patients with, or at risk for, fractures,” Dr. McClung added.
 

Osteoporosis prevention in young menopausal women

The NAMS statement covers a broad range of issues, and while most recommendations generally follow those of other societies’ guidelines, a unique aspect is the emphasis on preventing osteoporosis in young menopausal women with estrogen or other drugs.

While underscoring that all menopausal women should be encouraged to adopt healthy lifestyles, with good diets and physical activity to reduce the risk of bone loss and fractures, pharmacologic interventions also have a role, NAMS says.

Though long an issue of debate, NAMS voices support for estrogen therapy as having an important role in osteoporosis prevention, as estrogen deficiency is the principal cause of bone loss in postmenopausal women.

“Hormone therapy is the most appropriate choice to prevent bone loss at the time of menopause for healthy women, particularly those who have menopause symptoms,” the group states. Drug interventions are specifically supported in women with premature menopause, at least until the average age of natural menopause, in addition to those with low bone mineral density (BMD) (T-score < –1.0) and those experiencing relatively rapid bone loss related to acute estrogen deficiency in the menopause transition or on discontinuing estrogen therapy.

“Although using drugs to prevent osteoporosis is not included in national osteoporosis guidelines, a strong clinical argument can be made for doing so, especially in women who come to menopause with low bone mass,” the report states.

And therapy is also recommended if patients have a low BMD and other risk factors for fracture, such as family history, but do not meet the criteria for osteoporosis treatment.

Ultimately, clinicians should work with patients when deciding the options, Dr. McClung said. 

“After carefully weighing the small risks associated with hormone therapy or other therapies begun at the time of menopause, menopause practitioners and their patients can and should make informed decisions about the use of Food and Drug Administration–approved medications to prevent osteoporosis in women who are at risk for developing that condition,” he noted, adding that his view on the matter is his own and not necessarily that of NAMS.
 

New treatments endorsed for high-risk patients to avoid ‘bone attack’

While most patients are treated for osteoporosis with antiremodeling drugs such as bisphosphonates and denosumab, NAMS endorses “a new paradigm of beginning treatment with a bone-building agent followed by an antiremodeling agent” for women at very high risk of fracture.

“Consider osteoanabolic therapies for patients at very high risk of fracture, including older women with recent fractures, T-scores –3.0 and lower, or multiple other risk factors,” the statement suggests.

Among those at highest risk are women who have sustained a first fracture.

“A recent fracture in a postmenopausal woman is the strongest risk factor for another fracture,” Dr. McClung said.

In fact, “having a fracture should be thought of and assessed as a ‘bone attack,’ ” he asserted.

Therapy is recommended in such cases to rapidly increase bone density and reduce their subsequent fracture risk.

“For these patients, osteoanabolic or bone-building agents are more effective than bisphosphonates and are recommended as initial therapy,” Dr. McClung noted.

Treatment discontinuation?

On the issue of drug holidays and when or whether to stop therapy, as no therapies cure osteoporosis, medications should not be permanently stopped, even if bone density increases, NAMS recommends.

“By analogy, we do not stop diabetes therapy when A1c levels become normal,” Dr. McClung noted.

“Because the benefits of therapy on bone density and fracture protection wane, quickly for nonbisphosphonates and more slowly with bisphosphonates, short-term therapy, for instance 5 years, is not optimal treatment,” he said.

While the short-term interruption of bisphosphonate therapy may be considered in some patients, “the concept of ‘drug holidays’ does not pertain to nonbisphosphonate drugs,” Dr. McClung said.

NAMS adds that management of therapeutic choices should instead be ongoing.

“During therapy, reevaluate the treatment goals and the choice of medication on an ongoing basis through periodic medical examination and follow-up BMD testing,” NAMS recommends.

In terms of assessment, the measurement of bone mineral density while on treatment can gauge the current risk of fracture, and NAMS supports the use of the T-score at the hip as an appropriate clinical target in guiding choices of therapy.

Ultimately, “effective tools for diagnosing osteoporosis and assessing fracture risk are available, and well-studied strategies exist for managing bone health in women at both low and high risk of fracture,” NAMS concludes.

“By individualizing treatment approaches and monitoring and adjusting those approaches if the clinical picture changes, the consequences of osteoporosis on a menopausal woman’s activity and well-being can be minimized.”

Dr. McClung has reported receiving consulting fees from Amgen and Myovant, and honorarium for speaking from Amgen and Alexon. He serves on the boards of NAMS and the International Osteoporosis Foundation.

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

In the first revision to its guidance on the management of osteoporosis in a decade, the North American Menopause Society has issued an updated position statement addressing evolving evidence on osteoporosis issues ranging from screening and risk assessment to appropriate use of preventive therapy in postmenopausal women.

“Since the 2010 statement, there have been important new developments in our field, including better delineation of risk factors for fracture, resulting in better strategies for assessing fracture risk,” Michael R. McClung, MD, who is a NAMS board member and colead of the editorial panel for the 2021 position statement, told this news organization. Dr. McClung is also director emeritus of the Oregon Osteoporosis Center in Portland.

“There is much more information about the long-term safety of therapies,” he added. Dr. McClung also noted “the availability of four new drugs for the prevention and treatment of osteoporosis and clinical experience informing us of the effects of using different treatments in various sequences.”
 

Osteoporosis is substantially underdiagnosed and undertreated

A basis for the update, recently published in Menopause: The Journal of the North American Menopause Society, is the need to tackle the troubling fact that approximately half of postmenopausal women will experience a fracture related to osteoporosis in their lifetime, yet the condition is “substantially underdiagnosed and undertreated,” NAMS underscores.

With that in mind, osteoporosis should be considered by practitioners treating menopausal and postmenopausal women at all levels of care.

“All physicians and advanced care providers caring for postmenopausal women should be comfortable assessing and managing their patients with, or at risk for, fractures,” Dr. McClung added.
 

Osteoporosis prevention in young menopausal women

The NAMS statement covers a broad range of issues, and while most recommendations generally follow those of other societies’ guidelines, a unique aspect is the emphasis on preventing osteoporosis in young menopausal women with estrogen or other drugs.

While underscoring that all menopausal women should be encouraged to adopt healthy lifestyles, with good diets and physical activity to reduce the risk of bone loss and fractures, pharmacologic interventions also have a role, NAMS says.

Though long an issue of debate, NAMS voices support for estrogen therapy as having an important role in osteoporosis prevention, as estrogen deficiency is the principal cause of bone loss in postmenopausal women.

“Hormone therapy is the most appropriate choice to prevent bone loss at the time of menopause for healthy women, particularly those who have menopause symptoms,” the group states. Drug interventions are specifically supported in women with premature menopause, at least until the average age of natural menopause, in addition to those with low bone mineral density (BMD) (T-score < –1.0) and those experiencing relatively rapid bone loss related to acute estrogen deficiency in the menopause transition or on discontinuing estrogen therapy.

“Although using drugs to prevent osteoporosis is not included in national osteoporosis guidelines, a strong clinical argument can be made for doing so, especially in women who come to menopause with low bone mass,” the report states.

And therapy is also recommended if patients have a low BMD and other risk factors for fracture, such as family history, but do not meet the criteria for osteoporosis treatment.

Ultimately, clinicians should work with patients when deciding the options, Dr. McClung said. 

“After carefully weighing the small risks associated with hormone therapy or other therapies begun at the time of menopause, menopause practitioners and their patients can and should make informed decisions about the use of Food and Drug Administration–approved medications to prevent osteoporosis in women who are at risk for developing that condition,” he noted, adding that his view on the matter is his own and not necessarily that of NAMS.
 

New treatments endorsed for high-risk patients to avoid ‘bone attack’

While most patients are treated for osteoporosis with antiremodeling drugs such as bisphosphonates and denosumab, NAMS endorses “a new paradigm of beginning treatment with a bone-building agent followed by an antiremodeling agent” for women at very high risk of fracture.

“Consider osteoanabolic therapies for patients at very high risk of fracture, including older women with recent fractures, T-scores –3.0 and lower, or multiple other risk factors,” the statement suggests.

Among those at highest risk are women who have sustained a first fracture.

“A recent fracture in a postmenopausal woman is the strongest risk factor for another fracture,” Dr. McClung said.

In fact, “having a fracture should be thought of and assessed as a ‘bone attack,’ ” he asserted.

Therapy is recommended in such cases to rapidly increase bone density and reduce their subsequent fracture risk.

“For these patients, osteoanabolic or bone-building agents are more effective than bisphosphonates and are recommended as initial therapy,” Dr. McClung noted.

Treatment discontinuation?

On the issue of drug holidays and when or whether to stop therapy, as no therapies cure osteoporosis, medications should not be permanently stopped, even if bone density increases, NAMS recommends.

“By analogy, we do not stop diabetes therapy when A1c levels become normal,” Dr. McClung noted.

“Because the benefits of therapy on bone density and fracture protection wane, quickly for nonbisphosphonates and more slowly with bisphosphonates, short-term therapy, for instance 5 years, is not optimal treatment,” he said.

While the short-term interruption of bisphosphonate therapy may be considered in some patients, “the concept of ‘drug holidays’ does not pertain to nonbisphosphonate drugs,” Dr. McClung said.

NAMS adds that management of therapeutic choices should instead be ongoing.

“During therapy, reevaluate the treatment goals and the choice of medication on an ongoing basis through periodic medical examination and follow-up BMD testing,” NAMS recommends.

In terms of assessment, the measurement of bone mineral density while on treatment can gauge the current risk of fracture, and NAMS supports the use of the T-score at the hip as an appropriate clinical target in guiding choices of therapy.

Ultimately, “effective tools for diagnosing osteoporosis and assessing fracture risk are available, and well-studied strategies exist for managing bone health in women at both low and high risk of fracture,” NAMS concludes.

“By individualizing treatment approaches and monitoring and adjusting those approaches if the clinical picture changes, the consequences of osteoporosis on a menopausal woman’s activity and well-being can be minimized.”

Dr. McClung has reported receiving consulting fees from Amgen and Myovant, and honorarium for speaking from Amgen and Alexon. He serves on the boards of NAMS and the International Osteoporosis Foundation.

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

The U.S. Preventive Services Task Force (USPSTF) announced on Tuesday that it is standing by its 2014 recommendations that sexually active girls and young women be screened for chlamydia and gonorrhea. But the panel is not ready to provide guidance about screening males even amid an outbreak of gonorrhea infections among men who have sex with men (MSM).

“For men in general, there’s not enough evidence to determine whether screening will reduce the risk of complications or spreading infections to others,” said Marti Kubik, PhD, RN, in an interview. Dr. Kubik is a professor at the George Mason University School of Nursing, Fairfax, Va., and is a member of the task force. “We need further research so we will know how to make those recommendations,” she said.

The screening recommendations for chlamydia and gonorrhea were published Sept. 14 in the Journal of the American Medical Association. The guidance is identical to the panel’s 2014 recommendations. The task force recommends screening for chlamydia and gonorrhea in all sexually active females aged 24 years or younger and in sexually active women aged 25 and older if they are at higher risk because of factors such as new or multiple sex partners.

“We continue to see rising rates of these infections in spite of consistent screening recommendations,” Dr. Kubik said. “In 2019, the CDC recorded nearly 2 million cases of chlamydia and a half million cases of gonorrhea. The big clincher is that chlamydia and gonorrhea can occur without symptoms. It’s critical to screen if we’re going to prevent serious health complications.”

The report notes that chlamydia and gonorrhea may lead to pelvic inflammatory disease in women and to multiple complications in infants born to infected mothers. Men can develop urethritis and epididymitis. Both diseases can boost the risk for HIV infection and transmission.

“We want clinicians to review the new recommendation and feel confident about the evidence base that supports a need for us to be screening young women and older women who are at increased risk,” Dr. Kubik said. She noted that almost two-thirds of chlamydia cases and more than half of gonorrhea cases occur in men and women aged 15-24.

Unlike the CDC, which recommends annual chlamydia and gonorrhea screening in appropriate female patients, the task force provides no guidance on screening frequency. “We didn’t have the evidence base to make a recommendation about how often to screen,” Dr. Kubik said. “But recognizing that these often occur without symptoms, it’s reasonable for clinicians to screen patients whose sexual history reveals new or consistent risk factors.”

Philip A. Chan, MD, an associate professor at Brown University, Providence, R.I., who directs a sexually transmitted disease clinic, told this news organization that he found it frustrating that the task force didn’t make recommendations about screening of MSM. According to a commentary accompanying the new recommendations, the rate of gonorrhea in MSM – 5,166 cases per 100,000, or more than 5% – is at a historic high.

In contrast to the task force, the CDC recommends annual or more frequent testing for gonorrhea and chlamydia plus HIV and syphilis in sexually active MSM.

Dr. Chan noted that the task force’s guidance “tends to be the most evidence-based recommendations that exist. If the evidence isn’t there, they usually don’t make a recommendation.” Still, he said, “I would argue that there’s good evidence that in MSM, the risk for HIV acquisition warrants routine screening.”

Jeanne Marrazzo, MD, MPH, director of the division of infectious diseases at the University of Alabama at Birmingham, also noted the limits of the task force’s insistence on certain kinds of evidence. Dr. Marrazzo, who coauthored a commentary that accompanies the recommendations, said in an interview that the panel’s “reliance on randomized-controlled-trial-level evidence tends to limit its ability to evolve their recommendations in a way that could account for evolving epidemiology or advances in our understanding of pathophysiology of these infections.”

Dr. Chan noted that obstacles exist for patients even when screening recommendations are in place. Although insurers typically cover costs of chlamydia and gonorrhea screening tests, he said, the uninsured may have to pay $100 or more each.

The USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Kubik, Dr. Chan, and Dr. Marrazzo report no relevant financial relationships.

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

The U.S. Preventive Services Task Force (USPSTF) announced on Tuesday that it is standing by its 2014 recommendations that sexually active girls and young women be screened for chlamydia and gonorrhea. But the panel is not ready to provide guidance about screening males even amid an outbreak of gonorrhea infections among men who have sex with men (MSM).

“For men in general, there’s not enough evidence to determine whether screening will reduce the risk of complications or spreading infections to others,” said Marti Kubik, PhD, RN, in an interview. Dr. Kubik is a professor at the George Mason University School of Nursing, Fairfax, Va., and is a member of the task force. “We need further research so we will know how to make those recommendations,” she said.

The screening recommendations for chlamydia and gonorrhea were published Sept. 14 in the Journal of the American Medical Association. The guidance is identical to the panel’s 2014 recommendations. The task force recommends screening for chlamydia and gonorrhea in all sexually active females aged 24 years or younger and in sexually active women aged 25 and older if they are at higher risk because of factors such as new or multiple sex partners.

“We continue to see rising rates of these infections in spite of consistent screening recommendations,” Dr. Kubik said. “In 2019, the CDC recorded nearly 2 million cases of chlamydia and a half million cases of gonorrhea. The big clincher is that chlamydia and gonorrhea can occur without symptoms. It’s critical to screen if we’re going to prevent serious health complications.”

The report notes that chlamydia and gonorrhea may lead to pelvic inflammatory disease in women and to multiple complications in infants born to infected mothers. Men can develop urethritis and epididymitis. Both diseases can boost the risk for HIV infection and transmission.

“We want clinicians to review the new recommendation and feel confident about the evidence base that supports a need for us to be screening young women and older women who are at increased risk,” Dr. Kubik said. She noted that almost two-thirds of chlamydia cases and more than half of gonorrhea cases occur in men and women aged 15-24.

Unlike the CDC, which recommends annual chlamydia and gonorrhea screening in appropriate female patients, the task force provides no guidance on screening frequency. “We didn’t have the evidence base to make a recommendation about how often to screen,” Dr. Kubik said. “But recognizing that these often occur without symptoms, it’s reasonable for clinicians to screen patients whose sexual history reveals new or consistent risk factors.”

Philip A. Chan, MD, an associate professor at Brown University, Providence, R.I., who directs a sexually transmitted disease clinic, told this news organization that he found it frustrating that the task force didn’t make recommendations about screening of MSM. According to a commentary accompanying the new recommendations, the rate of gonorrhea in MSM – 5,166 cases per 100,000, or more than 5% – is at a historic high.

In contrast to the task force, the CDC recommends annual or more frequent testing for gonorrhea and chlamydia plus HIV and syphilis in sexually active MSM.

Dr. Chan noted that the task force’s guidance “tends to be the most evidence-based recommendations that exist. If the evidence isn’t there, they usually don’t make a recommendation.” Still, he said, “I would argue that there’s good evidence that in MSM, the risk for HIV acquisition warrants routine screening.”

Jeanne Marrazzo, MD, MPH, director of the division of infectious diseases at the University of Alabama at Birmingham, also noted the limits of the task force’s insistence on certain kinds of evidence. Dr. Marrazzo, who coauthored a commentary that accompanies the recommendations, said in an interview that the panel’s “reliance on randomized-controlled-trial-level evidence tends to limit its ability to evolve their recommendations in a way that could account for evolving epidemiology or advances in our understanding of pathophysiology of these infections.”

Dr. Chan noted that obstacles exist for patients even when screening recommendations are in place. Although insurers typically cover costs of chlamydia and gonorrhea screening tests, he said, the uninsured may have to pay $100 or more each.

The USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Kubik, Dr. Chan, and Dr. Marrazzo report no relevant financial relationships.

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

The U.S. Preventive Services Task Force (USPSTF) announced on Tuesday that it is standing by its 2014 recommendations that sexually active girls and young women be screened for chlamydia and gonorrhea. But the panel is not ready to provide guidance about screening males even amid an outbreak of gonorrhea infections among men who have sex with men (MSM).

“For men in general, there’s not enough evidence to determine whether screening will reduce the risk of complications or spreading infections to others,” said Marti Kubik, PhD, RN, in an interview. Dr. Kubik is a professor at the George Mason University School of Nursing, Fairfax, Va., and is a member of the task force. “We need further research so we will know how to make those recommendations,” she said.

The screening recommendations for chlamydia and gonorrhea were published Sept. 14 in the Journal of the American Medical Association. The guidance is identical to the panel’s 2014 recommendations. The task force recommends screening for chlamydia and gonorrhea in all sexually active females aged 24 years or younger and in sexually active women aged 25 and older if they are at higher risk because of factors such as new or multiple sex partners.

“We continue to see rising rates of these infections in spite of consistent screening recommendations,” Dr. Kubik said. “In 2019, the CDC recorded nearly 2 million cases of chlamydia and a half million cases of gonorrhea. The big clincher is that chlamydia and gonorrhea can occur without symptoms. It’s critical to screen if we’re going to prevent serious health complications.”

The report notes that chlamydia and gonorrhea may lead to pelvic inflammatory disease in women and to multiple complications in infants born to infected mothers. Men can develop urethritis and epididymitis. Both diseases can boost the risk for HIV infection and transmission.

“We want clinicians to review the new recommendation and feel confident about the evidence base that supports a need for us to be screening young women and older women who are at increased risk,” Dr. Kubik said. She noted that almost two-thirds of chlamydia cases and more than half of gonorrhea cases occur in men and women aged 15-24.

Unlike the CDC, which recommends annual chlamydia and gonorrhea screening in appropriate female patients, the task force provides no guidance on screening frequency. “We didn’t have the evidence base to make a recommendation about how often to screen,” Dr. Kubik said. “But recognizing that these often occur without symptoms, it’s reasonable for clinicians to screen patients whose sexual history reveals new or consistent risk factors.”

Philip A. Chan, MD, an associate professor at Brown University, Providence, R.I., who directs a sexually transmitted disease clinic, told this news organization that he found it frustrating that the task force didn’t make recommendations about screening of MSM. According to a commentary accompanying the new recommendations, the rate of gonorrhea in MSM – 5,166 cases per 100,000, or more than 5% – is at a historic high.

In contrast to the task force, the CDC recommends annual or more frequent testing for gonorrhea and chlamydia plus HIV and syphilis in sexually active MSM.

Dr. Chan noted that the task force’s guidance “tends to be the most evidence-based recommendations that exist. If the evidence isn’t there, they usually don’t make a recommendation.” Still, he said, “I would argue that there’s good evidence that in MSM, the risk for HIV acquisition warrants routine screening.”

Jeanne Marrazzo, MD, MPH, director of the division of infectious diseases at the University of Alabama at Birmingham, also noted the limits of the task force’s insistence on certain kinds of evidence. Dr. Marrazzo, who coauthored a commentary that accompanies the recommendations, said in an interview that the panel’s “reliance on randomized-controlled-trial-level evidence tends to limit its ability to evolve their recommendations in a way that could account for evolving epidemiology or advances in our understanding of pathophysiology of these infections.”

Dr. Chan noted that obstacles exist for patients even when screening recommendations are in place. Although insurers typically cover costs of chlamydia and gonorrhea screening tests, he said, the uninsured may have to pay $100 or more each.

The USPSTF is supported by the U.S. Agency for Healthcare Research and Quality. Dr. Kubik, Dr. Chan, and Dr. Marrazzo report no relevant financial relationships.

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

The U.S. Preventive Services Task Force has updated its 2014 statement on screening asymptomatic individuals for chlamydia and gonorrhea infection.

Published online in JAMA, the 2021 version recommends that all sexually active women aged 24 years or younger and at-risk women 25 years or older should be screened for chlamydia and gonorrhea.

As in 2014, the task force made no screening recommendation for men owing to inconclusive evidence of benefit.

With cases of sexually transmitted infections reaching all-time highs, Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University, Portland, and colleagues noted that chlamydia and gonorrhea are among the most common STIs in this country. According to the Centers for Disease Control and Prevention, 2019 saw approximately 1.8 million reported cases of chlamydia and more than 600,000 of gonorrhea.

In the current analysis of 27 observational and randomized studies comprising 179,515 patients, the USPSTF panel found that, compared with no screening, chlamydia screening was significantly associated with a reduced risk of pelvic inflammatory disease (PID) in young women in 2 out of 4 trials.

The authors cautioned, however, that the magnitude of benefit was relatively small. No studies reported on screening effectiveness in men, except for one reporting rates of epididymitis, and no studies were done on pregnant women for any outcome.

The largest and newest study, the Australian Chlamydia Control Effectiveness Pilot trial of 2018, assessed chlamydia screening against usual care in 180,355 men and women aged 16-29 years in 130 rural Australian primary care clinics. Screening was associated with a reduced risk of hospital-diagnosed PID: the absolute risk was 0.24% for screening versus 0.38% for usual care (unadjusted risk ratio, 0.6; 95% confidence interval, 0.4-1.0). It was not, however, significantly associated with a reduced risk of clinic-diagnosed PID, with an absolute risk of 0.45% versus 0.39% (RR, 1.1; 95% CI, 0.7-18). Nor did it correlate with a risk reduction for clinic-diagnosed epididymitis: 0.26% vs. 0.27% (RR, 0.9; 95% CI, 0.6-1.4).

While risk prediction criteria apart from age were only minimally accurate, testing for asymptomatic chlamydial and gonococcal infections was highly accurate at most anatomical sites, including urine and self-collected specimens, the investigators observed. Age 22 years or younger alone versus multi-item risk criteria demonstrated similar discrimination in a study that included symptomatic and asymptomatic women.

Sensitivity of chlamydial testing was similar at endocervical (89%-100%) and self- and clinician-collected vaginal (90%-100%) sites for women and at meatal (100%), urethral (99%), and rectal (92%) sites for men. It was lower, however, at pharyngeal sites (69.2%) for men who have sex with men (MSM).

Sensitivity of gonococcal testing was 89% or greater for all anatomical samples. False-positive and false-negative testing rates were low across anatomical sites and collection methods.

“Effectiveness of screening in men and during pregnancy, optimal screening intervals, and adverse effects of screening require further evaluation, Dr. Cantor and associates concluded.

In an accompanying editorial, Jeanne Marrazzo, MD, MPH, and Jodie Dionne-Odom, MD, MSPH, of the division of infectious diseases at the University of Alabama at Birmingham, called the guidelines “timely” and “powerful agents of change” that “influence a wide spectrum of health-based metrics, from quality assurance measures to criteria for financial reimbursement.”

They pointed out that men who have sex with men are experiencing historically high rates of gonorrhea, with most infections occurring extragenitally at the pharynx or rectum. In 2019 CDC data, MSM had substantially higher rates of gonorrhea than men who had sex only with women. They recommended that guidelines for men consider STI risk because of sexual relations with men, women, or both.

“Comprehensive screening guidelines for common STIs like chlamydia and gonorrhea could incorporate the limited evidence base for MSM, whether it is regular practice or not,” they wrote, with the same approach for women who have sex with women but may be at risk for chlamydia, particularly if they also have sex with men.

In their view, these latest guidelines appropriately prioritize high-level clinically based data. They pointed, however, to recent progress in understanding the pathogenesis of upper reproductive tract infection in women and the sexual networks behind the current resurgence of STIs in the United States in the failure to manage exposed sex partners.

“Considering these critical advances in the evolution of clinic-based screening guidelines is a work in progress,” they wrote, “the dialogue among basic scientists, clinical trial investigators, and public health professionals to inform the next version of updated USPSTF chlamydia and gonorrhea screening guidelines should start now.”

In the opinion of Jennifer L. Reed, MD, MS, a professor of pediatrics and an emergency medicine physician at Cincinnati Children’s Hospital Medical Center and not involved in the updated statement, the recommendations are very reasonable. “The highest rates of infection occur in females 15-24 years of age, and therefore asymptomatic screening for chlamydia and gonorrhea is imperative at least annually or more often if they are high risk,” she said in an interview.

“I would hope that providers increase their asymptomatic screening as a result of these recommendations and highly consider it in the younger men,” Dr. Reed added. “I see a very high rate of gonorrhea and chlamydia infections.” Her center is studying the implementation of gonorrhea and chlamydia asymptomatic screening for adolescents in the pediatric emergency department, a high-risk patient population that will benefit from STI screening opportunities in nontraditional settings.

This research was funded by the Agency for Healthcare Research and Quality and the Department of Health & Human Services under a contract to support the USPSTF. One statement coauthor reported personal fees from Insmed, Paratek, RedHill, and Spero, as well as grants from Insmed. No other disclosures were reported. Dr. Dionne-Odom reported grants from the National Institutes of Health/National Institute of Child Health and Development. Dr. Reed reported a grant from NIH/NICHD for a pragmatic trial of improving STI detection in the pediatric ED.
 

The U.S. Preventive Services Task Force has updated its 2014 statement on screening asymptomatic individuals for chlamydia and gonorrhea infection.

Published online in JAMA, the 2021 version recommends that all sexually active women aged 24 years or younger and at-risk women 25 years or older should be screened for chlamydia and gonorrhea.

As in 2014, the task force made no screening recommendation for men owing to inconclusive evidence of benefit.

With cases of sexually transmitted infections reaching all-time highs, Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University, Portland, and colleagues noted that chlamydia and gonorrhea are among the most common STIs in this country. According to the Centers for Disease Control and Prevention, 2019 saw approximately 1.8 million reported cases of chlamydia and more than 600,000 of gonorrhea.

In the current analysis of 27 observational and randomized studies comprising 179,515 patients, the USPSTF panel found that, compared with no screening, chlamydia screening was significantly associated with a reduced risk of pelvic inflammatory disease (PID) in young women in 2 out of 4 trials.

The authors cautioned, however, that the magnitude of benefit was relatively small. No studies reported on screening effectiveness in men, except for one reporting rates of epididymitis, and no studies were done on pregnant women for any outcome.

The largest and newest study, the Australian Chlamydia Control Effectiveness Pilot trial of 2018, assessed chlamydia screening against usual care in 180,355 men and women aged 16-29 years in 130 rural Australian primary care clinics. Screening was associated with a reduced risk of hospital-diagnosed PID: the absolute risk was 0.24% for screening versus 0.38% for usual care (unadjusted risk ratio, 0.6; 95% confidence interval, 0.4-1.0). It was not, however, significantly associated with a reduced risk of clinic-diagnosed PID, with an absolute risk of 0.45% versus 0.39% (RR, 1.1; 95% CI, 0.7-18). Nor did it correlate with a risk reduction for clinic-diagnosed epididymitis: 0.26% vs. 0.27% (RR, 0.9; 95% CI, 0.6-1.4).

While risk prediction criteria apart from age were only minimally accurate, testing for asymptomatic chlamydial and gonococcal infections was highly accurate at most anatomical sites, including urine and self-collected specimens, the investigators observed. Age 22 years or younger alone versus multi-item risk criteria demonstrated similar discrimination in a study that included symptomatic and asymptomatic women.

Sensitivity of chlamydial testing was similar at endocervical (89%-100%) and self- and clinician-collected vaginal (90%-100%) sites for women and at meatal (100%), urethral (99%), and rectal (92%) sites for men. It was lower, however, at pharyngeal sites (69.2%) for men who have sex with men (MSM).

Sensitivity of gonococcal testing was 89% or greater for all anatomical samples. False-positive and false-negative testing rates were low across anatomical sites and collection methods.

“Effectiveness of screening in men and during pregnancy, optimal screening intervals, and adverse effects of screening require further evaluation, Dr. Cantor and associates concluded.

In an accompanying editorial, Jeanne Marrazzo, MD, MPH, and Jodie Dionne-Odom, MD, MSPH, of the division of infectious diseases at the University of Alabama at Birmingham, called the guidelines “timely” and “powerful agents of change” that “influence a wide spectrum of health-based metrics, from quality assurance measures to criteria for financial reimbursement.”

They pointed out that men who have sex with men are experiencing historically high rates of gonorrhea, with most infections occurring extragenitally at the pharynx or rectum. In 2019 CDC data, MSM had substantially higher rates of gonorrhea than men who had sex only with women. They recommended that guidelines for men consider STI risk because of sexual relations with men, women, or both.

“Comprehensive screening guidelines for common STIs like chlamydia and gonorrhea could incorporate the limited evidence base for MSM, whether it is regular practice or not,” they wrote, with the same approach for women who have sex with women but may be at risk for chlamydia, particularly if they also have sex with men.

In their view, these latest guidelines appropriately prioritize high-level clinically based data. They pointed, however, to recent progress in understanding the pathogenesis of upper reproductive tract infection in women and the sexual networks behind the current resurgence of STIs in the United States in the failure to manage exposed sex partners.

“Considering these critical advances in the evolution of clinic-based screening guidelines is a work in progress,” they wrote, “the dialogue among basic scientists, clinical trial investigators, and public health professionals to inform the next version of updated USPSTF chlamydia and gonorrhea screening guidelines should start now.”

In the opinion of Jennifer L. Reed, MD, MS, a professor of pediatrics and an emergency medicine physician at Cincinnati Children’s Hospital Medical Center and not involved in the updated statement, the recommendations are very reasonable. “The highest rates of infection occur in females 15-24 years of age, and therefore asymptomatic screening for chlamydia and gonorrhea is imperative at least annually or more often if they are high risk,” she said in an interview.

“I would hope that providers increase their asymptomatic screening as a result of these recommendations and highly consider it in the younger men,” Dr. Reed added. “I see a very high rate of gonorrhea and chlamydia infections.” Her center is studying the implementation of gonorrhea and chlamydia asymptomatic screening for adolescents in the pediatric emergency department, a high-risk patient population that will benefit from STI screening opportunities in nontraditional settings.

This research was funded by the Agency for Healthcare Research and Quality and the Department of Health & Human Services under a contract to support the USPSTF. One statement coauthor reported personal fees from Insmed, Paratek, RedHill, and Spero, as well as grants from Insmed. No other disclosures were reported. Dr. Dionne-Odom reported grants from the National Institutes of Health/National Institute of Child Health and Development. Dr. Reed reported a grant from NIH/NICHD for a pragmatic trial of improving STI detection in the pediatric ED.
 

The U.S. Preventive Services Task Force has updated its 2014 statement on screening asymptomatic individuals for chlamydia and gonorrhea infection.

Published online in JAMA, the 2021 version recommends that all sexually active women aged 24 years or younger and at-risk women 25 years or older should be screened for chlamydia and gonorrhea.

As in 2014, the task force made no screening recommendation for men owing to inconclusive evidence of benefit.

With cases of sexually transmitted infections reaching all-time highs, Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University, Portland, and colleagues noted that chlamydia and gonorrhea are among the most common STIs in this country. According to the Centers for Disease Control and Prevention, 2019 saw approximately 1.8 million reported cases of chlamydia and more than 600,000 of gonorrhea.

In the current analysis of 27 observational and randomized studies comprising 179,515 patients, the USPSTF panel found that, compared with no screening, chlamydia screening was significantly associated with a reduced risk of pelvic inflammatory disease (PID) in young women in 2 out of 4 trials.

The authors cautioned, however, that the magnitude of benefit was relatively small. No studies reported on screening effectiveness in men, except for one reporting rates of epididymitis, and no studies were done on pregnant women for any outcome.

The largest and newest study, the Australian Chlamydia Control Effectiveness Pilot trial of 2018, assessed chlamydia screening against usual care in 180,355 men and women aged 16-29 years in 130 rural Australian primary care clinics. Screening was associated with a reduced risk of hospital-diagnosed PID: the absolute risk was 0.24% for screening versus 0.38% for usual care (unadjusted risk ratio, 0.6; 95% confidence interval, 0.4-1.0). It was not, however, significantly associated with a reduced risk of clinic-diagnosed PID, with an absolute risk of 0.45% versus 0.39% (RR, 1.1; 95% CI, 0.7-18). Nor did it correlate with a risk reduction for clinic-diagnosed epididymitis: 0.26% vs. 0.27% (RR, 0.9; 95% CI, 0.6-1.4).

While risk prediction criteria apart from age were only minimally accurate, testing for asymptomatic chlamydial and gonococcal infections was highly accurate at most anatomical sites, including urine and self-collected specimens, the investigators observed. Age 22 years or younger alone versus multi-item risk criteria demonstrated similar discrimination in a study that included symptomatic and asymptomatic women.

Sensitivity of chlamydial testing was similar at endocervical (89%-100%) and self- and clinician-collected vaginal (90%-100%) sites for women and at meatal (100%), urethral (99%), and rectal (92%) sites for men. It was lower, however, at pharyngeal sites (69.2%) for men who have sex with men (MSM).

Sensitivity of gonococcal testing was 89% or greater for all anatomical samples. False-positive and false-negative testing rates were low across anatomical sites and collection methods.

“Effectiveness of screening in men and during pregnancy, optimal screening intervals, and adverse effects of screening require further evaluation, Dr. Cantor and associates concluded.

In an accompanying editorial, Jeanne Marrazzo, MD, MPH, and Jodie Dionne-Odom, MD, MSPH, of the division of infectious diseases at the University of Alabama at Birmingham, called the guidelines “timely” and “powerful agents of change” that “influence a wide spectrum of health-based metrics, from quality assurance measures to criteria for financial reimbursement.”

They pointed out that men who have sex with men are experiencing historically high rates of gonorrhea, with most infections occurring extragenitally at the pharynx or rectum. In 2019 CDC data, MSM had substantially higher rates of gonorrhea than men who had sex only with women. They recommended that guidelines for men consider STI risk because of sexual relations with men, women, or both.

“Comprehensive screening guidelines for common STIs like chlamydia and gonorrhea could incorporate the limited evidence base for MSM, whether it is regular practice or not,” they wrote, with the same approach for women who have sex with women but may be at risk for chlamydia, particularly if they also have sex with men.

In their view, these latest guidelines appropriately prioritize high-level clinically based data. They pointed, however, to recent progress in understanding the pathogenesis of upper reproductive tract infection in women and the sexual networks behind the current resurgence of STIs in the United States in the failure to manage exposed sex partners.

“Considering these critical advances in the evolution of clinic-based screening guidelines is a work in progress,” they wrote, “the dialogue among basic scientists, clinical trial investigators, and public health professionals to inform the next version of updated USPSTF chlamydia and gonorrhea screening guidelines should start now.”

In the opinion of Jennifer L. Reed, MD, MS, a professor of pediatrics and an emergency medicine physician at Cincinnati Children’s Hospital Medical Center and not involved in the updated statement, the recommendations are very reasonable. “The highest rates of infection occur in females 15-24 years of age, and therefore asymptomatic screening for chlamydia and gonorrhea is imperative at least annually or more often if they are high risk,” she said in an interview.

“I would hope that providers increase their asymptomatic screening as a result of these recommendations and highly consider it in the younger men,” Dr. Reed added. “I see a very high rate of gonorrhea and chlamydia infections.” Her center is studying the implementation of gonorrhea and chlamydia asymptomatic screening for adolescents in the pediatric emergency department, a high-risk patient population that will benefit from STI screening opportunities in nontraditional settings.

This research was funded by the Agency for Healthcare Research and Quality and the Department of Health & Human Services under a contract to support the USPSTF. One statement coauthor reported personal fees from Insmed, Paratek, RedHill, and Spero, as well as grants from Insmed. No other disclosures were reported. Dr. Dionne-Odom reported grants from the National Institutes of Health/National Institute of Child Health and Development. Dr. Reed reported a grant from NIH/NICHD for a pragmatic trial of improving STI detection in the pediatric ED.