Women's Health

The American Cancer Society (ACS) has released updated guidelines for cervical cancer screening. The key recommendation is that primary human papillomavirus (HPV) testing is the preferred screening method, starting at the age of 25 and repeated every 5 years.

In the past, guidelines for cervical cancer screening recommended cytology (the Pap test) starting at 21 years of age and repeated every 3 years. In more recent years, cotesting (with both Pap and HPV tests) has been recommended.

Since the last ACS guidelines on cervical cancer screening were published in 2012, two HPV tests have been approved by the Food and Drug Administration (FDA) for use in primary HPV screening.

The new “streamlined recommendations can improve compliance and reduce potential harms,” commented Debbie Saslow, PhD, managing director, HPV/GYN Cancers, American Cancer Society.

The updated guidelines were published online July 30 in CA: A Cancer Journal for Clinicians.

“We now have stronger evidence to support starting cervical cancer screening at a later age and to recommend screening with the HPV test as the preferred test,” Saslow told Medscape Medical News. This also reflects the phasing out of cytology and cotesting, she added.

“This update is based on decades of studies comparing the effectiveness of HPV testing to cytology and is bolstered by evidence of the impact of HPV vaccination, including a dramatic decline in cervical precancers and, more recently, cervical cancers among young women,” she said.

The American Society for Colposcopy and Cervical Pathology (ASCCP) said that it was preparing a response to these new guidelines, as is the American College of Obstetricians and Gynecologists (ACOG).
 

Cotesting or cytology alone

The updated guidelines recommend primary HPV testing as the preferred screening method for all women with a cervix. If primary HPV testing is not available, women should be screened with cotesting, which should also be performed every 5 years.

If only cytology is available, then women should be screened every 3 years.

The ACS authors point out that cotesting or cytology testing alone is still an acceptable option for cervical cancer screening, insofar as primary HPV testing using FDA-approved tests may not be available in some settings.

As more laboratories in the United States transition to FDA-approved tests for primary HPV testing, it is expected that the use of cotesting or cytology alone will be phased out.

The new guidelines also emphasize that women may discontinue screening at the age of 65 if they have not had cervical intraepitheal neoplasia of grade 2 or higher within the past 25 years and if they have tested negative over the past 10 years on all past screens.

The authors caution that past screens should only be considered negative if the patient has had two consecutive negative HPV tests or two consecutive negative cotests or three consecutive negative cytology tests within the past 10 years.

“These criteria do not apply to individuals who are currently under surveillance for abnormal screening results,” the authors state.

Women older than 65 for whom adequate documentation of prior screening is not available should continue to be screened until criteria for screening discontinuation are met, they add.

Screening may be discontinued among women with a limited life expectancy.
 

HPV vaccination

The authors note that HPV vaccination is expected to substantially change cervical cancer screening strategies.

In 2018, the National Immunization Survey–Teen, involving adolescents aged 13 to 17 years, showed that 68.1% of female patients were up to date on HPV vaccine recommendations, as were 51.1% of male patients.

“Cytology-based screening is much less efficient in vaccinated populations, as abnormal cytology disproportionately identifies minor abnormalities resulting from HPV types that are associated with lower cancer risk,” the reports’ authors point out.

As the prevalence of high-grade cervical abnormalities and the incidence of cervical cancer continue to decline, “the proportion of false-positive findings [on cytology alone] is expected to increase significantly,” they caution.

As a result, the ACS suggests that physicians will likely have to consider a patient’s vaccination status in tandem with cervical cancer screening results to arrive at an accurate assessment.
 

Raising starting age to 25 years

Saslow also noted that there were several reasons why it is now recommended that screening begin at the age of 25 instead of the age of 21, as in earlier guidelines.

“Firstly, less than 1% of cervical cancers are diagnosed before the age of 25 – so this is about 130 cases per year,” she explained.

Thanks to HPV vaccination, this percentage is further declining, “so screening is just not beneficial at this age,” Saslow emphasized.

Furthermore, the rate of false positives is much higher in younger patients, and a false-positive result can have a negative impact on pregnancy outcomes, she added.

Saslow also dismissed an article in favor of cotesting instead of HPV testing alone. That study, carried out by researchers at Quest Diagnostics and the University of Pittsburgh Medical Center, recommended cotesting, claiming that primary HPV testing is significantly less likely to detect cervical precancers or cervical cancer than cotesting.

“These data come from parties with a vested interest in preserving cytology as a screening test,” Saslow told Medscape Medical News. She noted that “these findings are not at all credible as judged by the scientific community.”

On the basis of their own modeling, ACS researchers estimate that “starting with primary HPV testing at age 25 will prevent 13% more cervical cancers and 7% more cervical cancer deaths” in comparison with cytology (Pap testing alone) beginning at the age of 21, then cotesting at the age of 30, Saslow said in a statement.

“Our model showed we could do that with a 9% increase in follow-up procedures but with 45% fewer tests required overall,” she added.

The new recommendations are not expected to create any change in the type or amount of care required by providers, and patients will not notice any difference, inasmuch as cotesting and primary HPV testing are performed the same way in the examination room, she added.

“Resistance [to the changes] is expected – and is already occurring – from laboratories and manufacturers of tests that will no longer be used once we transition from cotesting and, less commonly, Pap testing to primary HPV testing,” Saslow said.

However, providers need to be aware that HPV infection, as with any sexually transmitted disease, is associated with a certain stigma, and they need to take care in discussing potential HPV infection with their patients.
 

Good method

Medscape Medical News approached Mark Einstein, MD, president of the ASCCP and professor and chair of obstetrics, gynecology, and reproductive health at Rutgers Biomedical and Health Sciences, Newark, New Jersey, to comment on the new guidelines.

“First and foremost,” he said, “everything we want to do when it comes to screening is to maximize the identification of picking up a cancer and minimize the risk or potential harm of not only screening itself but of missing cancers, so any strategy that improves on the sensitivity of picking up a cancer is a good method.”

Nevertheless, inasmuch as the ASCCP is one of the foremost organizations involved in cervical cancer screening and management, its members need more time to take a closer look at the updated ACS guidelines before they, together with sister organizations, such as the ACOG, release an official statement as to whether or not they fully endorse the new guidelines.

The United States Preventive Services Task Force recently endorsed primary HPV testing (starting at age 30), but it also said that an alternative strategy is cotesting for women between 30 and 65 years of age, Einstein observed.

Asked to comment on the article from Quest Diagnostics and the University of Pittsburgh that recommended cotesting instead of primary HPV testing, Einstein said that suggestion should not be dismissed out of hand.

The ASCCP has asked the authors of that study for their data in order conduct an independent assessment of it, largely because the study was retrospective in nature. Because of that, “there may have been a few pieces of information that were missing in true real-time fashion,” he said. “Not having [both the primary HPV testing and the cytology results] in front of me might change the next thing I might recommend to the patient,” Einstein explained.

The bottom line is that, when comparing primary HPV testing alone, cytology alone, and cotesting and rates of cervical cancer at 5 years, “the biggest driver for true performance of positive predictive value is HPV,” Einstein said.

Nevertheless, cotesting does bring more information into the equation compared with primary HPV testing alone, although it also increases the potential for harm, including the harm of overtesting and conducting needless colposcopies, he added.

That said, starting primary HPV testing at the age of 25 rather than the age of 30, as was previously recommended, is very likely to lead to detection of spurious HPV infections because HPV infections are very common among women in their 20s, Einstein pointed out.

“This, too, could potentially lead to more colposcopies, which may cause harm from the procedure itself but also create a certain amount of anxiety and concern, so there is some harm in testing for HPV at an earlier age as well,” Einstein said.

Saslow and Einstein have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The American Cancer Society (ACS) has released updated guidelines for cervical cancer screening. The key recommendation is that primary human papillomavirus (HPV) testing is the preferred screening method, starting at the age of 25 and repeated every 5 years.

In the past, guidelines for cervical cancer screening recommended cytology (the Pap test) starting at 21 years of age and repeated every 3 years. In more recent years, cotesting (with both Pap and HPV tests) has been recommended.

Since the last ACS guidelines on cervical cancer screening were published in 2012, two HPV tests have been approved by the Food and Drug Administration (FDA) for use in primary HPV screening.

The new “streamlined recommendations can improve compliance and reduce potential harms,” commented Debbie Saslow, PhD, managing director, HPV/GYN Cancers, American Cancer Society.

The updated guidelines were published online July 30 in CA: A Cancer Journal for Clinicians.

“We now have stronger evidence to support starting cervical cancer screening at a later age and to recommend screening with the HPV test as the preferred test,” Saslow told Medscape Medical News. This also reflects the phasing out of cytology and cotesting, she added.

“This update is based on decades of studies comparing the effectiveness of HPV testing to cytology and is bolstered by evidence of the impact of HPV vaccination, including a dramatic decline in cervical precancers and, more recently, cervical cancers among young women,” she said.

The American Society for Colposcopy and Cervical Pathology (ASCCP) said that it was preparing a response to these new guidelines, as is the American College of Obstetricians and Gynecologists (ACOG).
 

Cotesting or cytology alone

The updated guidelines recommend primary HPV testing as the preferred screening method for all women with a cervix. If primary HPV testing is not available, women should be screened with cotesting, which should also be performed every 5 years.

If only cytology is available, then women should be screened every 3 years.

The ACS authors point out that cotesting or cytology testing alone is still an acceptable option for cervical cancer screening, insofar as primary HPV testing using FDA-approved tests may not be available in some settings.

As more laboratories in the United States transition to FDA-approved tests for primary HPV testing, it is expected that the use of cotesting or cytology alone will be phased out.

The new guidelines also emphasize that women may discontinue screening at the age of 65 if they have not had cervical intraepitheal neoplasia of grade 2 or higher within the past 25 years and if they have tested negative over the past 10 years on all past screens.

The authors caution that past screens should only be considered negative if the patient has had two consecutive negative HPV tests or two consecutive negative cotests or three consecutive negative cytology tests within the past 10 years.

“These criteria do not apply to individuals who are currently under surveillance for abnormal screening results,” the authors state.

Women older than 65 for whom adequate documentation of prior screening is not available should continue to be screened until criteria for screening discontinuation are met, they add.

Screening may be discontinued among women with a limited life expectancy.
 

HPV vaccination

The authors note that HPV vaccination is expected to substantially change cervical cancer screening strategies.

In 2018, the National Immunization Survey–Teen, involving adolescents aged 13 to 17 years, showed that 68.1% of female patients were up to date on HPV vaccine recommendations, as were 51.1% of male patients.

“Cytology-based screening is much less efficient in vaccinated populations, as abnormal cytology disproportionately identifies minor abnormalities resulting from HPV types that are associated with lower cancer risk,” the reports’ authors point out.

As the prevalence of high-grade cervical abnormalities and the incidence of cervical cancer continue to decline, “the proportion of false-positive findings [on cytology alone] is expected to increase significantly,” they caution.

As a result, the ACS suggests that physicians will likely have to consider a patient’s vaccination status in tandem with cervical cancer screening results to arrive at an accurate assessment.
 

Raising starting age to 25 years

Saslow also noted that there were several reasons why it is now recommended that screening begin at the age of 25 instead of the age of 21, as in earlier guidelines.

“Firstly, less than 1% of cervical cancers are diagnosed before the age of 25 – so this is about 130 cases per year,” she explained.

Thanks to HPV vaccination, this percentage is further declining, “so screening is just not beneficial at this age,” Saslow emphasized.

Furthermore, the rate of false positives is much higher in younger patients, and a false-positive result can have a negative impact on pregnancy outcomes, she added.

Saslow also dismissed an article in favor of cotesting instead of HPV testing alone. That study, carried out by researchers at Quest Diagnostics and the University of Pittsburgh Medical Center, recommended cotesting, claiming that primary HPV testing is significantly less likely to detect cervical precancers or cervical cancer than cotesting.

“These data come from parties with a vested interest in preserving cytology as a screening test,” Saslow told Medscape Medical News. She noted that “these findings are not at all credible as judged by the scientific community.”

On the basis of their own modeling, ACS researchers estimate that “starting with primary HPV testing at age 25 will prevent 13% more cervical cancers and 7% more cervical cancer deaths” in comparison with cytology (Pap testing alone) beginning at the age of 21, then cotesting at the age of 30, Saslow said in a statement.

“Our model showed we could do that with a 9% increase in follow-up procedures but with 45% fewer tests required overall,” she added.

The new recommendations are not expected to create any change in the type or amount of care required by providers, and patients will not notice any difference, inasmuch as cotesting and primary HPV testing are performed the same way in the examination room, she added.

“Resistance [to the changes] is expected – and is already occurring – from laboratories and manufacturers of tests that will no longer be used once we transition from cotesting and, less commonly, Pap testing to primary HPV testing,” Saslow said.

However, providers need to be aware that HPV infection, as with any sexually transmitted disease, is associated with a certain stigma, and they need to take care in discussing potential HPV infection with their patients.
 

Good method

Medscape Medical News approached Mark Einstein, MD, president of the ASCCP and professor and chair of obstetrics, gynecology, and reproductive health at Rutgers Biomedical and Health Sciences, Newark, New Jersey, to comment on the new guidelines.

“First and foremost,” he said, “everything we want to do when it comes to screening is to maximize the identification of picking up a cancer and minimize the risk or potential harm of not only screening itself but of missing cancers, so any strategy that improves on the sensitivity of picking up a cancer is a good method.”

Nevertheless, inasmuch as the ASCCP is one of the foremost organizations involved in cervical cancer screening and management, its members need more time to take a closer look at the updated ACS guidelines before they, together with sister organizations, such as the ACOG, release an official statement as to whether or not they fully endorse the new guidelines.

The United States Preventive Services Task Force recently endorsed primary HPV testing (starting at age 30), but it also said that an alternative strategy is cotesting for women between 30 and 65 years of age, Einstein observed.

Asked to comment on the article from Quest Diagnostics and the University of Pittsburgh that recommended cotesting instead of primary HPV testing, Einstein said that suggestion should not be dismissed out of hand.

The ASCCP has asked the authors of that study for their data in order conduct an independent assessment of it, largely because the study was retrospective in nature. Because of that, “there may have been a few pieces of information that were missing in true real-time fashion,” he said. “Not having [both the primary HPV testing and the cytology results] in front of me might change the next thing I might recommend to the patient,” Einstein explained.

The bottom line is that, when comparing primary HPV testing alone, cytology alone, and cotesting and rates of cervical cancer at 5 years, “the biggest driver for true performance of positive predictive value is HPV,” Einstein said.

Nevertheless, cotesting does bring more information into the equation compared with primary HPV testing alone, although it also increases the potential for harm, including the harm of overtesting and conducting needless colposcopies, he added.

That said, starting primary HPV testing at the age of 25 rather than the age of 30, as was previously recommended, is very likely to lead to detection of spurious HPV infections because HPV infections are very common among women in their 20s, Einstein pointed out.

“This, too, could potentially lead to more colposcopies, which may cause harm from the procedure itself but also create a certain amount of anxiety and concern, so there is some harm in testing for HPV at an earlier age as well,” Einstein said.

Saslow and Einstein have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The American Cancer Society (ACS) has released updated guidelines for cervical cancer screening. The key recommendation is that primary human papillomavirus (HPV) testing is the preferred screening method, starting at the age of 25 and repeated every 5 years.

In the past, guidelines for cervical cancer screening recommended cytology (the Pap test) starting at 21 years of age and repeated every 3 years. In more recent years, cotesting (with both Pap and HPV tests) has been recommended.

Since the last ACS guidelines on cervical cancer screening were published in 2012, two HPV tests have been approved by the Food and Drug Administration (FDA) for use in primary HPV screening.

The new “streamlined recommendations can improve compliance and reduce potential harms,” commented Debbie Saslow, PhD, managing director, HPV/GYN Cancers, American Cancer Society.

The updated guidelines were published online July 30 in CA: A Cancer Journal for Clinicians.

“We now have stronger evidence to support starting cervical cancer screening at a later age and to recommend screening with the HPV test as the preferred test,” Saslow told Medscape Medical News. This also reflects the phasing out of cytology and cotesting, she added.

“This update is based on decades of studies comparing the effectiveness of HPV testing to cytology and is bolstered by evidence of the impact of HPV vaccination, including a dramatic decline in cervical precancers and, more recently, cervical cancers among young women,” she said.

The American Society for Colposcopy and Cervical Pathology (ASCCP) said that it was preparing a response to these new guidelines, as is the American College of Obstetricians and Gynecologists (ACOG).
 

Cotesting or cytology alone

The updated guidelines recommend primary HPV testing as the preferred screening method for all women with a cervix. If primary HPV testing is not available, women should be screened with cotesting, which should also be performed every 5 years.

If only cytology is available, then women should be screened every 3 years.

The ACS authors point out that cotesting or cytology testing alone is still an acceptable option for cervical cancer screening, insofar as primary HPV testing using FDA-approved tests may not be available in some settings.

As more laboratories in the United States transition to FDA-approved tests for primary HPV testing, it is expected that the use of cotesting or cytology alone will be phased out.

The new guidelines also emphasize that women may discontinue screening at the age of 65 if they have not had cervical intraepitheal neoplasia of grade 2 or higher within the past 25 years and if they have tested negative over the past 10 years on all past screens.

The authors caution that past screens should only be considered negative if the patient has had two consecutive negative HPV tests or two consecutive negative cotests or three consecutive negative cytology tests within the past 10 years.

“These criteria do not apply to individuals who are currently under surveillance for abnormal screening results,” the authors state.

Women older than 65 for whom adequate documentation of prior screening is not available should continue to be screened until criteria for screening discontinuation are met, they add.

Screening may be discontinued among women with a limited life expectancy.
 

HPV vaccination

The authors note that HPV vaccination is expected to substantially change cervical cancer screening strategies.

In 2018, the National Immunization Survey–Teen, involving adolescents aged 13 to 17 years, showed that 68.1% of female patients were up to date on HPV vaccine recommendations, as were 51.1% of male patients.

“Cytology-based screening is much less efficient in vaccinated populations, as abnormal cytology disproportionately identifies minor abnormalities resulting from HPV types that are associated with lower cancer risk,” the reports’ authors point out.

As the prevalence of high-grade cervical abnormalities and the incidence of cervical cancer continue to decline, “the proportion of false-positive findings [on cytology alone] is expected to increase significantly,” they caution.

As a result, the ACS suggests that physicians will likely have to consider a patient’s vaccination status in tandem with cervical cancer screening results to arrive at an accurate assessment.
 

Raising starting age to 25 years

Saslow also noted that there were several reasons why it is now recommended that screening begin at the age of 25 instead of the age of 21, as in earlier guidelines.

“Firstly, less than 1% of cervical cancers are diagnosed before the age of 25 – so this is about 130 cases per year,” she explained.

Thanks to HPV vaccination, this percentage is further declining, “so screening is just not beneficial at this age,” Saslow emphasized.

Furthermore, the rate of false positives is much higher in younger patients, and a false-positive result can have a negative impact on pregnancy outcomes, she added.

Saslow also dismissed an article in favor of cotesting instead of HPV testing alone. That study, carried out by researchers at Quest Diagnostics and the University of Pittsburgh Medical Center, recommended cotesting, claiming that primary HPV testing is significantly less likely to detect cervical precancers or cervical cancer than cotesting.

“These data come from parties with a vested interest in preserving cytology as a screening test,” Saslow told Medscape Medical News. She noted that “these findings are not at all credible as judged by the scientific community.”

On the basis of their own modeling, ACS researchers estimate that “starting with primary HPV testing at age 25 will prevent 13% more cervical cancers and 7% more cervical cancer deaths” in comparison with cytology (Pap testing alone) beginning at the age of 21, then cotesting at the age of 30, Saslow said in a statement.

“Our model showed we could do that with a 9% increase in follow-up procedures but with 45% fewer tests required overall,” she added.

The new recommendations are not expected to create any change in the type or amount of care required by providers, and patients will not notice any difference, inasmuch as cotesting and primary HPV testing are performed the same way in the examination room, she added.

“Resistance [to the changes] is expected – and is already occurring – from laboratories and manufacturers of tests that will no longer be used once we transition from cotesting and, less commonly, Pap testing to primary HPV testing,” Saslow said.

However, providers need to be aware that HPV infection, as with any sexually transmitted disease, is associated with a certain stigma, and they need to take care in discussing potential HPV infection with their patients.
 

Good method

Medscape Medical News approached Mark Einstein, MD, president of the ASCCP and professor and chair of obstetrics, gynecology, and reproductive health at Rutgers Biomedical and Health Sciences, Newark, New Jersey, to comment on the new guidelines.

“First and foremost,” he said, “everything we want to do when it comes to screening is to maximize the identification of picking up a cancer and minimize the risk or potential harm of not only screening itself but of missing cancers, so any strategy that improves on the sensitivity of picking up a cancer is a good method.”

Nevertheless, inasmuch as the ASCCP is one of the foremost organizations involved in cervical cancer screening and management, its members need more time to take a closer look at the updated ACS guidelines before they, together with sister organizations, such as the ACOG, release an official statement as to whether or not they fully endorse the new guidelines.

The United States Preventive Services Task Force recently endorsed primary HPV testing (starting at age 30), but it also said that an alternative strategy is cotesting for women between 30 and 65 years of age, Einstein observed.

Asked to comment on the article from Quest Diagnostics and the University of Pittsburgh that recommended cotesting instead of primary HPV testing, Einstein said that suggestion should not be dismissed out of hand.

The ASCCP has asked the authors of that study for their data in order conduct an independent assessment of it, largely because the study was retrospective in nature. Because of that, “there may have been a few pieces of information that were missing in true real-time fashion,” he said. “Not having [both the primary HPV testing and the cytology results] in front of me might change the next thing I might recommend to the patient,” Einstein explained.

The bottom line is that, when comparing primary HPV testing alone, cytology alone, and cotesting and rates of cervical cancer at 5 years, “the biggest driver for true performance of positive predictive value is HPV,” Einstein said.

Nevertheless, cotesting does bring more information into the equation compared with primary HPV testing alone, although it also increases the potential for harm, including the harm of overtesting and conducting needless colposcopies, he added.

That said, starting primary HPV testing at the age of 25 rather than the age of 30, as was previously recommended, is very likely to lead to detection of spurious HPV infections because HPV infections are very common among women in their 20s, Einstein pointed out.

“This, too, could potentially lead to more colposcopies, which may cause harm from the procedure itself but also create a certain amount of anxiety and concern, so there is some harm in testing for HPV at an earlier age as well,” Einstein said.

Saslow and Einstein have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Repeat bone mineral density testing did not improve fracture-risk prediction in a large prospective cohort of postmenopausal women beyond baseline BMD measurement alone, according to new 12-year follow-up data.

Thinkstock

On the basis of the findings, published online in JAMA Internal Medicine, the authors recommend against routine repeat testing in postmenopausal women. Other experts, however, caution that the results may not be so broadly generalizable.

For the investigation, Carolyn J. Crandall, MD, of the division of general internal medicine and health services research at the University of California, Los Angeles, and colleagues analyzed data from 7,419 women enrolled in the prospective Women’s Health Initiative study and who underwent baseline and repeat dual-energy x-ray absorptiometry (DXA) between 1993 and 2010. The researchers excluded patients who reported using bisphosphonates, calcitonin, or selective estrogen-receptor modulators, those with a history of major osteoporotic fracture, or those who lacked follow-up visits. The mean body mass index (BMI) of the study population was 28.7 kg/m², and the mean age was 66.1 years.

The mean follow-up after the repeat BMD test was 9.0 years, during which period 732 (9.9%) of the women experienced a major osteoporotic fracture, and 139 (1.9%) experienced hip fractures.

To determine whether repeat testing improved fracture risk discrimination, the researchers calculated area under the receiver operating characteristic curve (AUROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD.

With respect to any major osteoporotic fracture risk, the AUROC values for total hip BMD at baseline, change in total hip BMD at 3 years, and the combination of the two, respectively, were 0.61 (95% confidence interval, 0.59-0.63), 0.53 (95% CI, 0.51-0.55), and 0.61 (95% CI, 0.59-0.63). For hip fracture risk, the respective AUROC values were 0.71 (95% CI, 0.67-0.75), 0.61 (95% CI, 0.56-0.65), and 0.73 (95% CI, 0.69-0.77), the authors reported.

Similar results were observed for femoral neck and lumbar spine BMD measurements. The associations between BMD changes and fracture risk were consistent across age, race, ethnicity, BMI, and baseline BMD T-score subgroups.

Although baseline BMD and change in BMD were independently associated with incident fracture, the association was stronger for lower baseline BMD than the 3-year absolute change in BMD, the authors stated.

The findings, which are consistent with those of previous investigations that involved older adults, are notable because of the age range of the population, according to the authors. “To our knowledge, this is the first prospective study that addressed this issue in a study cohort that included younger postmenopausal U.S. women,” they wrote. “Forty-four percent of our study population was younger than 65 years.”

The authors wrote that, given the lack of benefit associated with repeat BMD testing, such tests should no longer be routinely performed. “Our findings further suggest that resources should be devoted to increasing the underuse of baseline BMD testing among women aged [between] 65 and 85 years, one-quarter of whom do not receive an initial BMD test.”

Loyola University

However, some experts are not comfortable with the broad recommendation to skip repeat testing in the general population. “This is a great study, and it gives important information. However, we know, even in the real world, that patients can lose BMD in this time frame and not really fracture. This does not mean that they will not fracture further down the road,” said Pauline Camacho, MD, director of Loyola University Medical Center’s Osteoporosis and Metabolic Bone Disease Center in Chicago,. “The value of doing BMD goes beyond predicting fracture risk. It also helps assess patient compliance and detect the presence of uncorrected secondary causes of osteoporosis that are limiting the response to therapy, including failure to absorb oral bisphosphonates, vitamin D deficiency, or hyperparathyroidism.”

In addition, patients for whom treatment is initiated would want to know whether it’s working. “Seeing the BMD response to therapy is helpful to both clinicians and patients,” Dr. Camacho said in an interview.

Another concern is the study population. “The study was designed to assess the clinical utility of repeating a screening BMD test in a population of low-risk women -- older postmenopausal women with remarkably good BMD on initial testing,” according to E. Michael Lewiecki, MD, vice president of the National Osteoporosis Foundation and director of the New Mexico Clinical Research and Osteoporosis Center in Albuquerque. “Not surprisingly, with what we know about the expected age-related rate of bone loss, there was only a modest decrease in BMD and little clinical utility in repeating DXA in 3 years. However, repeat testing is an important component in the care of many patients seen in clinical practice.”

UNM Health Sciences Center

There are numerous situations in clinical practice in which repeat BMD testing can enhance patient care and potentially improve outcomes, Dr. Lewiecki said in an interview. “Repeating BMD 1-2 years after starting osteoporosis therapy is a useful way to assess response and determine whether the patient is on a pathway to achieving an acceptable level of fracture risk with a strategy called treat to target.”

Additionally, patients starting high-dose glucocorticoids who are at high risk for rapid bone loss may benefit from undergoing baseline BMD testing and having a follow-up test 1 year later or even sooner, he said. Further, for early postmenopausal women, the rate of bone loss may be accelerated and may be faster than age-related bone loss later in life. For this reason, “close monitoring of BMD may be used to determine when a treatment threshold has been crossed and pharmacological therapy is indicated.”

The most important message from this study for clinicians and healthcare policymakers is not the relative value of the repeat BMD testing, Dr. Lewiecki stated. Rather, it is the call to action regarding the underuse of BMD testing. “There is a global crisis in the care of osteoporosis that is characterized by underdiagnosis and undertreatment of patients at risk for fracture. Many patients who could benefit from treatment to reduce fracture risk are not receiving it, resulting in disability and deaths from fractures that might have been prevented. We need more bone density testing in appropriately selected patients to identify high-risk patients and intervene to reduce fracture risk,” he said. “DXA is an inexpensive and highly versatile clinical tool with many applications in clinical practice. When used wisely, it can be extraordinarily useful to identify and monitor high-risk patients, with the goal of reducing the burden of osteoporotic fractures.”

The barriers to performing baseline BMD measurement in this population are poorly understood and not well researched, Dr. Crandall said in an interview. “I expect that they relate to the multiple competing demands on primary care physicians, who are, for example, trying to juggle hypertension, a sprained ankle, diabetes, and complex social situations simultaneously with identifying appropriate candidates for osteoporosis screening and considering numerous other screening guidelines.”

The Women’s Health Initiative is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The study authors reported relationships with multiple companies, including Amgen, Pfizer, Bayer, Mithra, Norton Rose Fulbright, TherapeuticsMD, AbbVie, Radius, and Allergan. Dr. Camacho reported relationships with Amgen and Shire. Dr. Lewiecki reported relationships with Amgen, Radius Health, Alexion, Samsung Bioepis, Sandoz, Mereo, and Bindex.

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

Repeat bone mineral density testing did not improve fracture-risk prediction in a large prospective cohort of postmenopausal women beyond baseline BMD measurement alone, according to new 12-year follow-up data.

Thinkstock

On the basis of the findings, published online in JAMA Internal Medicine, the authors recommend against routine repeat testing in postmenopausal women. Other experts, however, caution that the results may not be so broadly generalizable.

For the investigation, Carolyn J. Crandall, MD, of the division of general internal medicine and health services research at the University of California, Los Angeles, and colleagues analyzed data from 7,419 women enrolled in the prospective Women’s Health Initiative study and who underwent baseline and repeat dual-energy x-ray absorptiometry (DXA) between 1993 and 2010. The researchers excluded patients who reported using bisphosphonates, calcitonin, or selective estrogen-receptor modulators, those with a history of major osteoporotic fracture, or those who lacked follow-up visits. The mean body mass index (BMI) of the study population was 28.7 kg/m², and the mean age was 66.1 years.

The mean follow-up after the repeat BMD test was 9.0 years, during which period 732 (9.9%) of the women experienced a major osteoporotic fracture, and 139 (1.9%) experienced hip fractures.

To determine whether repeat testing improved fracture risk discrimination, the researchers calculated area under the receiver operating characteristic curve (AUROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD.

With respect to any major osteoporotic fracture risk, the AUROC values for total hip BMD at baseline, change in total hip BMD at 3 years, and the combination of the two, respectively, were 0.61 (95% confidence interval, 0.59-0.63), 0.53 (95% CI, 0.51-0.55), and 0.61 (95% CI, 0.59-0.63). For hip fracture risk, the respective AUROC values were 0.71 (95% CI, 0.67-0.75), 0.61 (95% CI, 0.56-0.65), and 0.73 (95% CI, 0.69-0.77), the authors reported.

Similar results were observed for femoral neck and lumbar spine BMD measurements. The associations between BMD changes and fracture risk were consistent across age, race, ethnicity, BMI, and baseline BMD T-score subgroups.

Although baseline BMD and change in BMD were independently associated with incident fracture, the association was stronger for lower baseline BMD than the 3-year absolute change in BMD, the authors stated.

The findings, which are consistent with those of previous investigations that involved older adults, are notable because of the age range of the population, according to the authors. “To our knowledge, this is the first prospective study that addressed this issue in a study cohort that included younger postmenopausal U.S. women,” they wrote. “Forty-four percent of our study population was younger than 65 years.”

The authors wrote that, given the lack of benefit associated with repeat BMD testing, such tests should no longer be routinely performed. “Our findings further suggest that resources should be devoted to increasing the underuse of baseline BMD testing among women aged [between] 65 and 85 years, one-quarter of whom do not receive an initial BMD test.”

Loyola University

However, some experts are not comfortable with the broad recommendation to skip repeat testing in the general population. “This is a great study, and it gives important information. However, we know, even in the real world, that patients can lose BMD in this time frame and not really fracture. This does not mean that they will not fracture further down the road,” said Pauline Camacho, MD, director of Loyola University Medical Center’s Osteoporosis and Metabolic Bone Disease Center in Chicago,. “The value of doing BMD goes beyond predicting fracture risk. It also helps assess patient compliance and detect the presence of uncorrected secondary causes of osteoporosis that are limiting the response to therapy, including failure to absorb oral bisphosphonates, vitamin D deficiency, or hyperparathyroidism.”

In addition, patients for whom treatment is initiated would want to know whether it’s working. “Seeing the BMD response to therapy is helpful to both clinicians and patients,” Dr. Camacho said in an interview.

Another concern is the study population. “The study was designed to assess the clinical utility of repeating a screening BMD test in a population of low-risk women -- older postmenopausal women with remarkably good BMD on initial testing,” according to E. Michael Lewiecki, MD, vice president of the National Osteoporosis Foundation and director of the New Mexico Clinical Research and Osteoporosis Center in Albuquerque. “Not surprisingly, with what we know about the expected age-related rate of bone loss, there was only a modest decrease in BMD and little clinical utility in repeating DXA in 3 years. However, repeat testing is an important component in the care of many patients seen in clinical practice.”

UNM Health Sciences Center

There are numerous situations in clinical practice in which repeat BMD testing can enhance patient care and potentially improve outcomes, Dr. Lewiecki said in an interview. “Repeating BMD 1-2 years after starting osteoporosis therapy is a useful way to assess response and determine whether the patient is on a pathway to achieving an acceptable level of fracture risk with a strategy called treat to target.”

Additionally, patients starting high-dose glucocorticoids who are at high risk for rapid bone loss may benefit from undergoing baseline BMD testing and having a follow-up test 1 year later or even sooner, he said. Further, for early postmenopausal women, the rate of bone loss may be accelerated and may be faster than age-related bone loss later in life. For this reason, “close monitoring of BMD may be used to determine when a treatment threshold has been crossed and pharmacological therapy is indicated.”

The most important message from this study for clinicians and healthcare policymakers is not the relative value of the repeat BMD testing, Dr. Lewiecki stated. Rather, it is the call to action regarding the underuse of BMD testing. “There is a global crisis in the care of osteoporosis that is characterized by underdiagnosis and undertreatment of patients at risk for fracture. Many patients who could benefit from treatment to reduce fracture risk are not receiving it, resulting in disability and deaths from fractures that might have been prevented. We need more bone density testing in appropriately selected patients to identify high-risk patients and intervene to reduce fracture risk,” he said. “DXA is an inexpensive and highly versatile clinical tool with many applications in clinical practice. When used wisely, it can be extraordinarily useful to identify and monitor high-risk patients, with the goal of reducing the burden of osteoporotic fractures.”

The barriers to performing baseline BMD measurement in this population are poorly understood and not well researched, Dr. Crandall said in an interview. “I expect that they relate to the multiple competing demands on primary care physicians, who are, for example, trying to juggle hypertension, a sprained ankle, diabetes, and complex social situations simultaneously with identifying appropriate candidates for osteoporosis screening and considering numerous other screening guidelines.”

The Women’s Health Initiative is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The study authors reported relationships with multiple companies, including Amgen, Pfizer, Bayer, Mithra, Norton Rose Fulbright, TherapeuticsMD, AbbVie, Radius, and Allergan. Dr. Camacho reported relationships with Amgen and Shire. Dr. Lewiecki reported relationships with Amgen, Radius Health, Alexion, Samsung Bioepis, Sandoz, Mereo, and Bindex.

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

Repeat bone mineral density testing did not improve fracture-risk prediction in a large prospective cohort of postmenopausal women beyond baseline BMD measurement alone, according to new 12-year follow-up data.

Thinkstock

On the basis of the findings, published online in JAMA Internal Medicine, the authors recommend against routine repeat testing in postmenopausal women. Other experts, however, caution that the results may not be so broadly generalizable.

For the investigation, Carolyn J. Crandall, MD, of the division of general internal medicine and health services research at the University of California, Los Angeles, and colleagues analyzed data from 7,419 women enrolled in the prospective Women’s Health Initiative study and who underwent baseline and repeat dual-energy x-ray absorptiometry (DXA) between 1993 and 2010. The researchers excluded patients who reported using bisphosphonates, calcitonin, or selective estrogen-receptor modulators, those with a history of major osteoporotic fracture, or those who lacked follow-up visits. The mean body mass index (BMI) of the study population was 28.7 kg/m², and the mean age was 66.1 years.

The mean follow-up after the repeat BMD test was 9.0 years, during which period 732 (9.9%) of the women experienced a major osteoporotic fracture, and 139 (1.9%) experienced hip fractures.

To determine whether repeat testing improved fracture risk discrimination, the researchers calculated area under the receiver operating characteristic curve (AUROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD.

With respect to any major osteoporotic fracture risk, the AUROC values for total hip BMD at baseline, change in total hip BMD at 3 years, and the combination of the two, respectively, were 0.61 (95% confidence interval, 0.59-0.63), 0.53 (95% CI, 0.51-0.55), and 0.61 (95% CI, 0.59-0.63). For hip fracture risk, the respective AUROC values were 0.71 (95% CI, 0.67-0.75), 0.61 (95% CI, 0.56-0.65), and 0.73 (95% CI, 0.69-0.77), the authors reported.

Similar results were observed for femoral neck and lumbar spine BMD measurements. The associations between BMD changes and fracture risk were consistent across age, race, ethnicity, BMI, and baseline BMD T-score subgroups.

Although baseline BMD and change in BMD were independently associated with incident fracture, the association was stronger for lower baseline BMD than the 3-year absolute change in BMD, the authors stated.

The findings, which are consistent with those of previous investigations that involved older adults, are notable because of the age range of the population, according to the authors. “To our knowledge, this is the first prospective study that addressed this issue in a study cohort that included younger postmenopausal U.S. women,” they wrote. “Forty-four percent of our study population was younger than 65 years.”

The authors wrote that, given the lack of benefit associated with repeat BMD testing, such tests should no longer be routinely performed. “Our findings further suggest that resources should be devoted to increasing the underuse of baseline BMD testing among women aged [between] 65 and 85 years, one-quarter of whom do not receive an initial BMD test.”

Loyola University

However, some experts are not comfortable with the broad recommendation to skip repeat testing in the general population. “This is a great study, and it gives important information. However, we know, even in the real world, that patients can lose BMD in this time frame and not really fracture. This does not mean that they will not fracture further down the road,” said Pauline Camacho, MD, director of Loyola University Medical Center’s Osteoporosis and Metabolic Bone Disease Center in Chicago,. “The value of doing BMD goes beyond predicting fracture risk. It also helps assess patient compliance and detect the presence of uncorrected secondary causes of osteoporosis that are limiting the response to therapy, including failure to absorb oral bisphosphonates, vitamin D deficiency, or hyperparathyroidism.”

In addition, patients for whom treatment is initiated would want to know whether it’s working. “Seeing the BMD response to therapy is helpful to both clinicians and patients,” Dr. Camacho said in an interview.

Another concern is the study population. “The study was designed to assess the clinical utility of repeating a screening BMD test in a population of low-risk women -- older postmenopausal women with remarkably good BMD on initial testing,” according to E. Michael Lewiecki, MD, vice president of the National Osteoporosis Foundation and director of the New Mexico Clinical Research and Osteoporosis Center in Albuquerque. “Not surprisingly, with what we know about the expected age-related rate of bone loss, there was only a modest decrease in BMD and little clinical utility in repeating DXA in 3 years. However, repeat testing is an important component in the care of many patients seen in clinical practice.”

UNM Health Sciences Center

There are numerous situations in clinical practice in which repeat BMD testing can enhance patient care and potentially improve outcomes, Dr. Lewiecki said in an interview. “Repeating BMD 1-2 years after starting osteoporosis therapy is a useful way to assess response and determine whether the patient is on a pathway to achieving an acceptable level of fracture risk with a strategy called treat to target.”

Additionally, patients starting high-dose glucocorticoids who are at high risk for rapid bone loss may benefit from undergoing baseline BMD testing and having a follow-up test 1 year later or even sooner, he said. Further, for early postmenopausal women, the rate of bone loss may be accelerated and may be faster than age-related bone loss later in life. For this reason, “close monitoring of BMD may be used to determine when a treatment threshold has been crossed and pharmacological therapy is indicated.”

The most important message from this study for clinicians and healthcare policymakers is not the relative value of the repeat BMD testing, Dr. Lewiecki stated. Rather, it is the call to action regarding the underuse of BMD testing. “There is a global crisis in the care of osteoporosis that is characterized by underdiagnosis and undertreatment of patients at risk for fracture. Many patients who could benefit from treatment to reduce fracture risk are not receiving it, resulting in disability and deaths from fractures that might have been prevented. We need more bone density testing in appropriately selected patients to identify high-risk patients and intervene to reduce fracture risk,” he said. “DXA is an inexpensive and highly versatile clinical tool with many applications in clinical practice. When used wisely, it can be extraordinarily useful to identify and monitor high-risk patients, with the goal of reducing the burden of osteoporotic fractures.”

The barriers to performing baseline BMD measurement in this population are poorly understood and not well researched, Dr. Crandall said in an interview. “I expect that they relate to the multiple competing demands on primary care physicians, who are, for example, trying to juggle hypertension, a sprained ankle, diabetes, and complex social situations simultaneously with identifying appropriate candidates for osteoporosis screening and considering numerous other screening guidelines.”

The Women’s Health Initiative is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The study authors reported relationships with multiple companies, including Amgen, Pfizer, Bayer, Mithra, Norton Rose Fulbright, TherapeuticsMD, AbbVie, Radius, and Allergan. Dr. Camacho reported relationships with Amgen and Shire. Dr. Lewiecki reported relationships with Amgen, Radius Health, Alexion, Samsung Bioepis, Sandoz, Mereo, and Bindex.

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

Women with a high body mass index who request tubal ligation immediately post partum face no increased risk of complications, compared with normal-weight woman, according to a large, single-institution, retrospective study.

“Our study underscores the overall safety of postpartum tubal ligation among overweight and obese women,” John J. Byrne, MD, MPH, and colleagues at the University of Texas, Dallas, reported in Obstetrics & Gynecology.

“Even among women in the highest BMI category, this procedure is safe and effective,” they noted, despite previous studies identifying body mass index (BMI) higher than 40 kg/m² “as a significant barrier to this procedure.”

“For the woman who is appropriately counseled and desires permanent contraception, BMI should not impede her access to the procedure,” Dr. Byrne and associates said.

The study included 3,670 women undergoing postpartum tubal ligation after a vaginal delivery between August 2015 and March 2019 at Parkland Hospital, which is operated by the Dallas County Hospital District.

The method used was the Parkland-type tubal ligation – a bilateral midsegment partial salpingectomy performed through a 2-3 cm infraumbilical incision. Women were excluded if they were planning additional surgery, such as ovarian cyst removal or hernia repair at the same time.

Comparing a composite outcome of surgical complications and subsequent pregnancies over a 5-year follow-up, the study found no differences across all maternal BMI categories, which were stratified as: underweight or normal weight (BMI, 24.9 or lower), overweight (25-29.9), class I obesity (30-34.9), class II obesity (35-39.9), and class III obesity (40 or higher).

A full breakdown of the composite morbidity included “blood transfusion, aborted procedure, intraoperative complications (bleeding requiring additional surgery, extension of incision), anesthetic complication (high spinal, bronchospasm, postdural puncture headaches requiring blood patch, and allergic reaction to anesthetic), postoperative complication (deep wound infection, venous thromboembolism, ileus, small bowel obstruction, acute intestinal herniation, peritonitis), return to operating room, incomplete transection of fallopian tube, and subsequent pregnancy,” they reported.

Among the study subjects, the mean BMI was 32.2, with 263 being underweight or normal weight at the time of admission, 1,044 being overweight, 1,371 having class I obesity, 689 having class II obesity, 303 having class III obesity, and 11 patients classified as supermorbidly obese (a BMI of 50 or higher).

Overall, “composite morbidity occurred in 49 (1.3%) women and was not significantly different across BMI categories (P = .07),” noted the authors.

More specifically, there were 19 (1.5%) composite morbidity events in the nonobese cohort and 30 (1.3%) in the obese cohort. “Even among women who had undergone prior abdominal surgery, there was no association of BMI with the rate of procedural complication,” Dr. Byrne and associates added.

The subsequent pregnancy rate was 1.63 per 1,000 procedures performed, which is “significantly lower than previously reported estimates,” they noted. In total, there were six subsequent pregnancies in the cohort: three full term, two ectopic, and one of unknown location.

“Although there was variability in operative time in all BMI categories, this is likely not clinically relevant as the range in operative time overlapped across groups,” reported the authors. “Other surgical metrics, such as estimated blood loss and length of hospitalization after tubal ligation, were found to be no different between BMI categories.”

Their findings “can be generalized to other tubal ligation forms, such as modified Pomeroy and even possibly salpingectomy, if the minilaparotomy incision is the same,” Dr. Byrne and colleagues suggested.

“This innovative study adds an important practical perspective to the literature on postpartum permanent contraception – a finding that should be reassuring for obstetrician/gynecologists,” commented Eve Espey, MD MPH, who was not involved in the research.

“Women with high BMI are significantly less likely to receive desired postvaginal delivery tubal ligation, compared to lower-BMI women, as documented in several prior studies,” said Dr. Espey, who is professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque.

“Although those studies did not explore the reasons for nonfulfillment, intuitively concerns about complications or inability to complete the procedure are the most likely explanations,” she added.

“Although this study is limited by its retrospective nature, the smaller number of women in the highest BMI category, and lack of information on patients with unfulfilled requests for tubal ligation, it is overall well designed and should serve to encourage physicians to proceed with postvaginal delivery tubal ligation in patients across all BMI categories,” Dr. Espey concluded.

The study received no external funding; Dr. Byrne and associates reported no relevant financial disclosures. Dr. Espey is a member of the Ob.Gyn. News editorial advisory board, and said she has no relevant financial disclosures.

SOURCE: Byrne JJ et al. Obstet Gynecol. 2020;136:342-8.
 

Women with a high body mass index who request tubal ligation immediately post partum face no increased risk of complications, compared with normal-weight woman, according to a large, single-institution, retrospective study.

“Our study underscores the overall safety of postpartum tubal ligation among overweight and obese women,” John J. Byrne, MD, MPH, and colleagues at the University of Texas, Dallas, reported in Obstetrics & Gynecology.

“Even among women in the highest BMI category, this procedure is safe and effective,” they noted, despite previous studies identifying body mass index (BMI) higher than 40 kg/m² “as a significant barrier to this procedure.”

“For the woman who is appropriately counseled and desires permanent contraception, BMI should not impede her access to the procedure,” Dr. Byrne and associates said.

The study included 3,670 women undergoing postpartum tubal ligation after a vaginal delivery between August 2015 and March 2019 at Parkland Hospital, which is operated by the Dallas County Hospital District.

The method used was the Parkland-type tubal ligation – a bilateral midsegment partial salpingectomy performed through a 2-3 cm infraumbilical incision. Women were excluded if they were planning additional surgery, such as ovarian cyst removal or hernia repair at the same time.

Comparing a composite outcome of surgical complications and subsequent pregnancies over a 5-year follow-up, the study found no differences across all maternal BMI categories, which were stratified as: underweight or normal weight (BMI, 24.9 or lower), overweight (25-29.9), class I obesity (30-34.9), class II obesity (35-39.9), and class III obesity (40 or higher).

A full breakdown of the composite morbidity included “blood transfusion, aborted procedure, intraoperative complications (bleeding requiring additional surgery, extension of incision), anesthetic complication (high spinal, bronchospasm, postdural puncture headaches requiring blood patch, and allergic reaction to anesthetic), postoperative complication (deep wound infection, venous thromboembolism, ileus, small bowel obstruction, acute intestinal herniation, peritonitis), return to operating room, incomplete transection of fallopian tube, and subsequent pregnancy,” they reported.

Among the study subjects, the mean BMI was 32.2, with 263 being underweight or normal weight at the time of admission, 1,044 being overweight, 1,371 having class I obesity, 689 having class II obesity, 303 having class III obesity, and 11 patients classified as supermorbidly obese (a BMI of 50 or higher).

Overall, “composite morbidity occurred in 49 (1.3%) women and was not significantly different across BMI categories (P = .07),” noted the authors.

More specifically, there were 19 (1.5%) composite morbidity events in the nonobese cohort and 30 (1.3%) in the obese cohort. “Even among women who had undergone prior abdominal surgery, there was no association of BMI with the rate of procedural complication,” Dr. Byrne and associates added.

The subsequent pregnancy rate was 1.63 per 1,000 procedures performed, which is “significantly lower than previously reported estimates,” they noted. In total, there were six subsequent pregnancies in the cohort: three full term, two ectopic, and one of unknown location.

“Although there was variability in operative time in all BMI categories, this is likely not clinically relevant as the range in operative time overlapped across groups,” reported the authors. “Other surgical metrics, such as estimated blood loss and length of hospitalization after tubal ligation, were found to be no different between BMI categories.”

Their findings “can be generalized to other tubal ligation forms, such as modified Pomeroy and even possibly salpingectomy, if the minilaparotomy incision is the same,” Dr. Byrne and colleagues suggested.

“This innovative study adds an important practical perspective to the literature on postpartum permanent contraception – a finding that should be reassuring for obstetrician/gynecologists,” commented Eve Espey, MD MPH, who was not involved in the research.

“Women with high BMI are significantly less likely to receive desired postvaginal delivery tubal ligation, compared to lower-BMI women, as documented in several prior studies,” said Dr. Espey, who is professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque.

“Although those studies did not explore the reasons for nonfulfillment, intuitively concerns about complications or inability to complete the procedure are the most likely explanations,” she added.

“Although this study is limited by its retrospective nature, the smaller number of women in the highest BMI category, and lack of information on patients with unfulfilled requests for tubal ligation, it is overall well designed and should serve to encourage physicians to proceed with postvaginal delivery tubal ligation in patients across all BMI categories,” Dr. Espey concluded.

The study received no external funding; Dr. Byrne and associates reported no relevant financial disclosures. Dr. Espey is a member of the Ob.Gyn. News editorial advisory board, and said she has no relevant financial disclosures.

SOURCE: Byrne JJ et al. Obstet Gynecol. 2020;136:342-8.
 

Women with a high body mass index who request tubal ligation immediately post partum face no increased risk of complications, compared with normal-weight woman, according to a large, single-institution, retrospective study.

“Our study underscores the overall safety of postpartum tubal ligation among overweight and obese women,” John J. Byrne, MD, MPH, and colleagues at the University of Texas, Dallas, reported in Obstetrics & Gynecology.

“Even among women in the highest BMI category, this procedure is safe and effective,” they noted, despite previous studies identifying body mass index (BMI) higher than 40 kg/m² “as a significant barrier to this procedure.”

“For the woman who is appropriately counseled and desires permanent contraception, BMI should not impede her access to the procedure,” Dr. Byrne and associates said.

The study included 3,670 women undergoing postpartum tubal ligation after a vaginal delivery between August 2015 and March 2019 at Parkland Hospital, which is operated by the Dallas County Hospital District.

The method used was the Parkland-type tubal ligation – a bilateral midsegment partial salpingectomy performed through a 2-3 cm infraumbilical incision. Women were excluded if they were planning additional surgery, such as ovarian cyst removal or hernia repair at the same time.

Comparing a composite outcome of surgical complications and subsequent pregnancies over a 5-year follow-up, the study found no differences across all maternal BMI categories, which were stratified as: underweight or normal weight (BMI, 24.9 or lower), overweight (25-29.9), class I obesity (30-34.9), class II obesity (35-39.9), and class III obesity (40 or higher).

A full breakdown of the composite morbidity included “blood transfusion, aborted procedure, intraoperative complications (bleeding requiring additional surgery, extension of incision), anesthetic complication (high spinal, bronchospasm, postdural puncture headaches requiring blood patch, and allergic reaction to anesthetic), postoperative complication (deep wound infection, venous thromboembolism, ileus, small bowel obstruction, acute intestinal herniation, peritonitis), return to operating room, incomplete transection of fallopian tube, and subsequent pregnancy,” they reported.

Among the study subjects, the mean BMI was 32.2, with 263 being underweight or normal weight at the time of admission, 1,044 being overweight, 1,371 having class I obesity, 689 having class II obesity, 303 having class III obesity, and 11 patients classified as supermorbidly obese (a BMI of 50 or higher).

Overall, “composite morbidity occurred in 49 (1.3%) women and was not significantly different across BMI categories (P = .07),” noted the authors.

More specifically, there were 19 (1.5%) composite morbidity events in the nonobese cohort and 30 (1.3%) in the obese cohort. “Even among women who had undergone prior abdominal surgery, there was no association of BMI with the rate of procedural complication,” Dr. Byrne and associates added.

The subsequent pregnancy rate was 1.63 per 1,000 procedures performed, which is “significantly lower than previously reported estimates,” they noted. In total, there were six subsequent pregnancies in the cohort: three full term, two ectopic, and one of unknown location.

“Although there was variability in operative time in all BMI categories, this is likely not clinically relevant as the range in operative time overlapped across groups,” reported the authors. “Other surgical metrics, such as estimated blood loss and length of hospitalization after tubal ligation, were found to be no different between BMI categories.”

Their findings “can be generalized to other tubal ligation forms, such as modified Pomeroy and even possibly salpingectomy, if the minilaparotomy incision is the same,” Dr. Byrne and colleagues suggested.

“This innovative study adds an important practical perspective to the literature on postpartum permanent contraception – a finding that should be reassuring for obstetrician/gynecologists,” commented Eve Espey, MD MPH, who was not involved in the research.

“Women with high BMI are significantly less likely to receive desired postvaginal delivery tubal ligation, compared to lower-BMI women, as documented in several prior studies,” said Dr. Espey, who is professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque.

“Although those studies did not explore the reasons for nonfulfillment, intuitively concerns about complications or inability to complete the procedure are the most likely explanations,” she added.

“Although this study is limited by its retrospective nature, the smaller number of women in the highest BMI category, and lack of information on patients with unfulfilled requests for tubal ligation, it is overall well designed and should serve to encourage physicians to proceed with postvaginal delivery tubal ligation in patients across all BMI categories,” Dr. Espey concluded.

The study received no external funding; Dr. Byrne and associates reported no relevant financial disclosures. Dr. Espey is a member of the Ob.Gyn. News editorial advisory board, and said she has no relevant financial disclosures.

SOURCE: Byrne JJ et al. Obstet Gynecol. 2020;136:342-8.
 

Although female genital mutilation or cutting (FGM/C) is outlawed in much of the world, it still occurs for cultural reasons despite having no medical benefit, according to a clinical report from the American Academy of Pediatrics.

FGM/C is mainly performed on children and adolescents, but most of the research and teaching to date has addressed the impact of FGM/C on women of childbearing age and management during pregnancy and post partum, wrote Janine Young, MD, of the University of Colorado Denver in Aurora and colleagues. They are members of the AAP section on global health, committee on medical liability and risk management, or the committee on bioethics.

“This work seeks to educate pediatric health care providers on the occurrence of FGM/C, and the broader applications to the patients/population it impacts as well as the intersecting issues of diagnosis, complications, treatment, counseling needs, and the ethical and legal implications,” M. Susan Jay, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview.

However, challenges in implementing the recommendations “relate to the complexity of the issue and also the need for greater education of primary providers,” Dr. Jay said. “The overall message for providers, I believe, is a greater understanding of the practice [of FGM/C] as most providers have limited knowledge of this practice in the United States.”

“I believe the case-based presentations allow for a better understanding of how best to approach patients and families,” she added.

Kelly Curran, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, said, “I think one of largest barriers to implementing the strategies [from] this report is the limited knowledge of FGM/C by most clinicians.”

“In general, many pediatricians are uncomfortable with genital examinations,” she said in an interview. “I suspect most feel uncomfortable with identifying FGM/C versus other genital pathology and may not have ready access to FGM/C experts. Additionally, having these difficult conversations with families about this sensitive topic may be challenging,” said Dr. Curran. “Fortunately, this report is incredibly comprehensive, providing extensive background into FGM/C, effectively using diagrams and pictures, and explaining the legal and ethical issues that arise in the care of these patients.”

“Ultimately, I think there will need to be more education within medical training and further research into FGM/C,” Dr. Curran added. “Clinicians should be knowledgeable about FGM/C, including prevalence, identification, health complications, and treatment, as well as legal and ethical implications.” However, “in addition to knowledge, clinicians must be able to navigate counseling patients and their families around this culturally sensitive topic.”

The report is thorough and well written, yet “there still remains significant gaps in knowledge about FGM/C in children and adolescents,” she said. “I think future research into prevalence, along with the health effects of FGM/C, including its impact on mental and sexual health, in the pediatric population will be essential.”

The study received no outside funding. Coauthor Christa Johnson-Agbakwu, MD, disclosed a grant relationship with Arizona State University from the 2018 copyright of “Female Genital Mutilation/Cutting (FGM/C): A Visual Reference and Learning Tool for Health Care Professionals.” The other researchers had no financial conflicts to disclose. Dr. Jay and Dr. Curran had no relevant financial conflicts to disclose. They are members of the Pediatric News editorial advisory board.

SOURCE: Young J et al. Pediatrics. 2020 Jul 27. doi: 10.1542/peds.2020-1012.

Although female genital mutilation or cutting (FGM/C) is outlawed in much of the world, it still occurs for cultural reasons despite having no medical benefit, according to a clinical report from the American Academy of Pediatrics.

FGM/C is mainly performed on children and adolescents, but most of the research and teaching to date has addressed the impact of FGM/C on women of childbearing age and management during pregnancy and post partum, wrote Janine Young, MD, of the University of Colorado Denver in Aurora and colleagues. They are members of the AAP section on global health, committee on medical liability and risk management, or the committee on bioethics.

“This work seeks to educate pediatric health care providers on the occurrence of FGM/C, and the broader applications to the patients/population it impacts as well as the intersecting issues of diagnosis, complications, treatment, counseling needs, and the ethical and legal implications,” M. Susan Jay, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview.

However, challenges in implementing the recommendations “relate to the complexity of the issue and also the need for greater education of primary providers,” Dr. Jay said. “The overall message for providers, I believe, is a greater understanding of the practice [of FGM/C] as most providers have limited knowledge of this practice in the United States.”

“I believe the case-based presentations allow for a better understanding of how best to approach patients and families,” she added.

Kelly Curran, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, said, “I think one of largest barriers to implementing the strategies [from] this report is the limited knowledge of FGM/C by most clinicians.”

“In general, many pediatricians are uncomfortable with genital examinations,” she said in an interview. “I suspect most feel uncomfortable with identifying FGM/C versus other genital pathology and may not have ready access to FGM/C experts. Additionally, having these difficult conversations with families about this sensitive topic may be challenging,” said Dr. Curran. “Fortunately, this report is incredibly comprehensive, providing extensive background into FGM/C, effectively using diagrams and pictures, and explaining the legal and ethical issues that arise in the care of these patients.”

“Ultimately, I think there will need to be more education within medical training and further research into FGM/C,” Dr. Curran added. “Clinicians should be knowledgeable about FGM/C, including prevalence, identification, health complications, and treatment, as well as legal and ethical implications.” However, “in addition to knowledge, clinicians must be able to navigate counseling patients and their families around this culturally sensitive topic.”

The report is thorough and well written, yet “there still remains significant gaps in knowledge about FGM/C in children and adolescents,” she said. “I think future research into prevalence, along with the health effects of FGM/C, including its impact on mental and sexual health, in the pediatric population will be essential.”

The study received no outside funding. Coauthor Christa Johnson-Agbakwu, MD, disclosed a grant relationship with Arizona State University from the 2018 copyright of “Female Genital Mutilation/Cutting (FGM/C): A Visual Reference and Learning Tool for Health Care Professionals.” The other researchers had no financial conflicts to disclose. Dr. Jay and Dr. Curran had no relevant financial conflicts to disclose. They are members of the Pediatric News editorial advisory board.

SOURCE: Young J et al. Pediatrics. 2020 Jul 27. doi: 10.1542/peds.2020-1012.

Although female genital mutilation or cutting (FGM/C) is outlawed in much of the world, it still occurs for cultural reasons despite having no medical benefit, according to a clinical report from the American Academy of Pediatrics.

FGM/C is mainly performed on children and adolescents, but most of the research and teaching to date has addressed the impact of FGM/C on women of childbearing age and management during pregnancy and post partum, wrote Janine Young, MD, of the University of Colorado Denver in Aurora and colleagues. They are members of the AAP section on global health, committee on medical liability and risk management, or the committee on bioethics.

“This work seeks to educate pediatric health care providers on the occurrence of FGM/C, and the broader applications to the patients/population it impacts as well as the intersecting issues of diagnosis, complications, treatment, counseling needs, and the ethical and legal implications,” M. Susan Jay, MD, of the Medical College of Wisconsin, Milwaukee, said in an interview.

However, challenges in implementing the recommendations “relate to the complexity of the issue and also the need for greater education of primary providers,” Dr. Jay said. “The overall message for providers, I believe, is a greater understanding of the practice [of FGM/C] as most providers have limited knowledge of this practice in the United States.”

“I believe the case-based presentations allow for a better understanding of how best to approach patients and families,” she added.

Kelly Curran, MD, of the University of Oklahoma Health Sciences Center, Oklahoma City, said, “I think one of largest barriers to implementing the strategies [from] this report is the limited knowledge of FGM/C by most clinicians.”

“In general, many pediatricians are uncomfortable with genital examinations,” she said in an interview. “I suspect most feel uncomfortable with identifying FGM/C versus other genital pathology and may not have ready access to FGM/C experts. Additionally, having these difficult conversations with families about this sensitive topic may be challenging,” said Dr. Curran. “Fortunately, this report is incredibly comprehensive, providing extensive background into FGM/C, effectively using diagrams and pictures, and explaining the legal and ethical issues that arise in the care of these patients.”

“Ultimately, I think there will need to be more education within medical training and further research into FGM/C,” Dr. Curran added. “Clinicians should be knowledgeable about FGM/C, including prevalence, identification, health complications, and treatment, as well as legal and ethical implications.” However, “in addition to knowledge, clinicians must be able to navigate counseling patients and their families around this culturally sensitive topic.”

The report is thorough and well written, yet “there still remains significant gaps in knowledge about FGM/C in children and adolescents,” she said. “I think future research into prevalence, along with the health effects of FGM/C, including its impact on mental and sexual health, in the pediatric population will be essential.”

The study received no outside funding. Coauthor Christa Johnson-Agbakwu, MD, disclosed a grant relationship with Arizona State University from the 2018 copyright of “Female Genital Mutilation/Cutting (FGM/C): A Visual Reference and Learning Tool for Health Care Professionals.” The other researchers had no financial conflicts to disclose. Dr. Jay and Dr. Curran had no relevant financial conflicts to disclose. They are members of the Pediatric News editorial advisory board.

SOURCE: Young J et al. Pediatrics. 2020 Jul 27. doi: 10.1542/peds.2020-1012.

A new follow-up study of menopausal hormone therapy found that prior use of conjugated equine estrogen (CEE) decreased both breast cancer incidence and mortality, while prior use of CEE plus medroxyprogesterone acetate (MPA) was associated with an increase in incidence.

“Prior use of CEE alone is, to our knowledge, the first pharmacologic intervention demonstrated to be associated with a statistically significantly reduction in deaths from breast cancer,” wrote Rowan T. Chlebowski, MD, PhD, of the Lundquist Institute for Biomedical Innovation in Torrance, Calif., and his coauthors. The study was published July 28 in JAMA.

To further investigate the outcomes of the Women’s Health Initiative in regard to hormone therapy and breast cancer risk, the researchers analyzed the long-term follow-up of two randomized trials that included 27,347 postmenopausal women with no prior breast cancer and negative mammograms at baseline. Their mean (SD) age was 63.4 (7.2) years. Enrollment took place from 1993 to 1998; participants were contacted for follow-up every 6 months through 2005 and annually from then on. Mortality data were gathered from follow-up and the National Death Index.

The first trial included 16,608 women with a uterus. Among these women, 8,506 received 0.625 mg/day of CEE plus 2.5 mg/day of MPA, and 8,102 received placebo. The second trial included 10,739 women who’d gotten a hysterectomy, 5,310 of whom received 0.625 mg/day of CEE alone and 5,429 of whom received placebo. The first trial ended in 2002 after a median intervention period of 5.6 years, and the second trial ended in 2004 after a period of 7.2 years.

An analysis in 2015 found that CEE alone was associated with lower risk of breast cancer and CEE plus MPA was associated with increased risk.

The current analysis confirmed that, after a median of 20.3 years of follow-up, and with mortality data now available for more than 98% of participants, CEE alone was associated with fewer cases of breast cancer (238 cases, annualized rate 0.30%), compared with placebo (296 cases, annualized rate 0.37%; hazard ratio 0.78; 95% confidence interval, 0.65-0.93; P = .005).

Furthermore, CEE alone was also associated with lower mortality (30 deaths, annualized mortality rate 0.031%), compared with placebo (46 deaths, annualized mortality rate 0.046%; HR 0.60; 95% CI, 0.37-0.97; P = .04).

By comparison, CEE plus MPA was linked with more cases of breast cancer (584 cases, annualized rate 0.45%) than placebo (447 cases, annualized rate 0.36%; HR 1.28; 95% CI, 1.13-1.45; P < .001). In regard to mortality, there was no statistically significant difference between CEE plus MPA (71 deaths, annualized mortality rate 0.045%) and placebo (53 deaths, annualized mortality rate 0.035%; HR 1.35; 95% CI, 0.94-1.95; P = .11).

“The big thing to think about is estrogen alone reducing breast cancer mortality by 40%,” said Dr. Chlebowski in an interview. “None of the other interventions, including tamoxifen, had any change on mortality. This should change the way we look at breast cancer prevention, though we might have to be a little creative about it. I think you have to be a little away from menopause for it to reduce breast cancer. But we wanted to start that debate.

“On the other hand,” he said, “a woman takes estrogen plus progestin and when you look at that curve, it’s staying about 25% increased. You take it for 5.6 years and the increase continues through 20 years, so you’re maybe buying a lifetime of increase in breast cancer by taking estrogen plus progestin for 5 years.”

He also highlighted the comprehensiveness of the mortality data, noting that “when you hook up to the National Death Index, they find 98% of all deaths in the United States. That’s really remarkable; you retain the whole power of the randomization. It means our data, between the death index and our follow-up of participants, is essentially complete.”

Use of hormone therapy, and decoding the outcomes, remains ‘complex’

Decades after the data were gathered from the Women’s Health Initiative clinical trials, they continue to assist researchers and patients alike, wrote Christina A. Minami, MD, of Brigham and Women’s Hospital in Boston and Rachel A. Freedman, MD, of the Dana-Farber Cancer Institute in Boston, in an accompanying editorial.

That said, in regard to the findings of this latest analysis, “many questions still remain on whether (and how) a hormone therapy intervention that occurred many years earlier may continue to affect breast cancer risk and mortality at 20 years,” they wrote. They noted that it’s “impossible” to isolate how exposure to certain therapies can impact long-term outcomes, and that a high percentage of patients who discontinued the drugs during each trial muddy the waters even further.

“Decisions to initiate these medications remain complex,” they added, emphasizing that breast cancer risk is just one of many factors that physicians must consider when considering hormone therapy for their patients.

Dr. Chlebowski and his coauthors acknowledged their study’s limitations, including the use of very specifically administered and formulated dosages making their findings “not necessarily generalizable to other preparations.” In addition, they noted the significant percentage of patients – 54% with CEE alone and 42% with CEE plus MPA – who discontinued drug usage during their respective trials.

The Women’s Health Initiative is supported by the National Institutes of Health and the Department of Health and Human Services. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various government organizations, foundations, and pharmaceutical companies. The editorial’s authors reported no conflicts of interest.

SOURCE: Chlebowski RT et al. JAMA. 2020 Jul 28. doi: 10.1001/jama.2020.9482.

A new follow-up study of menopausal hormone therapy found that prior use of conjugated equine estrogen (CEE) decreased both breast cancer incidence and mortality, while prior use of CEE plus medroxyprogesterone acetate (MPA) was associated with an increase in incidence.

“Prior use of CEE alone is, to our knowledge, the first pharmacologic intervention demonstrated to be associated with a statistically significantly reduction in deaths from breast cancer,” wrote Rowan T. Chlebowski, MD, PhD, of the Lundquist Institute for Biomedical Innovation in Torrance, Calif., and his coauthors. The study was published July 28 in JAMA.

To further investigate the outcomes of the Women’s Health Initiative in regard to hormone therapy and breast cancer risk, the researchers analyzed the long-term follow-up of two randomized trials that included 27,347 postmenopausal women with no prior breast cancer and negative mammograms at baseline. Their mean (SD) age was 63.4 (7.2) years. Enrollment took place from 1993 to 1998; participants were contacted for follow-up every 6 months through 2005 and annually from then on. Mortality data were gathered from follow-up and the National Death Index.

The first trial included 16,608 women with a uterus. Among these women, 8,506 received 0.625 mg/day of CEE plus 2.5 mg/day of MPA, and 8,102 received placebo. The second trial included 10,739 women who’d gotten a hysterectomy, 5,310 of whom received 0.625 mg/day of CEE alone and 5,429 of whom received placebo. The first trial ended in 2002 after a median intervention period of 5.6 years, and the second trial ended in 2004 after a period of 7.2 years.

An analysis in 2015 found that CEE alone was associated with lower risk of breast cancer and CEE plus MPA was associated with increased risk.

The current analysis confirmed that, after a median of 20.3 years of follow-up, and with mortality data now available for more than 98% of participants, CEE alone was associated with fewer cases of breast cancer (238 cases, annualized rate 0.30%), compared with placebo (296 cases, annualized rate 0.37%; hazard ratio 0.78; 95% confidence interval, 0.65-0.93; P = .005).

Furthermore, CEE alone was also associated with lower mortality (30 deaths, annualized mortality rate 0.031%), compared with placebo (46 deaths, annualized mortality rate 0.046%; HR 0.60; 95% CI, 0.37-0.97; P = .04).

By comparison, CEE plus MPA was linked with more cases of breast cancer (584 cases, annualized rate 0.45%) than placebo (447 cases, annualized rate 0.36%; HR 1.28; 95% CI, 1.13-1.45; P < .001). In regard to mortality, there was no statistically significant difference between CEE plus MPA (71 deaths, annualized mortality rate 0.045%) and placebo (53 deaths, annualized mortality rate 0.035%; HR 1.35; 95% CI, 0.94-1.95; P = .11).

“The big thing to think about is estrogen alone reducing breast cancer mortality by 40%,” said Dr. Chlebowski in an interview. “None of the other interventions, including tamoxifen, had any change on mortality. This should change the way we look at breast cancer prevention, though we might have to be a little creative about it. I think you have to be a little away from menopause for it to reduce breast cancer. But we wanted to start that debate.

“On the other hand,” he said, “a woman takes estrogen plus progestin and when you look at that curve, it’s staying about 25% increased. You take it for 5.6 years and the increase continues through 20 years, so you’re maybe buying a lifetime of increase in breast cancer by taking estrogen plus progestin for 5 years.”

He also highlighted the comprehensiveness of the mortality data, noting that “when you hook up to the National Death Index, they find 98% of all deaths in the United States. That’s really remarkable; you retain the whole power of the randomization. It means our data, between the death index and our follow-up of participants, is essentially complete.”

Use of hormone therapy, and decoding the outcomes, remains ‘complex’

Decades after the data were gathered from the Women’s Health Initiative clinical trials, they continue to assist researchers and patients alike, wrote Christina A. Minami, MD, of Brigham and Women’s Hospital in Boston and Rachel A. Freedman, MD, of the Dana-Farber Cancer Institute in Boston, in an accompanying editorial.

That said, in regard to the findings of this latest analysis, “many questions still remain on whether (and how) a hormone therapy intervention that occurred many years earlier may continue to affect breast cancer risk and mortality at 20 years,” they wrote. They noted that it’s “impossible” to isolate how exposure to certain therapies can impact long-term outcomes, and that a high percentage of patients who discontinued the drugs during each trial muddy the waters even further.

“Decisions to initiate these medications remain complex,” they added, emphasizing that breast cancer risk is just one of many factors that physicians must consider when considering hormone therapy for their patients.

Dr. Chlebowski and his coauthors acknowledged their study’s limitations, including the use of very specifically administered and formulated dosages making their findings “not necessarily generalizable to other preparations.” In addition, they noted the significant percentage of patients – 54% with CEE alone and 42% with CEE plus MPA – who discontinued drug usage during their respective trials.

The Women’s Health Initiative is supported by the National Institutes of Health and the Department of Health and Human Services. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various government organizations, foundations, and pharmaceutical companies. The editorial’s authors reported no conflicts of interest.

SOURCE: Chlebowski RT et al. JAMA. 2020 Jul 28. doi: 10.1001/jama.2020.9482.

A new follow-up study of menopausal hormone therapy found that prior use of conjugated equine estrogen (CEE) decreased both breast cancer incidence and mortality, while prior use of CEE plus medroxyprogesterone acetate (MPA) was associated with an increase in incidence.

“Prior use of CEE alone is, to our knowledge, the first pharmacologic intervention demonstrated to be associated with a statistically significantly reduction in deaths from breast cancer,” wrote Rowan T. Chlebowski, MD, PhD, of the Lundquist Institute for Biomedical Innovation in Torrance, Calif., and his coauthors. The study was published July 28 in JAMA.

To further investigate the outcomes of the Women’s Health Initiative in regard to hormone therapy and breast cancer risk, the researchers analyzed the long-term follow-up of two randomized trials that included 27,347 postmenopausal women with no prior breast cancer and negative mammograms at baseline. Their mean (SD) age was 63.4 (7.2) years. Enrollment took place from 1993 to 1998; participants were contacted for follow-up every 6 months through 2005 and annually from then on. Mortality data were gathered from follow-up and the National Death Index.

The first trial included 16,608 women with a uterus. Among these women, 8,506 received 0.625 mg/day of CEE plus 2.5 mg/day of MPA, and 8,102 received placebo. The second trial included 10,739 women who’d gotten a hysterectomy, 5,310 of whom received 0.625 mg/day of CEE alone and 5,429 of whom received placebo. The first trial ended in 2002 after a median intervention period of 5.6 years, and the second trial ended in 2004 after a period of 7.2 years.

An analysis in 2015 found that CEE alone was associated with lower risk of breast cancer and CEE plus MPA was associated with increased risk.

The current analysis confirmed that, after a median of 20.3 years of follow-up, and with mortality data now available for more than 98% of participants, CEE alone was associated with fewer cases of breast cancer (238 cases, annualized rate 0.30%), compared with placebo (296 cases, annualized rate 0.37%; hazard ratio 0.78; 95% confidence interval, 0.65-0.93; P = .005).

Furthermore, CEE alone was also associated with lower mortality (30 deaths, annualized mortality rate 0.031%), compared with placebo (46 deaths, annualized mortality rate 0.046%; HR 0.60; 95% CI, 0.37-0.97; P = .04).

By comparison, CEE plus MPA was linked with more cases of breast cancer (584 cases, annualized rate 0.45%) than placebo (447 cases, annualized rate 0.36%; HR 1.28; 95% CI, 1.13-1.45; P < .001). In regard to mortality, there was no statistically significant difference between CEE plus MPA (71 deaths, annualized mortality rate 0.045%) and placebo (53 deaths, annualized mortality rate 0.035%; HR 1.35; 95% CI, 0.94-1.95; P = .11).

“The big thing to think about is estrogen alone reducing breast cancer mortality by 40%,” said Dr. Chlebowski in an interview. “None of the other interventions, including tamoxifen, had any change on mortality. This should change the way we look at breast cancer prevention, though we might have to be a little creative about it. I think you have to be a little away from menopause for it to reduce breast cancer. But we wanted to start that debate.

“On the other hand,” he said, “a woman takes estrogen plus progestin and when you look at that curve, it’s staying about 25% increased. You take it for 5.6 years and the increase continues through 20 years, so you’re maybe buying a lifetime of increase in breast cancer by taking estrogen plus progestin for 5 years.”

He also highlighted the comprehensiveness of the mortality data, noting that “when you hook up to the National Death Index, they find 98% of all deaths in the United States. That’s really remarkable; you retain the whole power of the randomization. It means our data, between the death index and our follow-up of participants, is essentially complete.”

Use of hormone therapy, and decoding the outcomes, remains ‘complex’

Decades after the data were gathered from the Women’s Health Initiative clinical trials, they continue to assist researchers and patients alike, wrote Christina A. Minami, MD, of Brigham and Women’s Hospital in Boston and Rachel A. Freedman, MD, of the Dana-Farber Cancer Institute in Boston, in an accompanying editorial.

That said, in regard to the findings of this latest analysis, “many questions still remain on whether (and how) a hormone therapy intervention that occurred many years earlier may continue to affect breast cancer risk and mortality at 20 years,” they wrote. They noted that it’s “impossible” to isolate how exposure to certain therapies can impact long-term outcomes, and that a high percentage of patients who discontinued the drugs during each trial muddy the waters even further.

“Decisions to initiate these medications remain complex,” they added, emphasizing that breast cancer risk is just one of many factors that physicians must consider when considering hormone therapy for their patients.

Dr. Chlebowski and his coauthors acknowledged their study’s limitations, including the use of very specifically administered and formulated dosages making their findings “not necessarily generalizable to other preparations.” In addition, they noted the significant percentage of patients – 54% with CEE alone and 42% with CEE plus MPA – who discontinued drug usage during their respective trials.

The Women’s Health Initiative is supported by the National Institutes of Health and the Department of Health and Human Services. The authors reported numerous potential conflicts of interest, including receiving personal fees and grants from various government organizations, foundations, and pharmaceutical companies. The editorial’s authors reported no conflicts of interest.

SOURCE: Chlebowski RT et al. JAMA. 2020 Jul 28. doi: 10.1001/jama.2020.9482.

“Anytime you have a maternal death, it sticks with you for life,” said Elliott Main, MD, a maternal fetal medicine specialist at Stanford (Calif.) University and one of the nation’s leaders in combating maternal mortality.

Courtesy Dr. Elliott Main

Dr. Main has had two maternal deaths in his career, years ago. One woman had a fatal stroke because of severe hypertension, and another died of cardiac complications. “We tried to do everything we possibly could, but you scrounge your memory for years and years [afterward]. To have a young healthy person go into labor and delivery and not come out is a tragedy at all levels. It charged me to not ever want to see that happen again,” he said.

Today, Dr. Main is the medical director of the California Maternal Quality Care Collaborative (CMQCC), a wide-ranging group of clinicians, state officials, hospitals, and others who have come together to address the issue. About 30 states have similar perinatal quality collaboratives (PQCs), and other states are forming them.

They work in collaboration with maternal mortality review committees (MMRCs), state-level groups that review maternal deaths, identify problems to address, and make recommendations to the quality collaboratives on how to prevent maternal deaths.

About 600-800 women die in the United States each year due to pregnancy-related complications, which ranks the United States behind other industrialized nations. Leading causes include hemorrhage and hemorrhagic strokes secondary to hypertension. It’s estimated that the majority of maternal deaths could be prevented with proper care.

To that end, states are enacting safety bundles from the Alliance for Innovation on Maternal Health (AIM), which was established by the American College of Obstetricians and Gynecologist several years ago. There are bundles that address obstetric hypertension, hemorrhage, mental health, venous thromboembolism, opioid use, racial disparities, and other problems. They were developed by experts in the field and published in multiple journals. California and other states have issued toolkits on how to implement them based on local circumstances.

The goal is to standardize best practices nationwide to prevent maternal morbidity and mortality, Dr. Main said.

AIM bundle implementation is “what’s happening in New Mexico and a lot of states, mostly through the efforts of state level quality care collaboratives. Some [states] are further ahead than others,” said Eve Espey, MD, professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, and president of the New Mexico PQC.

“Most states now have a [MMRC] that collects maternal mortality and near-miss data. Those data are used by the action arm,” which is the PQC. “If the review committee says” opioid use disorder is a significant contributor “like in our state, the collaborative rolls out the opioid use disorder bundle,” she said.

Beginning next January, the Joint Commission, formerly known as the Joint Commission on Accreditation of Healthcare Organizations, will require that accredited hospitals enact key elements of the AIM bundles for both obstetric hemorrhage and severe hypertension. “Everyone’s [now] motivated to get on that bandwagon,” Dr. Espey said.

“The bundles are here to stay,” and the Joint Commission requirements are “a really important step for sustainability and basic implementation. We really want to get them adopted everywhere,” said Dr. Main, who is also the national implementation director for the AIM initiative.

“The key thing is to work on implementing the hemorrhage and hypertension bundles in your hospital. I would suggest contacting [your] state” PQC, he said.

The California model

California, which has been working to reduce maternal mortality and morbidity since the mid 2000s, has produced among the strongest evidence to date that the efforts make a difference.

By 2013, the state had halved its maternal mortality rate to a 3-year average of 7 deaths per 100,000 live births, which is comparable with the average Western Europe rate of 7.2 deaths. Nationwide, the rate was about 17.4 deaths per 100,000 live births in 2018, according to the Centers for Disease Control and Prevention

The reasons are multifactorial, but “we think” the quality improvement efforts have been “an important contributor,” Dr. Main said.
 

Improvements especially for Black women

Among the success stories has been California’s implementation of the AIM obstetric hemorrhage bundle about 5 years ago. Among other steps, the 17 evidence-based recommendations included early recognition, immediate access to oxytocin and other medications, immediate access to a hemorrhage cart with instructions for intrauterine balloons and compression stitches, the establishment of a hemorrhage response protocol and team, and regular unit-based drills with debriefing sessions afterward.

Mentoring teams consisting of a physician and nurse with maternal quality improvement experience were created to help hospitals come on board, with each team working with five to eight hospitals. Efforts included monthly telephone calls and face-to-face meetings, and providers were held accountable for progress. Hospitals shared data and tips on implementation, under the aegis of the CMQCC.

When the baseline period of 2011-2014 to the postintervention period of October 2015 to December 2016 were compared, the rate of severe maternal morbidity from hemorrhage fell from 22.1% to 18.5% across 99 hospitals and 73,476 women.

The benefit among Black women exceeded that among White women, with a 9% absolute rate reduction versus 2.1%. “If you adjusted for risk factors, [we found] you could eliminate [racial differences] completely,” which is something that hadn’t been shown before. “This is a really big deal,” Dr. Main said, because the risk of maternal morbidity and mortality is three to four times higher among Black women, compared with White women.

Dr. Main and his team found that the biggest clinical risk factor that accounted for racial differences was a higher rate of cesarean deliveries among Black women, followed by higher rates of anemia at hospital admission. “If you have a C-section when you are anemic, you are going to have a transfusion,” he explained.

More recently, there’s been a push in California to reduce the rate of primary cesarean deliveries by enacting the associated AIM bundle with use of the same approach as with the hemorrhage bundle. Dr. Main and his team recently reported a rate reduction from 29.3% to 25% without compromising birth outcomes.

However, “some changes are easier than others. Hemorrhage was an easy one to change because it didn’t deal with physician autonomy as much, and you saw more immediate results” with fewer hemorrhages. Reducing cesarean delivery rates is “a bigger lift” because “it’s really changing the culture of labor and delivery. It involves more group pressure and more reinforcing, but we were able to do that,” he said.
 

Problems in the Show Me State

“We’ve patterned a lot” of what’s being done in New Mexico “after California,” Dr. Espey said.

The AIM hemorrhage bundle, for instance, is being rolled out to New Mexico hospitals, with the help of virtual meetings and mentoring programs, plus outreach to the Navajo and others reservations because, as with Black women, rates of maternal morbidity and mortality are higher among Native American women.

It’s been tougher going, however, in states such as Missouri, which recently ranked 44th in the country for maternal mortality.

“We started a little bit late, and we are a little bit behind,” said ob.gyn. Karen L. Florio, DO, at the University of Missouri–Kansas City and also a leader of the state MMRC and member of its PQC.

The main problem is money. California’s efforts are funded by the Centers for Disease Control and Prevention, the state health department, and hospitals, among others.

But Missouri is “not as well funded as California for our mortality review board, and our [PQC] is mostly not funded. If we could get that funding, we would have more resources to implement these AIM bundles,” she said.

In addition to the issue, Missouri didn’t expand Medicaid under the Accountable Care Act – something that’s been linked to reduced maternal morbidity and mortality – and there are entire rural areas with no maternity care. Plus after generations of mistreatment, “our African American population has a valid distrust of the medical system that contributes to maternal mortality,” she said.

Obesity-related heart disease is also prevalent in Missouri, even among young people. “I cannot tell you how many women I have had who have had a heart attack at the age of 30 and who have had stents placed,” Dr. Florio said.

Dr. Florio and her colleagues are currently using teleconferences and other means to roll out the AIM hypertension bundle but can do so only selectively. “We don’t have the resources to reach every single rural hospital all over the state,” she said; they are working to address the funding issues.
 

For rural hospitals, implementation is “daunting”

Meanwhile, rural hospitals have been a particular concern in South Dakota, said Kimberlee McKay, MD, an ob.gyn. who is the clinical vice president of the ob.gyn. service line at Avera Health, a hospital system based in Sioux Falls, S.D.

She’s been overseeing Avera’s implementation of the hypertension, hemorrhage, and venous thromboembolism bundles. “What’s hard is that” the AIM protocols come “out of academic centers. Implementation of complex algorithms is daunting” for hospitals that only do a couple hundred deliveries a year, she said.

For small hospitals, the approach she’s found that works is to first assess what they can offer, and then have them “do what’s reasonable” for their resources. The second part is making sure high-risk women get to a regional center – with an adequate blood supply, in the case of hemorrhage, for instance – for complications. Dr. McKay and colleagues are working on a system by which regional centers can monitor smaller hospitals for potential maternity problems, and contact them proactively before they emerge.

They’ve also made access to hemorrhage and hypertension drugs easier on labor and delivery units with the help of close-by dedicated medicine boxes, and standardized protocols and order sets across Avera. “We try to make the right thing the easy thing to do,” Dr. McKay said.

Dr. Espey is an editorial adviser for Ob.Gyn. News. The physicians have no relevant financial disclosures.

[email protected]

“Anytime you have a maternal death, it sticks with you for life,” said Elliott Main, MD, a maternal fetal medicine specialist at Stanford (Calif.) University and one of the nation’s leaders in combating maternal mortality.

Courtesy Dr. Elliott Main

Dr. Main has had two maternal deaths in his career, years ago. One woman had a fatal stroke because of severe hypertension, and another died of cardiac complications. “We tried to do everything we possibly could, but you scrounge your memory for years and years [afterward]. To have a young healthy person go into labor and delivery and not come out is a tragedy at all levels. It charged me to not ever want to see that happen again,” he said.

Today, Dr. Main is the medical director of the California Maternal Quality Care Collaborative (CMQCC), a wide-ranging group of clinicians, state officials, hospitals, and others who have come together to address the issue. About 30 states have similar perinatal quality collaboratives (PQCs), and other states are forming them.

They work in collaboration with maternal mortality review committees (MMRCs), state-level groups that review maternal deaths, identify problems to address, and make recommendations to the quality collaboratives on how to prevent maternal deaths.

About 600-800 women die in the United States each year due to pregnancy-related complications, which ranks the United States behind other industrialized nations. Leading causes include hemorrhage and hemorrhagic strokes secondary to hypertension. It’s estimated that the majority of maternal deaths could be prevented with proper care.

To that end, states are enacting safety bundles from the Alliance for Innovation on Maternal Health (AIM), which was established by the American College of Obstetricians and Gynecologist several years ago. There are bundles that address obstetric hypertension, hemorrhage, mental health, venous thromboembolism, opioid use, racial disparities, and other problems. They were developed by experts in the field and published in multiple journals. California and other states have issued toolkits on how to implement them based on local circumstances.

The goal is to standardize best practices nationwide to prevent maternal morbidity and mortality, Dr. Main said.

AIM bundle implementation is “what’s happening in New Mexico and a lot of states, mostly through the efforts of state level quality care collaboratives. Some [states] are further ahead than others,” said Eve Espey, MD, professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, and president of the New Mexico PQC.

“Most states now have a [MMRC] that collects maternal mortality and near-miss data. Those data are used by the action arm,” which is the PQC. “If the review committee says” opioid use disorder is a significant contributor “like in our state, the collaborative rolls out the opioid use disorder bundle,” she said.

Beginning next January, the Joint Commission, formerly known as the Joint Commission on Accreditation of Healthcare Organizations, will require that accredited hospitals enact key elements of the AIM bundles for both obstetric hemorrhage and severe hypertension. “Everyone’s [now] motivated to get on that bandwagon,” Dr. Espey said.

“The bundles are here to stay,” and the Joint Commission requirements are “a really important step for sustainability and basic implementation. We really want to get them adopted everywhere,” said Dr. Main, who is also the national implementation director for the AIM initiative.

“The key thing is to work on implementing the hemorrhage and hypertension bundles in your hospital. I would suggest contacting [your] state” PQC, he said.

The California model

California, which has been working to reduce maternal mortality and morbidity since the mid 2000s, has produced among the strongest evidence to date that the efforts make a difference.

By 2013, the state had halved its maternal mortality rate to a 3-year average of 7 deaths per 100,000 live births, which is comparable with the average Western Europe rate of 7.2 deaths. Nationwide, the rate was about 17.4 deaths per 100,000 live births in 2018, according to the Centers for Disease Control and Prevention

The reasons are multifactorial, but “we think” the quality improvement efforts have been “an important contributor,” Dr. Main said.
 

Improvements especially for Black women

Among the success stories has been California’s implementation of the AIM obstetric hemorrhage bundle about 5 years ago. Among other steps, the 17 evidence-based recommendations included early recognition, immediate access to oxytocin and other medications, immediate access to a hemorrhage cart with instructions for intrauterine balloons and compression stitches, the establishment of a hemorrhage response protocol and team, and regular unit-based drills with debriefing sessions afterward.

Mentoring teams consisting of a physician and nurse with maternal quality improvement experience were created to help hospitals come on board, with each team working with five to eight hospitals. Efforts included monthly telephone calls and face-to-face meetings, and providers were held accountable for progress. Hospitals shared data and tips on implementation, under the aegis of the CMQCC.

When the baseline period of 2011-2014 to the postintervention period of October 2015 to December 2016 were compared, the rate of severe maternal morbidity from hemorrhage fell from 22.1% to 18.5% across 99 hospitals and 73,476 women.

The benefit among Black women exceeded that among White women, with a 9% absolute rate reduction versus 2.1%. “If you adjusted for risk factors, [we found] you could eliminate [racial differences] completely,” which is something that hadn’t been shown before. “This is a really big deal,” Dr. Main said, because the risk of maternal morbidity and mortality is three to four times higher among Black women, compared with White women.

Dr. Main and his team found that the biggest clinical risk factor that accounted for racial differences was a higher rate of cesarean deliveries among Black women, followed by higher rates of anemia at hospital admission. “If you have a C-section when you are anemic, you are going to have a transfusion,” he explained.

More recently, there’s been a push in California to reduce the rate of primary cesarean deliveries by enacting the associated AIM bundle with use of the same approach as with the hemorrhage bundle. Dr. Main and his team recently reported a rate reduction from 29.3% to 25% without compromising birth outcomes.

However, “some changes are easier than others. Hemorrhage was an easy one to change because it didn’t deal with physician autonomy as much, and you saw more immediate results” with fewer hemorrhages. Reducing cesarean delivery rates is “a bigger lift” because “it’s really changing the culture of labor and delivery. It involves more group pressure and more reinforcing, but we were able to do that,” he said.
 

Problems in the Show Me State

“We’ve patterned a lot” of what’s being done in New Mexico “after California,” Dr. Espey said.

The AIM hemorrhage bundle, for instance, is being rolled out to New Mexico hospitals, with the help of virtual meetings and mentoring programs, plus outreach to the Navajo and others reservations because, as with Black women, rates of maternal morbidity and mortality are higher among Native American women.

It’s been tougher going, however, in states such as Missouri, which recently ranked 44th in the country for maternal mortality.

“We started a little bit late, and we are a little bit behind,” said ob.gyn. Karen L. Florio, DO, at the University of Missouri–Kansas City and also a leader of the state MMRC and member of its PQC.

The main problem is money. California’s efforts are funded by the Centers for Disease Control and Prevention, the state health department, and hospitals, among others.

But Missouri is “not as well funded as California for our mortality review board, and our [PQC] is mostly not funded. If we could get that funding, we would have more resources to implement these AIM bundles,” she said.

In addition to the issue, Missouri didn’t expand Medicaid under the Accountable Care Act – something that’s been linked to reduced maternal morbidity and mortality – and there are entire rural areas with no maternity care. Plus after generations of mistreatment, “our African American population has a valid distrust of the medical system that contributes to maternal mortality,” she said.

Obesity-related heart disease is also prevalent in Missouri, even among young people. “I cannot tell you how many women I have had who have had a heart attack at the age of 30 and who have had stents placed,” Dr. Florio said.

Dr. Florio and her colleagues are currently using teleconferences and other means to roll out the AIM hypertension bundle but can do so only selectively. “We don’t have the resources to reach every single rural hospital all over the state,” she said; they are working to address the funding issues.
 

For rural hospitals, implementation is “daunting”

Meanwhile, rural hospitals have been a particular concern in South Dakota, said Kimberlee McKay, MD, an ob.gyn. who is the clinical vice president of the ob.gyn. service line at Avera Health, a hospital system based in Sioux Falls, S.D.

She’s been overseeing Avera’s implementation of the hypertension, hemorrhage, and venous thromboembolism bundles. “What’s hard is that” the AIM protocols come “out of academic centers. Implementation of complex algorithms is daunting” for hospitals that only do a couple hundred deliveries a year, she said.

For small hospitals, the approach she’s found that works is to first assess what they can offer, and then have them “do what’s reasonable” for their resources. The second part is making sure high-risk women get to a regional center – with an adequate blood supply, in the case of hemorrhage, for instance – for complications. Dr. McKay and colleagues are working on a system by which regional centers can monitor smaller hospitals for potential maternity problems, and contact them proactively before they emerge.

They’ve also made access to hemorrhage and hypertension drugs easier on labor and delivery units with the help of close-by dedicated medicine boxes, and standardized protocols and order sets across Avera. “We try to make the right thing the easy thing to do,” Dr. McKay said.

Dr. Espey is an editorial adviser for Ob.Gyn. News. The physicians have no relevant financial disclosures.

[email protected]

“Anytime you have a maternal death, it sticks with you for life,” said Elliott Main, MD, a maternal fetal medicine specialist at Stanford (Calif.) University and one of the nation’s leaders in combating maternal mortality.

Courtesy Dr. Elliott Main

Dr. Main has had two maternal deaths in his career, years ago. One woman had a fatal stroke because of severe hypertension, and another died of cardiac complications. “We tried to do everything we possibly could, but you scrounge your memory for years and years [afterward]. To have a young healthy person go into labor and delivery and not come out is a tragedy at all levels. It charged me to not ever want to see that happen again,” he said.

Today, Dr. Main is the medical director of the California Maternal Quality Care Collaborative (CMQCC), a wide-ranging group of clinicians, state officials, hospitals, and others who have come together to address the issue. About 30 states have similar perinatal quality collaboratives (PQCs), and other states are forming them.

They work in collaboration with maternal mortality review committees (MMRCs), state-level groups that review maternal deaths, identify problems to address, and make recommendations to the quality collaboratives on how to prevent maternal deaths.

About 600-800 women die in the United States each year due to pregnancy-related complications, which ranks the United States behind other industrialized nations. Leading causes include hemorrhage and hemorrhagic strokes secondary to hypertension. It’s estimated that the majority of maternal deaths could be prevented with proper care.

To that end, states are enacting safety bundles from the Alliance for Innovation on Maternal Health (AIM), which was established by the American College of Obstetricians and Gynecologist several years ago. There are bundles that address obstetric hypertension, hemorrhage, mental health, venous thromboembolism, opioid use, racial disparities, and other problems. They were developed by experts in the field and published in multiple journals. California and other states have issued toolkits on how to implement them based on local circumstances.

The goal is to standardize best practices nationwide to prevent maternal morbidity and mortality, Dr. Main said.

AIM bundle implementation is “what’s happening in New Mexico and a lot of states, mostly through the efforts of state level quality care collaboratives. Some [states] are further ahead than others,” said Eve Espey, MD, professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, and president of the New Mexico PQC.

“Most states now have a [MMRC] that collects maternal mortality and near-miss data. Those data are used by the action arm,” which is the PQC. “If the review committee says” opioid use disorder is a significant contributor “like in our state, the collaborative rolls out the opioid use disorder bundle,” she said.

Beginning next January, the Joint Commission, formerly known as the Joint Commission on Accreditation of Healthcare Organizations, will require that accredited hospitals enact key elements of the AIM bundles for both obstetric hemorrhage and severe hypertension. “Everyone’s [now] motivated to get on that bandwagon,” Dr. Espey said.

“The bundles are here to stay,” and the Joint Commission requirements are “a really important step for sustainability and basic implementation. We really want to get them adopted everywhere,” said Dr. Main, who is also the national implementation director for the AIM initiative.

“The key thing is to work on implementing the hemorrhage and hypertension bundles in your hospital. I would suggest contacting [your] state” PQC, he said.

The California model

California, which has been working to reduce maternal mortality and morbidity since the mid 2000s, has produced among the strongest evidence to date that the efforts make a difference.

By 2013, the state had halved its maternal mortality rate to a 3-year average of 7 deaths per 100,000 live births, which is comparable with the average Western Europe rate of 7.2 deaths. Nationwide, the rate was about 17.4 deaths per 100,000 live births in 2018, according to the Centers for Disease Control and Prevention

The reasons are multifactorial, but “we think” the quality improvement efforts have been “an important contributor,” Dr. Main said.
 

Improvements especially for Black women

Among the success stories has been California’s implementation of the AIM obstetric hemorrhage bundle about 5 years ago. Among other steps, the 17 evidence-based recommendations included early recognition, immediate access to oxytocin and other medications, immediate access to a hemorrhage cart with instructions for intrauterine balloons and compression stitches, the establishment of a hemorrhage response protocol and team, and regular unit-based drills with debriefing sessions afterward.

Mentoring teams consisting of a physician and nurse with maternal quality improvement experience were created to help hospitals come on board, with each team working with five to eight hospitals. Efforts included monthly telephone calls and face-to-face meetings, and providers were held accountable for progress. Hospitals shared data and tips on implementation, under the aegis of the CMQCC.

When the baseline period of 2011-2014 to the postintervention period of October 2015 to December 2016 were compared, the rate of severe maternal morbidity from hemorrhage fell from 22.1% to 18.5% across 99 hospitals and 73,476 women.

The benefit among Black women exceeded that among White women, with a 9% absolute rate reduction versus 2.1%. “If you adjusted for risk factors, [we found] you could eliminate [racial differences] completely,” which is something that hadn’t been shown before. “This is a really big deal,” Dr. Main said, because the risk of maternal morbidity and mortality is three to four times higher among Black women, compared with White women.

Dr. Main and his team found that the biggest clinical risk factor that accounted for racial differences was a higher rate of cesarean deliveries among Black women, followed by higher rates of anemia at hospital admission. “If you have a C-section when you are anemic, you are going to have a transfusion,” he explained.

More recently, there’s been a push in California to reduce the rate of primary cesarean deliveries by enacting the associated AIM bundle with use of the same approach as with the hemorrhage bundle. Dr. Main and his team recently reported a rate reduction from 29.3% to 25% without compromising birth outcomes.

However, “some changes are easier than others. Hemorrhage was an easy one to change because it didn’t deal with physician autonomy as much, and you saw more immediate results” with fewer hemorrhages. Reducing cesarean delivery rates is “a bigger lift” because “it’s really changing the culture of labor and delivery. It involves more group pressure and more reinforcing, but we were able to do that,” he said.
 

Problems in the Show Me State

“We’ve patterned a lot” of what’s being done in New Mexico “after California,” Dr. Espey said.

The AIM hemorrhage bundle, for instance, is being rolled out to New Mexico hospitals, with the help of virtual meetings and mentoring programs, plus outreach to the Navajo and others reservations because, as with Black women, rates of maternal morbidity and mortality are higher among Native American women.

It’s been tougher going, however, in states such as Missouri, which recently ranked 44th in the country for maternal mortality.

“We started a little bit late, and we are a little bit behind,” said ob.gyn. Karen L. Florio, DO, at the University of Missouri–Kansas City and also a leader of the state MMRC and member of its PQC.

The main problem is money. California’s efforts are funded by the Centers for Disease Control and Prevention, the state health department, and hospitals, among others.

But Missouri is “not as well funded as California for our mortality review board, and our [PQC] is mostly not funded. If we could get that funding, we would have more resources to implement these AIM bundles,” she said.

In addition to the issue, Missouri didn’t expand Medicaid under the Accountable Care Act – something that’s been linked to reduced maternal morbidity and mortality – and there are entire rural areas with no maternity care. Plus after generations of mistreatment, “our African American population has a valid distrust of the medical system that contributes to maternal mortality,” she said.

Obesity-related heart disease is also prevalent in Missouri, even among young people. “I cannot tell you how many women I have had who have had a heart attack at the age of 30 and who have had stents placed,” Dr. Florio said.

Dr. Florio and her colleagues are currently using teleconferences and other means to roll out the AIM hypertension bundle but can do so only selectively. “We don’t have the resources to reach every single rural hospital all over the state,” she said; they are working to address the funding issues.
 

For rural hospitals, implementation is “daunting”

Meanwhile, rural hospitals have been a particular concern in South Dakota, said Kimberlee McKay, MD, an ob.gyn. who is the clinical vice president of the ob.gyn. service line at Avera Health, a hospital system based in Sioux Falls, S.D.

She’s been overseeing Avera’s implementation of the hypertension, hemorrhage, and venous thromboembolism bundles. “What’s hard is that” the AIM protocols come “out of academic centers. Implementation of complex algorithms is daunting” for hospitals that only do a couple hundred deliveries a year, she said.

For small hospitals, the approach she’s found that works is to first assess what they can offer, and then have them “do what’s reasonable” for their resources. The second part is making sure high-risk women get to a regional center – with an adequate blood supply, in the case of hemorrhage, for instance – for complications. Dr. McKay and colleagues are working on a system by which regional centers can monitor smaller hospitals for potential maternity problems, and contact them proactively before they emerge.

They’ve also made access to hemorrhage and hypertension drugs easier on labor and delivery units with the help of close-by dedicated medicine boxes, and standardized protocols and order sets across Avera. “We try to make the right thing the easy thing to do,” Dr. McKay said.

Dr. Espey is an editorial adviser for Ob.Gyn. News. The physicians have no relevant financial disclosures.

[email protected]

A study has found that 7 days of treatment with tamoxifen can help treat troublesome bleeding in women who are using an etonogestrel implant for birth control.

“Our data support the use of tamoxifen as an effective option that offers the benefit of a shorter duration of treatment than other approaches such as combined oral contraceptives,” wrote Alison B. Edelman, MD, MPH, of Oregon Health & Science University, Portland, and coauthors. The report is in Obstetrics & Gynecology.

To determine if a short course of tamoxifen – typically used to treat breast cancer – could prove beneficial in reducing bothersome bleeding, the researchers launched a 90-day, double-blind randomized trial of women between the ages of 15 and 45 years who had been using the etonogestrel 68-mg subdermal contraceptive implant for at least 30 days. All participants suffered from frequent or prolonged bleeding or spotting during the previous month; their mean age was 24, and most (n = 62) identified as White.

Of the initial 112 participants, 107 began treatment and were split into two groups: 10 mg of tamoxifen twice a day for 7 days (n = 55) or placebo (n = 52). One hundred and four patients completed treatment one, and 88 completed 90 days. After the first treatment, women in the tamoxifen group experienced 9.8 more consecutive days of amenorrhea (95% confidence interval, 4.6-15.0) compared with the placebo group, as well as more total days of no bleeding in the first 90 days (median 73.5 [24-89] versus 68 [11-81], P = .001).

Afterward, both groups underwent a 90-day, open-label study where all participants took tamoxifen. The differences between the groups mostly disappeared, as they both experienced more amenorrhea days (median 56 [6-81] for tamoxifen and 67.5 [7-83] for placebo) and fewer bleeding days (median 12 [0-63] for tamoxifen and 12 [0-82] for placebo) compared with the placebo group during the initial 90 days. Although no serious adverse events occurred, more women taking tamoxifen reported fluid retention (12 versus 1), headache (19 versus 1), and mood changes (13 versus 2).

“This is a very promising drug for this purpose,” Catherine Cansino, MD, MPH, of the University of California, Davis, said in an interview, adding that it is “a bit unconventional because tamoxifen is traditionally used for cancer or precancer.”

As such, she recognized that young people of reproductive age might be a little wary of the drug. That said, having an effective treatment for troublesome bleeding beyond estrogen-based products should ultimately prove beneficial for clinicians and patients alike.

“Unfortunately, we don’t have long-term data so it’s unclear what the safety outcomes are,” she said, “but having another option to address bothersome bleeding can help women stay on birth control longer. The alternative would be pregnancy, with its own associated risks.”

The authors acknowledged their study’s limitations, including a lack of Black patients and the likelihood that their volunteer cohort “may not reflect the general population of implant users who present for discontinuation owing to bleeding problems.” They also enrolled a small but notable number of women who had been using the implant for less than 3 months, noting that bleeding patterns often change from the first 90 days and so “some of these women would likely experience better (or worse) bleeding irrespective of treatment.”

The study was supported by a Merck Women’s Health Investigator Initiated Studies Program and the Oregon Clinical and Translational Research Institute. Four of the authors acknowledged receiving consulting fees and research support from various organizations and pharmaceutical companies. The remaining three had no relevant financial disclosures. Dr. Cansino is a member of the Ob.Gyn. News editorial advisory board. She said she had no relevant financial disclosures.

SOURCE: Edelman AB et al. Obstet Gynecol. 2020 Jul 9. doi: 10.1097/AOG.0000000000003896.

A study has found that 7 days of treatment with tamoxifen can help treat troublesome bleeding in women who are using an etonogestrel implant for birth control.

“Our data support the use of tamoxifen as an effective option that offers the benefit of a shorter duration of treatment than other approaches such as combined oral contraceptives,” wrote Alison B. Edelman, MD, MPH, of Oregon Health & Science University, Portland, and coauthors. The report is in Obstetrics & Gynecology.

To determine if a short course of tamoxifen – typically used to treat breast cancer – could prove beneficial in reducing bothersome bleeding, the researchers launched a 90-day, double-blind randomized trial of women between the ages of 15 and 45 years who had been using the etonogestrel 68-mg subdermal contraceptive implant for at least 30 days. All participants suffered from frequent or prolonged bleeding or spotting during the previous month; their mean age was 24, and most (n = 62) identified as White.

Of the initial 112 participants, 107 began treatment and were split into two groups: 10 mg of tamoxifen twice a day for 7 days (n = 55) or placebo (n = 52). One hundred and four patients completed treatment one, and 88 completed 90 days. After the first treatment, women in the tamoxifen group experienced 9.8 more consecutive days of amenorrhea (95% confidence interval, 4.6-15.0) compared with the placebo group, as well as more total days of no bleeding in the first 90 days (median 73.5 [24-89] versus 68 [11-81], P = .001).

Afterward, both groups underwent a 90-day, open-label study where all participants took tamoxifen. The differences between the groups mostly disappeared, as they both experienced more amenorrhea days (median 56 [6-81] for tamoxifen and 67.5 [7-83] for placebo) and fewer bleeding days (median 12 [0-63] for tamoxifen and 12 [0-82] for placebo) compared with the placebo group during the initial 90 days. Although no serious adverse events occurred, more women taking tamoxifen reported fluid retention (12 versus 1), headache (19 versus 1), and mood changes (13 versus 2).

“This is a very promising drug for this purpose,” Catherine Cansino, MD, MPH, of the University of California, Davis, said in an interview, adding that it is “a bit unconventional because tamoxifen is traditionally used for cancer or precancer.”

As such, she recognized that young people of reproductive age might be a little wary of the drug. That said, having an effective treatment for troublesome bleeding beyond estrogen-based products should ultimately prove beneficial for clinicians and patients alike.

“Unfortunately, we don’t have long-term data so it’s unclear what the safety outcomes are,” she said, “but having another option to address bothersome bleeding can help women stay on birth control longer. The alternative would be pregnancy, with its own associated risks.”

The authors acknowledged their study’s limitations, including a lack of Black patients and the likelihood that their volunteer cohort “may not reflect the general population of implant users who present for discontinuation owing to bleeding problems.” They also enrolled a small but notable number of women who had been using the implant for less than 3 months, noting that bleeding patterns often change from the first 90 days and so “some of these women would likely experience better (or worse) bleeding irrespective of treatment.”

The study was supported by a Merck Women’s Health Investigator Initiated Studies Program and the Oregon Clinical and Translational Research Institute. Four of the authors acknowledged receiving consulting fees and research support from various organizations and pharmaceutical companies. The remaining three had no relevant financial disclosures. Dr. Cansino is a member of the Ob.Gyn. News editorial advisory board. She said she had no relevant financial disclosures.

SOURCE: Edelman AB et al. Obstet Gynecol. 2020 Jul 9. doi: 10.1097/AOG.0000000000003896.

A study has found that 7 days of treatment with tamoxifen can help treat troublesome bleeding in women who are using an etonogestrel implant for birth control.

“Our data support the use of tamoxifen as an effective option that offers the benefit of a shorter duration of treatment than other approaches such as combined oral contraceptives,” wrote Alison B. Edelman, MD, MPH, of Oregon Health & Science University, Portland, and coauthors. The report is in Obstetrics & Gynecology.

To determine if a short course of tamoxifen – typically used to treat breast cancer – could prove beneficial in reducing bothersome bleeding, the researchers launched a 90-day, double-blind randomized trial of women between the ages of 15 and 45 years who had been using the etonogestrel 68-mg subdermal contraceptive implant for at least 30 days. All participants suffered from frequent or prolonged bleeding or spotting during the previous month; their mean age was 24, and most (n = 62) identified as White.

Of the initial 112 participants, 107 began treatment and were split into two groups: 10 mg of tamoxifen twice a day for 7 days (n = 55) or placebo (n = 52). One hundred and four patients completed treatment one, and 88 completed 90 days. After the first treatment, women in the tamoxifen group experienced 9.8 more consecutive days of amenorrhea (95% confidence interval, 4.6-15.0) compared with the placebo group, as well as more total days of no bleeding in the first 90 days (median 73.5 [24-89] versus 68 [11-81], P = .001).

Afterward, both groups underwent a 90-day, open-label study where all participants took tamoxifen. The differences between the groups mostly disappeared, as they both experienced more amenorrhea days (median 56 [6-81] for tamoxifen and 67.5 [7-83] for placebo) and fewer bleeding days (median 12 [0-63] for tamoxifen and 12 [0-82] for placebo) compared with the placebo group during the initial 90 days. Although no serious adverse events occurred, more women taking tamoxifen reported fluid retention (12 versus 1), headache (19 versus 1), and mood changes (13 versus 2).

“This is a very promising drug for this purpose,” Catherine Cansino, MD, MPH, of the University of California, Davis, said in an interview, adding that it is “a bit unconventional because tamoxifen is traditionally used for cancer or precancer.”

As such, she recognized that young people of reproductive age might be a little wary of the drug. That said, having an effective treatment for troublesome bleeding beyond estrogen-based products should ultimately prove beneficial for clinicians and patients alike.

“Unfortunately, we don’t have long-term data so it’s unclear what the safety outcomes are,” she said, “but having another option to address bothersome bleeding can help women stay on birth control longer. The alternative would be pregnancy, with its own associated risks.”

The authors acknowledged their study’s limitations, including a lack of Black patients and the likelihood that their volunteer cohort “may not reflect the general population of implant users who present for discontinuation owing to bleeding problems.” They also enrolled a small but notable number of women who had been using the implant for less than 3 months, noting that bleeding patterns often change from the first 90 days and so “some of these women would likely experience better (or worse) bleeding irrespective of treatment.”

The study was supported by a Merck Women’s Health Investigator Initiated Studies Program and the Oregon Clinical and Translational Research Institute. Four of the authors acknowledged receiving consulting fees and research support from various organizations and pharmaceutical companies. The remaining three had no relevant financial disclosures. Dr. Cansino is a member of the Ob.Gyn. News editorial advisory board. She said she had no relevant financial disclosures.

SOURCE: Edelman AB et al. Obstet Gynecol. 2020 Jul 9. doi: 10.1097/AOG.0000000000003896.

Use of the 2019 EULAR/ACR criteria for systemic lupus erythematosus identified an additional 17% of lupus patients in a cohort of 133 women with undifferentiated connective tissue disease.

Several studies have applied the 2019 EULAR/ACR criteria for systemic lupus erythematosus (SLE) to different patient populations, wrote Massimo Radin, MD, of S. Giovanni Bosco Hospital, Turin, Italy, and colleagues.

“However, it is unknown if the new classifications criteria for SLE might impact on the categorization of patients previously diagnosed with undifferentiated connective tissue disease (UCTD),” they said in a brief report published in Arthritis Care & Research.

In addition, “being classified or not as having SLE may pose clinical and logistic consequences, as patients with a diagnosis of ‘SLE’ might be followed up according to a specific local protocol and have in-label access to certain medications (such as biologics) or may be eligible for the participation in clinical trials,” they wrote.

The investigators applied the 2019 EULAR/ACR criteria to a cohort of 133 women with UCTD but no other diagnosis. The average age of the women was 38 years; the average disease duration was 10 years. Patients who scored 10 points or more on positive clinical and immunological domains at the start of the study were classified as SLE under the 2019 EULAR/ACR criteria.

Overall, 22 patients (17%) met the classification criteria for SLE at the time of their first pregnancy.

Compared with the other patients in the cohort who were not classified as SLE, patients classified as SLE under the 2019 EULAR/ACR criteria had significantly higher frequency of mucocutaneous manifestations (5% vs. 23%), arthritis (17% vs. 59%), isolated urine abnormalities (1% vs. 18%), and highly specific antibodies (15% vs. 50%).

In addition, patients who met the 2019 EULAR/ACR SLE criteria were significantly more likely to meet the ACR 1997 and SLICC criteria after an average follow-up of 9 years compared with the rest of the cohort (18.2% vs. 1.8%). Patients who met the 2019 EULAR/ACR criteria also had significantly shorter disease duration than that of the other patients in the UCTD cohort (8.23 years vs. 10.7 years) and were significantly more likely to develop preeclampsia during pregnancy (18% vs. 0%).

The findings were limited by several factors including the retrospective design of the study and possible lack of generalizability to male patients, the researchers noted.

The results support the need for improved classification criteria for UCTD, as early identification of specific conditions can help guide treatment and reduce the risk of more severe symptoms and complications, the authors said.

“When discriminating between conditions with a marked overlap, such as SLE and UCTD, the proposal of new classification criteria should balance specificity and sensitivity,” the researchers wrote. “When developing new classification criteria, one approach is to select patients and the control groups as representative as possible of the settings (the medical practices) in which these criteria will be used.”

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Radin M et al. Arthritis Care Res. 2020 Jul 23. doi: 10.1002/ACR.24391.

Use of the 2019 EULAR/ACR criteria for systemic lupus erythematosus identified an additional 17% of lupus patients in a cohort of 133 women with undifferentiated connective tissue disease.

Several studies have applied the 2019 EULAR/ACR criteria for systemic lupus erythematosus (SLE) to different patient populations, wrote Massimo Radin, MD, of S. Giovanni Bosco Hospital, Turin, Italy, and colleagues.

“However, it is unknown if the new classifications criteria for SLE might impact on the categorization of patients previously diagnosed with undifferentiated connective tissue disease (UCTD),” they said in a brief report published in Arthritis Care & Research.

In addition, “being classified or not as having SLE may pose clinical and logistic consequences, as patients with a diagnosis of ‘SLE’ might be followed up according to a specific local protocol and have in-label access to certain medications (such as biologics) or may be eligible for the participation in clinical trials,” they wrote.

The investigators applied the 2019 EULAR/ACR criteria to a cohort of 133 women with UCTD but no other diagnosis. The average age of the women was 38 years; the average disease duration was 10 years. Patients who scored 10 points or more on positive clinical and immunological domains at the start of the study were classified as SLE under the 2019 EULAR/ACR criteria.

Overall, 22 patients (17%) met the classification criteria for SLE at the time of their first pregnancy.

Compared with the other patients in the cohort who were not classified as SLE, patients classified as SLE under the 2019 EULAR/ACR criteria had significantly higher frequency of mucocutaneous manifestations (5% vs. 23%), arthritis (17% vs. 59%), isolated urine abnormalities (1% vs. 18%), and highly specific antibodies (15% vs. 50%).

In addition, patients who met the 2019 EULAR/ACR SLE criteria were significantly more likely to meet the ACR 1997 and SLICC criteria after an average follow-up of 9 years compared with the rest of the cohort (18.2% vs. 1.8%). Patients who met the 2019 EULAR/ACR criteria also had significantly shorter disease duration than that of the other patients in the UCTD cohort (8.23 years vs. 10.7 years) and were significantly more likely to develop preeclampsia during pregnancy (18% vs. 0%).

The findings were limited by several factors including the retrospective design of the study and possible lack of generalizability to male patients, the researchers noted.

The results support the need for improved classification criteria for UCTD, as early identification of specific conditions can help guide treatment and reduce the risk of more severe symptoms and complications, the authors said.

“When discriminating between conditions with a marked overlap, such as SLE and UCTD, the proposal of new classification criteria should balance specificity and sensitivity,” the researchers wrote. “When developing new classification criteria, one approach is to select patients and the control groups as representative as possible of the settings (the medical practices) in which these criteria will be used.”

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Radin M et al. Arthritis Care Res. 2020 Jul 23. doi: 10.1002/ACR.24391.

Use of the 2019 EULAR/ACR criteria for systemic lupus erythematosus identified an additional 17% of lupus patients in a cohort of 133 women with undifferentiated connective tissue disease.

Several studies have applied the 2019 EULAR/ACR criteria for systemic lupus erythematosus (SLE) to different patient populations, wrote Massimo Radin, MD, of S. Giovanni Bosco Hospital, Turin, Italy, and colleagues.

“However, it is unknown if the new classifications criteria for SLE might impact on the categorization of patients previously diagnosed with undifferentiated connective tissue disease (UCTD),” they said in a brief report published in Arthritis Care & Research.

In addition, “being classified or not as having SLE may pose clinical and logistic consequences, as patients with a diagnosis of ‘SLE’ might be followed up according to a specific local protocol and have in-label access to certain medications (such as biologics) or may be eligible for the participation in clinical trials,” they wrote.

The investigators applied the 2019 EULAR/ACR criteria to a cohort of 133 women with UCTD but no other diagnosis. The average age of the women was 38 years; the average disease duration was 10 years. Patients who scored 10 points or more on positive clinical and immunological domains at the start of the study were classified as SLE under the 2019 EULAR/ACR criteria.

Overall, 22 patients (17%) met the classification criteria for SLE at the time of their first pregnancy.

Compared with the other patients in the cohort who were not classified as SLE, patients classified as SLE under the 2019 EULAR/ACR criteria had significantly higher frequency of mucocutaneous manifestations (5% vs. 23%), arthritis (17% vs. 59%), isolated urine abnormalities (1% vs. 18%), and highly specific antibodies (15% vs. 50%).

In addition, patients who met the 2019 EULAR/ACR SLE criteria were significantly more likely to meet the ACR 1997 and SLICC criteria after an average follow-up of 9 years compared with the rest of the cohort (18.2% vs. 1.8%). Patients who met the 2019 EULAR/ACR criteria also had significantly shorter disease duration than that of the other patients in the UCTD cohort (8.23 years vs. 10.7 years) and were significantly more likely to develop preeclampsia during pregnancy (18% vs. 0%).

The findings were limited by several factors including the retrospective design of the study and possible lack of generalizability to male patients, the researchers noted.

The results support the need for improved classification criteria for UCTD, as early identification of specific conditions can help guide treatment and reduce the risk of more severe symptoms and complications, the authors said.

“When discriminating between conditions with a marked overlap, such as SLE and UCTD, the proposal of new classification criteria should balance specificity and sensitivity,” the researchers wrote. “When developing new classification criteria, one approach is to select patients and the control groups as representative as possible of the settings (the medical practices) in which these criteria will be used.”

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Radin M et al. Arthritis Care Res. 2020 Jul 23. doi: 10.1002/ACR.24391.

Vulvar intraepithelial neoplasia (VIN) is a distressing condition that may require painful and disfiguring treatments. It is particularly problematic because more than a quarter of patients will experience recurrence of their disease after primary therapy. In this column we will explore the risk factors for recurrence, recommendations for early detection, and options to minimize its incidence.

VIN was traditionally characterized in three stages (I, II, III). However, as it became better understood that the previously named VIN I was not, in fact, a precursor for malignancy, but rather a benign manifestation of low-risk human papillomavirus (HPV) infection, it was removed from consideration as VIN. Furthermore, our understanding of VIN grew to recognize that there were two developmental pathways to vulvar neoplasia and malignancy. The first was via high-risk HPV infection, often with tobacco exposure as an accelerating factor, and typically among younger women. This has been named “usual type VIN” (uVIN). The second arises in the background of lichen sclerosus in older women and is named “differentiated type VIN” (dVIN). This type carries with it a higher risk for progression to cancer, coexisting in approximately 80% of cases of invasive squamous cell carcinoma. In addition, the progression to cancer appears to occur more quickly for dVIN lesions (22 months compared with 41 months in uVIN).¹

While observation of VIN can be considered for young, asymptomatic women, it is not universally recommended because the risk of progression to cancer is approximately 8% (5% for uVIN and 33% for dVIN).^1,2 Both subtypes of VIN can be treated with similar interventions including surgical excision (typically a wide local excision), ablative therapies (such as CO₂ laser) or topical medical therapy such as imiquimod or 5-fluorouracil. Excisional surgery remains the mainstay of therapy for VIN because it provides clinicians with certainty regarding the possibility of occult invasive disease (false-negative biopsies), and adequacy of margin status. However, given the proximity of this disease to vital structures such as the clitoris, urethral meatus, and anal verge, as well as issues with wound healing, and difficulty with reapproximation of vulvar tissues – particularly when large or multifocal disease is present – sometimes multimodal treatments or medical therapies are preferred to spare disfigurement or sexual, bladder, or bowel dysfunction.

Excision of VIN need not be deeper than the epidermis, although including a limited degree of dermis protects against incomplete resection of occult, coexisting early invasive disease. However, wide margins should ideally be at least 10 mm. This can prove to be a challenging goal for multiple reasons. First, while there are visual stigmata of VIN, its true extent can be determined only microscopically. In addition, the disease may be multifocal. Furthermore, particularly where it encroaches upon the anus, clitoris, or urethral meatus, resection margins may be limited because of the desire to preserve function of adjacent structures. The application of 2%-5% acetic acid in the operating room prior to marking the planned borders of excision can optimize the likelihood that the incisions will encompass the microscopic extent of VIN. As it does with cervical dysplasia, acetic acid is thought to cause reversible coagulation of nuclear proteins and cytokeratins, which are more abundant in dysplastic lesions, thus appearing white to the surgeon’s eye.

However, even with the surgeon’s best attempts to excise all disease, approximately half of VIN excisions will have positive margins. Fortunately, not all of these patients will go on to develop recurrent dysplasia. In fact, less than half of women with positive margins on excision will develop recurrent VIN disease.² This incomplete incidence of recurrence may be in part due to an ablative effect of inflammation at the cut skin edges. Therefore, provided that there is no macroscopic disease remaining, close observation, rather than immediate reexcision, is recommended.

Positive excisional margins are a major risk factor for recurrence, carrying an eightfold increased risk, and also are associated with a more rapid onset of recurrence than for those with negative margins. Other predisposing risk factors for recurrence include advancing age, coexistence of dysplasia at other lower genital sites (including vaginal and cervical), immunosuppressive conditions or therapies (especially steroid use), HPV exposure, and the presence of lichen sclerosus.² Continued tobacco use is a modifiable risk factor that has been shown to be associated with an increased recurrence risk of VIN. We should take the opportunity in the postoperative and surveillance period to educate our patients regarding the importance of smoking cessation in modifying their risk for recurrent or new disease.

HPV infection may not be a modifiable risk factor, but certainly can be prevented by encouraging the adoption of HPV vaccination.

Topical steroids used to treat lichen sclerosus can improve symptoms of this vulvar dystrophy as well as decrease the incidence of recurrent dVIN and invasive vulvar cancer. Treatment should continue until the skin has normalized its appearance and texture. This may involve chronic long-term therapy.³

Recognizing that more than a quarter of patients will recur, the recommended posttreatment follow-up for VIN is at 6 months, 12 months, and then annually. It should include close inspection of the vulva with consideration of application of topical 2%-5% acetic acid (I typically apply this with a soaked gauze sponge) and vulvar colposcopy (a hand-held magnification glass works well for this purpose). Patients should be counseled regarding their high risk for recurrence, informed of typical symptoms, and encouraged to perform regular vulva self-inspection (with use of a hand mirror).

For patients at the highest risk for recurrence (older patients, patients with positive excisional margins, HPV coinfection, lichen sclerosus, tobacco use, and immunosuppression), I recommend 6 monthly follow-up surveillance for 5 years. Most (75%) of recurrences will occur with the first 43 months after diagnosis with half occurring in the first 18 months.² Patients who have had positive margins on their excisional specimen are at the highest risk for an earlier recurrence.

VIN is an insidious disease with a high recurrence rate. It is challenging to completely resect with negative margins. Patients with a history of VIN should receive close observation in the years following their excision, particularly if resection margins were positive, and clinicians should attempt to modify risk factors wherever possible, paying particularly close attention to older postmenopausal women with a history of lichen sclerosus as progression to malignancy is highest for these women.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no relevant financial disclosures. Email Dr. Rossi at [email protected].

References

1. Pathology. 2016 Jun 1;48(4)291-302.

2. Gynecol Oncol. 2018 Jan;148(1):126-31.

3. JAMA Dermatol. 2015 Oct;151(10):1061-7.

Vulvar intraepithelial neoplasia (VIN) is a distressing condition that may require painful and disfiguring treatments. It is particularly problematic because more than a quarter of patients will experience recurrence of their disease after primary therapy. In this column we will explore the risk factors for recurrence, recommendations for early detection, and options to minimize its incidence.

VIN was traditionally characterized in three stages (I, II, III). However, as it became better understood that the previously named VIN I was not, in fact, a precursor for malignancy, but rather a benign manifestation of low-risk human papillomavirus (HPV) infection, it was removed from consideration as VIN. Furthermore, our understanding of VIN grew to recognize that there were two developmental pathways to vulvar neoplasia and malignancy. The first was via high-risk HPV infection, often with tobacco exposure as an accelerating factor, and typically among younger women. This has been named “usual type VIN” (uVIN). The second arises in the background of lichen sclerosus in older women and is named “differentiated type VIN” (dVIN). This type carries with it a higher risk for progression to cancer, coexisting in approximately 80% of cases of invasive squamous cell carcinoma. In addition, the progression to cancer appears to occur more quickly for dVIN lesions (22 months compared with 41 months in uVIN).¹

While observation of VIN can be considered for young, asymptomatic women, it is not universally recommended because the risk of progression to cancer is approximately 8% (5% for uVIN and 33% for dVIN).^1,2 Both subtypes of VIN can be treated with similar interventions including surgical excision (typically a wide local excision), ablative therapies (such as CO₂ laser) or topical medical therapy such as imiquimod or 5-fluorouracil. Excisional surgery remains the mainstay of therapy for VIN because it provides clinicians with certainty regarding the possibility of occult invasive disease (false-negative biopsies), and adequacy of margin status. However, given the proximity of this disease to vital structures such as the clitoris, urethral meatus, and anal verge, as well as issues with wound healing, and difficulty with reapproximation of vulvar tissues – particularly when large or multifocal disease is present – sometimes multimodal treatments or medical therapies are preferred to spare disfigurement or sexual, bladder, or bowel dysfunction.

Excision of VIN need not be deeper than the epidermis, although including a limited degree of dermis protects against incomplete resection of occult, coexisting early invasive disease. However, wide margins should ideally be at least 10 mm. This can prove to be a challenging goal for multiple reasons. First, while there are visual stigmata of VIN, its true extent can be determined only microscopically. In addition, the disease may be multifocal. Furthermore, particularly where it encroaches upon the anus, clitoris, or urethral meatus, resection margins may be limited because of the desire to preserve function of adjacent structures. The application of 2%-5% acetic acid in the operating room prior to marking the planned borders of excision can optimize the likelihood that the incisions will encompass the microscopic extent of VIN. As it does with cervical dysplasia, acetic acid is thought to cause reversible coagulation of nuclear proteins and cytokeratins, which are more abundant in dysplastic lesions, thus appearing white to the surgeon’s eye.

However, even with the surgeon’s best attempts to excise all disease, approximately half of VIN excisions will have positive margins. Fortunately, not all of these patients will go on to develop recurrent dysplasia. In fact, less than half of women with positive margins on excision will develop recurrent VIN disease.² This incomplete incidence of recurrence may be in part due to an ablative effect of inflammation at the cut skin edges. Therefore, provided that there is no macroscopic disease remaining, close observation, rather than immediate reexcision, is recommended.

Positive excisional margins are a major risk factor for recurrence, carrying an eightfold increased risk, and also are associated with a more rapid onset of recurrence than for those with negative margins. Other predisposing risk factors for recurrence include advancing age, coexistence of dysplasia at other lower genital sites (including vaginal and cervical), immunosuppressive conditions or therapies (especially steroid use), HPV exposure, and the presence of lichen sclerosus.² Continued tobacco use is a modifiable risk factor that has been shown to be associated with an increased recurrence risk of VIN. We should take the opportunity in the postoperative and surveillance period to educate our patients regarding the importance of smoking cessation in modifying their risk for recurrent or new disease.

HPV infection may not be a modifiable risk factor, but certainly can be prevented by encouraging the adoption of HPV vaccination.

Topical steroids used to treat lichen sclerosus can improve symptoms of this vulvar dystrophy as well as decrease the incidence of recurrent dVIN and invasive vulvar cancer. Treatment should continue until the skin has normalized its appearance and texture. This may involve chronic long-term therapy.³

Recognizing that more than a quarter of patients will recur, the recommended posttreatment follow-up for VIN is at 6 months, 12 months, and then annually. It should include close inspection of the vulva with consideration of application of topical 2%-5% acetic acid (I typically apply this with a soaked gauze sponge) and vulvar colposcopy (a hand-held magnification glass works well for this purpose). Patients should be counseled regarding their high risk for recurrence, informed of typical symptoms, and encouraged to perform regular vulva self-inspection (with use of a hand mirror).

For patients at the highest risk for recurrence (older patients, patients with positive excisional margins, HPV coinfection, lichen sclerosus, tobacco use, and immunosuppression), I recommend 6 monthly follow-up surveillance for 5 years. Most (75%) of recurrences will occur with the first 43 months after diagnosis with half occurring in the first 18 months.² Patients who have had positive margins on their excisional specimen are at the highest risk for an earlier recurrence.

VIN is an insidious disease with a high recurrence rate. It is challenging to completely resect with negative margins. Patients with a history of VIN should receive close observation in the years following their excision, particularly if resection margins were positive, and clinicians should attempt to modify risk factors wherever possible, paying particularly close attention to older postmenopausal women with a history of lichen sclerosus as progression to malignancy is highest for these women.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no relevant financial disclosures. Email Dr. Rossi at [email protected].

References

1. Pathology. 2016 Jun 1;48(4)291-302.

2. Gynecol Oncol. 2018 Jan;148(1):126-31.

3. JAMA Dermatol. 2015 Oct;151(10):1061-7.

Vulvar intraepithelial neoplasia (VIN) is a distressing condition that may require painful and disfiguring treatments. It is particularly problematic because more than a quarter of patients will experience recurrence of their disease after primary therapy. In this column we will explore the risk factors for recurrence, recommendations for early detection, and options to minimize its incidence.

VIN was traditionally characterized in three stages (I, II, III). However, as it became better understood that the previously named VIN I was not, in fact, a precursor for malignancy, but rather a benign manifestation of low-risk human papillomavirus (HPV) infection, it was removed from consideration as VIN. Furthermore, our understanding of VIN grew to recognize that there were two developmental pathways to vulvar neoplasia and malignancy. The first was via high-risk HPV infection, often with tobacco exposure as an accelerating factor, and typically among younger women. This has been named “usual type VIN” (uVIN). The second arises in the background of lichen sclerosus in older women and is named “differentiated type VIN” (dVIN). This type carries with it a higher risk for progression to cancer, coexisting in approximately 80% of cases of invasive squamous cell carcinoma. In addition, the progression to cancer appears to occur more quickly for dVIN lesions (22 months compared with 41 months in uVIN).¹

While observation of VIN can be considered for young, asymptomatic women, it is not universally recommended because the risk of progression to cancer is approximately 8% (5% for uVIN and 33% for dVIN).^1,2 Both subtypes of VIN can be treated with similar interventions including surgical excision (typically a wide local excision), ablative therapies (such as CO₂ laser) or topical medical therapy such as imiquimod or 5-fluorouracil. Excisional surgery remains the mainstay of therapy for VIN because it provides clinicians with certainty regarding the possibility of occult invasive disease (false-negative biopsies), and adequacy of margin status. However, given the proximity of this disease to vital structures such as the clitoris, urethral meatus, and anal verge, as well as issues with wound healing, and difficulty with reapproximation of vulvar tissues – particularly when large or multifocal disease is present – sometimes multimodal treatments or medical therapies are preferred to spare disfigurement or sexual, bladder, or bowel dysfunction.

Excision of VIN need not be deeper than the epidermis, although including a limited degree of dermis protects against incomplete resection of occult, coexisting early invasive disease. However, wide margins should ideally be at least 10 mm. This can prove to be a challenging goal for multiple reasons. First, while there are visual stigmata of VIN, its true extent can be determined only microscopically. In addition, the disease may be multifocal. Furthermore, particularly where it encroaches upon the anus, clitoris, or urethral meatus, resection margins may be limited because of the desire to preserve function of adjacent structures. The application of 2%-5% acetic acid in the operating room prior to marking the planned borders of excision can optimize the likelihood that the incisions will encompass the microscopic extent of VIN. As it does with cervical dysplasia, acetic acid is thought to cause reversible coagulation of nuclear proteins and cytokeratins, which are more abundant in dysplastic lesions, thus appearing white to the surgeon’s eye.

However, even with the surgeon’s best attempts to excise all disease, approximately half of VIN excisions will have positive margins. Fortunately, not all of these patients will go on to develop recurrent dysplasia. In fact, less than half of women with positive margins on excision will develop recurrent VIN disease.² This incomplete incidence of recurrence may be in part due to an ablative effect of inflammation at the cut skin edges. Therefore, provided that there is no macroscopic disease remaining, close observation, rather than immediate reexcision, is recommended.

Positive excisional margins are a major risk factor for recurrence, carrying an eightfold increased risk, and also are associated with a more rapid onset of recurrence than for those with negative margins. Other predisposing risk factors for recurrence include advancing age, coexistence of dysplasia at other lower genital sites (including vaginal and cervical), immunosuppressive conditions or therapies (especially steroid use), HPV exposure, and the presence of lichen sclerosus.² Continued tobacco use is a modifiable risk factor that has been shown to be associated with an increased recurrence risk of VIN. We should take the opportunity in the postoperative and surveillance period to educate our patients regarding the importance of smoking cessation in modifying their risk for recurrent or new disease.

HPV infection may not be a modifiable risk factor, but certainly can be prevented by encouraging the adoption of HPV vaccination.

Topical steroids used to treat lichen sclerosus can improve symptoms of this vulvar dystrophy as well as decrease the incidence of recurrent dVIN and invasive vulvar cancer. Treatment should continue until the skin has normalized its appearance and texture. This may involve chronic long-term therapy.³

Recognizing that more than a quarter of patients will recur, the recommended posttreatment follow-up for VIN is at 6 months, 12 months, and then annually. It should include close inspection of the vulva with consideration of application of topical 2%-5% acetic acid (I typically apply this with a soaked gauze sponge) and vulvar colposcopy (a hand-held magnification glass works well for this purpose). Patients should be counseled regarding their high risk for recurrence, informed of typical symptoms, and encouraged to perform regular vulva self-inspection (with use of a hand mirror).

For patients at the highest risk for recurrence (older patients, patients with positive excisional margins, HPV coinfection, lichen sclerosus, tobacco use, and immunosuppression), I recommend 6 monthly follow-up surveillance for 5 years. Most (75%) of recurrences will occur with the first 43 months after diagnosis with half occurring in the first 18 months.² Patients who have had positive margins on their excisional specimen are at the highest risk for an earlier recurrence.

VIN is an insidious disease with a high recurrence rate. It is challenging to completely resect with negative margins. Patients with a history of VIN should receive close observation in the years following their excision, particularly if resection margins were positive, and clinicians should attempt to modify risk factors wherever possible, paying particularly close attention to older postmenopausal women with a history of lichen sclerosus as progression to malignancy is highest for these women.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She said she had no relevant financial disclosures. Email Dr. Rossi at [email protected].

References

1. Pathology. 2016 Jun 1;48(4)291-302.

2. Gynecol Oncol. 2018 Jan;148(1):126-31.

3. JAMA Dermatol. 2015 Oct;151(10):1061-7.

Delaying doses of denosumab after the first injection dramatically boosts the risk that patients with osteoporosis will suffer vertebral fractures, a new study confirms. Physicians say they are especially concerned about the risk facing patients who are delaying the treatment during the coronavirus pandemic.

doble-d/Getty Images

The recommended doses of denosumab are at 6-month intervals. Patients who delayed a dose by more than 16 weeks were nearly four times more likely to suffer vertebral fractures, compared with those who received on-time injections, according to the study, which was published in Annals of Internal Medicine.

“Because patients who used denosumab were at high risk for vertebral fracture, strategies to improve timely administration of denosumab in routine clinical settings are needed,” wrote the study authors, led by Houchen Lyu, MD, PhD, of National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation at General Hospital of Chinese PLA in Beijing.

Denosumab, a human monoclonal antibody, is used to reduce bone loss in osteoporosis. The manufacturer of Prolia, a brand of the drug, recommends it be given every 6 months, but the study reports that it’s common for injections to be delayed.

Researchers have linked cessation of denosumab to higher risk of fractures, and Dr. Lyu led a study published earlier this year that linked less-frequent doses to less bone mineral density improvement. “However,” the authors of the new study wrote, “whether delaying subsequent injections beyond the recommended 6-month interval is associated with fractures is unknown.”

For their new study, researchers retrospectively analyzed data from 2,594 patients in the U.K. 45 years or older (mean age, 76; 94% female; 53% with a history of major osteoporotic fracture) who began taking denosumab between 2010 and 2019. They used a design that aimed to emulate a clinical trial, comparing three dosing intervals: “on time” (within 4 weeks of the recommended 6-month interval), “short delay” (within 4-16 weeks) and “long delay” (16 weeks to 6 months).

The study found that the risk of composite fracture over 6 months out of 1,000 was 27.3 for on-time dosing, 32.2 for short-delay dosing, and 42.4 for long-delay dosing. The hazard ratio for long-delay versus on-time was 1.44 (95% confidence interval, 0.96-2.17; P = .093).

Vertebral fractures were less likely, but delays boosted the risk significantly: Over 6 months, it grew from 2.2 in 1,000 (on time) to 3.6 in 1,000 (short delay) and 10.1 in 1,000 (long delay). The HR for long delay versus on time was 3.91 (95% CI, 1.62-9.45; P = .005).

“This study had limited statistical power for composite fracture and several secondary end points ... except for vertebral fracture. Thus, evidence was insufficient to conclude that fracture risk was increased at other anatomical sites.”

In an accompanying editorial, two physicians from the University of Minnesota, Minneapolis, noted that the study is “timely and relevant” since the coronavirus pandemic may disrupt dosage schedules more than usual. While the study has limitations, the “findings are consistent with known denosumab pharmacokinetics and prior studies of fracture incidence after denosumab treatment discontinuation, wrote Kristine E. Ensrud, MD, MPH, who is also of Minneapolis VA Health Care System, and John T. Schousboe, MD, PhD, who is also of HealthPartners Institute.

The editorial authors noted that, in light of the pandemic, “some organizations recommend temporary transition to an oral bisphosphonate in patients receiving denosumab treatment for whom continued treatment is not feasible within 7 to 8 months of their most recent injection.”

In an interview, endocrinologist and osteoporosis specialist Ethel Siris, MD, of Columbia University, New York, said many of her patients aren’t coming in for denosumab injections during the pandemic. “It’s hard enough to get people to show up every 6 months to get their shot when things are going nicely,” she said. “We’re talking older women who may be on a lot of other medications. People forget, and it’s difficult for the office to constantly remind some of them to get their shots at an infusion center.”

The lack of symptoms is another challenge to getting patients to return for doses, she said. “In osteoporosis, the only time something hurts is if you break it.”

Since the pandemic began, many patients have been avoiding medical offices because of fear of getting the coronavirus.

The new research is helpful because it shows that patients are “more likely to fracture if they delay,” Dr. Siris noted. The endocrinologist added that she has successfully convinced some patients to give themselves subcutaneous injections in the abdomen at home.

Dr. Siris said she has been able to watch patients do these injections on video to check their technique. Her patients have been impressed by “how easy it is and delighted to have accomplished it,” she said.

The study was funded by the National Institutes of Health China’s National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation. The study authors, commentary authors, and Dr. Siris report no relevant disclosures.
 

SOURCE: Lyu H et al. Ann Intern Med. 2020 Jul 28. doi: 10.7326/M20-0882.

Delaying doses of denosumab after the first injection dramatically boosts the risk that patients with osteoporosis will suffer vertebral fractures, a new study confirms. Physicians say they are especially concerned about the risk facing patients who are delaying the treatment during the coronavirus pandemic.

doble-d/Getty Images

The recommended doses of denosumab are at 6-month intervals. Patients who delayed a dose by more than 16 weeks were nearly four times more likely to suffer vertebral fractures, compared with those who received on-time injections, according to the study, which was published in Annals of Internal Medicine.

“Because patients who used denosumab were at high risk for vertebral fracture, strategies to improve timely administration of denosumab in routine clinical settings are needed,” wrote the study authors, led by Houchen Lyu, MD, PhD, of National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation at General Hospital of Chinese PLA in Beijing.

Denosumab, a human monoclonal antibody, is used to reduce bone loss in osteoporosis. The manufacturer of Prolia, a brand of the drug, recommends it be given every 6 months, but the study reports that it’s common for injections to be delayed.

Researchers have linked cessation of denosumab to higher risk of fractures, and Dr. Lyu led a study published earlier this year that linked less-frequent doses to less bone mineral density improvement. “However,” the authors of the new study wrote, “whether delaying subsequent injections beyond the recommended 6-month interval is associated with fractures is unknown.”

For their new study, researchers retrospectively analyzed data from 2,594 patients in the U.K. 45 years or older (mean age, 76; 94% female; 53% with a history of major osteoporotic fracture) who began taking denosumab between 2010 and 2019. They used a design that aimed to emulate a clinical trial, comparing three dosing intervals: “on time” (within 4 weeks of the recommended 6-month interval), “short delay” (within 4-16 weeks) and “long delay” (16 weeks to 6 months).

The study found that the risk of composite fracture over 6 months out of 1,000 was 27.3 for on-time dosing, 32.2 for short-delay dosing, and 42.4 for long-delay dosing. The hazard ratio for long-delay versus on-time was 1.44 (95% confidence interval, 0.96-2.17; P = .093).

Vertebral fractures were less likely, but delays boosted the risk significantly: Over 6 months, it grew from 2.2 in 1,000 (on time) to 3.6 in 1,000 (short delay) and 10.1 in 1,000 (long delay). The HR for long delay versus on time was 3.91 (95% CI, 1.62-9.45; P = .005).

“This study had limited statistical power for composite fracture and several secondary end points ... except for vertebral fracture. Thus, evidence was insufficient to conclude that fracture risk was increased at other anatomical sites.”

In an accompanying editorial, two physicians from the University of Minnesota, Minneapolis, noted that the study is “timely and relevant” since the coronavirus pandemic may disrupt dosage schedules more than usual. While the study has limitations, the “findings are consistent with known denosumab pharmacokinetics and prior studies of fracture incidence after denosumab treatment discontinuation, wrote Kristine E. Ensrud, MD, MPH, who is also of Minneapolis VA Health Care System, and John T. Schousboe, MD, PhD, who is also of HealthPartners Institute.

The editorial authors noted that, in light of the pandemic, “some organizations recommend temporary transition to an oral bisphosphonate in patients receiving denosumab treatment for whom continued treatment is not feasible within 7 to 8 months of their most recent injection.”

In an interview, endocrinologist and osteoporosis specialist Ethel Siris, MD, of Columbia University, New York, said many of her patients aren’t coming in for denosumab injections during the pandemic. “It’s hard enough to get people to show up every 6 months to get their shot when things are going nicely,” she said. “We’re talking older women who may be on a lot of other medications. People forget, and it’s difficult for the office to constantly remind some of them to get their shots at an infusion center.”

The lack of symptoms is another challenge to getting patients to return for doses, she said. “In osteoporosis, the only time something hurts is if you break it.”

Since the pandemic began, many patients have been avoiding medical offices because of fear of getting the coronavirus.

The new research is helpful because it shows that patients are “more likely to fracture if they delay,” Dr. Siris noted. The endocrinologist added that she has successfully convinced some patients to give themselves subcutaneous injections in the abdomen at home.

Dr. Siris said she has been able to watch patients do these injections on video to check their technique. Her patients have been impressed by “how easy it is and delighted to have accomplished it,” she said.

The study was funded by the National Institutes of Health China’s National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation. The study authors, commentary authors, and Dr. Siris report no relevant disclosures.
 

SOURCE: Lyu H et al. Ann Intern Med. 2020 Jul 28. doi: 10.7326/M20-0882.

Delaying doses of denosumab after the first injection dramatically boosts the risk that patients with osteoporosis will suffer vertebral fractures, a new study confirms. Physicians say they are especially concerned about the risk facing patients who are delaying the treatment during the coronavirus pandemic.

doble-d/Getty Images

The recommended doses of denosumab are at 6-month intervals. Patients who delayed a dose by more than 16 weeks were nearly four times more likely to suffer vertebral fractures, compared with those who received on-time injections, according to the study, which was published in Annals of Internal Medicine.

“Because patients who used denosumab were at high risk for vertebral fracture, strategies to improve timely administration of denosumab in routine clinical settings are needed,” wrote the study authors, led by Houchen Lyu, MD, PhD, of National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation at General Hospital of Chinese PLA in Beijing.

Denosumab, a human monoclonal antibody, is used to reduce bone loss in osteoporosis. The manufacturer of Prolia, a brand of the drug, recommends it be given every 6 months, but the study reports that it’s common for injections to be delayed.

Researchers have linked cessation of denosumab to higher risk of fractures, and Dr. Lyu led a study published earlier this year that linked less-frequent doses to less bone mineral density improvement. “However,” the authors of the new study wrote, “whether delaying subsequent injections beyond the recommended 6-month interval is associated with fractures is unknown.”

For their new study, researchers retrospectively analyzed data from 2,594 patients in the U.K. 45 years or older (mean age, 76; 94% female; 53% with a history of major osteoporotic fracture) who began taking denosumab between 2010 and 2019. They used a design that aimed to emulate a clinical trial, comparing three dosing intervals: “on time” (within 4 weeks of the recommended 6-month interval), “short delay” (within 4-16 weeks) and “long delay” (16 weeks to 6 months).

The study found that the risk of composite fracture over 6 months out of 1,000 was 27.3 for on-time dosing, 32.2 for short-delay dosing, and 42.4 for long-delay dosing. The hazard ratio for long-delay versus on-time was 1.44 (95% confidence interval, 0.96-2.17; P = .093).

Vertebral fractures were less likely, but delays boosted the risk significantly: Over 6 months, it grew from 2.2 in 1,000 (on time) to 3.6 in 1,000 (short delay) and 10.1 in 1,000 (long delay). The HR for long delay versus on time was 3.91 (95% CI, 1.62-9.45; P = .005).

“This study had limited statistical power for composite fracture and several secondary end points ... except for vertebral fracture. Thus, evidence was insufficient to conclude that fracture risk was increased at other anatomical sites.”

In an accompanying editorial, two physicians from the University of Minnesota, Minneapolis, noted that the study is “timely and relevant” since the coronavirus pandemic may disrupt dosage schedules more than usual. While the study has limitations, the “findings are consistent with known denosumab pharmacokinetics and prior studies of fracture incidence after denosumab treatment discontinuation, wrote Kristine E. Ensrud, MD, MPH, who is also of Minneapolis VA Health Care System, and John T. Schousboe, MD, PhD, who is also of HealthPartners Institute.

The editorial authors noted that, in light of the pandemic, “some organizations recommend temporary transition to an oral bisphosphonate in patients receiving denosumab treatment for whom continued treatment is not feasible within 7 to 8 months of their most recent injection.”

In an interview, endocrinologist and osteoporosis specialist Ethel Siris, MD, of Columbia University, New York, said many of her patients aren’t coming in for denosumab injections during the pandemic. “It’s hard enough to get people to show up every 6 months to get their shot when things are going nicely,” she said. “We’re talking older women who may be on a lot of other medications. People forget, and it’s difficult for the office to constantly remind some of them to get their shots at an infusion center.”

The lack of symptoms is another challenge to getting patients to return for doses, she said. “In osteoporosis, the only time something hurts is if you break it.”

Since the pandemic began, many patients have been avoiding medical offices because of fear of getting the coronavirus.

The new research is helpful because it shows that patients are “more likely to fracture if they delay,” Dr. Siris noted. The endocrinologist added that she has successfully convinced some patients to give themselves subcutaneous injections in the abdomen at home.

Dr. Siris said she has been able to watch patients do these injections on video to check their technique. Her patients have been impressed by “how easy it is and delighted to have accomplished it,” she said.

The study was funded by the National Institutes of Health China’s National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation. The study authors, commentary authors, and Dr. Siris report no relevant disclosures.
 

SOURCE: Lyu H et al. Ann Intern Med. 2020 Jul 28. doi: 10.7326/M20-0882.