Women's Health

All infants born to a cohort of 31 COVID-19–positive mothers tested negative for the virus during the height of the New York surge, according to a study out of New York-Presbyterian Hospital.

South_agency/Getty Images

“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.

But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.

“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.

The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.

Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.

The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.

“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.

They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”

The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.

Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”

Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”

Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”

The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”

Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:

• Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
• Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
• There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.

Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”

SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.

All infants born to a cohort of 31 COVID-19–positive mothers tested negative for the virus during the height of the New York surge, according to a study out of New York-Presbyterian Hospital.

South_agency/Getty Images

“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.

But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.

“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.

The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.

Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.

The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.

“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.

They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”

The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.

Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”

Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”

Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”

The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”

Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:

• Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
• Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
• There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.

Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”

SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.

All infants born to a cohort of 31 COVID-19–positive mothers tested negative for the virus during the height of the New York surge, according to a study out of New York-Presbyterian Hospital.

South_agency/Getty Images

“It is suggested in the cumulative data that the virus does not confer additional risk to the fetus during labor or during the early postnatal period in both preterm and term infants,” concluded Jeffrey Perlman, MB ChB, and colleagues in Pediatrics.

But other experts suggest substantial gaps remain in our understanding of maternal transmission of SARS-CoV-2.

“Much more needs to be known,” Munish Gupta, MD, and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, said in an accompanying editorial.

The prospective study is the first to describe a cohort of U.S. COVID-19–related deliveries, with the prior neonatal impact of COVID-19 “almost exclusively” reported from China, noted the authors. They included a cohort of 326 women who were tested for SARS-CoV-2 on admission to labor and delivery at New York-Presbyterian Hospital between March 22 and April 15th, 2020. Of the 31 (10%) mothers who tested positive, 15 (48%) were asymptomatic and 16 (52%) were symptomatic.

Two babies were born prematurely (one by Cesarean) and were isolated in negative pressure rooms with continuous positive airway pressure. Both were moved out of isolation after two negative test results and “have exhibited an unremarkable clinical course,” the authors reported.

The other 29 term babies were cared for in their mothers’ rooms, with breastfeeding allowed, if desired. These babies and their mothers were discharged from the hospital between 24 and 48 hours after delivery.

“Visitor restriction for mothers who were positive for COVID-19 included 14 days of no visitation from the start of symptoms,” noted the team.

They added “since the prepublication release there have been a total of 47 mothers positive for COVID-19, resulting in 47 infants; 4 have been admitted to neonatal intensive care. In addition, 32 other infants have been tested for a variety of indications within the unit. All infants test results have been negative.”

The brief report outlined the institution’s checklist for delivery preparedness in either the operating room or labor delivery room, including personal protective equipment, resuscitation, transportation to the neonatal intensive care unit, and early postresuscitation care. “Suspected or confirmed COVID-19 alone in an otherwise uncomplicated pregnancy is not an indication for the resuscitation team or the neonatal fellow,” they noted, adding delivery room preparation and management should include contact precautions. “With scrupulous attention to infectious precautions, horizontal viral transmission should be minimized,” they advised.

Dr. Perlman and associates emphasized that rapid turnaround SARSCoV-2 testing is “crucial to minimize the likelihood of a provider becoming infected and/or infecting the infant.”

Although the findings are “clearly reassuring,” Dr. Gupta and colleagues have reservations. “To what extent does this report address concerns for infection risk with a rooming-in approach to care?” they asked in their accompanying editorial. “The answer is likely some, but not much.”

Many questions remain, they said, including: “What precautions were used to minimize infection risk during the postbirth hospital course? What was the approach to skin-to-skin care and direct mother-newborn contact? Were restrictions placed on family members? Were changes made to routine interventions such as hearing screens or circumcisions? What practices were in place around environmental cleaning? Most important, how did the newborns do after discharge?”

The current uncertainty around neonatal COVID-19 infection risk has led to “disparate” variations in care recommendations, they pointed out. Whereas China’s consensus guidelines recommend a 14-day separation of COVID-19–positive mothers from their healthy infants, a practice supported by the American Academy of Pediatrics “when possible,” the Italian Society of Neonatology, the Royal College of Paediatrics and Child Health, and the Canadian Paediatric Society advise “rooming-in and breastfeeding with appropriate infection prevention measures.”

Dr. Gupta and colleagues pointed to the following as at least three “critical and time-sensitive needs for research around neonatal care and outcomes related to COVID-19”:

• Studies need to have much larger sample sizes and include diverse populations. This will allow for reliable measurement of outcomes.
• Descriptions of care practices must be in detail, especially about infection prevention; these should be presented in a way to compare the efficacy of different approaches.
• There needs to be follow-up information on outcomes of both the mother and the neonate after the birth hospitalization.

Asked to comment, Lillian Beard, MD, of George Washington University in Washington welcomed the data as “good news.”

SOURCE: Perlman J et al. Pediatrics. 2020;146(2):e20201567.

The Food and Drug Administration will not object to qualified health claims that consumption of certain cranberry juice products and cranberry supplement products may reduce the risk of recurrent urinary tract infections in otherwise healthy women.

EHStock/iStock/Getty Images

In a letter of enforcement discretion issued on July 21, the FDA responded to a health claim petition submitted by Ocean Spray Cranberries. “A health claim characterizes the relationship between a substance and a disease or health-related condition,” according to the FDA. Ocean Spray Cranberries asked the FDA for an authorized health claim regarding the relationship between the consumption of cranberry beverages and supplements and a reduction in the risk of recurrent urinary tract infections (UTIs) in healthy women.

After reviewing the evidence, the FDA determined that the existing science did not support an authorized health claim, but did allow for a qualified health claim for certain cranberry juice beverages and supplements. A qualified health claim does not constitute an FDA approval; the FDA instead issues a Letter of Enforcement Discretion that includes language reflecting the level of scientific evidence for the claim.

The currently available scientific evidence for a relationship between cranberry and recurrent UTIs includes five intervention studies, according to the FDA letter. Two of these were high-quality, randomized, controlled trials in which daily consumption of a cranberry juice beverage was significantly associated with a reduced risk of recurrent UTIs. Another randomized, controlled trial yielded mixed results, and two other intervention studies that were moderate-quality, randomized, controlled trials showed no effect of cranberry juice consumption on UTI risk reduction.

The FDA’s letter of enforcement discretion states that, with regard to cranberry juice beverages, “Limited and inconsistent scientific evidence shows that by consuming one serving (8 oz) each day of a cranberry juice beverage, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”

Similarly, for cranberry dietary supplements, the FDA states that “Limited scientific evidence shows that, by consuming 500 mg each day of cranberry dietary supplement, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”

The qualified health claims apply specifically to cranberry juice beverages that contain at least 27% cranberry juice, and cranberry dietary supplements containing at least 500 mg of cranberry fruit powder. “The claims do not include other conventional foods or food products made from or containing cranberries, such as dried cranberries or cranberry sauce,” according to the FDA statement.

“With recurrent UTI, a major concern is the frequent use of antibiotics,” Constance Bohon, MD, an ob.gyn. in private practice in Washington and an assistant clinical professor at George Washington University, Washington, said in an interview.

“The challenge is to identify habits and/or nonantibiotic treatment to prevent recurrent UTI and decrease the need for antibiotics,” she said. “The regular use of cranberry can decrease the frequency of UTI in some, but not all, people.

“It does not appear to mask the symptoms of a UTI, so if it is not effective to prevent the infection, the presumptive diagnosis can be made based on the common symptoms,” she explained.

Dr. Bohon said that she has recommended the use of cranberry to some of her patients who have recurrent UTIs and has had success with many of them.

“I think it is important to make it clear that cranberry can be beneficial for some patients to decrease the frequency of UTI. It will not be effective for everyone who has frequent UTI, but for those who use it and have fewer UTIs, there will be less frequent exposure to antibiotics,” she emphasized. “What we need to know is who benefits the most from cranberry to prevent recurrent UTIs; whether age, race, coexisting health problems [such as diabetes], and use of hormonal contraception or menopause impact on its success.”

Dr. Bohon had no relevant financial conflicts to disclose.

The Food and Drug Administration will not object to qualified health claims that consumption of certain cranberry juice products and cranberry supplement products may reduce the risk of recurrent urinary tract infections in otherwise healthy women.

EHStock/iStock/Getty Images

In a letter of enforcement discretion issued on July 21, the FDA responded to a health claim petition submitted by Ocean Spray Cranberries. “A health claim characterizes the relationship between a substance and a disease or health-related condition,” according to the FDA. Ocean Spray Cranberries asked the FDA for an authorized health claim regarding the relationship between the consumption of cranberry beverages and supplements and a reduction in the risk of recurrent urinary tract infections (UTIs) in healthy women.

After reviewing the evidence, the FDA determined that the existing science did not support an authorized health claim, but did allow for a qualified health claim for certain cranberry juice beverages and supplements. A qualified health claim does not constitute an FDA approval; the FDA instead issues a Letter of Enforcement Discretion that includes language reflecting the level of scientific evidence for the claim.

The currently available scientific evidence for a relationship between cranberry and recurrent UTIs includes five intervention studies, according to the FDA letter. Two of these were high-quality, randomized, controlled trials in which daily consumption of a cranberry juice beverage was significantly associated with a reduced risk of recurrent UTIs. Another randomized, controlled trial yielded mixed results, and two other intervention studies that were moderate-quality, randomized, controlled trials showed no effect of cranberry juice consumption on UTI risk reduction.

The FDA’s letter of enforcement discretion states that, with regard to cranberry juice beverages, “Limited and inconsistent scientific evidence shows that by consuming one serving (8 oz) each day of a cranberry juice beverage, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”

Similarly, for cranberry dietary supplements, the FDA states that “Limited scientific evidence shows that, by consuming 500 mg each day of cranberry dietary supplement, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”

The qualified health claims apply specifically to cranberry juice beverages that contain at least 27% cranberry juice, and cranberry dietary supplements containing at least 500 mg of cranberry fruit powder. “The claims do not include other conventional foods or food products made from or containing cranberries, such as dried cranberries or cranberry sauce,” according to the FDA statement.

“With recurrent UTI, a major concern is the frequent use of antibiotics,” Constance Bohon, MD, an ob.gyn. in private practice in Washington and an assistant clinical professor at George Washington University, Washington, said in an interview.

“The challenge is to identify habits and/or nonantibiotic treatment to prevent recurrent UTI and decrease the need for antibiotics,” she said. “The regular use of cranberry can decrease the frequency of UTI in some, but not all, people.

“It does not appear to mask the symptoms of a UTI, so if it is not effective to prevent the infection, the presumptive diagnosis can be made based on the common symptoms,” she explained.

Dr. Bohon said that she has recommended the use of cranberry to some of her patients who have recurrent UTIs and has had success with many of them.

“I think it is important to make it clear that cranberry can be beneficial for some patients to decrease the frequency of UTI. It will not be effective for everyone who has frequent UTI, but for those who use it and have fewer UTIs, there will be less frequent exposure to antibiotics,” she emphasized. “What we need to know is who benefits the most from cranberry to prevent recurrent UTIs; whether age, race, coexisting health problems [such as diabetes], and use of hormonal contraception or menopause impact on its success.”

Dr. Bohon had no relevant financial conflicts to disclose.

The Food and Drug Administration will not object to qualified health claims that consumption of certain cranberry juice products and cranberry supplement products may reduce the risk of recurrent urinary tract infections in otherwise healthy women.

EHStock/iStock/Getty Images

In a letter of enforcement discretion issued on July 21, the FDA responded to a health claim petition submitted by Ocean Spray Cranberries. “A health claim characterizes the relationship between a substance and a disease or health-related condition,” according to the FDA. Ocean Spray Cranberries asked the FDA for an authorized health claim regarding the relationship between the consumption of cranberry beverages and supplements and a reduction in the risk of recurrent urinary tract infections (UTIs) in healthy women.

After reviewing the evidence, the FDA determined that the existing science did not support an authorized health claim, but did allow for a qualified health claim for certain cranberry juice beverages and supplements. A qualified health claim does not constitute an FDA approval; the FDA instead issues a Letter of Enforcement Discretion that includes language reflecting the level of scientific evidence for the claim.

The currently available scientific evidence for a relationship between cranberry and recurrent UTIs includes five intervention studies, according to the FDA letter. Two of these were high-quality, randomized, controlled trials in which daily consumption of a cranberry juice beverage was significantly associated with a reduced risk of recurrent UTIs. Another randomized, controlled trial yielded mixed results, and two other intervention studies that were moderate-quality, randomized, controlled trials showed no effect of cranberry juice consumption on UTI risk reduction.

The FDA’s letter of enforcement discretion states that, with regard to cranberry juice beverages, “Limited and inconsistent scientific evidence shows that by consuming one serving (8 oz) each day of a cranberry juice beverage, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”

Similarly, for cranberry dietary supplements, the FDA states that “Limited scientific evidence shows that, by consuming 500 mg each day of cranberry dietary supplement, healthy women who have had a urinary tract infection may reduce their risk of recurrent UTI.”

The qualified health claims apply specifically to cranberry juice beverages that contain at least 27% cranberry juice, and cranberry dietary supplements containing at least 500 mg of cranberry fruit powder. “The claims do not include other conventional foods or food products made from or containing cranberries, such as dried cranberries or cranberry sauce,” according to the FDA statement.

“With recurrent UTI, a major concern is the frequent use of antibiotics,” Constance Bohon, MD, an ob.gyn. in private practice in Washington and an assistant clinical professor at George Washington University, Washington, said in an interview.

“The challenge is to identify habits and/or nonantibiotic treatment to prevent recurrent UTI and decrease the need for antibiotics,” she said. “The regular use of cranberry can decrease the frequency of UTI in some, but not all, people.

“It does not appear to mask the symptoms of a UTI, so if it is not effective to prevent the infection, the presumptive diagnosis can be made based on the common symptoms,” she explained.

Dr. Bohon said that she has recommended the use of cranberry to some of her patients who have recurrent UTIs and has had success with many of them.

“I think it is important to make it clear that cranberry can be beneficial for some patients to decrease the frequency of UTI. It will not be effective for everyone who has frequent UTI, but for those who use it and have fewer UTIs, there will be less frequent exposure to antibiotics,” she emphasized. “What we need to know is who benefits the most from cranberry to prevent recurrent UTIs; whether age, race, coexisting health problems [such as diabetes], and use of hormonal contraception or menopause impact on its success.”

Dr. Bohon had no relevant financial conflicts to disclose.

Recommendations on use of the new dual-action anabolic agent romosozumab (Evenity, Amgen) and how to safely transition between osteoporosis agents are two of the issues addressed in the latest clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis from the American Association of Clinical Endocrinologists and American College of Endocrinology.

“This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of postmenopausal osteoporosis,” the authors wrote.

The guidelines focus on 12 key clinical questions related to postmenopausal osteoporosis, with 52 specific recommendations, each graded according to the level of evidence.

They also include a treatment algorithm to help guide choice of therapy.
 

Reiterating role of FRAX in the diagnosis of patients with osteopenia

Among key updates is an emphasis on the role of the Fracture Risk Assessment Tool (FRAX) in the diagnosis of osteoporosis in patients with osteopenia.

While patients have traditionally been diagnosed with osteoporosis based on the presence of low bone mineral density (BMD) in the absence of fracture, the updated guidelines indicate that osteoporosis may be diagnosed in patients with osteopenia and an increased fracture risk using FRAX.

“The use of FRAX and osteopenia to diagnosis osteoporosis was first proposed by the National Bone Health Alliance years ago, and in the 2016 guideline, we agreed with it,” Pauline M. Camacho, MD, cochair of the guidelines task force, said in an interview.

“We reiterate in the 2020 guideline that we feel this is a valid diagnostic criteria,” said Dr. Camacho, professor of medicine and director of the Osteoporosis and Metabolic Bone Disease Center at Loyola University Chicago, Maywood, Ill. “It makes sense because when the thresholds are met by FRAX in patients with osteopenia, treatment is recommended. Therefore, why would they not fulfill treatment criteria for diagnosing osteoporosis?”

An increased risk of fracture based on a FRAX score may also be used to determine pharmacologic therapy, as can other traditional factors such as a low T score or a fragility fracture, the guidelines stated.
 

High risk vs. very high risk guides choice of first therapy

Another key update is the clarification of the risk stratification of patients who are high risk versus very high risk, which is key in determining the initial choice of agents and duration of therapy.

Specifically, patients should be considered at a very high fracture risk if they have the following criteria: a recent fracture (e.g., within the past 12 months), fractures while on approved osteoporosis therapy, multiple fractures, fractures while on drugs causing skeletal harm (e.g., long-term glucocorticoids), very low T score (e.g., less than −3.0), a high risk for falls or history of injurious falls, and a very high fracture probability by FRAX (e.g., major osteoporosis fracture >30%, hip fracture >4.5%) or other validated fracture risk algorithm.

Meanwhile, patients should be considered at high risk if they have been diagnosed with osteoporosis but do not meet the criteria for very high fracture risk.
 

Romosozumab brought into the mix

Another important update provides information on the role of one of the newest osteoporosis agents on the market, the anabolic drug romosozumab, a monoclonal antibody directed against sclerostin.

The drug’s approval by the Food and Drug Administration in 2019 for postmenopausal women at high risk of fracture was based on two large trials that showed dramatic increases in bone density through modeling as well as remodeling.

Those studies specifically showed significant reductions in radiographic vertebral fractures with romosozumab, compared with placebo and alendronate.

Dr. Camacho noted that romosozumab “will likely be for the very high risk group and those who have maxed out on teriparatide or abaloparatide.”

Romosozumab can safely be used in patients with prior radiation exposure, the guidelines noted.

Importantly, because of reports of a higher risk of serious cardiovascular events with romosozumab, compared with alendronate, romosozumab comes with a black-box warning that it should not be used in patients at high risk for cardiovascular events or who have had a recent myocardial infarction or stroke.

“Unfortunately, the very high risk group is often the older patients,” Dr. Camacho noted.

“The drug should not be given if there is a history of myocardial infarction or stroke in the past year,” she emphasized. “Clinical judgment is needed to decide who is at risk for cardiovascular complications.”

Notably, teriparatide and abaloparatide have black box warnings of their own regarding risk for osteosarcoma.

Switching therapies

Reflecting the evolving data on osteoporosis drug holidays, the guidelines also addressed the issue and the clinical challenges of switching therapies.

“In 2016, we said drug holidays are not recommended, and the treatment can be continued indefinitely, [however] in 2020, we felt that if some patients are no longer high risk, they can be transitioned off the drug,” Dr. Camacho said.

For teriparatide and abaloparatide, the FDA recommends treatment be limited to no more than 2 years, and for romosozumab, 1 year.

The updated guidelines recommend that upon discontinuation of an anabolic agent (e.g., abaloparatide, romosozumab, or teriparatide), a switch to therapy with an antiresorptive agent, such as denosumab or bisphosphonates, should be implemented to prevent loss of BMD and fracture efficacy.

Discontinuation of denosumab, however, can have notably negative effects. Clinical trials show rapid decreases in BMD when denosumab treatment is stopped after 2 or 8 years, as well as rapid loss of protection from vertebral fractures.

Therefore, if denosumab is going to be discontinued, there should be a proper transition to an antiresorptive agent for a limited time, such as one infusion of the bisphosphonate zoledronate.
 

Communicate the risks with and without treatment to patients

The authors underscored that, in addition to communicating the potential risk and expected benefits of osteoporosis treatments, clinicians should make sure patients fully appreciate the risk of fractures and their consequences, such as pain, disability, loss of independence, and death, when no treatment is given.

“It is incumbent on the clinician to provide this information to each patient in a manner that is fully understood, and it is equally important to learn from the patient about cultural beliefs, previous treatment experiences, fears, and concerns,” they wrote.

And in estimating patients’ fracture risk, T score must be combined with clinical risk factors, particularly advanced age and previous fracture, and clinicians should recognize that the absolute fracture risk is more useful than a risk ratio in developing treatment plans.

“Treatment recommendations may be quite different; an early postmenopausal woman with a T score of −2.5 has osteoporosis, although fracture risk is much lower than an 80-year-old woman with the same T score,” the authors explained.

Dr. Camacho reported financial relationships with Amgen and Shire. Disclosures for other task force members are detailed in the guidelines.

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

Recommendations on use of the new dual-action anabolic agent romosozumab (Evenity, Amgen) and how to safely transition between osteoporosis agents are two of the issues addressed in the latest clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis from the American Association of Clinical Endocrinologists and American College of Endocrinology.

“This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of postmenopausal osteoporosis,” the authors wrote.

The guidelines focus on 12 key clinical questions related to postmenopausal osteoporosis, with 52 specific recommendations, each graded according to the level of evidence.

They also include a treatment algorithm to help guide choice of therapy.
 

Reiterating role of FRAX in the diagnosis of patients with osteopenia

Among key updates is an emphasis on the role of the Fracture Risk Assessment Tool (FRAX) in the diagnosis of osteoporosis in patients with osteopenia.

While patients have traditionally been diagnosed with osteoporosis based on the presence of low bone mineral density (BMD) in the absence of fracture, the updated guidelines indicate that osteoporosis may be diagnosed in patients with osteopenia and an increased fracture risk using FRAX.

“The use of FRAX and osteopenia to diagnosis osteoporosis was first proposed by the National Bone Health Alliance years ago, and in the 2016 guideline, we agreed with it,” Pauline M. Camacho, MD, cochair of the guidelines task force, said in an interview.

“We reiterate in the 2020 guideline that we feel this is a valid diagnostic criteria,” said Dr. Camacho, professor of medicine and director of the Osteoporosis and Metabolic Bone Disease Center at Loyola University Chicago, Maywood, Ill. “It makes sense because when the thresholds are met by FRAX in patients with osteopenia, treatment is recommended. Therefore, why would they not fulfill treatment criteria for diagnosing osteoporosis?”

An increased risk of fracture based on a FRAX score may also be used to determine pharmacologic therapy, as can other traditional factors such as a low T score or a fragility fracture, the guidelines stated.
 

High risk vs. very high risk guides choice of first therapy

Another key update is the clarification of the risk stratification of patients who are high risk versus very high risk, which is key in determining the initial choice of agents and duration of therapy.

Specifically, patients should be considered at a very high fracture risk if they have the following criteria: a recent fracture (e.g., within the past 12 months), fractures while on approved osteoporosis therapy, multiple fractures, fractures while on drugs causing skeletal harm (e.g., long-term glucocorticoids), very low T score (e.g., less than −3.0), a high risk for falls or history of injurious falls, and a very high fracture probability by FRAX (e.g., major osteoporosis fracture >30%, hip fracture >4.5%) or other validated fracture risk algorithm.

Meanwhile, patients should be considered at high risk if they have been diagnosed with osteoporosis but do not meet the criteria for very high fracture risk.
 

Romosozumab brought into the mix

Another important update provides information on the role of one of the newest osteoporosis agents on the market, the anabolic drug romosozumab, a monoclonal antibody directed against sclerostin.

The drug’s approval by the Food and Drug Administration in 2019 for postmenopausal women at high risk of fracture was based on two large trials that showed dramatic increases in bone density through modeling as well as remodeling.

Those studies specifically showed significant reductions in radiographic vertebral fractures with romosozumab, compared with placebo and alendronate.

Dr. Camacho noted that romosozumab “will likely be for the very high risk group and those who have maxed out on teriparatide or abaloparatide.”

Romosozumab can safely be used in patients with prior radiation exposure, the guidelines noted.

Importantly, because of reports of a higher risk of serious cardiovascular events with romosozumab, compared with alendronate, romosozumab comes with a black-box warning that it should not be used in patients at high risk for cardiovascular events or who have had a recent myocardial infarction or stroke.

“Unfortunately, the very high risk group is often the older patients,” Dr. Camacho noted.

“The drug should not be given if there is a history of myocardial infarction or stroke in the past year,” she emphasized. “Clinical judgment is needed to decide who is at risk for cardiovascular complications.”

Notably, teriparatide and abaloparatide have black box warnings of their own regarding risk for osteosarcoma.

Switching therapies

Reflecting the evolving data on osteoporosis drug holidays, the guidelines also addressed the issue and the clinical challenges of switching therapies.

“In 2016, we said drug holidays are not recommended, and the treatment can be continued indefinitely, [however] in 2020, we felt that if some patients are no longer high risk, they can be transitioned off the drug,” Dr. Camacho said.

For teriparatide and abaloparatide, the FDA recommends treatment be limited to no more than 2 years, and for romosozumab, 1 year.

The updated guidelines recommend that upon discontinuation of an anabolic agent (e.g., abaloparatide, romosozumab, or teriparatide), a switch to therapy with an antiresorptive agent, such as denosumab or bisphosphonates, should be implemented to prevent loss of BMD and fracture efficacy.

Discontinuation of denosumab, however, can have notably negative effects. Clinical trials show rapid decreases in BMD when denosumab treatment is stopped after 2 or 8 years, as well as rapid loss of protection from vertebral fractures.

Therefore, if denosumab is going to be discontinued, there should be a proper transition to an antiresorptive agent for a limited time, such as one infusion of the bisphosphonate zoledronate.
 

Communicate the risks with and without treatment to patients

The authors underscored that, in addition to communicating the potential risk and expected benefits of osteoporosis treatments, clinicians should make sure patients fully appreciate the risk of fractures and their consequences, such as pain, disability, loss of independence, and death, when no treatment is given.

“It is incumbent on the clinician to provide this information to each patient in a manner that is fully understood, and it is equally important to learn from the patient about cultural beliefs, previous treatment experiences, fears, and concerns,” they wrote.

And in estimating patients’ fracture risk, T score must be combined with clinical risk factors, particularly advanced age and previous fracture, and clinicians should recognize that the absolute fracture risk is more useful than a risk ratio in developing treatment plans.

“Treatment recommendations may be quite different; an early postmenopausal woman with a T score of −2.5 has osteoporosis, although fracture risk is much lower than an 80-year-old woman with the same T score,” the authors explained.

Dr. Camacho reported financial relationships with Amgen and Shire. Disclosures for other task force members are detailed in the guidelines.

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

Recommendations on use of the new dual-action anabolic agent romosozumab (Evenity, Amgen) and how to safely transition between osteoporosis agents are two of the issues addressed in the latest clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis from the American Association of Clinical Endocrinologists and American College of Endocrinology.

“This guideline is a practical tool for endocrinologists, physicians in general, regulatory bodies, health-related organizations, and interested laypersons regarding the diagnosis, evaluation, and treatment of postmenopausal osteoporosis,” the authors wrote.

The guidelines focus on 12 key clinical questions related to postmenopausal osteoporosis, with 52 specific recommendations, each graded according to the level of evidence.

They also include a treatment algorithm to help guide choice of therapy.
 

Reiterating role of FRAX in the diagnosis of patients with osteopenia

Among key updates is an emphasis on the role of the Fracture Risk Assessment Tool (FRAX) in the diagnosis of osteoporosis in patients with osteopenia.

While patients have traditionally been diagnosed with osteoporosis based on the presence of low bone mineral density (BMD) in the absence of fracture, the updated guidelines indicate that osteoporosis may be diagnosed in patients with osteopenia and an increased fracture risk using FRAX.

“The use of FRAX and osteopenia to diagnosis osteoporosis was first proposed by the National Bone Health Alliance years ago, and in the 2016 guideline, we agreed with it,” Pauline M. Camacho, MD, cochair of the guidelines task force, said in an interview.

“We reiterate in the 2020 guideline that we feel this is a valid diagnostic criteria,” said Dr. Camacho, professor of medicine and director of the Osteoporosis and Metabolic Bone Disease Center at Loyola University Chicago, Maywood, Ill. “It makes sense because when the thresholds are met by FRAX in patients with osteopenia, treatment is recommended. Therefore, why would they not fulfill treatment criteria for diagnosing osteoporosis?”

An increased risk of fracture based on a FRAX score may also be used to determine pharmacologic therapy, as can other traditional factors such as a low T score or a fragility fracture, the guidelines stated.
 

High risk vs. very high risk guides choice of first therapy

Another key update is the clarification of the risk stratification of patients who are high risk versus very high risk, which is key in determining the initial choice of agents and duration of therapy.

Specifically, patients should be considered at a very high fracture risk if they have the following criteria: a recent fracture (e.g., within the past 12 months), fractures while on approved osteoporosis therapy, multiple fractures, fractures while on drugs causing skeletal harm (e.g., long-term glucocorticoids), very low T score (e.g., less than −3.0), a high risk for falls or history of injurious falls, and a very high fracture probability by FRAX (e.g., major osteoporosis fracture >30%, hip fracture >4.5%) or other validated fracture risk algorithm.

Meanwhile, patients should be considered at high risk if they have been diagnosed with osteoporosis but do not meet the criteria for very high fracture risk.
 

Romosozumab brought into the mix

Another important update provides information on the role of one of the newest osteoporosis agents on the market, the anabolic drug romosozumab, a monoclonal antibody directed against sclerostin.

The drug’s approval by the Food and Drug Administration in 2019 for postmenopausal women at high risk of fracture was based on two large trials that showed dramatic increases in bone density through modeling as well as remodeling.

Those studies specifically showed significant reductions in radiographic vertebral fractures with romosozumab, compared with placebo and alendronate.

Dr. Camacho noted that romosozumab “will likely be for the very high risk group and those who have maxed out on teriparatide or abaloparatide.”

Romosozumab can safely be used in patients with prior radiation exposure, the guidelines noted.

Importantly, because of reports of a higher risk of serious cardiovascular events with romosozumab, compared with alendronate, romosozumab comes with a black-box warning that it should not be used in patients at high risk for cardiovascular events or who have had a recent myocardial infarction or stroke.

“Unfortunately, the very high risk group is often the older patients,” Dr. Camacho noted.

“The drug should not be given if there is a history of myocardial infarction or stroke in the past year,” she emphasized. “Clinical judgment is needed to decide who is at risk for cardiovascular complications.”

Notably, teriparatide and abaloparatide have black box warnings of their own regarding risk for osteosarcoma.

Switching therapies

Reflecting the evolving data on osteoporosis drug holidays, the guidelines also addressed the issue and the clinical challenges of switching therapies.

“In 2016, we said drug holidays are not recommended, and the treatment can be continued indefinitely, [however] in 2020, we felt that if some patients are no longer high risk, they can be transitioned off the drug,” Dr. Camacho said.

For teriparatide and abaloparatide, the FDA recommends treatment be limited to no more than 2 years, and for romosozumab, 1 year.

The updated guidelines recommend that upon discontinuation of an anabolic agent (e.g., abaloparatide, romosozumab, or teriparatide), a switch to therapy with an antiresorptive agent, such as denosumab or bisphosphonates, should be implemented to prevent loss of BMD and fracture efficacy.

Discontinuation of denosumab, however, can have notably negative effects. Clinical trials show rapid decreases in BMD when denosumab treatment is stopped after 2 or 8 years, as well as rapid loss of protection from vertebral fractures.

Therefore, if denosumab is going to be discontinued, there should be a proper transition to an antiresorptive agent for a limited time, such as one infusion of the bisphosphonate zoledronate.
 

Communicate the risks with and without treatment to patients

The authors underscored that, in addition to communicating the potential risk and expected benefits of osteoporosis treatments, clinicians should make sure patients fully appreciate the risk of fractures and their consequences, such as pain, disability, loss of independence, and death, when no treatment is given.

“It is incumbent on the clinician to provide this information to each patient in a manner that is fully understood, and it is equally important to learn from the patient about cultural beliefs, previous treatment experiences, fears, and concerns,” they wrote.

And in estimating patients’ fracture risk, T score must be combined with clinical risk factors, particularly advanced age and previous fracture, and clinicians should recognize that the absolute fracture risk is more useful than a risk ratio in developing treatment plans.

“Treatment recommendations may be quite different; an early postmenopausal woman with a T score of −2.5 has osteoporosis, although fracture risk is much lower than an 80-year-old woman with the same T score,” the authors explained.

Dr. Camacho reported financial relationships with Amgen and Shire. Disclosures for other task force members are detailed in the guidelines.

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

Adolescents and young adults with physical, intellectual, and developmental disabilities can benefit from the use of levonorgestrel intrauterine devices for menstrual management and contraception, based on data from a retrospective study of 159 patients.

“Desire for menstrual management or suppression is common in young women with special needs, including complex medical conditions and physical, intellectual, and developmental disabilities,” and many of these patients require estrogen-free options because of comorbidities, medication interactions, or decreased mobility, wrote Beth I. Schwartz, MD, and colleagues at Cincinnati Children’s Hospital Medical Center. Dr. Schwartz currently is of Thomas Jefferson University, Philadelphia.

In a study published in Pediatrics, the researchers identified 159 nulliparous patients aged 22 years and younger with physical, intellectual, or developmental disabilities who received levonorgestrel IUDs at a tertiary care children’s hospital between July 1, 2004, and June 30, 2014.

A total of 185 levonorgestrel IUDs were placed. The patients ranged in age from 9 to 22 years with a mean age of 16 years; 4% had ever been sexually active.

Overall, the IUD continuation rate was 95% after 1 year and 73% after 5 years. Most of the IUDs (96%) were inserted in the operating room.

Device malposition and expulsion accounted for a 5% rate of complications. Of the five expulsions, four were completely expelled from the uterus, and a fifth was partial and identified on ultrasound. No cases of pelvic inflammatory disease, pregnancy, or uterine perforation were reported, and the amenorrhea rate was approximately 60%.

Unique concerns regarding the use of IUDs in the disabled population include the appropriateness of IUDs as a first strategy for menstrual management or contraception, as well as potential distress related to bleeding and cramping that patients might find hard to articulate, the researchers said. However, the high continuation rate and low reports of side effects in the study suggests that the devices were well tolerated, and the data show that complications were minimal and manageable, they said.

The study findings were limited primarily by the retrospective design, “which involved loss of patients to follow-up, missing data, and reliance on adequate documentation,” Dr. Schwartz and associates noted. However, the study is the largest to date on levonorgestrel IUD use in young people with disabilities, and provides needed data on the safety and benefits of IUDs for menstrual management and contraception in this population, they said. Prospective studies are needed to assess continuation, outcomes, and long-term satisfaction with IUDs.

“However, these data are promising and should be used to allow more accurate counseling of adolescents with special needs and their families,” and it should be considered as an option for them, Dr. Schwartz and colleagues concluded.

“Clinicians should recognize that adolescents with disabilities have a range of decision-making capacities,” Cynthia Robbins, MD, and Mary A. Ott, MD, of Indiana University, Indianapolis, wrote in an accompanying editorial. Adolescents with disabilities may be left out of reproductive health discussions even if they are able, and the decisions are made by parents and caregivers.

For adolescents with mild disability, a shared decision-making approach is appropriate, in which providers and adolescents discuss reproductive health, with parent involvement as needed; “the adolescent is supported by the provider to express their preferences,” the editorialists wrote.

For those with more significant disability, they advised supported decision-making, in which the adolescent identifies a parent, family member, or caregiver as a trusted adult. “This supportive adult helps the adolescent communicate their goals and understand the decision and assists the provider in communication with the adolescent,” they said. For adolescents with a profound disability, the risks of placement and use of IUDs “should be thought of in a similar manner as other procedures that are routinely done to improve quality of life.”

“As clinicians, it is up to us to highlight these adolescents’ abilities to exercise their rights to sexual and reproductive health,” Dr. Robbins and Dr. Ott conclude.

The study was supported by a Bayer Healthcare Investigator-Initiated Research grant for women’s health to Dr. Schwartz and coauthor Lesley L. Breech, MD. The researchers had no other financial conflicts to disclose.

Dr. Ott disclosed providing expert consultation to Bayer, and that her spouse is employed Eli Lilly. Dr. Robbins had no relevant financial conflicts to disclose. They received no external funding for their editorial.

SOURCE: Schwartz BI et al. Pediatrics. 2020 Jul 23. doi: 10.1542/peds.2020-0016. Robbins C and Ott MA. Pediatrics. 2020 Jul 23. doi: 10.1542/peds.2020-006296.

Adolescents and young adults with physical, intellectual, and developmental disabilities can benefit from the use of levonorgestrel intrauterine devices for menstrual management and contraception, based on data from a retrospective study of 159 patients.

“Desire for menstrual management or suppression is common in young women with special needs, including complex medical conditions and physical, intellectual, and developmental disabilities,” and many of these patients require estrogen-free options because of comorbidities, medication interactions, or decreased mobility, wrote Beth I. Schwartz, MD, and colleagues at Cincinnati Children’s Hospital Medical Center. Dr. Schwartz currently is of Thomas Jefferson University, Philadelphia.

In a study published in Pediatrics, the researchers identified 159 nulliparous patients aged 22 years and younger with physical, intellectual, or developmental disabilities who received levonorgestrel IUDs at a tertiary care children’s hospital between July 1, 2004, and June 30, 2014.

A total of 185 levonorgestrel IUDs were placed. The patients ranged in age from 9 to 22 years with a mean age of 16 years; 4% had ever been sexually active.

Overall, the IUD continuation rate was 95% after 1 year and 73% after 5 years. Most of the IUDs (96%) were inserted in the operating room.

Device malposition and expulsion accounted for a 5% rate of complications. Of the five expulsions, four were completely expelled from the uterus, and a fifth was partial and identified on ultrasound. No cases of pelvic inflammatory disease, pregnancy, or uterine perforation were reported, and the amenorrhea rate was approximately 60%.

Unique concerns regarding the use of IUDs in the disabled population include the appropriateness of IUDs as a first strategy for menstrual management or contraception, as well as potential distress related to bleeding and cramping that patients might find hard to articulate, the researchers said. However, the high continuation rate and low reports of side effects in the study suggests that the devices were well tolerated, and the data show that complications were minimal and manageable, they said.

The study findings were limited primarily by the retrospective design, “which involved loss of patients to follow-up, missing data, and reliance on adequate documentation,” Dr. Schwartz and associates noted. However, the study is the largest to date on levonorgestrel IUD use in young people with disabilities, and provides needed data on the safety and benefits of IUDs for menstrual management and contraception in this population, they said. Prospective studies are needed to assess continuation, outcomes, and long-term satisfaction with IUDs.

“However, these data are promising and should be used to allow more accurate counseling of adolescents with special needs and their families,” and it should be considered as an option for them, Dr. Schwartz and colleagues concluded.

“Clinicians should recognize that adolescents with disabilities have a range of decision-making capacities,” Cynthia Robbins, MD, and Mary A. Ott, MD, of Indiana University, Indianapolis, wrote in an accompanying editorial. Adolescents with disabilities may be left out of reproductive health discussions even if they are able, and the decisions are made by parents and caregivers.

For adolescents with mild disability, a shared decision-making approach is appropriate, in which providers and adolescents discuss reproductive health, with parent involvement as needed; “the adolescent is supported by the provider to express their preferences,” the editorialists wrote.

For those with more significant disability, they advised supported decision-making, in which the adolescent identifies a parent, family member, or caregiver as a trusted adult. “This supportive adult helps the adolescent communicate their goals and understand the decision and assists the provider in communication with the adolescent,” they said. For adolescents with a profound disability, the risks of placement and use of IUDs “should be thought of in a similar manner as other procedures that are routinely done to improve quality of life.”

“As clinicians, it is up to us to highlight these adolescents’ abilities to exercise their rights to sexual and reproductive health,” Dr. Robbins and Dr. Ott conclude.

The study was supported by a Bayer Healthcare Investigator-Initiated Research grant for women’s health to Dr. Schwartz and coauthor Lesley L. Breech, MD. The researchers had no other financial conflicts to disclose.

Dr. Ott disclosed providing expert consultation to Bayer, and that her spouse is employed Eli Lilly. Dr. Robbins had no relevant financial conflicts to disclose. They received no external funding for their editorial.

SOURCE: Schwartz BI et al. Pediatrics. 2020 Jul 23. doi: 10.1542/peds.2020-0016. Robbins C and Ott MA. Pediatrics. 2020 Jul 23. doi: 10.1542/peds.2020-006296.

Adolescents and young adults with physical, intellectual, and developmental disabilities can benefit from the use of levonorgestrel intrauterine devices for menstrual management and contraception, based on data from a retrospective study of 159 patients.

“Desire for menstrual management or suppression is common in young women with special needs, including complex medical conditions and physical, intellectual, and developmental disabilities,” and many of these patients require estrogen-free options because of comorbidities, medication interactions, or decreased mobility, wrote Beth I. Schwartz, MD, and colleagues at Cincinnati Children’s Hospital Medical Center. Dr. Schwartz currently is of Thomas Jefferson University, Philadelphia.

In a study published in Pediatrics, the researchers identified 159 nulliparous patients aged 22 years and younger with physical, intellectual, or developmental disabilities who received levonorgestrel IUDs at a tertiary care children’s hospital between July 1, 2004, and June 30, 2014.

A total of 185 levonorgestrel IUDs were placed. The patients ranged in age from 9 to 22 years with a mean age of 16 years; 4% had ever been sexually active.

Overall, the IUD continuation rate was 95% after 1 year and 73% after 5 years. Most of the IUDs (96%) were inserted in the operating room.

Device malposition and expulsion accounted for a 5% rate of complications. Of the five expulsions, four were completely expelled from the uterus, and a fifth was partial and identified on ultrasound. No cases of pelvic inflammatory disease, pregnancy, or uterine perforation were reported, and the amenorrhea rate was approximately 60%.

Unique concerns regarding the use of IUDs in the disabled population include the appropriateness of IUDs as a first strategy for menstrual management or contraception, as well as potential distress related to bleeding and cramping that patients might find hard to articulate, the researchers said. However, the high continuation rate and low reports of side effects in the study suggests that the devices were well tolerated, and the data show that complications were minimal and manageable, they said.

The study findings were limited primarily by the retrospective design, “which involved loss of patients to follow-up, missing data, and reliance on adequate documentation,” Dr. Schwartz and associates noted. However, the study is the largest to date on levonorgestrel IUD use in young people with disabilities, and provides needed data on the safety and benefits of IUDs for menstrual management and contraception in this population, they said. Prospective studies are needed to assess continuation, outcomes, and long-term satisfaction with IUDs.

“However, these data are promising and should be used to allow more accurate counseling of adolescents with special needs and their families,” and it should be considered as an option for them, Dr. Schwartz and colleagues concluded.

“Clinicians should recognize that adolescents with disabilities have a range of decision-making capacities,” Cynthia Robbins, MD, and Mary A. Ott, MD, of Indiana University, Indianapolis, wrote in an accompanying editorial. Adolescents with disabilities may be left out of reproductive health discussions even if they are able, and the decisions are made by parents and caregivers.

For adolescents with mild disability, a shared decision-making approach is appropriate, in which providers and adolescents discuss reproductive health, with parent involvement as needed; “the adolescent is supported by the provider to express their preferences,” the editorialists wrote.

For those with more significant disability, they advised supported decision-making, in which the adolescent identifies a parent, family member, or caregiver as a trusted adult. “This supportive adult helps the adolescent communicate their goals and understand the decision and assists the provider in communication with the adolescent,” they said. For adolescents with a profound disability, the risks of placement and use of IUDs “should be thought of in a similar manner as other procedures that are routinely done to improve quality of life.”

“As clinicians, it is up to us to highlight these adolescents’ abilities to exercise their rights to sexual and reproductive health,” Dr. Robbins and Dr. Ott conclude.

The study was supported by a Bayer Healthcare Investigator-Initiated Research grant for women’s health to Dr. Schwartz and coauthor Lesley L. Breech, MD. The researchers had no other financial conflicts to disclose.

Dr. Ott disclosed providing expert consultation to Bayer, and that her spouse is employed Eli Lilly. Dr. Robbins had no relevant financial conflicts to disclose. They received no external funding for their editorial.

SOURCE: Schwartz BI et al. Pediatrics. 2020 Jul 23. doi: 10.1542/peds.2020-0016. Robbins C and Ott MA. Pediatrics. 2020 Jul 23. doi: 10.1542/peds.2020-006296.

In early April, Maura Quinlan, MD, was working nights on the labor and delivery unit at Northwestern Medicine Prentice Women’s Hospital in Chicago. At the time, hospital policy was to test only patients with known COVID-19 symptoms for SARS-CoV-2. Women in labor wore N95 masks, but only while pushing – and practitioners didn’t always don proper protection in time.

Babies came and families rejoiced. But Dr. Quinlan looks back on those weeks with a degree of horror. “We were laboring a bunch of patients that probably had COVID,” she said, and they were doing so without proper protection.

She’s probably right. According to one study in the New England Journal of Medicine, 13.7% of 211 women who came into the labor and delivery unit at one New York City hospital between March 22 and April 2 were asymptomatic but infected, potentially putting staff and doctors at risk.

Dr. Quinlan already knew she and her fellow ob.gyns. had been walking a thin line and, upon seeing that research, her heart sank. In the middle of a pandemic, they had been racing to keep up with the reality of delivering babies. But despite their efforts to protect both practitioners and patients, some aspects slipped through the cracks. Today, every laboring patient admitted to Northwestern is now tested for the novel coronavirus.

Across the country, hospital labor and delivery wards have been working to find a careful and informed balance among multiple competing interests: the safety of their health care workers, the health of tiny and vulnerable new humans, and the stability of a birthing mother. Each hospital has been making the best decisions it can based on available data. The result is a patchwork of policies, but all of them center around rapid testing and appropriate protection.
 

Shifting recommendations

One case study of women in a New York City hospital during the height of the city’s surge found that, of seven confirmed COVID-19–positive patients, two were asymptomatic upon admission to the obstetrical service, and these same two patients ultimately required unplanned ICU admission. The women’s care prior to their positive diagnosis had exposed multiple health care workers, all of whom lacked appropriate personal protective equipment (PPE), the study authors wrote. “Further, five of seven confirmed COVID-19–positive women were afebrile on initial screen, and four did not first report a cough. In some locations where testing availability remains limited, the minimal symptoms reported for some of these cases might have been insufficient to prompt COVID-19 testing.”

As studies like this pour in, societies continue to update their recommendations accordingly. The latest guidance from the American College of Obstetricians and Gynecologists came on July 1. The group suggests testing all labor and delivery patients, particularly in high-prevalence areas. If tests are in short supply, it recommends prioritizing testing pregnant women with suspected COVID-19 and those who develop symptoms during admission.

At Northwestern, the hospital requests patients stay home and quarantine for the weeks leading up to their delivery date. Then, they rapidly test every patient who comes in for delivery and aim to have results available within a few hours.

The hospital’s 30-room labor and delivery wing remains reserved for patients who test negative. Those with positive COVID-19 results are sent to a 6-bed COVID labor and delivery unit elsewhere in the hospital. “We were lucky we had the space to do that, because smaller community hospitals wouldn’t have a separate unused unit where they could put these women,” Dr. Quinlan said.

In the COVID unit, women deliver without a support person – no partner, doula, or family member can join. Doctors and nurses wear full PPE and work only in that ward. And because some research shows that pregnant women who are asymptomatic or presymptomatic may develop symptoms quickly after starting labor with no measurable illness, Dr. Quinlan must decide on a case-by-case basis what to do, if anything at all.

Delaying an induction could allow the infection to resolve or it could result in her patient moving from presymptomatic disease to full-blown pneumonia. Accelerating labor could bring on symptoms or it could allow a mother to deliver safely and get out of the hospital as quickly as possible. “There is an advantage to having the baby now if you feel okay – even if it’s alone – and getting home,” Dr. Quinlan said.

The hospital also tests the partners of women who are COVID-19 positive. Those with negative results can take the newborn home and try to maintain distance until the mother is no longer symptomatic.

In different parts of the country, hospitals have developed different approaches. Southern California is experiencing its own surge, but at the Ronald Reagan University of California, Los Angeles, Medical Center there still haven’t been enough COVID-19 patients to warrant a separate labor and delivery unit.

At UCLA, staff swab patients when they enter the labor and delivery ward — those who test positive have specific room designations. For both COVID-19–positive patients and women who progress faster than test results can be returned, the goals are the same, said Rashmi Rao, MD, an ob.gyn. at UCLA: Deliver in the safest way possible for both mother and baby.

All women, positive or negative, must wear masks during labor – as much as they can tolerate, at least. For patients who are only mildly ill or asymptomatic, the only difference is that everyone wears protective gear. But if a patient’s oxygen levels dip, or her baby is in distress, the team moves more quickly to a cesarean delivery than they’d do with a healthy patient.

Just as hospital policies have been evolving, rules for visitors have been constantly changing too. Initially, UCLA allowed a support person to be present during delivery but had to leave immediately following. Now, each new mother is allowed one visitor for the duration of their stay. And the hospital suggests that patients who are COVID-19 positive recover in separate rooms from their babies and encourages them to maintain distance from their infants, except when breastfeeding.

“We respect and understand that this is a joyous occasion and we’re trying to keep families together as much as possible,” Dr. Rao said.
 

Care conundrums

How hospitals protect their smallest charges keeps changing too. Reports have been circulating about newborns being taken away from COVID-19-positive mothers, especially in marginalized communities. The stories have led many to worry they’d be forcibly separated from their babies. Most hospitals, however, leave it up to the woman and her doctors to decide how much separation is needed. “After delivery, it depends on how someone is feeling,” Dr. Rao said.

The American Academy of Pediatrics recommends that mothers who are COVID-19–positive pump breast milk and have a healthy caregiver use that milk, or formula, to bottle-feed the baby, with the new mother remaining 6 feet away from the child as much as she can. If that’s not possible, she should wear gloves and a mask while breastfeeding until she has been naturally afebrile for 72 hours and at least 1 week removed from the first appearance of her symptoms.

“It’s tragically hard,” said Dr. Quinlan, to keep a COVID-19–positive mother even 6 feet away from her newborn baby. “If a mother declines separation, we ask the acting pediatric team to discuss the theoretical risks and paucity of data.”

Until recently, research indicated that SARS-CoV-2 wasn’t being transmitted through the uterus from mothers to their babies. And despite a recent case study reporting transplacental transmission between a mother and her fetus in France, researchers still say that the risk of transference is low. To ensure newborn risk remains as low as possible, UCLA’s policy is to swab the baby when he/she is 24 hours old and keep watch for signs of infection: increased lethargy, difficulty waking, or gastrointestinal symptoms like vomiting.

Transmission via breast milk has also, to date, proven relatively unlikely. One study in The Lancet detected the novel coronavirus in breast milk, although it’s not clear that the virus can be passed on in the fluid, says Christina Chambers, PhD, a professor of pediatrics at the University of California, San Diego. Dr. Chambers is studying breast milk to see if the virus or antibodies to it are present. She is also investigating how infection with SARS-CoV-2 impacts women at different times in pregnancy, something that’s still an open question.

“[In] pregnant women with a deteriorating infection, the decisions are the same you would make with any delivery: Save the mom and save the baby,” Dr. Chambers said. “Beyond that, I am encouraged to see that pregnant women are prioritized to being tested,” something that will help researchers understand prevalence of disease in order to better understand whether some symptoms are more dangerous than others.

The situation is evolving so quickly that hospitals and providers are simply trying to stay abreast of the flood of new research. In the absence of definitive answers, they are using the information available and adjusting on the fly. “We are cautiously waiting for more data,” said Dr. Rao. “With the information we have we are doing the best we can to keep our patients safe. And we’re just going to keep at it.”

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

In early April, Maura Quinlan, MD, was working nights on the labor and delivery unit at Northwestern Medicine Prentice Women’s Hospital in Chicago. At the time, hospital policy was to test only patients with known COVID-19 symptoms for SARS-CoV-2. Women in labor wore N95 masks, but only while pushing – and practitioners didn’t always don proper protection in time.

Babies came and families rejoiced. But Dr. Quinlan looks back on those weeks with a degree of horror. “We were laboring a bunch of patients that probably had COVID,” she said, and they were doing so without proper protection.

She’s probably right. According to one study in the New England Journal of Medicine, 13.7% of 211 women who came into the labor and delivery unit at one New York City hospital between March 22 and April 2 were asymptomatic but infected, potentially putting staff and doctors at risk.

Dr. Quinlan already knew she and her fellow ob.gyns. had been walking a thin line and, upon seeing that research, her heart sank. In the middle of a pandemic, they had been racing to keep up with the reality of delivering babies. But despite their efforts to protect both practitioners and patients, some aspects slipped through the cracks. Today, every laboring patient admitted to Northwestern is now tested for the novel coronavirus.

Across the country, hospital labor and delivery wards have been working to find a careful and informed balance among multiple competing interests: the safety of their health care workers, the health of tiny and vulnerable new humans, and the stability of a birthing mother. Each hospital has been making the best decisions it can based on available data. The result is a patchwork of policies, but all of them center around rapid testing and appropriate protection.
 

Shifting recommendations

One case study of women in a New York City hospital during the height of the city’s surge found that, of seven confirmed COVID-19–positive patients, two were asymptomatic upon admission to the obstetrical service, and these same two patients ultimately required unplanned ICU admission. The women’s care prior to their positive diagnosis had exposed multiple health care workers, all of whom lacked appropriate personal protective equipment (PPE), the study authors wrote. “Further, five of seven confirmed COVID-19–positive women were afebrile on initial screen, and four did not first report a cough. In some locations where testing availability remains limited, the minimal symptoms reported for some of these cases might have been insufficient to prompt COVID-19 testing.”

As studies like this pour in, societies continue to update their recommendations accordingly. The latest guidance from the American College of Obstetricians and Gynecologists came on July 1. The group suggests testing all labor and delivery patients, particularly in high-prevalence areas. If tests are in short supply, it recommends prioritizing testing pregnant women with suspected COVID-19 and those who develop symptoms during admission.

At Northwestern, the hospital requests patients stay home and quarantine for the weeks leading up to their delivery date. Then, they rapidly test every patient who comes in for delivery and aim to have results available within a few hours.

The hospital’s 30-room labor and delivery wing remains reserved for patients who test negative. Those with positive COVID-19 results are sent to a 6-bed COVID labor and delivery unit elsewhere in the hospital. “We were lucky we had the space to do that, because smaller community hospitals wouldn’t have a separate unused unit where they could put these women,” Dr. Quinlan said.

In the COVID unit, women deliver without a support person – no partner, doula, or family member can join. Doctors and nurses wear full PPE and work only in that ward. And because some research shows that pregnant women who are asymptomatic or presymptomatic may develop symptoms quickly after starting labor with no measurable illness, Dr. Quinlan must decide on a case-by-case basis what to do, if anything at all.

Delaying an induction could allow the infection to resolve or it could result in her patient moving from presymptomatic disease to full-blown pneumonia. Accelerating labor could bring on symptoms or it could allow a mother to deliver safely and get out of the hospital as quickly as possible. “There is an advantage to having the baby now if you feel okay – even if it’s alone – and getting home,” Dr. Quinlan said.

The hospital also tests the partners of women who are COVID-19 positive. Those with negative results can take the newborn home and try to maintain distance until the mother is no longer symptomatic.

In different parts of the country, hospitals have developed different approaches. Southern California is experiencing its own surge, but at the Ronald Reagan University of California, Los Angeles, Medical Center there still haven’t been enough COVID-19 patients to warrant a separate labor and delivery unit.

At UCLA, staff swab patients when they enter the labor and delivery ward — those who test positive have specific room designations. For both COVID-19–positive patients and women who progress faster than test results can be returned, the goals are the same, said Rashmi Rao, MD, an ob.gyn. at UCLA: Deliver in the safest way possible for both mother and baby.

All women, positive or negative, must wear masks during labor – as much as they can tolerate, at least. For patients who are only mildly ill or asymptomatic, the only difference is that everyone wears protective gear. But if a patient’s oxygen levels dip, or her baby is in distress, the team moves more quickly to a cesarean delivery than they’d do with a healthy patient.

Just as hospital policies have been evolving, rules for visitors have been constantly changing too. Initially, UCLA allowed a support person to be present during delivery but had to leave immediately following. Now, each new mother is allowed one visitor for the duration of their stay. And the hospital suggests that patients who are COVID-19 positive recover in separate rooms from their babies and encourages them to maintain distance from their infants, except when breastfeeding.

“We respect and understand that this is a joyous occasion and we’re trying to keep families together as much as possible,” Dr. Rao said.
 

Care conundrums

How hospitals protect their smallest charges keeps changing too. Reports have been circulating about newborns being taken away from COVID-19-positive mothers, especially in marginalized communities. The stories have led many to worry they’d be forcibly separated from their babies. Most hospitals, however, leave it up to the woman and her doctors to decide how much separation is needed. “After delivery, it depends on how someone is feeling,” Dr. Rao said.

The American Academy of Pediatrics recommends that mothers who are COVID-19–positive pump breast milk and have a healthy caregiver use that milk, or formula, to bottle-feed the baby, with the new mother remaining 6 feet away from the child as much as she can. If that’s not possible, she should wear gloves and a mask while breastfeeding until she has been naturally afebrile for 72 hours and at least 1 week removed from the first appearance of her symptoms.

“It’s tragically hard,” said Dr. Quinlan, to keep a COVID-19–positive mother even 6 feet away from her newborn baby. “If a mother declines separation, we ask the acting pediatric team to discuss the theoretical risks and paucity of data.”

Until recently, research indicated that SARS-CoV-2 wasn’t being transmitted through the uterus from mothers to their babies. And despite a recent case study reporting transplacental transmission between a mother and her fetus in France, researchers still say that the risk of transference is low. To ensure newborn risk remains as low as possible, UCLA’s policy is to swab the baby when he/she is 24 hours old and keep watch for signs of infection: increased lethargy, difficulty waking, or gastrointestinal symptoms like vomiting.

Transmission via breast milk has also, to date, proven relatively unlikely. One study in The Lancet detected the novel coronavirus in breast milk, although it’s not clear that the virus can be passed on in the fluid, says Christina Chambers, PhD, a professor of pediatrics at the University of California, San Diego. Dr. Chambers is studying breast milk to see if the virus or antibodies to it are present. She is also investigating how infection with SARS-CoV-2 impacts women at different times in pregnancy, something that’s still an open question.

“[In] pregnant women with a deteriorating infection, the decisions are the same you would make with any delivery: Save the mom and save the baby,” Dr. Chambers said. “Beyond that, I am encouraged to see that pregnant women are prioritized to being tested,” something that will help researchers understand prevalence of disease in order to better understand whether some symptoms are more dangerous than others.

The situation is evolving so quickly that hospitals and providers are simply trying to stay abreast of the flood of new research. In the absence of definitive answers, they are using the information available and adjusting on the fly. “We are cautiously waiting for more data,” said Dr. Rao. “With the information we have we are doing the best we can to keep our patients safe. And we’re just going to keep at it.”

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

In early April, Maura Quinlan, MD, was working nights on the labor and delivery unit at Northwestern Medicine Prentice Women’s Hospital in Chicago. At the time, hospital policy was to test only patients with known COVID-19 symptoms for SARS-CoV-2. Women in labor wore N95 masks, but only while pushing – and practitioners didn’t always don proper protection in time.

Babies came and families rejoiced. But Dr. Quinlan looks back on those weeks with a degree of horror. “We were laboring a bunch of patients that probably had COVID,” she said, and they were doing so without proper protection.

She’s probably right. According to one study in the New England Journal of Medicine, 13.7% of 211 women who came into the labor and delivery unit at one New York City hospital between March 22 and April 2 were asymptomatic but infected, potentially putting staff and doctors at risk.

Dr. Quinlan already knew she and her fellow ob.gyns. had been walking a thin line and, upon seeing that research, her heart sank. In the middle of a pandemic, they had been racing to keep up with the reality of delivering babies. But despite their efforts to protect both practitioners and patients, some aspects slipped through the cracks. Today, every laboring patient admitted to Northwestern is now tested for the novel coronavirus.

Across the country, hospital labor and delivery wards have been working to find a careful and informed balance among multiple competing interests: the safety of their health care workers, the health of tiny and vulnerable new humans, and the stability of a birthing mother. Each hospital has been making the best decisions it can based on available data. The result is a patchwork of policies, but all of them center around rapid testing and appropriate protection.
 

Shifting recommendations

One case study of women in a New York City hospital during the height of the city’s surge found that, of seven confirmed COVID-19–positive patients, two were asymptomatic upon admission to the obstetrical service, and these same two patients ultimately required unplanned ICU admission. The women’s care prior to their positive diagnosis had exposed multiple health care workers, all of whom lacked appropriate personal protective equipment (PPE), the study authors wrote. “Further, five of seven confirmed COVID-19–positive women were afebrile on initial screen, and four did not first report a cough. In some locations where testing availability remains limited, the minimal symptoms reported for some of these cases might have been insufficient to prompt COVID-19 testing.”

As studies like this pour in, societies continue to update their recommendations accordingly. The latest guidance from the American College of Obstetricians and Gynecologists came on July 1. The group suggests testing all labor and delivery patients, particularly in high-prevalence areas. If tests are in short supply, it recommends prioritizing testing pregnant women with suspected COVID-19 and those who develop symptoms during admission.

At Northwestern, the hospital requests patients stay home and quarantine for the weeks leading up to their delivery date. Then, they rapidly test every patient who comes in for delivery and aim to have results available within a few hours.

The hospital’s 30-room labor and delivery wing remains reserved for patients who test negative. Those with positive COVID-19 results are sent to a 6-bed COVID labor and delivery unit elsewhere in the hospital. “We were lucky we had the space to do that, because smaller community hospitals wouldn’t have a separate unused unit where they could put these women,” Dr. Quinlan said.

In the COVID unit, women deliver without a support person – no partner, doula, or family member can join. Doctors and nurses wear full PPE and work only in that ward. And because some research shows that pregnant women who are asymptomatic or presymptomatic may develop symptoms quickly after starting labor with no measurable illness, Dr. Quinlan must decide on a case-by-case basis what to do, if anything at all.

Delaying an induction could allow the infection to resolve or it could result in her patient moving from presymptomatic disease to full-blown pneumonia. Accelerating labor could bring on symptoms or it could allow a mother to deliver safely and get out of the hospital as quickly as possible. “There is an advantage to having the baby now if you feel okay – even if it’s alone – and getting home,” Dr. Quinlan said.

The hospital also tests the partners of women who are COVID-19 positive. Those with negative results can take the newborn home and try to maintain distance until the mother is no longer symptomatic.

In different parts of the country, hospitals have developed different approaches. Southern California is experiencing its own surge, but at the Ronald Reagan University of California, Los Angeles, Medical Center there still haven’t been enough COVID-19 patients to warrant a separate labor and delivery unit.

At UCLA, staff swab patients when they enter the labor and delivery ward — those who test positive have specific room designations. For both COVID-19–positive patients and women who progress faster than test results can be returned, the goals are the same, said Rashmi Rao, MD, an ob.gyn. at UCLA: Deliver in the safest way possible for both mother and baby.

All women, positive or negative, must wear masks during labor – as much as they can tolerate, at least. For patients who are only mildly ill or asymptomatic, the only difference is that everyone wears protective gear. But if a patient’s oxygen levels dip, or her baby is in distress, the team moves more quickly to a cesarean delivery than they’d do with a healthy patient.

Just as hospital policies have been evolving, rules for visitors have been constantly changing too. Initially, UCLA allowed a support person to be present during delivery but had to leave immediately following. Now, each new mother is allowed one visitor for the duration of their stay. And the hospital suggests that patients who are COVID-19 positive recover in separate rooms from their babies and encourages them to maintain distance from their infants, except when breastfeeding.

“We respect and understand that this is a joyous occasion and we’re trying to keep families together as much as possible,” Dr. Rao said.
 

Care conundrums

How hospitals protect their smallest charges keeps changing too. Reports have been circulating about newborns being taken away from COVID-19-positive mothers, especially in marginalized communities. The stories have led many to worry they’d be forcibly separated from their babies. Most hospitals, however, leave it up to the woman and her doctors to decide how much separation is needed. “After delivery, it depends on how someone is feeling,” Dr. Rao said.

The American Academy of Pediatrics recommends that mothers who are COVID-19–positive pump breast milk and have a healthy caregiver use that milk, or formula, to bottle-feed the baby, with the new mother remaining 6 feet away from the child as much as she can. If that’s not possible, she should wear gloves and a mask while breastfeeding until she has been naturally afebrile for 72 hours and at least 1 week removed from the first appearance of her symptoms.

“It’s tragically hard,” said Dr. Quinlan, to keep a COVID-19–positive mother even 6 feet away from her newborn baby. “If a mother declines separation, we ask the acting pediatric team to discuss the theoretical risks and paucity of data.”

Until recently, research indicated that SARS-CoV-2 wasn’t being transmitted through the uterus from mothers to their babies. And despite a recent case study reporting transplacental transmission between a mother and her fetus in France, researchers still say that the risk of transference is low. To ensure newborn risk remains as low as possible, UCLA’s policy is to swab the baby when he/she is 24 hours old and keep watch for signs of infection: increased lethargy, difficulty waking, or gastrointestinal symptoms like vomiting.

Transmission via breast milk has also, to date, proven relatively unlikely. One study in The Lancet detected the novel coronavirus in breast milk, although it’s not clear that the virus can be passed on in the fluid, says Christina Chambers, PhD, a professor of pediatrics at the University of California, San Diego. Dr. Chambers is studying breast milk to see if the virus or antibodies to it are present. She is also investigating how infection with SARS-CoV-2 impacts women at different times in pregnancy, something that’s still an open question.

“[In] pregnant women with a deteriorating infection, the decisions are the same you would make with any delivery: Save the mom and save the baby,” Dr. Chambers said. “Beyond that, I am encouraged to see that pregnant women are prioritized to being tested,” something that will help researchers understand prevalence of disease in order to better understand whether some symptoms are more dangerous than others.

The situation is evolving so quickly that hospitals and providers are simply trying to stay abreast of the flood of new research. In the absence of definitive answers, they are using the information available and adjusting on the fly. “We are cautiously waiting for more data,” said Dr. Rao. “With the information we have we are doing the best we can to keep our patients safe. And we’re just going to keep at it.”

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

Use of weight-promoting medications may contribute to postmenopausal abdominal weight gain in women, based on data from more than 76,000 individuals in the Women’s Health Initiative.

“Many of the medications prescribed to treat obesity-related comorbidities such as hypertension, type 2 diabetes, and depression have been linked to weight gain,” but the impact of such medications in relation to changes in body mass index (BMI) and waist circumference in postmenopausal women in particular has not been studied, wrote Fatima Cody Stanford, MD, of Harvard Medical School, Boston, and colleagues.

“Postmenopausal women are of significant interest as those who have obesity and normal weight central obesity are at increased risk for conditions such as invasive breast cancer, sleep disturbances, and type 2 diabetes, as well as mortality,” they wrote.

In a study published in the journal Menopause, the researchers identified 76,252 postmenopausal women aged 50-79 years and measured body mass index at baseline and after 3 years. Medication use was determined by a medication inventory of pill bottles brought to baseline and year-3 visits.

During a 3-year follow-up period, the average BMI increase was 0.37 kg/m² in women taking at least one weight-promoting medication, compared with an average increase of 0.27 kg/m² in women not taking such medications (P = .0045). Weight-promoting medications in the study included antidepressants, beta-blockers, insulin, and/or glucocorticosteroids. The researchers used generalized linear models to assess the impact of these medications on increased BMI and waist circumference.

In addition, the average increase in waist circumference was 1.10 cm in women taking at least one weight-promoting medication, compared with 0.89 cm (P = .0077) for women not on such medications.

“Type of medication, dosage, and race/ethnicity may have important interrelationships,” in postmenopausal weight gain, as do individual susceptibility and genetics, the researchers noted. “Options to mitigate the weight gain may include proactive lifestyle modifications, reduction in dose, change to another agent, or discontinuation of the medication altogether. If alternative medications are not an option, lifestyle factors such as diet quality, physical activity level, and sleep quality and duration warrant emphasis.”

The study findings were limited by several factors, including a lack of data on indications and underlying health conditions surrounding the prescription of various medications, notably psychotropics and antipsychotics, the researchers wrote.

However, the data “may help to inform clinical decision-making and support increased attention to lifestyle modifications and other strategies” to mitigate the potential for weight gain in a population already at risk for overweight and obesity over time, they concluded.

“Given the obesity epidemic, addressing factors contributing to weight gain in midlife [a time associated with weight gain] women is critical,” Stephanie S. Faubion, MD, of the Mayo Clinic in Jacksonville, Fla., said in an interview. Dr. Faubion said that the study findings were not surprising given the widespread use of known weight-promoting medications by midlife women for such as hypertension, diabetes, and depression.

“Clinicians need to ensure that they prescribe medications that are truly needed and utilize the lowest dose required to achieve treatment goals,” Dr. Faubion said. “When possible, alternative therapies that do not cause weight gain should be considered. In addition, patients should be warned of the potential for weight gain, and clinicians should advocate for lifestyle measures aimed at mitigating these effects.”

The findings do not encourage the use of alternative therapies for menopausal symptoms per se, added Dr. Faubion, who is also medical director of the North American Menopause Society. “Hormone therapy is not associated with weight gain, and if anything, it is weight favorable and associated with less weight around the midsection. It is the alternative strategies for management of hot flashes that are associated with weight gain, such as antidepressants and gabapentin.

“We need to focus efforts on strategies to prevent weight gain in midlife to avoid the development of conditions that necessitate initiation of many of these weight-promoting medications,” Dr. Faubion said.

The study was supported by the National Institutes of Health and Massachusetts General Hospital Executive Committee on Research, the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases. The researchers had no financial conflicts to disclose. Dr. Faubion had no financial conflicts to disclose.

SOURCE: Stanford FC et al. Menopause. 2020 Jul 13. doi: 10.1097/GME.0000000000001589.

Use of weight-promoting medications may contribute to postmenopausal abdominal weight gain in women, based on data from more than 76,000 individuals in the Women’s Health Initiative.

“Many of the medications prescribed to treat obesity-related comorbidities such as hypertension, type 2 diabetes, and depression have been linked to weight gain,” but the impact of such medications in relation to changes in body mass index (BMI) and waist circumference in postmenopausal women in particular has not been studied, wrote Fatima Cody Stanford, MD, of Harvard Medical School, Boston, and colleagues.

“Postmenopausal women are of significant interest as those who have obesity and normal weight central obesity are at increased risk for conditions such as invasive breast cancer, sleep disturbances, and type 2 diabetes, as well as mortality,” they wrote.

In a study published in the journal Menopause, the researchers identified 76,252 postmenopausal women aged 50-79 years and measured body mass index at baseline and after 3 years. Medication use was determined by a medication inventory of pill bottles brought to baseline and year-3 visits.

During a 3-year follow-up period, the average BMI increase was 0.37 kg/m² in women taking at least one weight-promoting medication, compared with an average increase of 0.27 kg/m² in women not taking such medications (P = .0045). Weight-promoting medications in the study included antidepressants, beta-blockers, insulin, and/or glucocorticosteroids. The researchers used generalized linear models to assess the impact of these medications on increased BMI and waist circumference.

In addition, the average increase in waist circumference was 1.10 cm in women taking at least one weight-promoting medication, compared with 0.89 cm (P = .0077) for women not on such medications.

“Type of medication, dosage, and race/ethnicity may have important interrelationships,” in postmenopausal weight gain, as do individual susceptibility and genetics, the researchers noted. “Options to mitigate the weight gain may include proactive lifestyle modifications, reduction in dose, change to another agent, or discontinuation of the medication altogether. If alternative medications are not an option, lifestyle factors such as diet quality, physical activity level, and sleep quality and duration warrant emphasis.”

The study findings were limited by several factors, including a lack of data on indications and underlying health conditions surrounding the prescription of various medications, notably psychotropics and antipsychotics, the researchers wrote.

However, the data “may help to inform clinical decision-making and support increased attention to lifestyle modifications and other strategies” to mitigate the potential for weight gain in a population already at risk for overweight and obesity over time, they concluded.

“Given the obesity epidemic, addressing factors contributing to weight gain in midlife [a time associated with weight gain] women is critical,” Stephanie S. Faubion, MD, of the Mayo Clinic in Jacksonville, Fla., said in an interview. Dr. Faubion said that the study findings were not surprising given the widespread use of known weight-promoting medications by midlife women for such as hypertension, diabetes, and depression.

“Clinicians need to ensure that they prescribe medications that are truly needed and utilize the lowest dose required to achieve treatment goals,” Dr. Faubion said. “When possible, alternative therapies that do not cause weight gain should be considered. In addition, patients should be warned of the potential for weight gain, and clinicians should advocate for lifestyle measures aimed at mitigating these effects.”

The findings do not encourage the use of alternative therapies for menopausal symptoms per se, added Dr. Faubion, who is also medical director of the North American Menopause Society. “Hormone therapy is not associated with weight gain, and if anything, it is weight favorable and associated with less weight around the midsection. It is the alternative strategies for management of hot flashes that are associated with weight gain, such as antidepressants and gabapentin.

“We need to focus efforts on strategies to prevent weight gain in midlife to avoid the development of conditions that necessitate initiation of many of these weight-promoting medications,” Dr. Faubion said.

The study was supported by the National Institutes of Health and Massachusetts General Hospital Executive Committee on Research, the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases. The researchers had no financial conflicts to disclose. Dr. Faubion had no financial conflicts to disclose.

SOURCE: Stanford FC et al. Menopause. 2020 Jul 13. doi: 10.1097/GME.0000000000001589.

Use of weight-promoting medications may contribute to postmenopausal abdominal weight gain in women, based on data from more than 76,000 individuals in the Women’s Health Initiative.

“Many of the medications prescribed to treat obesity-related comorbidities such as hypertension, type 2 diabetes, and depression have been linked to weight gain,” but the impact of such medications in relation to changes in body mass index (BMI) and waist circumference in postmenopausal women in particular has not been studied, wrote Fatima Cody Stanford, MD, of Harvard Medical School, Boston, and colleagues.

“Postmenopausal women are of significant interest as those who have obesity and normal weight central obesity are at increased risk for conditions such as invasive breast cancer, sleep disturbances, and type 2 diabetes, as well as mortality,” they wrote.

In a study published in the journal Menopause, the researchers identified 76,252 postmenopausal women aged 50-79 years and measured body mass index at baseline and after 3 years. Medication use was determined by a medication inventory of pill bottles brought to baseline and year-3 visits.

During a 3-year follow-up period, the average BMI increase was 0.37 kg/m² in women taking at least one weight-promoting medication, compared with an average increase of 0.27 kg/m² in women not taking such medications (P = .0045). Weight-promoting medications in the study included antidepressants, beta-blockers, insulin, and/or glucocorticosteroids. The researchers used generalized linear models to assess the impact of these medications on increased BMI and waist circumference.

In addition, the average increase in waist circumference was 1.10 cm in women taking at least one weight-promoting medication, compared with 0.89 cm (P = .0077) for women not on such medications.

“Type of medication, dosage, and race/ethnicity may have important interrelationships,” in postmenopausal weight gain, as do individual susceptibility and genetics, the researchers noted. “Options to mitigate the weight gain may include proactive lifestyle modifications, reduction in dose, change to another agent, or discontinuation of the medication altogether. If alternative medications are not an option, lifestyle factors such as diet quality, physical activity level, and sleep quality and duration warrant emphasis.”

The study findings were limited by several factors, including a lack of data on indications and underlying health conditions surrounding the prescription of various medications, notably psychotropics and antipsychotics, the researchers wrote.

However, the data “may help to inform clinical decision-making and support increased attention to lifestyle modifications and other strategies” to mitigate the potential for weight gain in a population already at risk for overweight and obesity over time, they concluded.

“Given the obesity epidemic, addressing factors contributing to weight gain in midlife [a time associated with weight gain] women is critical,” Stephanie S. Faubion, MD, of the Mayo Clinic in Jacksonville, Fla., said in an interview. Dr. Faubion said that the study findings were not surprising given the widespread use of known weight-promoting medications by midlife women for such as hypertension, diabetes, and depression.

“Clinicians need to ensure that they prescribe medications that are truly needed and utilize the lowest dose required to achieve treatment goals,” Dr. Faubion said. “When possible, alternative therapies that do not cause weight gain should be considered. In addition, patients should be warned of the potential for weight gain, and clinicians should advocate for lifestyle measures aimed at mitigating these effects.”

The findings do not encourage the use of alternative therapies for menopausal symptoms per se, added Dr. Faubion, who is also medical director of the North American Menopause Society. “Hormone therapy is not associated with weight gain, and if anything, it is weight favorable and associated with less weight around the midsection. It is the alternative strategies for management of hot flashes that are associated with weight gain, such as antidepressants and gabapentin.

“We need to focus efforts on strategies to prevent weight gain in midlife to avoid the development of conditions that necessitate initiation of many of these weight-promoting medications,” Dr. Faubion said.

The study was supported by the National Institutes of Health and Massachusetts General Hospital Executive Committee on Research, the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases. The researchers had no financial conflicts to disclose. Dr. Faubion had no financial conflicts to disclose.

SOURCE: Stanford FC et al. Menopause. 2020 Jul 13. doi: 10.1097/GME.0000000000001589.

Osteoporosis treatment with abaloparatide in postmenopausal women does not lead to increased cardiovascular risk, according to a post hoc analysis of the pivotal ACTIVE and ACTIVExtend trials.

iStock/Thinkstock

“Neither treatment with abaloparatide or teriparatide was associated with an increase in serious cardiac [adverse events],” wrote Felicia Cosman, MD, of Columbia University, New York, and coauthors. The study was published in the Journal of Clinical Endocrinology.

To assess the cardiovascular safety profile of abaloparatide, a synthetic analogue of parathyroid hormone–related peptide, the researchers analyzed data on heart rate, blood pressure and cardiovascular-related adverse events (AEs) from patients taking part in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial and its ACTIVExtend extension study.

The 2,460 participants in the ACTIVE trial were postmenopausal women between the ages of 49 and 86 years with osteoporosis; they were given 80 mcg of daily subcutaneous abaloparatide, 20 mcg of open-label daily subcutaneous teriparatide, or placebo in roughly equal numbers for 18 months. After a 1-month treatment-free period, 1,133 eligible participants from either the abaloparatide or placebo groups were enrolled in ACTIVExtend and given 70 mg of open-label alendronate once a week for 24 months. Because heart rate was only assessed pre- and post dose in the ACTIVE trial, an additional pharmacology study of abaloparatide involving 55 healthy volunteers (32 men and 23 women) was undertaken. After a dose of either abaloparatide or placebo, heart rate was measured at 15, 30, and 45 minutes and 1, 1.5, 2, 2.5, 4, 6, 8, and 12 hours.

Overall, treatment-emergent AEs were higher in the abaloparatide (165, 20.1%) and teriparatide (106, 13%) groups, compared with placebo (74, 9%), as were AEs that led to discontinuation of the study and were potentially associated with changes in heart rate or BP (27 in abaloparatide, 11 in teriparatide, and 5 in placebo). However, the percentage of patients with serious cardiac AEs was similar across groups (1%, 1%, and 0.9%, respectively).

During the ACTIVE trial, major cardiac adverse events plus heart failure were more common in the placebo group (1.7%) than the abaloparatide (0.5%) or teriparatide (0.6%) groups. During ACTIVExtend, major cardiac adverse plus heart failure were similarly common in the abaloparatide/alendronate (1.6%) and the placebo/alendronate (1.6%) groups.

On day 1 of treatment during ACTIVE, the mean change in heart rate from pretreatment to an hour post treatment was 7.9 bpm, 5.3 bpm, and 1.2 bpm for abaloparatide, teriparatide, and placebo, respectively (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .05 for abaloparatide vs. teriparatide).

Subsequent visits saw similar changes. The mean maximum heart rate at 1 hour post dose was 80.7 bpm for abaloparatide, 79.0 bpm for teriparatide, and 73.7 bpm for placebo (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .01 for abaloparatide vs. teriparatide). In the study of healthy volunteers, HR peaked at 15 minutes after dosing and then declined, resolving within 2.5-4 hours.

From predose to 1 hour post dose, small but significant decreases were observed in mean supine systolic and diastolic BP across groups (–2.7/–3.6 mm Hg with abaloparatide, –2.0/–3.6 with teriparatide, –1.5/–2.3 with placebo). During the first year of ACTIVE, the mean maximal decrease in BP from predose to 1 hour post dose was slightly higher (1-2 mm Hg) in the abaloparatide and teriparatide groups, compared with the placebo group (P < .05).

The authors acknowledged their study’s limitations, including the analysis of major cardiac adverse plus heart failure in ACTIVE being limited because of a low number of events and the trial not being designed in that regard.

Abaloparatide was approved by the Food and Drug Administration in 2017 on the basis of results from the ACTIVE and ACTIVExtend trials showing significant reductions in new vertebral and nonvertebral fractures, compared with placebo.

The analysis was partially funded by Radius Health. Its authors acknowledged numerous potential conflicts of interest, including receiving grants and research support from various organizations and pharmaceutical companies.

SOURCE: Cosman F et al. J Clin Endocrinol Metab. 2020 Jul 13. doi: 10.1210/clinem/dgaa450.

Osteoporosis treatment with abaloparatide in postmenopausal women does not lead to increased cardiovascular risk, according to a post hoc analysis of the pivotal ACTIVE and ACTIVExtend trials.

iStock/Thinkstock

“Neither treatment with abaloparatide or teriparatide was associated with an increase in serious cardiac [adverse events],” wrote Felicia Cosman, MD, of Columbia University, New York, and coauthors. The study was published in the Journal of Clinical Endocrinology.

To assess the cardiovascular safety profile of abaloparatide, a synthetic analogue of parathyroid hormone–related peptide, the researchers analyzed data on heart rate, blood pressure and cardiovascular-related adverse events (AEs) from patients taking part in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial and its ACTIVExtend extension study.

The 2,460 participants in the ACTIVE trial were postmenopausal women between the ages of 49 and 86 years with osteoporosis; they were given 80 mcg of daily subcutaneous abaloparatide, 20 mcg of open-label daily subcutaneous teriparatide, or placebo in roughly equal numbers for 18 months. After a 1-month treatment-free period, 1,133 eligible participants from either the abaloparatide or placebo groups were enrolled in ACTIVExtend and given 70 mg of open-label alendronate once a week for 24 months. Because heart rate was only assessed pre- and post dose in the ACTIVE trial, an additional pharmacology study of abaloparatide involving 55 healthy volunteers (32 men and 23 women) was undertaken. After a dose of either abaloparatide or placebo, heart rate was measured at 15, 30, and 45 minutes and 1, 1.5, 2, 2.5, 4, 6, 8, and 12 hours.

Overall, treatment-emergent AEs were higher in the abaloparatide (165, 20.1%) and teriparatide (106, 13%) groups, compared with placebo (74, 9%), as were AEs that led to discontinuation of the study and were potentially associated with changes in heart rate or BP (27 in abaloparatide, 11 in teriparatide, and 5 in placebo). However, the percentage of patients with serious cardiac AEs was similar across groups (1%, 1%, and 0.9%, respectively).

During the ACTIVE trial, major cardiac adverse events plus heart failure were more common in the placebo group (1.7%) than the abaloparatide (0.5%) or teriparatide (0.6%) groups. During ACTIVExtend, major cardiac adverse plus heart failure were similarly common in the abaloparatide/alendronate (1.6%) and the placebo/alendronate (1.6%) groups.

On day 1 of treatment during ACTIVE, the mean change in heart rate from pretreatment to an hour post treatment was 7.9 bpm, 5.3 bpm, and 1.2 bpm for abaloparatide, teriparatide, and placebo, respectively (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .05 for abaloparatide vs. teriparatide).

Subsequent visits saw similar changes. The mean maximum heart rate at 1 hour post dose was 80.7 bpm for abaloparatide, 79.0 bpm for teriparatide, and 73.7 bpm for placebo (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .01 for abaloparatide vs. teriparatide). In the study of healthy volunteers, HR peaked at 15 minutes after dosing and then declined, resolving within 2.5-4 hours.

From predose to 1 hour post dose, small but significant decreases were observed in mean supine systolic and diastolic BP across groups (–2.7/–3.6 mm Hg with abaloparatide, –2.0/–3.6 with teriparatide, –1.5/–2.3 with placebo). During the first year of ACTIVE, the mean maximal decrease in BP from predose to 1 hour post dose was slightly higher (1-2 mm Hg) in the abaloparatide and teriparatide groups, compared with the placebo group (P < .05).

The authors acknowledged their study’s limitations, including the analysis of major cardiac adverse plus heart failure in ACTIVE being limited because of a low number of events and the trial not being designed in that regard.

Abaloparatide was approved by the Food and Drug Administration in 2017 on the basis of results from the ACTIVE and ACTIVExtend trials showing significant reductions in new vertebral and nonvertebral fractures, compared with placebo.

The analysis was partially funded by Radius Health. Its authors acknowledged numerous potential conflicts of interest, including receiving grants and research support from various organizations and pharmaceutical companies.

SOURCE: Cosman F et al. J Clin Endocrinol Metab. 2020 Jul 13. doi: 10.1210/clinem/dgaa450.

Osteoporosis treatment with abaloparatide in postmenopausal women does not lead to increased cardiovascular risk, according to a post hoc analysis of the pivotal ACTIVE and ACTIVExtend trials.

iStock/Thinkstock

“Neither treatment with abaloparatide or teriparatide was associated with an increase in serious cardiac [adverse events],” wrote Felicia Cosman, MD, of Columbia University, New York, and coauthors. The study was published in the Journal of Clinical Endocrinology.

To assess the cardiovascular safety profile of abaloparatide, a synthetic analogue of parathyroid hormone–related peptide, the researchers analyzed data on heart rate, blood pressure and cardiovascular-related adverse events (AEs) from patients taking part in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial and its ACTIVExtend extension study.

The 2,460 participants in the ACTIVE trial were postmenopausal women between the ages of 49 and 86 years with osteoporosis; they were given 80 mcg of daily subcutaneous abaloparatide, 20 mcg of open-label daily subcutaneous teriparatide, or placebo in roughly equal numbers for 18 months. After a 1-month treatment-free period, 1,133 eligible participants from either the abaloparatide or placebo groups were enrolled in ACTIVExtend and given 70 mg of open-label alendronate once a week for 24 months. Because heart rate was only assessed pre- and post dose in the ACTIVE trial, an additional pharmacology study of abaloparatide involving 55 healthy volunteers (32 men and 23 women) was undertaken. After a dose of either abaloparatide or placebo, heart rate was measured at 15, 30, and 45 minutes and 1, 1.5, 2, 2.5, 4, 6, 8, and 12 hours.

Overall, treatment-emergent AEs were higher in the abaloparatide (165, 20.1%) and teriparatide (106, 13%) groups, compared with placebo (74, 9%), as were AEs that led to discontinuation of the study and were potentially associated with changes in heart rate or BP (27 in abaloparatide, 11 in teriparatide, and 5 in placebo). However, the percentage of patients with serious cardiac AEs was similar across groups (1%, 1%, and 0.9%, respectively).

During the ACTIVE trial, major cardiac adverse events plus heart failure were more common in the placebo group (1.7%) than the abaloparatide (0.5%) or teriparatide (0.6%) groups. During ACTIVExtend, major cardiac adverse plus heart failure were similarly common in the abaloparatide/alendronate (1.6%) and the placebo/alendronate (1.6%) groups.

On day 1 of treatment during ACTIVE, the mean change in heart rate from pretreatment to an hour post treatment was 7.9 bpm, 5.3 bpm, and 1.2 bpm for abaloparatide, teriparatide, and placebo, respectively (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .05 for abaloparatide vs. teriparatide).

Subsequent visits saw similar changes. The mean maximum heart rate at 1 hour post dose was 80.7 bpm for abaloparatide, 79.0 bpm for teriparatide, and 73.7 bpm for placebo (P < .0001 for abaloparatide and teriparatide vs. placebo; P < .01 for abaloparatide vs. teriparatide). In the study of healthy volunteers, HR peaked at 15 minutes after dosing and then declined, resolving within 2.5-4 hours.

From predose to 1 hour post dose, small but significant decreases were observed in mean supine systolic and diastolic BP across groups (–2.7/–3.6 mm Hg with abaloparatide, –2.0/–3.6 with teriparatide, –1.5/–2.3 with placebo). During the first year of ACTIVE, the mean maximal decrease in BP from predose to 1 hour post dose was slightly higher (1-2 mm Hg) in the abaloparatide and teriparatide groups, compared with the placebo group (P < .05).

The authors acknowledged their study’s limitations, including the analysis of major cardiac adverse plus heart failure in ACTIVE being limited because of a low number of events and the trial not being designed in that regard.

Abaloparatide was approved by the Food and Drug Administration in 2017 on the basis of results from the ACTIVE and ACTIVExtend trials showing significant reductions in new vertebral and nonvertebral fractures, compared with placebo.

The analysis was partially funded by Radius Health. Its authors acknowledged numerous potential conflicts of interest, including receiving grants and research support from various organizations and pharmaceutical companies.

SOURCE: Cosman F et al. J Clin Endocrinol Metab. 2020 Jul 13. doi: 10.1210/clinem/dgaa450.

ILLUSTRATIVE CASE

A 35-year-old healthy woman without a history of high-grade precancerous cervical lesions, immunodeficiency, or exposure to diethylstilbestrol presents to your office for her routine health visit. During your conversation with her, she shares, “I read on the Internet that I only need to be tested for human papillomavirus, but I’m wondering how I’ll be checked for cervical cancer.” She asks for your opinion about cervical cancer screening methods.

The National Cancer Institute predicts that there will be 13,800 new cases of cervical cancer this year, with an estimated 4290 deaths.³ This type of cancer is primarily caused by high-risk human papillomavirus (hrHPV) infections. Fortunately, high-grade precancerous cervical lesions and cervical cancer can be detected with routine Papanicolaou (Pap) smears, which have led to a substantial decrease in the number of deaths from cervical cancer in the United States—from 2.8 per 100,000 women in 2000 to 2.3 deaths per 100,000 women in 2015.³ In addition to hrHPV infection, risk factors for cervical cancer include low socioeconomic status, cigarette smoking, marrying before 18 years of age, young age at first coitus, multiple sexual partners, multiple sexual partners of a partner, and multiple childbirths.⁴

Cervical cancer is associated with numerous negative outcomes, including a decrease in quality of life, decreased libido, poor mental health, infertility, negative body image, and death.⁵ This is particularly true among women of lower socioeconomic status or whose language differs from that of their primary health care provider.^1,5

Given the enormous impact cervical cancer screening has made on the detection and mortality rate of this devastating disease,^4,5 it is crucial to identify the types of screening tests and screening intervals that lead to the greatest benefit and least harm for all patient populations. The US Preventive Services Task Force (USPSTF) previously addressed this issue in 2012, concluding that cytology alone every 3 years for women ages 21 to 65 years and cytology alone every 3 years or co-testing with cytology and hrHPV every 5 years in women ages 30 to 65 years was of substantial benefit (strength of recommendation [SOR]: A).⁶

STUDY SUMMARY

Another option for some women: hrHPV testing alone every 5 years

In this 2018 systematic review and modeling study by the USPSTF, randomized controlled trials (RCTs) and cohort studies that compared cytology to hrHPV testing alone or co-testing (cytology with hrHPV) were used to determine the optimal frequency of, and age group for, cervical cancer screening that would yield the least harm and the most benefit from each of these screening methods.^7-9

Similar to the previous recommendation, the USPSTF found that screening women < 21 years or > 65 years if previously adequately screened (defined as 3 consecutive negative screenings or 2 negative screenings within the past 10 years with the most recent being within the past 5 years) led to more harm than benefit. They therefore concluded that women in these age groups should not be screened routinely (SOR: D). The USPSTF also recommends against cervical cancer screening in women who have had a hysterectomy with removal of the cervix and who do not have a history of a high-grade precancerous lesion or cervical cancer (SOR: D).

Any 1 of 3 screening methods is adequately sensitive for detecting precancerous high-grade cervical lesions or cervical cancer in women ages 30 to 65 years.

However, for women ages 21 to 65 years, the USPSTF found that screening substantially reduces cervical cancer incidence and mortality, and that for women ages 21 to 29 years, screening every 3 years with cytology alone offers the best balance of benefits and harms (SOR: A). For women ages 30 to 65 years, the USPSTF recommends screening every 3 years with cytology alone or every 5 years with either primary hrHPV testing or co-testing (hrHPV with cytology) (SOR: A). The recommendations apply to all ­asymptomatic women with a cervix; exceptions include those with a history of a high-grade precancerous cervical lesion or cancer, in utero exposure to diethylstilbestrol, or a compromised immune system.

Continue to: The change

The change in this current set of recommendations by the USPSTF is the inclusion of screening with hrHPV alone every 5 years as an additional cervical cancer screening option for women ages 30 to 65 years. The decision to include this option was based largely on a decision analysis model commissioned by the USPSTF and reviewed along with clinical trials and cohort studies. The modeling studies found that both primary hrHPV testing alone and co-testing every 5 years prevented a similar number of cervical cancer cases and required a similar number of colposcopies.

Finally, the USPSTF emphasized that screening alone is not sufficient for the prevention of cervical cancer and that efforts should be made to create equitable access to follow-up of abnormal results and the provision of appropriate treatment.^1,2

WHAT’S NEW

When it comes to cervical cancer screening, 3 solid options now exist

The previous USPSTF recommendation concluded that women ages 30 to 65 years should be screened with either cytology alone every 3 years or co-testing (cytology and hrHPV) every 5 years. This systematic review and modeling study concluded that any one of the stated screening methods would be adequately sensitive for detecting precancerous high-grade cervical lesions or cervical cancer: cytology every 3 years, primary hrHPV every 5 years, or co-testing every 5 years.^7-9

CAVEATS

No studies comparing hrHPVto co-testing and no meta-analysis

No studies were found that directly compared primary hrHPV testing with co-testing.¹ A meta-analysis could not be performed due to the methodological differences in RCTs and cohort studies reviewed. The new recommendation is unique in its reliance on modeling to simulate a direct comparison of these 2 screening methods.

CHALLENGES TO IMPLEMENTATION

Getting the word out and increasing comfort levels

The principal challenge to implementation lies in practitioners’ knowledge of this new recommendation and a possible low comfort level with ordering hrHPV testing alone. Patients will need to be engaged in shared decision-making to understand and make use of the 3 options.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 35-year-old healthy woman without a history of high-grade precancerous cervical lesions, immunodeficiency, or exposure to diethylstilbestrol presents to your office for her routine health visit. During your conversation with her, she shares, “I read on the Internet that I only need to be tested for human papillomavirus, but I’m wondering how I’ll be checked for cervical cancer.” She asks for your opinion about cervical cancer screening methods.

The National Cancer Institute predicts that there will be 13,800 new cases of cervical cancer this year, with an estimated 4290 deaths.³ This type of cancer is primarily caused by high-risk human papillomavirus (hrHPV) infections. Fortunately, high-grade precancerous cervical lesions and cervical cancer can be detected with routine Papanicolaou (Pap) smears, which have led to a substantial decrease in the number of deaths from cervical cancer in the United States—from 2.8 per 100,000 women in 2000 to 2.3 deaths per 100,000 women in 2015.³ In addition to hrHPV infection, risk factors for cervical cancer include low socioeconomic status, cigarette smoking, marrying before 18 years of age, young age at first coitus, multiple sexual partners, multiple sexual partners of a partner, and multiple childbirths.⁴

Cervical cancer is associated with numerous negative outcomes, including a decrease in quality of life, decreased libido, poor mental health, infertility, negative body image, and death.⁵ This is particularly true among women of lower socioeconomic status or whose language differs from that of their primary health care provider.^1,5

Given the enormous impact cervical cancer screening has made on the detection and mortality rate of this devastating disease,^4,5 it is crucial to identify the types of screening tests and screening intervals that lead to the greatest benefit and least harm for all patient populations. The US Preventive Services Task Force (USPSTF) previously addressed this issue in 2012, concluding that cytology alone every 3 years for women ages 21 to 65 years and cytology alone every 3 years or co-testing with cytology and hrHPV every 5 years in women ages 30 to 65 years was of substantial benefit (strength of recommendation [SOR]: A).⁶

STUDY SUMMARY

Another option for some women: hrHPV testing alone every 5 years

In this 2018 systematic review and modeling study by the USPSTF, randomized controlled trials (RCTs) and cohort studies that compared cytology to hrHPV testing alone or co-testing (cytology with hrHPV) were used to determine the optimal frequency of, and age group for, cervical cancer screening that would yield the least harm and the most benefit from each of these screening methods.^7-9

Similar to the previous recommendation, the USPSTF found that screening women < 21 years or > 65 years if previously adequately screened (defined as 3 consecutive negative screenings or 2 negative screenings within the past 10 years with the most recent being within the past 5 years) led to more harm than benefit. They therefore concluded that women in these age groups should not be screened routinely (SOR: D). The USPSTF also recommends against cervical cancer screening in women who have had a hysterectomy with removal of the cervix and who do not have a history of a high-grade precancerous lesion or cervical cancer (SOR: D).

Any 1 of 3 screening methods is adequately sensitive for detecting precancerous high-grade cervical lesions or cervical cancer in women ages 30 to 65 years.

However, for women ages 21 to 65 years, the USPSTF found that screening substantially reduces cervical cancer incidence and mortality, and that for women ages 21 to 29 years, screening every 3 years with cytology alone offers the best balance of benefits and harms (SOR: A). For women ages 30 to 65 years, the USPSTF recommends screening every 3 years with cytology alone or every 5 years with either primary hrHPV testing or co-testing (hrHPV with cytology) (SOR: A). The recommendations apply to all ­asymptomatic women with a cervix; exceptions include those with a history of a high-grade precancerous cervical lesion or cancer, in utero exposure to diethylstilbestrol, or a compromised immune system.

Continue to: The change

The change in this current set of recommendations by the USPSTF is the inclusion of screening with hrHPV alone every 5 years as an additional cervical cancer screening option for women ages 30 to 65 years. The decision to include this option was based largely on a decision analysis model commissioned by the USPSTF and reviewed along with clinical trials and cohort studies. The modeling studies found that both primary hrHPV testing alone and co-testing every 5 years prevented a similar number of cervical cancer cases and required a similar number of colposcopies.

Finally, the USPSTF emphasized that screening alone is not sufficient for the prevention of cervical cancer and that efforts should be made to create equitable access to follow-up of abnormal results and the provision of appropriate treatment.^1,2

WHAT’S NEW

When it comes to cervical cancer screening, 3 solid options now exist

The previous USPSTF recommendation concluded that women ages 30 to 65 years should be screened with either cytology alone every 3 years or co-testing (cytology and hrHPV) every 5 years. This systematic review and modeling study concluded that any one of the stated screening methods would be adequately sensitive for detecting precancerous high-grade cervical lesions or cervical cancer: cytology every 3 years, primary hrHPV every 5 years, or co-testing every 5 years.^7-9

CAVEATS

No studies comparing hrHPVto co-testing and no meta-analysis

No studies were found that directly compared primary hrHPV testing with co-testing.¹ A meta-analysis could not be performed due to the methodological differences in RCTs and cohort studies reviewed. The new recommendation is unique in its reliance on modeling to simulate a direct comparison of these 2 screening methods.

CHALLENGES TO IMPLEMENTATION

Getting the word out and increasing comfort levels

The principal challenge to implementation lies in practitioners’ knowledge of this new recommendation and a possible low comfort level with ordering hrHPV testing alone. Patients will need to be engaged in shared decision-making to understand and make use of the 3 options.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 35-year-old healthy woman without a history of high-grade precancerous cervical lesions, immunodeficiency, or exposure to diethylstilbestrol presents to your office for her routine health visit. During your conversation with her, she shares, “I read on the Internet that I only need to be tested for human papillomavirus, but I’m wondering how I’ll be checked for cervical cancer.” She asks for your opinion about cervical cancer screening methods.

The National Cancer Institute predicts that there will be 13,800 new cases of cervical cancer this year, with an estimated 4290 deaths.³ This type of cancer is primarily caused by high-risk human papillomavirus (hrHPV) infections. Fortunately, high-grade precancerous cervical lesions and cervical cancer can be detected with routine Papanicolaou (Pap) smears, which have led to a substantial decrease in the number of deaths from cervical cancer in the United States—from 2.8 per 100,000 women in 2000 to 2.3 deaths per 100,000 women in 2015.³ In addition to hrHPV infection, risk factors for cervical cancer include low socioeconomic status, cigarette smoking, marrying before 18 years of age, young age at first coitus, multiple sexual partners, multiple sexual partners of a partner, and multiple childbirths.⁴

Cervical cancer is associated with numerous negative outcomes, including a decrease in quality of life, decreased libido, poor mental health, infertility, negative body image, and death.⁵ This is particularly true among women of lower socioeconomic status or whose language differs from that of their primary health care provider.^1,5

Given the enormous impact cervical cancer screening has made on the detection and mortality rate of this devastating disease,^4,5 it is crucial to identify the types of screening tests and screening intervals that lead to the greatest benefit and least harm for all patient populations. The US Preventive Services Task Force (USPSTF) previously addressed this issue in 2012, concluding that cytology alone every 3 years for women ages 21 to 65 years and cytology alone every 3 years or co-testing with cytology and hrHPV every 5 years in women ages 30 to 65 years was of substantial benefit (strength of recommendation [SOR]: A).⁶

STUDY SUMMARY

Another option for some women: hrHPV testing alone every 5 years

In this 2018 systematic review and modeling study by the USPSTF, randomized controlled trials (RCTs) and cohort studies that compared cytology to hrHPV testing alone or co-testing (cytology with hrHPV) were used to determine the optimal frequency of, and age group for, cervical cancer screening that would yield the least harm and the most benefit from each of these screening methods.^7-9

Similar to the previous recommendation, the USPSTF found that screening women < 21 years or > 65 years if previously adequately screened (defined as 3 consecutive negative screenings or 2 negative screenings within the past 10 years with the most recent being within the past 5 years) led to more harm than benefit. They therefore concluded that women in these age groups should not be screened routinely (SOR: D). The USPSTF also recommends against cervical cancer screening in women who have had a hysterectomy with removal of the cervix and who do not have a history of a high-grade precancerous lesion or cervical cancer (SOR: D).

Any 1 of 3 screening methods is adequately sensitive for detecting precancerous high-grade cervical lesions or cervical cancer in women ages 30 to 65 years.

However, for women ages 21 to 65 years, the USPSTF found that screening substantially reduces cervical cancer incidence and mortality, and that for women ages 21 to 29 years, screening every 3 years with cytology alone offers the best balance of benefits and harms (SOR: A). For women ages 30 to 65 years, the USPSTF recommends screening every 3 years with cytology alone or every 5 years with either primary hrHPV testing or co-testing (hrHPV with cytology) (SOR: A). The recommendations apply to all ­asymptomatic women with a cervix; exceptions include those with a history of a high-grade precancerous cervical lesion or cancer, in utero exposure to diethylstilbestrol, or a compromised immune system.

Continue to: The change

The change in this current set of recommendations by the USPSTF is the inclusion of screening with hrHPV alone every 5 years as an additional cervical cancer screening option for women ages 30 to 65 years. The decision to include this option was based largely on a decision analysis model commissioned by the USPSTF and reviewed along with clinical trials and cohort studies. The modeling studies found that both primary hrHPV testing alone and co-testing every 5 years prevented a similar number of cervical cancer cases and required a similar number of colposcopies.

Finally, the USPSTF emphasized that screening alone is not sufficient for the prevention of cervical cancer and that efforts should be made to create equitable access to follow-up of abnormal results and the provision of appropriate treatment.^1,2

WHAT’S NEW

When it comes to cervical cancer screening, 3 solid options now exist

The previous USPSTF recommendation concluded that women ages 30 to 65 years should be screened with either cytology alone every 3 years or co-testing (cytology and hrHPV) every 5 years. This systematic review and modeling study concluded that any one of the stated screening methods would be adequately sensitive for detecting precancerous high-grade cervical lesions or cervical cancer: cytology every 3 years, primary hrHPV every 5 years, or co-testing every 5 years.^7-9

CAVEATS

No studies comparing hrHPVto co-testing and no meta-analysis

No studies were found that directly compared primary hrHPV testing with co-testing.¹ A meta-analysis could not be performed due to the methodological differences in RCTs and cohort studies reviewed. The new recommendation is unique in its reliance on modeling to simulate a direct comparison of these 2 screening methods.

CHALLENGES TO IMPLEMENTATION

Getting the word out and increasing comfort levels

The principal challenge to implementation lies in practitioners’ knowledge of this new recommendation and a possible low comfort level with ordering hrHPV testing alone. Patients will need to be engaged in shared decision-making to understand and make use of the 3 options.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Starting breast cancer screening in young adulthood has the potential to sharply reduce deaths from the disease among women who have received chest radiation for childhood cancer, a modeling study suggests.

Two strategies – annual mammography with MRI and annual MRI alone – at least halved breast cancer mortality when started at the ages of 25 or 30 years.

Jennifer M. Yeh, PhD, of Harvard Medical School in Boston and colleagues reported these results in the Annals of Internal Medicine.

When cost was also considered, 30 years emerged as the preferred starting age, dropping the incremental cost-effectiveness ratio (ICER) below the generally accepted threshold of $100,000 per quality-adjusted life-year gained.

“Our findings underscore the importance of making sure that young women previously treated with chest radiation are informed about their elevated breast cancer risk and the benefits of routine screening. Both primary care providers and oncologists who care for survivors should discuss breast cancer screening with these patients,” Dr. Yeh and colleagues wrote.

“Screening guidelines should emphasize the importance of MRI screening (with or without mammography) among survivors,” the authors recommended. “Our findings also highlight the importance of ensuring that survivors have access to health insurance coverage for MRI screening.”
 

Implications for awareness, coverage

“My hope is that, by showing the significantly decreased risk of death associated with early breast cancer screening, with harm-benefit ratios considerably lower than benchmarks for average-risk women, this study will help health insurance companies see the benefit in covering early screening for at-risk survivors,” commented Karen E. Effinger, MD, of Emory University, Atlanta, and the Aflac Cancer & Blood Disorders Center at Children’s Healthcare of Atlanta.

“In many survivors, the cost of current screening [as recommended by] guidelines is prohibitive,” added Dr. Effinger, who was not involved in the current study.

The main concern regarding the study’s findings is generalizability to the contemporary era, given the use of a cohort diagnosed and treated decades ago and changes in radiation techniques and dosing since then, she noted in an interview. This limitation was addressed in a sensitivity analysis that halved the women’s base-case lifetime risk of breast cancer and still netted similar results.

“However, it will take many years to determine the true risk reduction of our current treatment strategies,” Dr. Effinger acknowledged.

“It is crucial that we improve our education of both survivors and our colleagues who care for these survivors, especially in regard to risk of subsequent malignancies and the benefits of screening,” Dr. Effinger maintained. “While many people are aware of the risk of breast cancer associated with BRCA mutations, the increased risk in survivors of childhood cancer is not as recognized by nononcologists. This study reinforces that increasing this awareness can save lives.”

In educating their patients about preventive care, health care providers must strike “a fine balance between discussing the risks and benefits of screening without provoking significant anxiety,” she concluded. “It is important for survivors to establish care with a primary care provider in order to develop trust and receive the guidance they need to decrease the risk of early mortality.”
 

Study details

Dr. Yeh and colleagues developed models to compare outcomes with various screening strategies among women aged 20 years who had received chest radiotherapy for childhood cancer during 1970-1986. The women had been diagnosed with Hodgkin lymphoma (55%), Wilms tumor (12%), non-Hodgkin lymphoma (8%), and other cancers.

The investigators conducted their analysis using data from the Childhood Cancer Survivor Study and other published sources, a lifetime time horizon, and a payer perspective.

The team assessed three strategies: no screening; digital mammography with MRI screening starting at 25 years of age (the current Children’s Oncology Group recommendation), 30 years, or 35 years and continuing to 74 years of age; and MRI only starting at age 25, 30, or 35 years and continuing to age 74 years.

The main study results showed that, without screening, women who had received chest radiation for childhood cancer had a 10%-11% lifetime risk of breast cancer mortality across models.

Relative to no screening, starting at age 25 years, the largest share of deaths was averted with the strategy of annual mammography with MRI – 56.3%-71.2% – or with the strategy of annual MRI alone – 55.7%-62.0%.

These two strategies also yielded the most screening tests, as well as the most false-positive test results and benign biopsy results.

For women who started screening at age 25, there were 4,188-4,879 false-positive test results per 1,000 women for mammography plus MRI and 3,283-3,764 false-positive results per 1,000 women for MRI alone.

For women who started screening at age 25, there were 1,340-1,561 benign biopsy results per 1,000 women for mammography plus MRI and 1,248-1,430 benign results per 1,000 women for MRI alone.

After cost was factored in, beginning screening at age 30 emerged as the preferred strategy to achieve an ICER threshold of less than $100,000 per quality-adjusted life-year gained.

When started at 30 years of age, annual mammography with MRI averted 54.7%-68.8% of breast cancer deaths, with an ICER of $25,400-$113,200 per quality-adjusted life-year gained. Annual MRI alone averted 54.0%-60.0% of breast cancer deaths, with an ICER of $21,800-$50,580 per quality-adjusted life-year gained.

This research was supported by grants from the National Cancer Institute, American Cancer Society, and American Lebanese Syrian Associated Charities. The authors disclosed relationships with GE Healthcare and Biovector. Dr. Effinger disclosed no relevant conflicts of interest.

SOURCE: Yeh JM et al. Ann Intern Med. 2020 Jul 7. doi: 10.7326/M19-3481.

Starting breast cancer screening in young adulthood has the potential to sharply reduce deaths from the disease among women who have received chest radiation for childhood cancer, a modeling study suggests.

Two strategies – annual mammography with MRI and annual MRI alone – at least halved breast cancer mortality when started at the ages of 25 or 30 years.

Jennifer M. Yeh, PhD, of Harvard Medical School in Boston and colleagues reported these results in the Annals of Internal Medicine.

When cost was also considered, 30 years emerged as the preferred starting age, dropping the incremental cost-effectiveness ratio (ICER) below the generally accepted threshold of $100,000 per quality-adjusted life-year gained.

“Our findings underscore the importance of making sure that young women previously treated with chest radiation are informed about their elevated breast cancer risk and the benefits of routine screening. Both primary care providers and oncologists who care for survivors should discuss breast cancer screening with these patients,” Dr. Yeh and colleagues wrote.

“Screening guidelines should emphasize the importance of MRI screening (with or without mammography) among survivors,” the authors recommended. “Our findings also highlight the importance of ensuring that survivors have access to health insurance coverage for MRI screening.”
 

Implications for awareness, coverage

“My hope is that, by showing the significantly decreased risk of death associated with early breast cancer screening, with harm-benefit ratios considerably lower than benchmarks for average-risk women, this study will help health insurance companies see the benefit in covering early screening for at-risk survivors,” commented Karen E. Effinger, MD, of Emory University, Atlanta, and the Aflac Cancer & Blood Disorders Center at Children’s Healthcare of Atlanta.

“In many survivors, the cost of current screening [as recommended by] guidelines is prohibitive,” added Dr. Effinger, who was not involved in the current study.

The main concern regarding the study’s findings is generalizability to the contemporary era, given the use of a cohort diagnosed and treated decades ago and changes in radiation techniques and dosing since then, she noted in an interview. This limitation was addressed in a sensitivity analysis that halved the women’s base-case lifetime risk of breast cancer and still netted similar results.

“However, it will take many years to determine the true risk reduction of our current treatment strategies,” Dr. Effinger acknowledged.

“It is crucial that we improve our education of both survivors and our colleagues who care for these survivors, especially in regard to risk of subsequent malignancies and the benefits of screening,” Dr. Effinger maintained. “While many people are aware of the risk of breast cancer associated with BRCA mutations, the increased risk in survivors of childhood cancer is not as recognized by nononcologists. This study reinforces that increasing this awareness can save lives.”

In educating their patients about preventive care, health care providers must strike “a fine balance between discussing the risks and benefits of screening without provoking significant anxiety,” she concluded. “It is important for survivors to establish care with a primary care provider in order to develop trust and receive the guidance they need to decrease the risk of early mortality.”
 

Study details

Dr. Yeh and colleagues developed models to compare outcomes with various screening strategies among women aged 20 years who had received chest radiotherapy for childhood cancer during 1970-1986. The women had been diagnosed with Hodgkin lymphoma (55%), Wilms tumor (12%), non-Hodgkin lymphoma (8%), and other cancers.

The investigators conducted their analysis using data from the Childhood Cancer Survivor Study and other published sources, a lifetime time horizon, and a payer perspective.

The team assessed three strategies: no screening; digital mammography with MRI screening starting at 25 years of age (the current Children’s Oncology Group recommendation), 30 years, or 35 years and continuing to 74 years of age; and MRI only starting at age 25, 30, or 35 years and continuing to age 74 years.

The main study results showed that, without screening, women who had received chest radiation for childhood cancer had a 10%-11% lifetime risk of breast cancer mortality across models.

Relative to no screening, starting at age 25 years, the largest share of deaths was averted with the strategy of annual mammography with MRI – 56.3%-71.2% – or with the strategy of annual MRI alone – 55.7%-62.0%.

These two strategies also yielded the most screening tests, as well as the most false-positive test results and benign biopsy results.

For women who started screening at age 25, there were 4,188-4,879 false-positive test results per 1,000 women for mammography plus MRI and 3,283-3,764 false-positive results per 1,000 women for MRI alone.

For women who started screening at age 25, there were 1,340-1,561 benign biopsy results per 1,000 women for mammography plus MRI and 1,248-1,430 benign results per 1,000 women for MRI alone.

After cost was factored in, beginning screening at age 30 emerged as the preferred strategy to achieve an ICER threshold of less than $100,000 per quality-adjusted life-year gained.

When started at 30 years of age, annual mammography with MRI averted 54.7%-68.8% of breast cancer deaths, with an ICER of $25,400-$113,200 per quality-adjusted life-year gained. Annual MRI alone averted 54.0%-60.0% of breast cancer deaths, with an ICER of $21,800-$50,580 per quality-adjusted life-year gained.

This research was supported by grants from the National Cancer Institute, American Cancer Society, and American Lebanese Syrian Associated Charities. The authors disclosed relationships with GE Healthcare and Biovector. Dr. Effinger disclosed no relevant conflicts of interest.

SOURCE: Yeh JM et al. Ann Intern Med. 2020 Jul 7. doi: 10.7326/M19-3481.

Starting breast cancer screening in young adulthood has the potential to sharply reduce deaths from the disease among women who have received chest radiation for childhood cancer, a modeling study suggests.

Two strategies – annual mammography with MRI and annual MRI alone – at least halved breast cancer mortality when started at the ages of 25 or 30 years.

Jennifer M. Yeh, PhD, of Harvard Medical School in Boston and colleagues reported these results in the Annals of Internal Medicine.

When cost was also considered, 30 years emerged as the preferred starting age, dropping the incremental cost-effectiveness ratio (ICER) below the generally accepted threshold of $100,000 per quality-adjusted life-year gained.

“Our findings underscore the importance of making sure that young women previously treated with chest radiation are informed about their elevated breast cancer risk and the benefits of routine screening. Both primary care providers and oncologists who care for survivors should discuss breast cancer screening with these patients,” Dr. Yeh and colleagues wrote.

“Screening guidelines should emphasize the importance of MRI screening (with or without mammography) among survivors,” the authors recommended. “Our findings also highlight the importance of ensuring that survivors have access to health insurance coverage for MRI screening.”
 

Implications for awareness, coverage

“My hope is that, by showing the significantly decreased risk of death associated with early breast cancer screening, with harm-benefit ratios considerably lower than benchmarks for average-risk women, this study will help health insurance companies see the benefit in covering early screening for at-risk survivors,” commented Karen E. Effinger, MD, of Emory University, Atlanta, and the Aflac Cancer & Blood Disorders Center at Children’s Healthcare of Atlanta.

“In many survivors, the cost of current screening [as recommended by] guidelines is prohibitive,” added Dr. Effinger, who was not involved in the current study.

The main concern regarding the study’s findings is generalizability to the contemporary era, given the use of a cohort diagnosed and treated decades ago and changes in radiation techniques and dosing since then, she noted in an interview. This limitation was addressed in a sensitivity analysis that halved the women’s base-case lifetime risk of breast cancer and still netted similar results.

“However, it will take many years to determine the true risk reduction of our current treatment strategies,” Dr. Effinger acknowledged.

“It is crucial that we improve our education of both survivors and our colleagues who care for these survivors, especially in regard to risk of subsequent malignancies and the benefits of screening,” Dr. Effinger maintained. “While many people are aware of the risk of breast cancer associated with BRCA mutations, the increased risk in survivors of childhood cancer is not as recognized by nononcologists. This study reinforces that increasing this awareness can save lives.”

In educating their patients about preventive care, health care providers must strike “a fine balance between discussing the risks and benefits of screening without provoking significant anxiety,” she concluded. “It is important for survivors to establish care with a primary care provider in order to develop trust and receive the guidance they need to decrease the risk of early mortality.”
 

Study details

Dr. Yeh and colleagues developed models to compare outcomes with various screening strategies among women aged 20 years who had received chest radiotherapy for childhood cancer during 1970-1986. The women had been diagnosed with Hodgkin lymphoma (55%), Wilms tumor (12%), non-Hodgkin lymphoma (8%), and other cancers.

The investigators conducted their analysis using data from the Childhood Cancer Survivor Study and other published sources, a lifetime time horizon, and a payer perspective.

The team assessed three strategies: no screening; digital mammography with MRI screening starting at 25 years of age (the current Children’s Oncology Group recommendation), 30 years, or 35 years and continuing to 74 years of age; and MRI only starting at age 25, 30, or 35 years and continuing to age 74 years.

The main study results showed that, without screening, women who had received chest radiation for childhood cancer had a 10%-11% lifetime risk of breast cancer mortality across models.

Relative to no screening, starting at age 25 years, the largest share of deaths was averted with the strategy of annual mammography with MRI – 56.3%-71.2% – or with the strategy of annual MRI alone – 55.7%-62.0%.

These two strategies also yielded the most screening tests, as well as the most false-positive test results and benign biopsy results.

For women who started screening at age 25, there were 4,188-4,879 false-positive test results per 1,000 women for mammography plus MRI and 3,283-3,764 false-positive results per 1,000 women for MRI alone.

For women who started screening at age 25, there were 1,340-1,561 benign biopsy results per 1,000 women for mammography plus MRI and 1,248-1,430 benign results per 1,000 women for MRI alone.

After cost was factored in, beginning screening at age 30 emerged as the preferred strategy to achieve an ICER threshold of less than $100,000 per quality-adjusted life-year gained.

When started at 30 years of age, annual mammography with MRI averted 54.7%-68.8% of breast cancer deaths, with an ICER of $25,400-$113,200 per quality-adjusted life-year gained. Annual MRI alone averted 54.0%-60.0% of breast cancer deaths, with an ICER of $21,800-$50,580 per quality-adjusted life-year gained.

This research was supported by grants from the National Cancer Institute, American Cancer Society, and American Lebanese Syrian Associated Charities. The authors disclosed relationships with GE Healthcare and Biovector. Dr. Effinger disclosed no relevant conflicts of interest.

SOURCE: Yeh JM et al. Ann Intern Med. 2020 Jul 7. doi: 10.7326/M19-3481.

ILLUSTRATIVE CASE

A 40-year-old woman presents to your office to establish care. During your interview you realize that she has never been screened for cervical cancer. In fact, she has not had a pelvic exam because she is fearful of the procedure. She would like to know if alternatives exist for cervical cancer screening. What can you suggest?

Although deaths from cervical cancer decreased in the United States from 1975 to 2017, demographic and social disparities in the burden of the disease remain.^2,3 Data from 2016 reveal that cervical cancer incidence per 100,000 women is lowest among white (7.5), Asian-Pacific Islander (5.8), and American Indian/Alaska native (5.6) women, and highest among Hispanic (9.8) and black (8.7) women, which could be explained by lower screening rates in these populations.^4,5 The National Cancer Institute’s publication on reducing cancer health disparities states that the most effective way to reduce cervical cancer incidence and mortality is by increasing screening rates among women who have not been screened or who have not been screened regularly.⁶

The US Food and Drug Administration (FDA) approved the first human papillomavirus (HPV) screening test in 2003.⁷ Evidence now suggests that high-risk HPV screening provides greater protection against cervical cancer than screening with cytology alone.⁸ The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) have changed their recommendations to include primary HPV testing as an alternative method to Pap smears for cervical cancer screening.⁹

An advantage of primary HPV screening is that it can be performed on a specimen collected by the patient, which could potentially increase rates of screening and help to decrease demographic and social disparities. A randomized trial of almost 2000 women ages 21 to 65 years that evaluated the acceptability of this method to patients revealed that more than half of women prefer the idea of a self-collected specimen to one that is collected by a clinician because it is more convenient and obviates the need for a pelvic exam.¹⁰

A meta-analysis of 36 studies and more than 150,000 women concluded that when self-collected samples were used with signal-based assays, the tests were not as sensitive or specific as when clinician-collected samples were used.¹¹ However, the meta-analysis also found that some polymerase chain reaction (PCR)-based HPV tests were similarly sensitive for both self- and clinician-collected samples.

STUDY SUMMARY

PCR vs signal amplification HPV tests with collection by patients vs clinicians

This meta-analysis compared the accuracy of high-risk HPV self-screening with clinician collection of samples (56 diagnostic accuracy trials; total N not provided) in identifying cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) with signal amplification and PCR tests evaluated separately.¹ In addition, this review evaluated strategies to screen women who are underscreened or not screened, which was defined as women who were irregularly or never screened, or did not respond to reminder letters about cervical cancer screening (25 randomized controlled trials [RCTs]; total N not provided).

In the diagnostic accuracy studies, patients collected a vaginal sample themselves and then had a sample taken by a clinician. CIN 2+ or 3+ was confirmed by either colposcopy and biopsy performed on all patients or by a positive high-risk HPV test result. Studies were further divided into those using assays based on signal amplification or PCR.

Continue to: In signal amplification assays...

In signal amplification assays, the pooled sensitivity for CIN 2+ was lower in the group with the self-collected samples than in the clinician-collected sample group (77%; 95% confidence interval [CI], 69%-82% vs 93%; 95% CI, 89%-96%). The pooled specificity to exclude CIN 2+ was also lower in the group with the self-collected samples (84%; 95% CI, 77%-88% vs 86%; 95% CI, 81%-90%). In high-risk HPV assays based on PCR, there was no difference in sensitivity (96%) or specificity (79%) between the specimen groups.

This study offers robust evidence that high-risk HPV PCR-based assays using patient-collected specimens are as sensitive at diagnosing CIN 2+ or 3+ as using clinician-collected samples.

With regard to the pooled relative sensitivity and specificity of signal amplification assays, those using self-swab samples were less sensitive and less specific for CIN 2+ (sensitivity ratio = 0.85; 95% CI, 0.80-0.89; specificity ratio = 0.96; 95% CI, 0.93-0.98) and CIN 3+ (sensitivity ratio = 0.86; 95% CI, 0.76-0.98; specificity ratio = 0.97; 95% CI, 0.95-0.99). Using PCR assays, there was no difference between groups in relative sensitivity for the diagnosis of CIN 2+ (sensitivity ratio = 0.99; 95% CI, 0.97-1.02) and CIN 3+ (sensitivity ratio = 0.99; 95% CI, 0.96-1.02). Relative specificity was slightly lower in the self-swab group for CIN 2+ (specificity ratio = 0.98; 95% CI, 0.97-0.99) and CIN 3+ (specificity ratio = 0.98; 95% CI, 0.97-0.99).

The second analysis to evaluate which outreach strategies are effective methods for screening underscreened/unscreened women found that delivering self-sample kits to patients was more effective than the control method, which was sending reminders to women to undergo conventional screening (95% vs 53%; mean difference [MD], 41%; 95% CI, 3%-78%). Similarly, mailing kits to patients compared favorably to the control method (25% vs 12%; MD, 13%; 95% CI, 10%-15%).

WHAT’S NEW

Self-collected specimens can beas reliable as clinician-collected ones

This is the first study to provide robust evidence that high-risk HPV PCR-based assays using patient self-collected specimens are as sensitive at diagnosing CIN 2+ or 3+ as using clinician-collected samples.

CAVEATS

Balancing lower specificity with reaching underscreened populations

Patients with a positive HPV test result require additional testing. The success rates for this follow-up are not known and could be a barrier to accurate diagnoses because of accessibility and patient willingness to follow up with a pelvic exam. In addition, self-collection may be less specific than cytology and could increase colposcopy referrals that lead to negative findings and overtreatment.¹² However, the increased acceptance of this screening method could make it an effective strategy to reach underscreened or reluctant patients.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Availability of PCR-based HPV assays may be an issue

HPV PCR assays may not be available at all laboratories, but signal amplification HPV tests have been shown to be inferior to PCR assays. Physicians will have to confirm with their laboratories whether PCR-based HPV assays are available.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 40-year-old woman presents to your office to establish care. During your interview you realize that she has never been screened for cervical cancer. In fact, she has not had a pelvic exam because she is fearful of the procedure. She would like to know if alternatives exist for cervical cancer screening. What can you suggest?

Although deaths from cervical cancer decreased in the United States from 1975 to 2017, demographic and social disparities in the burden of the disease remain.^2,3 Data from 2016 reveal that cervical cancer incidence per 100,000 women is lowest among white (7.5), Asian-Pacific Islander (5.8), and American Indian/Alaska native (5.6) women, and highest among Hispanic (9.8) and black (8.7) women, which could be explained by lower screening rates in these populations.^4,5 The National Cancer Institute’s publication on reducing cancer health disparities states that the most effective way to reduce cervical cancer incidence and mortality is by increasing screening rates among women who have not been screened or who have not been screened regularly.⁶

The US Food and Drug Administration (FDA) approved the first human papillomavirus (HPV) screening test in 2003.⁷ Evidence now suggests that high-risk HPV screening provides greater protection against cervical cancer than screening with cytology alone.⁸ The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) have changed their recommendations to include primary HPV testing as an alternative method to Pap smears for cervical cancer screening.⁹

An advantage of primary HPV screening is that it can be performed on a specimen collected by the patient, which could potentially increase rates of screening and help to decrease demographic and social disparities. A randomized trial of almost 2000 women ages 21 to 65 years that evaluated the acceptability of this method to patients revealed that more than half of women prefer the idea of a self-collected specimen to one that is collected by a clinician because it is more convenient and obviates the need for a pelvic exam.¹⁰

A meta-analysis of 36 studies and more than 150,000 women concluded that when self-collected samples were used with signal-based assays, the tests were not as sensitive or specific as when clinician-collected samples were used.¹¹ However, the meta-analysis also found that some polymerase chain reaction (PCR)-based HPV tests were similarly sensitive for both self- and clinician-collected samples.

STUDY SUMMARY

PCR vs signal amplification HPV tests with collection by patients vs clinicians

This meta-analysis compared the accuracy of high-risk HPV self-screening with clinician collection of samples (56 diagnostic accuracy trials; total N not provided) in identifying cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) with signal amplification and PCR tests evaluated separately.¹ In addition, this review evaluated strategies to screen women who are underscreened or not screened, which was defined as women who were irregularly or never screened, or did not respond to reminder letters about cervical cancer screening (25 randomized controlled trials [RCTs]; total N not provided).

In the diagnostic accuracy studies, patients collected a vaginal sample themselves and then had a sample taken by a clinician. CIN 2+ or 3+ was confirmed by either colposcopy and biopsy performed on all patients or by a positive high-risk HPV test result. Studies were further divided into those using assays based on signal amplification or PCR.

Continue to: In signal amplification assays...

In signal amplification assays, the pooled sensitivity for CIN 2+ was lower in the group with the self-collected samples than in the clinician-collected sample group (77%; 95% confidence interval [CI], 69%-82% vs 93%; 95% CI, 89%-96%). The pooled specificity to exclude CIN 2+ was also lower in the group with the self-collected samples (84%; 95% CI, 77%-88% vs 86%; 95% CI, 81%-90%). In high-risk HPV assays based on PCR, there was no difference in sensitivity (96%) or specificity (79%) between the specimen groups.

This study offers robust evidence that high-risk HPV PCR-based assays using patient-collected specimens are as sensitive at diagnosing CIN 2+ or 3+ as using clinician-collected samples.

With regard to the pooled relative sensitivity and specificity of signal amplification assays, those using self-swab samples were less sensitive and less specific for CIN 2+ (sensitivity ratio = 0.85; 95% CI, 0.80-0.89; specificity ratio = 0.96; 95% CI, 0.93-0.98) and CIN 3+ (sensitivity ratio = 0.86; 95% CI, 0.76-0.98; specificity ratio = 0.97; 95% CI, 0.95-0.99). Using PCR assays, there was no difference between groups in relative sensitivity for the diagnosis of CIN 2+ (sensitivity ratio = 0.99; 95% CI, 0.97-1.02) and CIN 3+ (sensitivity ratio = 0.99; 95% CI, 0.96-1.02). Relative specificity was slightly lower in the self-swab group for CIN 2+ (specificity ratio = 0.98; 95% CI, 0.97-0.99) and CIN 3+ (specificity ratio = 0.98; 95% CI, 0.97-0.99).

The second analysis to evaluate which outreach strategies are effective methods for screening underscreened/unscreened women found that delivering self-sample kits to patients was more effective than the control method, which was sending reminders to women to undergo conventional screening (95% vs 53%; mean difference [MD], 41%; 95% CI, 3%-78%). Similarly, mailing kits to patients compared favorably to the control method (25% vs 12%; MD, 13%; 95% CI, 10%-15%).

WHAT’S NEW

Self-collected specimens can beas reliable as clinician-collected ones

This is the first study to provide robust evidence that high-risk HPV PCR-based assays using patient self-collected specimens are as sensitive at diagnosing CIN 2+ or 3+ as using clinician-collected samples.

CAVEATS

Balancing lower specificity with reaching underscreened populations

Patients with a positive HPV test result require additional testing. The success rates for this follow-up are not known and could be a barrier to accurate diagnoses because of accessibility and patient willingness to follow up with a pelvic exam. In addition, self-collection may be less specific than cytology and could increase colposcopy referrals that lead to negative findings and overtreatment.¹² However, the increased acceptance of this screening method could make it an effective strategy to reach underscreened or reluctant patients.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Availability of PCR-based HPV assays may be an issue

HPV PCR assays may not be available at all laboratories, but signal amplification HPV tests have been shown to be inferior to PCR assays. Physicians will have to confirm with their laboratories whether PCR-based HPV assays are available.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 40-year-old woman presents to your office to establish care. During your interview you realize that she has never been screened for cervical cancer. In fact, she has not had a pelvic exam because she is fearful of the procedure. She would like to know if alternatives exist for cervical cancer screening. What can you suggest?

Although deaths from cervical cancer decreased in the United States from 1975 to 2017, demographic and social disparities in the burden of the disease remain.^2,3 Data from 2016 reveal that cervical cancer incidence per 100,000 women is lowest among white (7.5), Asian-Pacific Islander (5.8), and American Indian/Alaska native (5.6) women, and highest among Hispanic (9.8) and black (8.7) women, which could be explained by lower screening rates in these populations.^4,5 The National Cancer Institute’s publication on reducing cancer health disparities states that the most effective way to reduce cervical cancer incidence and mortality is by increasing screening rates among women who have not been screened or who have not been screened regularly.⁶

The US Food and Drug Administration (FDA) approved the first human papillomavirus (HPV) screening test in 2003.⁷ Evidence now suggests that high-risk HPV screening provides greater protection against cervical cancer than screening with cytology alone.⁸ The American College of Obstetricians and Gynecologists (ACOG) and the US Preventive Services Task Force (USPSTF) have changed their recommendations to include primary HPV testing as an alternative method to Pap smears for cervical cancer screening.⁹

An advantage of primary HPV screening is that it can be performed on a specimen collected by the patient, which could potentially increase rates of screening and help to decrease demographic and social disparities. A randomized trial of almost 2000 women ages 21 to 65 years that evaluated the acceptability of this method to patients revealed that more than half of women prefer the idea of a self-collected specimen to one that is collected by a clinician because it is more convenient and obviates the need for a pelvic exam.¹⁰

A meta-analysis of 36 studies and more than 150,000 women concluded that when self-collected samples were used with signal-based assays, the tests were not as sensitive or specific as when clinician-collected samples were used.¹¹ However, the meta-analysis also found that some polymerase chain reaction (PCR)-based HPV tests were similarly sensitive for both self- and clinician-collected samples.

STUDY SUMMARY

PCR vs signal amplification HPV tests with collection by patients vs clinicians

This meta-analysis compared the accuracy of high-risk HPV self-screening with clinician collection of samples (56 diagnostic accuracy trials; total N not provided) in identifying cervical intraepithelial neoplasia grade 2 or worse (CIN 2+) with signal amplification and PCR tests evaluated separately.¹ In addition, this review evaluated strategies to screen women who are underscreened or not screened, which was defined as women who were irregularly or never screened, or did not respond to reminder letters about cervical cancer screening (25 randomized controlled trials [RCTs]; total N not provided).

In the diagnostic accuracy studies, patients collected a vaginal sample themselves and then had a sample taken by a clinician. CIN 2+ or 3+ was confirmed by either colposcopy and biopsy performed on all patients or by a positive high-risk HPV test result. Studies were further divided into those using assays based on signal amplification or PCR.

Continue to: In signal amplification assays...

In signal amplification assays, the pooled sensitivity for CIN 2+ was lower in the group with the self-collected samples than in the clinician-collected sample group (77%; 95% confidence interval [CI], 69%-82% vs 93%; 95% CI, 89%-96%). The pooled specificity to exclude CIN 2+ was also lower in the group with the self-collected samples (84%; 95% CI, 77%-88% vs 86%; 95% CI, 81%-90%). In high-risk HPV assays based on PCR, there was no difference in sensitivity (96%) or specificity (79%) between the specimen groups.

This study offers robust evidence that high-risk HPV PCR-based assays using patient-collected specimens are as sensitive at diagnosing CIN 2+ or 3+ as using clinician-collected samples.

With regard to the pooled relative sensitivity and specificity of signal amplification assays, those using self-swab samples were less sensitive and less specific for CIN 2+ (sensitivity ratio = 0.85; 95% CI, 0.80-0.89; specificity ratio = 0.96; 95% CI, 0.93-0.98) and CIN 3+ (sensitivity ratio = 0.86; 95% CI, 0.76-0.98; specificity ratio = 0.97; 95% CI, 0.95-0.99). Using PCR assays, there was no difference between groups in relative sensitivity for the diagnosis of CIN 2+ (sensitivity ratio = 0.99; 95% CI, 0.97-1.02) and CIN 3+ (sensitivity ratio = 0.99; 95% CI, 0.96-1.02). Relative specificity was slightly lower in the self-swab group for CIN 2+ (specificity ratio = 0.98; 95% CI, 0.97-0.99) and CIN 3+ (specificity ratio = 0.98; 95% CI, 0.97-0.99).

The second analysis to evaluate which outreach strategies are effective methods for screening underscreened/unscreened women found that delivering self-sample kits to patients was more effective than the control method, which was sending reminders to women to undergo conventional screening (95% vs 53%; mean difference [MD], 41%; 95% CI, 3%-78%). Similarly, mailing kits to patients compared favorably to the control method (25% vs 12%; MD, 13%; 95% CI, 10%-15%).

WHAT’S NEW

Self-collected specimens can beas reliable as clinician-collected ones

This is the first study to provide robust evidence that high-risk HPV PCR-based assays using patient self-collected specimens are as sensitive at diagnosing CIN 2+ or 3+ as using clinician-collected samples.

CAVEATS

Balancing lower specificity with reaching underscreened populations

Patients with a positive HPV test result require additional testing. The success rates for this follow-up are not known and could be a barrier to accurate diagnoses because of accessibility and patient willingness to follow up with a pelvic exam. In addition, self-collection may be less specific than cytology and could increase colposcopy referrals that lead to negative findings and overtreatment.¹² However, the increased acceptance of this screening method could make it an effective strategy to reach underscreened or reluctant patients.

Continue to: CHALLENGES TO IMPLEMENTATION

 

 

CHALLENGES TO IMPLEMENTATION

Availability of PCR-based HPV assays may be an issue

HPV PCR assays may not be available at all laboratories, but signal amplification HPV tests have been shown to be inferior to PCR assays. Physicians will have to confirm with their laboratories whether PCR-based HPV assays are available.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.