Black women who undergo axillary lymph node dissection (ALND) as part of their treatment for breast cancer are at much higher risk of developing lymphedema than comparably treated White women, according to a prospective cohort screening study.

“Axillary lymph node dissection remains the main risk factor for the development of lymphedema,” Andrea Barrio, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, New York, said at a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

“We observed a higher incidence of lymphedema in Black women treated with ALND and RT [radiotherapy] after adjustment for other variables,” Dr. Barrio added. “While the etiology for this increased incidence is largely unknown, future studies should address the biologic mechanisms behind racial disparities in lymphedema development.”

Dr. Barrio and colleagues included 276 patients in the analysis – 60% were White, 20% Black, 11% Asian, and 6% Hispanic. The remaining 3% did not report race or ethnicity. Patients’ median age at baseline was 48 years, and the median body mass index was 26.4 kg/m2. Slightly over-two thirds of participants had hormone receptor (HR)–positive/HER2-negative breast cancer.

All patients underwent unilateral ALND. About 70% received neoadjuvant chemotherapy (NAC), and the remainder had upfront surgery followed by adjuvant chemotherapy. Ninety-five percent of patients received radiotherapy, and almost all underwent nodal radiotherapy as well.

The median number of lymph nodes removed was 18, and the median number of positive lymph nodes was two. Using a perometer, arm volume was measured at baseline, postoperatively, and every 6 months for a total of 2 years. Lymphedema was defined as a relative increase in arm volume of greater than or equal to 10% from baseline.

At 24 months, almost 25% of the group had lymphedema, but the incidence differed significantly by race and ethnicity. The highest incidence was observed among Black women, at 39.4%, compared to 27.7% of Hispanic women, 23.4% of Asian women, and 20.5% of White women in the study.

The incidence of lymphedema also varied significantly by treatment group. The incidence was twofold greater among women treated with NAC in comparison with those who underwent upfront surgery (30.9% vs. 11.1%), Dr. Barrio noted.

On multivariate analysis, Black race was the strongest predictor of lymphedema. Compared to White women, Black women had a 3.5-fold greater risk of lymphedema. Hispanic women also had a threefold increased risk compared to White women, but Dr. Barrio cautioned that there were only 16 Hispanic patients in the study.

Older age and increasing time from surgery were also both modestly associated with an increased risk of lymphedema. Among women who ultimately developed lymphedema, “severity did not vary across race or ethnicity with similar relative volume changes observed,” Dr. Barrio said.

Given that the study found that NAC was an independent predictor of lymphedema, should alternatives to NAC be favored?

Although oncologists provide NAC for a variety of reasons, women with HR-positive/HER2-negative disease – which represent the majority of patients in the current analysis – are most likely to have residual disease after NAC, Dr. Barrio noted. This suggests that oncologists need to start looking at surgical de-escalation trials in this group of patients to help them avoid ALND.

Asked whether oncologists still underestimate the impact that lymphedema has on patients’ quality of life, Virginia Kaklamani, MD, professor of medicine, UT Health San Antonio MD Anderson Cancer Center, Texas, said the oncology community has come a long way.

“Any surgeon or medical oncologist will tell you that in the 1960s and 70s, women were having much higher rates of lymphedema than they are now, so this is something that we do recognize and we are a lot more careful about,” she told this news organization.

Surgical techniques are also better now, and the number of lymph nodes that are being removed is much reduced. Nevertheless, when physicians add ALND and radiation to the axilla, “rates of lymphedema go up,” Dr. Kaklamani acknowledged. “We need these women to have physical therapy before they develop lymphedema.”

Dr. Barrio agreed, adding that if oncologists could identify earlier thresholds for lymphedema, before patients develop arm swelling, “we may be able to intervene and see a reduction in its development.”

In the meantime, Dr. Barrio and colleagues are testing the protective value of offering immediate lymphatic reconstruction following ALND versus no reconstruction. In addition, they will be studying banked tissue from Black women to better understand any racial differences in inflammatory responses, the risk of fibrosis, and the reaction to radiotherapy.

“I think we see that inflammation is a key driver of lymphedema development, and so maybe Black women are predisposed to a different inflammatory reaction to treatment or perhaps have higher levels of inflammation at baseline,” Dr. Barrio speculated.

“I think it’s also important to stratify a woman’s risk for lymphedema, and once we can tailor that risk, we can start to identify which patients might benefit from preventative strategies,” she added.

Dr. Barrio has disclosed no relevant financial relationships. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics and as a speaker for Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, Novartis, AstraZeneca, Daiichi Sankyo, and Seattle Genetics. She has also received research funding from Eisai.

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

Black women who undergo axillary lymph node dissection (ALND) as part of their treatment for breast cancer are at much higher risk of developing lymphedema than comparably treated White women, according to a prospective cohort screening study.

“Axillary lymph node dissection remains the main risk factor for the development of lymphedema,” Andrea Barrio, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, New York, said at a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

“We observed a higher incidence of lymphedema in Black women treated with ALND and RT [radiotherapy] after adjustment for other variables,” Dr. Barrio added. “While the etiology for this increased incidence is largely unknown, future studies should address the biologic mechanisms behind racial disparities in lymphedema development.”

Dr. Barrio and colleagues included 276 patients in the analysis – 60% were White, 20% Black, 11% Asian, and 6% Hispanic. The remaining 3% did not report race or ethnicity. Patients’ median age at baseline was 48 years, and the median body mass index was 26.4 kg/m2. Slightly over-two thirds of participants had hormone receptor (HR)–positive/HER2-negative breast cancer.

All patients underwent unilateral ALND. About 70% received neoadjuvant chemotherapy (NAC), and the remainder had upfront surgery followed by adjuvant chemotherapy. Ninety-five percent of patients received radiotherapy, and almost all underwent nodal radiotherapy as well.

The median number of lymph nodes removed was 18, and the median number of positive lymph nodes was two. Using a perometer, arm volume was measured at baseline, postoperatively, and every 6 months for a total of 2 years. Lymphedema was defined as a relative increase in arm volume of greater than or equal to 10% from baseline.

At 24 months, almost 25% of the group had lymphedema, but the incidence differed significantly by race and ethnicity. The highest incidence was observed among Black women, at 39.4%, compared to 27.7% of Hispanic women, 23.4% of Asian women, and 20.5% of White women in the study.

The incidence of lymphedema also varied significantly by treatment group. The incidence was twofold greater among women treated with NAC in comparison with those who underwent upfront surgery (30.9% vs. 11.1%), Dr. Barrio noted.

On multivariate analysis, Black race was the strongest predictor of lymphedema. Compared to White women, Black women had a 3.5-fold greater risk of lymphedema. Hispanic women also had a threefold increased risk compared to White women, but Dr. Barrio cautioned that there were only 16 Hispanic patients in the study.

Older age and increasing time from surgery were also both modestly associated with an increased risk of lymphedema. Among women who ultimately developed lymphedema, “severity did not vary across race or ethnicity with similar relative volume changes observed,” Dr. Barrio said.

Given that the study found that NAC was an independent predictor of lymphedema, should alternatives to NAC be favored?

Although oncologists provide NAC for a variety of reasons, women with HR-positive/HER2-negative disease – which represent the majority of patients in the current analysis – are most likely to have residual disease after NAC, Dr. Barrio noted. This suggests that oncologists need to start looking at surgical de-escalation trials in this group of patients to help them avoid ALND.

Asked whether oncologists still underestimate the impact that lymphedema has on patients’ quality of life, Virginia Kaklamani, MD, professor of medicine, UT Health San Antonio MD Anderson Cancer Center, Texas, said the oncology community has come a long way.

“Any surgeon or medical oncologist will tell you that in the 1960s and 70s, women were having much higher rates of lymphedema than they are now, so this is something that we do recognize and we are a lot more careful about,” she told this news organization.

Surgical techniques are also better now, and the number of lymph nodes that are being removed is much reduced. Nevertheless, when physicians add ALND and radiation to the axilla, “rates of lymphedema go up,” Dr. Kaklamani acknowledged. “We need these women to have physical therapy before they develop lymphedema.”

Dr. Barrio agreed, adding that if oncologists could identify earlier thresholds for lymphedema, before patients develop arm swelling, “we may be able to intervene and see a reduction in its development.”

In the meantime, Dr. Barrio and colleagues are testing the protective value of offering immediate lymphatic reconstruction following ALND versus no reconstruction. In addition, they will be studying banked tissue from Black women to better understand any racial differences in inflammatory responses, the risk of fibrosis, and the reaction to radiotherapy.

“I think we see that inflammation is a key driver of lymphedema development, and so maybe Black women are predisposed to a different inflammatory reaction to treatment or perhaps have higher levels of inflammation at baseline,” Dr. Barrio speculated.

“I think it’s also important to stratify a woman’s risk for lymphedema, and once we can tailor that risk, we can start to identify which patients might benefit from preventative strategies,” she added.

Dr. Barrio has disclosed no relevant financial relationships. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics and as a speaker for Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, Novartis, AstraZeneca, Daiichi Sankyo, and Seattle Genetics. She has also received research funding from Eisai.

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

Black women who undergo axillary lymph node dissection (ALND) as part of their treatment for breast cancer are at much higher risk of developing lymphedema than comparably treated White women, according to a prospective cohort screening study.

“Axillary lymph node dissection remains the main risk factor for the development of lymphedema,” Andrea Barrio, MD, associate attending physician, Memorial Sloan Kettering Cancer Center, New York, said at a virtual press briefing at the San Antonio Breast Cancer Symposium (SABCS) 2021.

“We observed a higher incidence of lymphedema in Black women treated with ALND and RT [radiotherapy] after adjustment for other variables,” Dr. Barrio added. “While the etiology for this increased incidence is largely unknown, future studies should address the biologic mechanisms behind racial disparities in lymphedema development.”

Dr. Barrio and colleagues included 276 patients in the analysis – 60% were White, 20% Black, 11% Asian, and 6% Hispanic. The remaining 3% did not report race or ethnicity. Patients’ median age at baseline was 48 years, and the median body mass index was 26.4 kg/m2. Slightly over-two thirds of participants had hormone receptor (HR)–positive/HER2-negative breast cancer.

All patients underwent unilateral ALND. About 70% received neoadjuvant chemotherapy (NAC), and the remainder had upfront surgery followed by adjuvant chemotherapy. Ninety-five percent of patients received radiotherapy, and almost all underwent nodal radiotherapy as well.

The median number of lymph nodes removed was 18, and the median number of positive lymph nodes was two. Using a perometer, arm volume was measured at baseline, postoperatively, and every 6 months for a total of 2 years. Lymphedema was defined as a relative increase in arm volume of greater than or equal to 10% from baseline.

At 24 months, almost 25% of the group had lymphedema, but the incidence differed significantly by race and ethnicity. The highest incidence was observed among Black women, at 39.4%, compared to 27.7% of Hispanic women, 23.4% of Asian women, and 20.5% of White women in the study.

The incidence of lymphedema also varied significantly by treatment group. The incidence was twofold greater among women treated with NAC in comparison with those who underwent upfront surgery (30.9% vs. 11.1%), Dr. Barrio noted.

On multivariate analysis, Black race was the strongest predictor of lymphedema. Compared to White women, Black women had a 3.5-fold greater risk of lymphedema. Hispanic women also had a threefold increased risk compared to White women, but Dr. Barrio cautioned that there were only 16 Hispanic patients in the study.

Older age and increasing time from surgery were also both modestly associated with an increased risk of lymphedema. Among women who ultimately developed lymphedema, “severity did not vary across race or ethnicity with similar relative volume changes observed,” Dr. Barrio said.

Given that the study found that NAC was an independent predictor of lymphedema, should alternatives to NAC be favored?

Although oncologists provide NAC for a variety of reasons, women with HR-positive/HER2-negative disease – which represent the majority of patients in the current analysis – are most likely to have residual disease after NAC, Dr. Barrio noted. This suggests that oncologists need to start looking at surgical de-escalation trials in this group of patients to help them avoid ALND.

Asked whether oncologists still underestimate the impact that lymphedema has on patients’ quality of life, Virginia Kaklamani, MD, professor of medicine, UT Health San Antonio MD Anderson Cancer Center, Texas, said the oncology community has come a long way.

“Any surgeon or medical oncologist will tell you that in the 1960s and 70s, women were having much higher rates of lymphedema than they are now, so this is something that we do recognize and we are a lot more careful about,” she told this news organization.

Surgical techniques are also better now, and the number of lymph nodes that are being removed is much reduced. Nevertheless, when physicians add ALND and radiation to the axilla, “rates of lymphedema go up,” Dr. Kaklamani acknowledged. “We need these women to have physical therapy before they develop lymphedema.”

Dr. Barrio agreed, adding that if oncologists could identify earlier thresholds for lymphedema, before patients develop arm swelling, “we may be able to intervene and see a reduction in its development.”

In the meantime, Dr. Barrio and colleagues are testing the protective value of offering immediate lymphatic reconstruction following ALND versus no reconstruction. In addition, they will be studying banked tissue from Black women to better understand any racial differences in inflammatory responses, the risk of fibrosis, and the reaction to radiotherapy.

“I think we see that inflammation is a key driver of lymphedema development, and so maybe Black women are predisposed to a different inflammatory reaction to treatment or perhaps have higher levels of inflammation at baseline,” Dr. Barrio speculated.

“I think it’s also important to stratify a woman’s risk for lymphedema, and once we can tailor that risk, we can start to identify which patients might benefit from preventative strategies,” she added.

Dr. Barrio has disclosed no relevant financial relationships. Dr. Kaklamani has served as a consultant for Puma, AstraZeneca, Athenex, and Immunomedics and as a speaker for Pfizer, Celgene, Genentech, Genomic Health, Puma, Eisai, Novartis, AstraZeneca, Daiichi Sankyo, and Seattle Genetics. She has also received research funding from Eisai.

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

The surgical resection rates of the primary tumor in metastatic breast cancer has declined in recent years, possibly reflecting changes in practice following randomized, controlled trials that have not consistently shown a survival benefit.

Retrospective studies have suggested a possible benefit to resection, according to Sasha Douglas, MD, who presented the study (abstract PD7-06) at the 2021 San Antonio Breast Cancer Symposium. “Intuitively, you would think that you would want to get the primary tumor out even if it’s metastasized, so that it couldn’t metastasize more,” said Dr. Douglas, who is a surgical resident at the University of California, San Diego.

However, clinical trials have yielded mixed results, and the picture is complicated by the various molecular subtypes of breast cancer, metastatic sites, and other factors. “Different studies, whether it’s retrospective, and a really large database that has lots of numbers of patients, can give you a different answer than a smaller prospective randomized, controlled study in a different cohort of patients. So, we just thought it would be really interesting to look at all the trends over time at Commission on Cancer–accredited hospitals. Do they seem to be following what the latest literature is showing?” Dr. Douglas said in an interview.

The researchers used data from 87,331 cases from the National Cancer Database (NCDB) and examined rates of primary surgery as well as palliative care in women with metastatic breast cancer who had responded well to systemic therapy.

Between 2004 and 2009, the frequency of primary tumor resection remained near 35% (with a peak of 37% in 2009), then began a steady descent to 18% by 2017. The researchers found similar trends in estrogen receptor–positive/progesterone receptor–positive, HER2-negative (ER/PR+HERer2–); HER2-positive; and triple-negative subtypes.

In 2004, 48% of patients received only systemic therapy, while 37% received some combination of surgery and radiation to the primary tumor. By 2019, 69% received only systemic therapy and 20% received locoregional therapy (P < .001). “It seems that surgeons and providers and medical oncologists are becoming more selective about who they’re going to offer surgery to, and I think that’s very appropriate,” said Dr. Douglas.

But another finding suggests room for improvement: Just 21% of patients received palliative care. “I think that everybody with a major systemic illness like this would benefit from palliative care, just on a supportive basis. The palliative care team can really help people with quality of life, but I think it still has that stigma, and I think that’s what we’ve seen from our study,” said Dr. Douglas.

“We’re just postulating, [but] a lot of that could be from the stigma of thinking that palliative care means giving up. It doesn’t necessarily mean that. It means you’re dealing with a difficult chronic illness, and [palliative care] can be very, very helpful for patients,” said Dr. Douglas.

The study is limited by its retrospective nature, and palliative care might be underreported in the NCDB.

The study was funded by the National Cancer Institute and the University of California, San Diego. Dr. Douglas has no financial disclosures.

The surgical resection rates of the primary tumor in metastatic breast cancer has declined in recent years, possibly reflecting changes in practice following randomized, controlled trials that have not consistently shown a survival benefit.

Retrospective studies have suggested a possible benefit to resection, according to Sasha Douglas, MD, who presented the study (abstract PD7-06) at the 2021 San Antonio Breast Cancer Symposium. “Intuitively, you would think that you would want to get the primary tumor out even if it’s metastasized, so that it couldn’t metastasize more,” said Dr. Douglas, who is a surgical resident at the University of California, San Diego.

However, clinical trials have yielded mixed results, and the picture is complicated by the various molecular subtypes of breast cancer, metastatic sites, and other factors. “Different studies, whether it’s retrospective, and a really large database that has lots of numbers of patients, can give you a different answer than a smaller prospective randomized, controlled study in a different cohort of patients. So, we just thought it would be really interesting to look at all the trends over time at Commission on Cancer–accredited hospitals. Do they seem to be following what the latest literature is showing?” Dr. Douglas said in an interview.

The researchers used data from 87,331 cases from the National Cancer Database (NCDB) and examined rates of primary surgery as well as palliative care in women with metastatic breast cancer who had responded well to systemic therapy.

Between 2004 and 2009, the frequency of primary tumor resection remained near 35% (with a peak of 37% in 2009), then began a steady descent to 18% by 2017. The researchers found similar trends in estrogen receptor–positive/progesterone receptor–positive, HER2-negative (ER/PR+HERer2–); HER2-positive; and triple-negative subtypes.

In 2004, 48% of patients received only systemic therapy, while 37% received some combination of surgery and radiation to the primary tumor. By 2019, 69% received only systemic therapy and 20% received locoregional therapy (P < .001). “It seems that surgeons and providers and medical oncologists are becoming more selective about who they’re going to offer surgery to, and I think that’s very appropriate,” said Dr. Douglas.

But another finding suggests room for improvement: Just 21% of patients received palliative care. “I think that everybody with a major systemic illness like this would benefit from palliative care, just on a supportive basis. The palliative care team can really help people with quality of life, but I think it still has that stigma, and I think that’s what we’ve seen from our study,” said Dr. Douglas.

“We’re just postulating, [but] a lot of that could be from the stigma of thinking that palliative care means giving up. It doesn’t necessarily mean that. It means you’re dealing with a difficult chronic illness, and [palliative care] can be very, very helpful for patients,” said Dr. Douglas.

The study is limited by its retrospective nature, and palliative care might be underreported in the NCDB.

The study was funded by the National Cancer Institute and the University of California, San Diego. Dr. Douglas has no financial disclosures.

The surgical resection rates of the primary tumor in metastatic breast cancer has declined in recent years, possibly reflecting changes in practice following randomized, controlled trials that have not consistently shown a survival benefit.

Retrospective studies have suggested a possible benefit to resection, according to Sasha Douglas, MD, who presented the study (abstract PD7-06) at the 2021 San Antonio Breast Cancer Symposium. “Intuitively, you would think that you would want to get the primary tumor out even if it’s metastasized, so that it couldn’t metastasize more,” said Dr. Douglas, who is a surgical resident at the University of California, San Diego.

However, clinical trials have yielded mixed results, and the picture is complicated by the various molecular subtypes of breast cancer, metastatic sites, and other factors. “Different studies, whether it’s retrospective, and a really large database that has lots of numbers of patients, can give you a different answer than a smaller prospective randomized, controlled study in a different cohort of patients. So, we just thought it would be really interesting to look at all the trends over time at Commission on Cancer–accredited hospitals. Do they seem to be following what the latest literature is showing?” Dr. Douglas said in an interview.

The researchers used data from 87,331 cases from the National Cancer Database (NCDB) and examined rates of primary surgery as well as palliative care in women with metastatic breast cancer who had responded well to systemic therapy.

Between 2004 and 2009, the frequency of primary tumor resection remained near 35% (with a peak of 37% in 2009), then began a steady descent to 18% by 2017. The researchers found similar trends in estrogen receptor–positive/progesterone receptor–positive, HER2-negative (ER/PR+HERer2–); HER2-positive; and triple-negative subtypes.

In 2004, 48% of patients received only systemic therapy, while 37% received some combination of surgery and radiation to the primary tumor. By 2019, 69% received only systemic therapy and 20% received locoregional therapy (P < .001). “It seems that surgeons and providers and medical oncologists are becoming more selective about who they’re going to offer surgery to, and I think that’s very appropriate,” said Dr. Douglas.

But another finding suggests room for improvement: Just 21% of patients received palliative care. “I think that everybody with a major systemic illness like this would benefit from palliative care, just on a supportive basis. The palliative care team can really help people with quality of life, but I think it still has that stigma, and I think that’s what we’ve seen from our study,” said Dr. Douglas.

“We’re just postulating, [but] a lot of that could be from the stigma of thinking that palliative care means giving up. It doesn’t necessarily mean that. It means you’re dealing with a difficult chronic illness, and [palliative care] can be very, very helpful for patients,” said Dr. Douglas.

The study is limited by its retrospective nature, and palliative care might be underreported in the NCDB.

The study was funded by the National Cancer Institute and the University of California, San Diego. Dr. Douglas has no financial disclosures.

In 2011, the Mayo Clinic began surveying physicians about burnout and found 45% of physicians experienced at least one symptom, such as emotional exhaustion, finding work no longer meaningful, feelings of ineffectiveness, and depersonalizing patients. Associated manifestations can range from headache and insomnia to impaired memory and decreased attention. 

Marija Jovovic/Getty Images

Fast forward 10 years to the Medscape National Physician Burnout and Suicide Report, which found that a similar number of physicians (42%) feel burned out. The COVID-19 pandemic only added insult to injury. A Medscape survey that included nearly 5,000 U.S. physicians revealed that about two-thirds (64%) of them reported burnout had intensified during the crisis.

These elevated numbers are being labeled as “a public health crisis” for the impact widespread physician burnout could have on the health of the doctor and patient safety. The relatively consistent levels across the decade seem to suggest that, if health organizations are attempting to improve physician well-being, it doesn’t appear to be working, forcing doctors to find solutions for themselves.

Jill Wener, MD, considers herself part of the 45% burned out 10 years ago. She was working as an internist at Rush University Medical Center in Chicago, but the “existential reality of being a doctor in this world” was wearing on her. “Staying up with the literature, knowing that every day you’re going to go into work without knowing what you’re going to find, threats of lawsuits, the pressure of perfectionism,” Dr. Wener told this news organization. “By the time I hit burnout, everything made me feel like the world was crashing down on me.”

When Dr. Wener encountered someone who meditated twice a day, she was intrigued, even though the self-described “most Type-A, inside-the-box, nonspiritual type, anxious, linear-path doctor” didn’t think people like her could meditate. Dr. Wener is not alone in her hesitation to explore meditation as a means to help prevent burnout because the causes of burnout are primarily linked to external rather than internal factors. Issues including a loss of autonomy, the burden and distraction of electronic health records, and the intense pressure to comply with rules from the government are not things mindfulness can fix. 

And because the sources of burnout are primarily environmental and inherent to the current medical system, the suggestion that physicians need to fix themselves with meditation can come as a slap in the face. However, when up against a system slow to change, mindfulness can provide physicians access to the one thing they can control: How they perceive and react to what’s in front of them.

At the recommendation of an acquaintance, Dr. Wener enrolled in a Vedic Meditation (also known as Conscious Health Meditation) course taught by Light Watkins, a well-known traveling instructor, author, and speaker. By the second meeting she was successfully practicing 20 minutes twice a day. This form of mediation traces its roots to the Vedas, ancient Indian texts (also the foundation for yoga), and uses a mantra to settle the mind, transitioning to an awake state of inner contentment. 

Three weeks later, Dr. Wener’s daily crying jags ended as did her propensity for road rage. “I felt like I was on the cusp of something life-changing, I just didn’t understand it,” she recalled. “But I knew I was never going to give it up.”
 

Defining mindfulness

“Mindfulness is being able to be present in the moment that you’re in with acceptance of what it is and without judging it,” said Donna Rockwell, PsyD, a leading mindfulness meditation teacher. The practice of mindfulness is really meditation. Dr. Rockwell explained that the noise of our mind is most often focused on either the past or the future. “We’re either bemoaning something that happened earlier or we’re catastrophizing the future,” she said, which prevents us from being present in the moment. 

Meditation allows you to notice when your mind has drifted from the present moment into the past or future. “You gently notice it, label it with a lot of self-compassion, and then bring your mind back by focusing on your breath – going out, going in – and the incoming stimuli through your five senses,” said Dr. Rockwell. “When you’re doing that, you can’t be in the past or future.”

Dr. Rockwell also pointed out that we constantly categorize incoming data of the moment as either “good for me or bad for me,” which gets in the way of simply being present for what you’re facing. “When you’re more fully present, you become more skillful and able to do what this moment is asking of you,” she said. Being mindful allows us to better navigate incoming stimuli, which could be a “code blue” in the ED or a patient who needs another 2 minutes during an office visit. 

When Dr. Wener was burned out, she felt unable to adapt whenever something unexpected happened. “When you have no emotional reserves, everything feels like a big deal,” she said. “The meditation gave me what we call adaptation energy; it filled up my tank and kept me from feeling like I was going to lose it at 10 o’clock in the morning.”

Dr. Rockwell explained burnout as an overactive fight or flight response activated by the amygdala. It starts pumping cortisol, our pupils dilate, and our pores open. The prefrontal cortex is offline when we’re experiencing this physiological response because they both can’t be operational at the same time. “When we’re constantly in a ‘fight or flight’ response and don’t have any access to our prefrontal cortex, we are coming from a brain that is pumping cortisol and that leads to burnout,” said Dr. Rockwell.

“Any fight or flight response leaves a mark on your body,” Dr. Wener echoed. “When we go into our state of deep rest in the meditation practice, which is two to five times more restful than sleep, it heals those stress scars.”
 

Making time for mindfulness

Prescribing mindfulness for physicians is not new. Molecular biologist Jon Kabat-Zinn, PhD, developed Mindfulness-Based Stress Reduction (MBSR) in 1979, a practice that incorporates mindfulness exercises to help people become familiar with their behavior patterns in stressful situations. Thus, instead of reacting, they can respond with a clearer understanding of the circumstance. Dr. Kabat-Zinn initially targeted people with chronic health problems to help them cope with the effects of pain and the condition of their illness, but it has expanded to anyone experiencing challenges in their life, including physicians. A standard MBSR course runs 8 weeks, making it a commitment for most people. 

Mindfulness training requires that physicians use what they already have so little of: time.

Dr. Wener was able to take a sabbatical, embarking on a 3-month trip to India to immerse herself in the study of Vedic Meditation. Upon her return, Dr. Wener took a position at Emory University, Atlanta, and has launched a number of CME-accredited meditation courses and retreats. Unlike Dr. Kabat-Zinn, her programs are by physicians and for physicians. She also created an online version of the meditation course to make it more accessible. 

For these reasons, Kara Pepper, MD, an internist in outpatient primary care in Atlanta, was drawn to the meditation course. Dr. Pepper was 7 years into practice when she burned out. “The program dovetailed into my burnout recovery,” she said. “It allowed me space to separate myself from the thoughts I was having about work and just recognize them as just that – as thoughts.”

In the course, Dr. Wener teaches the REST Technique, which she says is different than mindfulness in that she encourages the mind to run rampant. “Trying to control the mind can feel very uncomfortable because we always have thoughts,” she says. “We can’t tell the mind to stop thinking just like we can’t tell the heart to stop beating.” Dr. Wener said the REST Technique lets “the mind swim downstream,” allowing the brain to go into a deep state of rest and start to heal from the scars caused by stress. 

Dr. Pepper said the self-paced online course gave her all the tools she needed, and it was pragmatic and evidence based. “I didn’t feel ‘woo’ or like another gimmick,” she said. Pepper, who continues to practice medicine, became a life coach in 2019 to teach others the skills she uses daily. 
 

An integrated strategy

Dr. Wener acknowledges that meditation is not the panacea for everyone’s burnout, which data support. In a review published in The American Journal of Medicine in 2019, Scott Yates, MD, MBA, from the Center for Executive Medicine in Plano, Tex., found that physicians who had adopted mediation and mindfulness training to decrease anxiety and perceived work stress only experienced modest benefits. In fact, Dr. Yates claims that there’s little data to suggest the long-term benefit of any particular stress management intervention in the prevention of burnout symptoms. 

“The often-repeated goals of the Triple Aim [enhancing patient experience, improving population health, and reducing costs] may be unreachable until we recognize and address burnout in health care providers,” Dr. Yates wrote. He recommends adding a fourth goal to specifically address physician wellness, which certainly could include mindfulness training and meditation.

Burnout coach, trainer, and consultant Dike Drummond, MD, also professes that physician wellness must be added as the key fourth ingredient to improving health care. “Burnout is a dilemma, a balancing act,” he said. “It takes an integrated strategy.” The CEO and founder of TheHappyMD.com, Dr. Drummond’s integrated strategy to stop physician burnout has been taught to more than 40,000 physicians in 175 organizations, and one element of that strategy can be mindfulness training. 

Dr. Drummond said he doesn’t use the word meditation “because that scares most people”; it takes a commitment and isn’t accessible for a lot of doctors. Instead, he coaches doctors to use a ‘single-breath’ technique to help them reset multiple times throughout the day. “I teach people how to breathe up to the top of their head and then down to the bottom of their feet,” Dr. Drummond said. He calls it the Squeegee Breath Technique because when they exhale, they “wipe away” anything that doesn’t need to be there right now. “If you happen to have a mindfulness practice like meditation, they work synergistically because the calmness you feel in your mediation is available to you at the bottom of these releasing breaths.”

Various studies and surveys provide great detail as to the “why” of physician burnout. And while mindfulness is not the sole answer, it’s something physicians can explore for themselves while health care as an industry looks for a more comprehensive solution. 

“It’s not rocket science,” Dr. Drummond insisted. “You want a different result? You’re not satisfied with the way things are now and you want to feel different? You absolutely must do something different.”

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

In 2011, the Mayo Clinic began surveying physicians about burnout and found 45% of physicians experienced at least one symptom, such as emotional exhaustion, finding work no longer meaningful, feelings of ineffectiveness, and depersonalizing patients. Associated manifestations can range from headache and insomnia to impaired memory and decreased attention. 

Marija Jovovic/Getty Images

Fast forward 10 years to the Medscape National Physician Burnout and Suicide Report, which found that a similar number of physicians (42%) feel burned out. The COVID-19 pandemic only added insult to injury. A Medscape survey that included nearly 5,000 U.S. physicians revealed that about two-thirds (64%) of them reported burnout had intensified during the crisis.

These elevated numbers are being labeled as “a public health crisis” for the impact widespread physician burnout could have on the health of the doctor and patient safety. The relatively consistent levels across the decade seem to suggest that, if health organizations are attempting to improve physician well-being, it doesn’t appear to be working, forcing doctors to find solutions for themselves.

Jill Wener, MD, considers herself part of the 45% burned out 10 years ago. She was working as an internist at Rush University Medical Center in Chicago, but the “existential reality of being a doctor in this world” was wearing on her. “Staying up with the literature, knowing that every day you’re going to go into work without knowing what you’re going to find, threats of lawsuits, the pressure of perfectionism,” Dr. Wener told this news organization. “By the time I hit burnout, everything made me feel like the world was crashing down on me.”

When Dr. Wener encountered someone who meditated twice a day, she was intrigued, even though the self-described “most Type-A, inside-the-box, nonspiritual type, anxious, linear-path doctor” didn’t think people like her could meditate. Dr. Wener is not alone in her hesitation to explore meditation as a means to help prevent burnout because the causes of burnout are primarily linked to external rather than internal factors. Issues including a loss of autonomy, the burden and distraction of electronic health records, and the intense pressure to comply with rules from the government are not things mindfulness can fix. 

And because the sources of burnout are primarily environmental and inherent to the current medical system, the suggestion that physicians need to fix themselves with meditation can come as a slap in the face. However, when up against a system slow to change, mindfulness can provide physicians access to the one thing they can control: How they perceive and react to what’s in front of them.

At the recommendation of an acquaintance, Dr. Wener enrolled in a Vedic Meditation (also known as Conscious Health Meditation) course taught by Light Watkins, a well-known traveling instructor, author, and speaker. By the second meeting she was successfully practicing 20 minutes twice a day. This form of mediation traces its roots to the Vedas, ancient Indian texts (also the foundation for yoga), and uses a mantra to settle the mind, transitioning to an awake state of inner contentment. 

Three weeks later, Dr. Wener’s daily crying jags ended as did her propensity for road rage. “I felt like I was on the cusp of something life-changing, I just didn’t understand it,” she recalled. “But I knew I was never going to give it up.”
 

Defining mindfulness

“Mindfulness is being able to be present in the moment that you’re in with acceptance of what it is and without judging it,” said Donna Rockwell, PsyD, a leading mindfulness meditation teacher. The practice of mindfulness is really meditation. Dr. Rockwell explained that the noise of our mind is most often focused on either the past or the future. “We’re either bemoaning something that happened earlier or we’re catastrophizing the future,” she said, which prevents us from being present in the moment. 

Meditation allows you to notice when your mind has drifted from the present moment into the past or future. “You gently notice it, label it with a lot of self-compassion, and then bring your mind back by focusing on your breath – going out, going in – and the incoming stimuli through your five senses,” said Dr. Rockwell. “When you’re doing that, you can’t be in the past or future.”

Dr. Rockwell also pointed out that we constantly categorize incoming data of the moment as either “good for me or bad for me,” which gets in the way of simply being present for what you’re facing. “When you’re more fully present, you become more skillful and able to do what this moment is asking of you,” she said. Being mindful allows us to better navigate incoming stimuli, which could be a “code blue” in the ED or a patient who needs another 2 minutes during an office visit. 

When Dr. Wener was burned out, she felt unable to adapt whenever something unexpected happened. “When you have no emotional reserves, everything feels like a big deal,” she said. “The meditation gave me what we call adaptation energy; it filled up my tank and kept me from feeling like I was going to lose it at 10 o’clock in the morning.”

Dr. Rockwell explained burnout as an overactive fight or flight response activated by the amygdala. It starts pumping cortisol, our pupils dilate, and our pores open. The prefrontal cortex is offline when we’re experiencing this physiological response because they both can’t be operational at the same time. “When we’re constantly in a ‘fight or flight’ response and don’t have any access to our prefrontal cortex, we are coming from a brain that is pumping cortisol and that leads to burnout,” said Dr. Rockwell.

“Any fight or flight response leaves a mark on your body,” Dr. Wener echoed. “When we go into our state of deep rest in the meditation practice, which is two to five times more restful than sleep, it heals those stress scars.”
 

Making time for mindfulness

Prescribing mindfulness for physicians is not new. Molecular biologist Jon Kabat-Zinn, PhD, developed Mindfulness-Based Stress Reduction (MBSR) in 1979, a practice that incorporates mindfulness exercises to help people become familiar with their behavior patterns in stressful situations. Thus, instead of reacting, they can respond with a clearer understanding of the circumstance. Dr. Kabat-Zinn initially targeted people with chronic health problems to help them cope with the effects of pain and the condition of their illness, but it has expanded to anyone experiencing challenges in their life, including physicians. A standard MBSR course runs 8 weeks, making it a commitment for most people. 

Mindfulness training requires that physicians use what they already have so little of: time.

Dr. Wener was able to take a sabbatical, embarking on a 3-month trip to India to immerse herself in the study of Vedic Meditation. Upon her return, Dr. Wener took a position at Emory University, Atlanta, and has launched a number of CME-accredited meditation courses and retreats. Unlike Dr. Kabat-Zinn, her programs are by physicians and for physicians. She also created an online version of the meditation course to make it more accessible. 

For these reasons, Kara Pepper, MD, an internist in outpatient primary care in Atlanta, was drawn to the meditation course. Dr. Pepper was 7 years into practice when she burned out. “The program dovetailed into my burnout recovery,” she said. “It allowed me space to separate myself from the thoughts I was having about work and just recognize them as just that – as thoughts.”

In the course, Dr. Wener teaches the REST Technique, which she says is different than mindfulness in that she encourages the mind to run rampant. “Trying to control the mind can feel very uncomfortable because we always have thoughts,” she says. “We can’t tell the mind to stop thinking just like we can’t tell the heart to stop beating.” Dr. Wener said the REST Technique lets “the mind swim downstream,” allowing the brain to go into a deep state of rest and start to heal from the scars caused by stress. 

Dr. Pepper said the self-paced online course gave her all the tools she needed, and it was pragmatic and evidence based. “I didn’t feel ‘woo’ or like another gimmick,” she said. Pepper, who continues to practice medicine, became a life coach in 2019 to teach others the skills she uses daily. 
 

An integrated strategy

Dr. Wener acknowledges that meditation is not the panacea for everyone’s burnout, which data support. In a review published in The American Journal of Medicine in 2019, Scott Yates, MD, MBA, from the Center for Executive Medicine in Plano, Tex., found that physicians who had adopted mediation and mindfulness training to decrease anxiety and perceived work stress only experienced modest benefits. In fact, Dr. Yates claims that there’s little data to suggest the long-term benefit of any particular stress management intervention in the prevention of burnout symptoms. 

“The often-repeated goals of the Triple Aim [enhancing patient experience, improving population health, and reducing costs] may be unreachable until we recognize and address burnout in health care providers,” Dr. Yates wrote. He recommends adding a fourth goal to specifically address physician wellness, which certainly could include mindfulness training and meditation.

Burnout coach, trainer, and consultant Dike Drummond, MD, also professes that physician wellness must be added as the key fourth ingredient to improving health care. “Burnout is a dilemma, a balancing act,” he said. “It takes an integrated strategy.” The CEO and founder of TheHappyMD.com, Dr. Drummond’s integrated strategy to stop physician burnout has been taught to more than 40,000 physicians in 175 organizations, and one element of that strategy can be mindfulness training. 

Dr. Drummond said he doesn’t use the word meditation “because that scares most people”; it takes a commitment and isn’t accessible for a lot of doctors. Instead, he coaches doctors to use a ‘single-breath’ technique to help them reset multiple times throughout the day. “I teach people how to breathe up to the top of their head and then down to the bottom of their feet,” Dr. Drummond said. He calls it the Squeegee Breath Technique because when they exhale, they “wipe away” anything that doesn’t need to be there right now. “If you happen to have a mindfulness practice like meditation, they work synergistically because the calmness you feel in your mediation is available to you at the bottom of these releasing breaths.”

Various studies and surveys provide great detail as to the “why” of physician burnout. And while mindfulness is not the sole answer, it’s something physicians can explore for themselves while health care as an industry looks for a more comprehensive solution. 

“It’s not rocket science,” Dr. Drummond insisted. “You want a different result? You’re not satisfied with the way things are now and you want to feel different? You absolutely must do something different.”

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

In 2011, the Mayo Clinic began surveying physicians about burnout and found 45% of physicians experienced at least one symptom, such as emotional exhaustion, finding work no longer meaningful, feelings of ineffectiveness, and depersonalizing patients. Associated manifestations can range from headache and insomnia to impaired memory and decreased attention. 

Marija Jovovic/Getty Images

Fast forward 10 years to the Medscape National Physician Burnout and Suicide Report, which found that a similar number of physicians (42%) feel burned out. The COVID-19 pandemic only added insult to injury. A Medscape survey that included nearly 5,000 U.S. physicians revealed that about two-thirds (64%) of them reported burnout had intensified during the crisis.

These elevated numbers are being labeled as “a public health crisis” for the impact widespread physician burnout could have on the health of the doctor and patient safety. The relatively consistent levels across the decade seem to suggest that, if health organizations are attempting to improve physician well-being, it doesn’t appear to be working, forcing doctors to find solutions for themselves.

Jill Wener, MD, considers herself part of the 45% burned out 10 years ago. She was working as an internist at Rush University Medical Center in Chicago, but the “existential reality of being a doctor in this world” was wearing on her. “Staying up with the literature, knowing that every day you’re going to go into work without knowing what you’re going to find, threats of lawsuits, the pressure of perfectionism,” Dr. Wener told this news organization. “By the time I hit burnout, everything made me feel like the world was crashing down on me.”

When Dr. Wener encountered someone who meditated twice a day, she was intrigued, even though the self-described “most Type-A, inside-the-box, nonspiritual type, anxious, linear-path doctor” didn’t think people like her could meditate. Dr. Wener is not alone in her hesitation to explore meditation as a means to help prevent burnout because the causes of burnout are primarily linked to external rather than internal factors. Issues including a loss of autonomy, the burden and distraction of electronic health records, and the intense pressure to comply with rules from the government are not things mindfulness can fix. 

And because the sources of burnout are primarily environmental and inherent to the current medical system, the suggestion that physicians need to fix themselves with meditation can come as a slap in the face. However, when up against a system slow to change, mindfulness can provide physicians access to the one thing they can control: How they perceive and react to what’s in front of them.

At the recommendation of an acquaintance, Dr. Wener enrolled in a Vedic Meditation (also known as Conscious Health Meditation) course taught by Light Watkins, a well-known traveling instructor, author, and speaker. By the second meeting she was successfully practicing 20 minutes twice a day. This form of mediation traces its roots to the Vedas, ancient Indian texts (also the foundation for yoga), and uses a mantra to settle the mind, transitioning to an awake state of inner contentment. 

Three weeks later, Dr. Wener’s daily crying jags ended as did her propensity for road rage. “I felt like I was on the cusp of something life-changing, I just didn’t understand it,” she recalled. “But I knew I was never going to give it up.”
 

Defining mindfulness

“Mindfulness is being able to be present in the moment that you’re in with acceptance of what it is and without judging it,” said Donna Rockwell, PsyD, a leading mindfulness meditation teacher. The practice of mindfulness is really meditation. Dr. Rockwell explained that the noise of our mind is most often focused on either the past or the future. “We’re either bemoaning something that happened earlier or we’re catastrophizing the future,” she said, which prevents us from being present in the moment. 

Meditation allows you to notice when your mind has drifted from the present moment into the past or future. “You gently notice it, label it with a lot of self-compassion, and then bring your mind back by focusing on your breath – going out, going in – and the incoming stimuli through your five senses,” said Dr. Rockwell. “When you’re doing that, you can’t be in the past or future.”

Dr. Rockwell also pointed out that we constantly categorize incoming data of the moment as either “good for me or bad for me,” which gets in the way of simply being present for what you’re facing. “When you’re more fully present, you become more skillful and able to do what this moment is asking of you,” she said. Being mindful allows us to better navigate incoming stimuli, which could be a “code blue” in the ED or a patient who needs another 2 minutes during an office visit. 

When Dr. Wener was burned out, she felt unable to adapt whenever something unexpected happened. “When you have no emotional reserves, everything feels like a big deal,” she said. “The meditation gave me what we call adaptation energy; it filled up my tank and kept me from feeling like I was going to lose it at 10 o’clock in the morning.”

Dr. Rockwell explained burnout as an overactive fight or flight response activated by the amygdala. It starts pumping cortisol, our pupils dilate, and our pores open. The prefrontal cortex is offline when we’re experiencing this physiological response because they both can’t be operational at the same time. “When we’re constantly in a ‘fight or flight’ response and don’t have any access to our prefrontal cortex, we are coming from a brain that is pumping cortisol and that leads to burnout,” said Dr. Rockwell.

“Any fight or flight response leaves a mark on your body,” Dr. Wener echoed. “When we go into our state of deep rest in the meditation practice, which is two to five times more restful than sleep, it heals those stress scars.”
 

Making time for mindfulness

Prescribing mindfulness for physicians is not new. Molecular biologist Jon Kabat-Zinn, PhD, developed Mindfulness-Based Stress Reduction (MBSR) in 1979, a practice that incorporates mindfulness exercises to help people become familiar with their behavior patterns in stressful situations. Thus, instead of reacting, they can respond with a clearer understanding of the circumstance. Dr. Kabat-Zinn initially targeted people with chronic health problems to help them cope with the effects of pain and the condition of their illness, but it has expanded to anyone experiencing challenges in their life, including physicians. A standard MBSR course runs 8 weeks, making it a commitment for most people. 

Mindfulness training requires that physicians use what they already have so little of: time.

Dr. Wener was able to take a sabbatical, embarking on a 3-month trip to India to immerse herself in the study of Vedic Meditation. Upon her return, Dr. Wener took a position at Emory University, Atlanta, and has launched a number of CME-accredited meditation courses and retreats. Unlike Dr. Kabat-Zinn, her programs are by physicians and for physicians. She also created an online version of the meditation course to make it more accessible. 

For these reasons, Kara Pepper, MD, an internist in outpatient primary care in Atlanta, was drawn to the meditation course. Dr. Pepper was 7 years into practice when she burned out. “The program dovetailed into my burnout recovery,” she said. “It allowed me space to separate myself from the thoughts I was having about work and just recognize them as just that – as thoughts.”

In the course, Dr. Wener teaches the REST Technique, which she says is different than mindfulness in that she encourages the mind to run rampant. “Trying to control the mind can feel very uncomfortable because we always have thoughts,” she says. “We can’t tell the mind to stop thinking just like we can’t tell the heart to stop beating.” Dr. Wener said the REST Technique lets “the mind swim downstream,” allowing the brain to go into a deep state of rest and start to heal from the scars caused by stress. 

Dr. Pepper said the self-paced online course gave her all the tools she needed, and it was pragmatic and evidence based. “I didn’t feel ‘woo’ or like another gimmick,” she said. Pepper, who continues to practice medicine, became a life coach in 2019 to teach others the skills she uses daily. 
 

An integrated strategy

Dr. Wener acknowledges that meditation is not the panacea for everyone’s burnout, which data support. In a review published in The American Journal of Medicine in 2019, Scott Yates, MD, MBA, from the Center for Executive Medicine in Plano, Tex., found that physicians who had adopted mediation and mindfulness training to decrease anxiety and perceived work stress only experienced modest benefits. In fact, Dr. Yates claims that there’s little data to suggest the long-term benefit of any particular stress management intervention in the prevention of burnout symptoms. 

“The often-repeated goals of the Triple Aim [enhancing patient experience, improving population health, and reducing costs] may be unreachable until we recognize and address burnout in health care providers,” Dr. Yates wrote. He recommends adding a fourth goal to specifically address physician wellness, which certainly could include mindfulness training and meditation.

Burnout coach, trainer, and consultant Dike Drummond, MD, also professes that physician wellness must be added as the key fourth ingredient to improving health care. “Burnout is a dilemma, a balancing act,” he said. “It takes an integrated strategy.” The CEO and founder of TheHappyMD.com, Dr. Drummond’s integrated strategy to stop physician burnout has been taught to more than 40,000 physicians in 175 organizations, and one element of that strategy can be mindfulness training. 

Dr. Drummond said he doesn’t use the word meditation “because that scares most people”; it takes a commitment and isn’t accessible for a lot of doctors. Instead, he coaches doctors to use a ‘single-breath’ technique to help them reset multiple times throughout the day. “I teach people how to breathe up to the top of their head and then down to the bottom of their feet,” Dr. Drummond said. He calls it the Squeegee Breath Technique because when they exhale, they “wipe away” anything that doesn’t need to be there right now. “If you happen to have a mindfulness practice like meditation, they work synergistically because the calmness you feel in your mediation is available to you at the bottom of these releasing breaths.”

Various studies and surveys provide great detail as to the “why” of physician burnout. And while mindfulness is not the sole answer, it’s something physicians can explore for themselves while health care as an industry looks for a more comprehensive solution. 

“It’s not rocket science,” Dr. Drummond insisted. “You want a different result? You’re not satisfied with the way things are now and you want to feel different? You absolutely must do something different.”

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

Dr Javed Butler, from the University of Mississippi Medical Center, reports on key presentations on heart failure from the 2021 annual meeting of the American Heart Association.  

Dr Butler starts with the EMPULSE trial, which looked at the use of empagliflozin in hospitalized patients with acute heart failure. The study found that patients randomly assigned to empagliflozin had a 36% chance of improved outcomes by 3 months. 

He next looks at two reports from the EMPEROR-Preserved trials, which examined the effects of empagliflozin on patients with ejection fraction greater than 50%. The study found a 17% relative risk reduction in cardiovascular death and a 22% reduction in risk for first heart failure hospitalization. The second EMPEROR report, which examined quality-of-life metrics, found a benefit in favor of empagliflozin over placebo. 

Next, Dr Butler discusses the CHIEF-HF trial, in which heart failure patients were randomly assigned to canagliflozin regardless of ejection fraction. Canagliflozin showed benefit in symptom improvement consistently, regardless of patients having diabetes or heart failure with reduced or preserved ejection fraction. 

Finally, Dr Butler examined the results of the FIGARO-DKD trial, which studied finerenone in patients with diabetic kidney disease. The study reported a 32% relative risk reduction in heart failure events, and reduced hospitalization and cardiovascular death in patients who had a history of heart failure events and those who did not.  

--

 Javed Butler, MD, Professor, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 

Javed Butler, MD, has disclosed the following relevant financial relationships: 
 
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Abbott; Amgen; Array; AstraZeneca; Bayer; Boehringer-Ingelheim; Bristol-Myers Squibb; CVRx; Janssen; LivaNova; Luitpold; Medtronic; Merck; Novartis; Novo Nordisk; Vifor 
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novartis; Boehringer-Ingelheim; Eli Lilly; Janssen

Dr Javed Butler, from the University of Mississippi Medical Center, reports on key presentations on heart failure from the 2021 annual meeting of the American Heart Association.  

Dr Butler starts with the EMPULSE trial, which looked at the use of empagliflozin in hospitalized patients with acute heart failure. The study found that patients randomly assigned to empagliflozin had a 36% chance of improved outcomes by 3 months. 

He next looks at two reports from the EMPEROR-Preserved trials, which examined the effects of empagliflozin on patients with ejection fraction greater than 50%. The study found a 17% relative risk reduction in cardiovascular death and a 22% reduction in risk for first heart failure hospitalization. The second EMPEROR report, which examined quality-of-life metrics, found a benefit in favor of empagliflozin over placebo. 

Next, Dr Butler discusses the CHIEF-HF trial, in which heart failure patients were randomly assigned to canagliflozin regardless of ejection fraction. Canagliflozin showed benefit in symptom improvement consistently, regardless of patients having diabetes or heart failure with reduced or preserved ejection fraction. 

Finally, Dr Butler examined the results of the FIGARO-DKD trial, which studied finerenone in patients with diabetic kidney disease. The study reported a 32% relative risk reduction in heart failure events, and reduced hospitalization and cardiovascular death in patients who had a history of heart failure events and those who did not.  

--

 Javed Butler, MD, Professor, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 

Javed Butler, MD, has disclosed the following relevant financial relationships: 
 
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Abbott; Amgen; Array; AstraZeneca; Bayer; Boehringer-Ingelheim; Bristol-Myers Squibb; CVRx; Janssen; LivaNova; Luitpold; Medtronic; Merck; Novartis; Novo Nordisk; Vifor 
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novartis; Boehringer-Ingelheim; Eli Lilly; Janssen

Dr Javed Butler, from the University of Mississippi Medical Center, reports on key presentations on heart failure from the 2021 annual meeting of the American Heart Association.  

Dr Butler starts with the EMPULSE trial, which looked at the use of empagliflozin in hospitalized patients with acute heart failure. The study found that patients randomly assigned to empagliflozin had a 36% chance of improved outcomes by 3 months. 

He next looks at two reports from the EMPEROR-Preserved trials, which examined the effects of empagliflozin on patients with ejection fraction greater than 50%. The study found a 17% relative risk reduction in cardiovascular death and a 22% reduction in risk for first heart failure hospitalization. The second EMPEROR report, which examined quality-of-life metrics, found a benefit in favor of empagliflozin over placebo. 

Next, Dr Butler discusses the CHIEF-HF trial, in which heart failure patients were randomly assigned to canagliflozin regardless of ejection fraction. Canagliflozin showed benefit in symptom improvement consistently, regardless of patients having diabetes or heart failure with reduced or preserved ejection fraction. 

Finally, Dr Butler examined the results of the FIGARO-DKD trial, which studied finerenone in patients with diabetic kidney disease. The study reported a 32% relative risk reduction in heart failure events, and reduced hospitalization and cardiovascular death in patients who had a history of heart failure events and those who did not.  

--

 Javed Butler, MD, Professor, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi 

Javed Butler, MD, has disclosed the following relevant financial relationships: 
 
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Abbott; Amgen; Array; AstraZeneca; Bayer; Boehringer-Ingelheim; Bristol-Myers Squibb; CVRx; Janssen; LivaNova; Luitpold; Medtronic; Merck; Novartis; Novo Nordisk; Vifor 
Serve(d) as a speaker or a member of a speakers bureau for: AstraZeneca; Novartis; Boehringer-Ingelheim; Eli Lilly; Janssen

The intention to vaccinate children against COVID-19 was lower among vaccine-hesitant parents when compared with parents who were willing to or had already received the COVID vaccine, a new survey finds.

“Parental vaccine hesitancy is a major issue for schools resuming in-person instruction, potentially requiring regular testing, strict mask wearing, and physical distancing for safe operation,” wrote lead author Madhura S. Rane, PhD, from the City University of New York in New York City, and colleagues in their paper, published online in JAMA Pediatrics.

The survey was conducted in June 2021 of 1,162 parents with children ranging in age from 2 to 17 years. The majority of parents (74.4%) were already vaccinated/vaccine-willing ,while 25.6% were vaccine hesitant. The study cohort, including both 1,652 children and their parents, was part of the nationwide CHASING COVID.

Vaccinated parents overall were more willing to vaccinate or had already vaccinated their eligible children when compared with vaccine-hesitant parents: 64.9% vs. 8.3% for children 2-4 years of age; 77.6% vs. 12.1% for children 5-11 years of age; 81.3% vs. 13.9% for children 12-15 years of age; and 86.4% vs. 12.7% for children 16-17 years of age; P < .001.

The researchers found greater hesitancy among Black and Hispanic parents, compared with parents who were non-Hispanic White, women, younger, and did not have a college education. Parents of children who were currently attending school remotely or only partially, were found to be more willing to vaccinate their children when compared to parents of children who were attending school fully in person.

The authors also found that parents who knew someone who had died of COVID-19 or had experienced a prior COVID-19 infection, were more willing to vaccinate their children.

Hesitance in vaccinated parents

Interestingly, 10% of COVID-vaccinated parents said they were still hesitant to vaccinate their kids because of concern for long-term adverse effects of the vaccine.

“These data point out that vaccine concerns may exist even among vaccinated or vaccine-favorable parents, so we should ask any parent who has not vaccinated their child whether we can discuss their concerns and perhaps move their opinions,” said William T. Basco Jr, MD, MS, a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics.

In an interview, when asked whether recent approval of the vaccine for children aged 5-11 will likely aid in overcoming parental hesitancy, Dr. Basco replied: “Absolutely. As more children get the vaccine and people know a neighbor or nephew or cousin, etc., who received the vaccine and did fine, it will engender greater comfort and allow parents to feel better about having their own child receive the vaccine.”

Advice for clinicians from outside expert

“We can always start by asking parents if we can help them understand the vaccine and the need for it. The tidal wave of disinformation is huge, but we can, on a daily basis, offer to help families navigate this decision,” concluded Dr. Basco, who was not involved with the new paper.

Funding for this study was provided through grants from the National Institute of Allergy and Infectious Diseases, the CUNY Institute of Implementation Science in Population Health, and the COVID-19 Grant Program of the CUNY Graduate School of Public Health and Health Policy. The authors and Dr. Basco have disclosed no relevant financial relationships.

The intention to vaccinate children against COVID-19 was lower among vaccine-hesitant parents when compared with parents who were willing to or had already received the COVID vaccine, a new survey finds.

“Parental vaccine hesitancy is a major issue for schools resuming in-person instruction, potentially requiring regular testing, strict mask wearing, and physical distancing for safe operation,” wrote lead author Madhura S. Rane, PhD, from the City University of New York in New York City, and colleagues in their paper, published online in JAMA Pediatrics.

The survey was conducted in June 2021 of 1,162 parents with children ranging in age from 2 to 17 years. The majority of parents (74.4%) were already vaccinated/vaccine-willing ,while 25.6% were vaccine hesitant. The study cohort, including both 1,652 children and their parents, was part of the nationwide CHASING COVID.

Vaccinated parents overall were more willing to vaccinate or had already vaccinated their eligible children when compared with vaccine-hesitant parents: 64.9% vs. 8.3% for children 2-4 years of age; 77.6% vs. 12.1% for children 5-11 years of age; 81.3% vs. 13.9% for children 12-15 years of age; and 86.4% vs. 12.7% for children 16-17 years of age; P < .001.

The researchers found greater hesitancy among Black and Hispanic parents, compared with parents who were non-Hispanic White, women, younger, and did not have a college education. Parents of children who were currently attending school remotely or only partially, were found to be more willing to vaccinate their children when compared to parents of children who were attending school fully in person.

The authors also found that parents who knew someone who had died of COVID-19 or had experienced a prior COVID-19 infection, were more willing to vaccinate their children.

Hesitance in vaccinated parents

Interestingly, 10% of COVID-vaccinated parents said they were still hesitant to vaccinate their kids because of concern for long-term adverse effects of the vaccine.

“These data point out that vaccine concerns may exist even among vaccinated or vaccine-favorable parents, so we should ask any parent who has not vaccinated their child whether we can discuss their concerns and perhaps move their opinions,” said William T. Basco Jr, MD, MS, a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics.

In an interview, when asked whether recent approval of the vaccine for children aged 5-11 will likely aid in overcoming parental hesitancy, Dr. Basco replied: “Absolutely. As more children get the vaccine and people know a neighbor or nephew or cousin, etc., who received the vaccine and did fine, it will engender greater comfort and allow parents to feel better about having their own child receive the vaccine.”

Advice for clinicians from outside expert

“We can always start by asking parents if we can help them understand the vaccine and the need for it. The tidal wave of disinformation is huge, but we can, on a daily basis, offer to help families navigate this decision,” concluded Dr. Basco, who was not involved with the new paper.

Funding for this study was provided through grants from the National Institute of Allergy and Infectious Diseases, the CUNY Institute of Implementation Science in Population Health, and the COVID-19 Grant Program of the CUNY Graduate School of Public Health and Health Policy. The authors and Dr. Basco have disclosed no relevant financial relationships.

The intention to vaccinate children against COVID-19 was lower among vaccine-hesitant parents when compared with parents who were willing to or had already received the COVID vaccine, a new survey finds.

“Parental vaccine hesitancy is a major issue for schools resuming in-person instruction, potentially requiring regular testing, strict mask wearing, and physical distancing for safe operation,” wrote lead author Madhura S. Rane, PhD, from the City University of New York in New York City, and colleagues in their paper, published online in JAMA Pediatrics.

The survey was conducted in June 2021 of 1,162 parents with children ranging in age from 2 to 17 years. The majority of parents (74.4%) were already vaccinated/vaccine-willing ,while 25.6% were vaccine hesitant. The study cohort, including both 1,652 children and their parents, was part of the nationwide CHASING COVID.

Vaccinated parents overall were more willing to vaccinate or had already vaccinated their eligible children when compared with vaccine-hesitant parents: 64.9% vs. 8.3% for children 2-4 years of age; 77.6% vs. 12.1% for children 5-11 years of age; 81.3% vs. 13.9% for children 12-15 years of age; and 86.4% vs. 12.7% for children 16-17 years of age; P < .001.

The researchers found greater hesitancy among Black and Hispanic parents, compared with parents who were non-Hispanic White, women, younger, and did not have a college education. Parents of children who were currently attending school remotely or only partially, were found to be more willing to vaccinate their children when compared to parents of children who were attending school fully in person.

The authors also found that parents who knew someone who had died of COVID-19 or had experienced a prior COVID-19 infection, were more willing to vaccinate their children.

Hesitance in vaccinated parents

Interestingly, 10% of COVID-vaccinated parents said they were still hesitant to vaccinate their kids because of concern for long-term adverse effects of the vaccine.

“These data point out that vaccine concerns may exist even among vaccinated or vaccine-favorable parents, so we should ask any parent who has not vaccinated their child whether we can discuss their concerns and perhaps move their opinions,” said William T. Basco Jr, MD, MS, a professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics.

In an interview, when asked whether recent approval of the vaccine for children aged 5-11 will likely aid in overcoming parental hesitancy, Dr. Basco replied: “Absolutely. As more children get the vaccine and people know a neighbor or nephew or cousin, etc., who received the vaccine and did fine, it will engender greater comfort and allow parents to feel better about having their own child receive the vaccine.”

Advice for clinicians from outside expert

“We can always start by asking parents if we can help them understand the vaccine and the need for it. The tidal wave of disinformation is huge, but we can, on a daily basis, offer to help families navigate this decision,” concluded Dr. Basco, who was not involved with the new paper.

Funding for this study was provided through grants from the National Institute of Allergy and Infectious Diseases, the CUNY Institute of Implementation Science in Population Health, and the COVID-19 Grant Program of the CUNY Graduate School of Public Health and Health Policy. The authors and Dr. Basco have disclosed no relevant financial relationships.

Large, physician-owned group practices are gaining ground as a popular form of practice, even as the number of physicians in solo and small practices declines, and employment maintains its appeal.

Ridofranz/Thinkstock

As physicians shift from owning private practices to employment in hospital systems, this countertrend is also taking place. Large group practices are growing in number, even as solo and small practices are in decline.

Do large, physician-owned groups bring benefits that beat employment? And how do large groups compare with smaller practices and new opportunities, such as private equity? You’ll find some answers here.
 

Working in large group practices

Large group practices with 50 or more physicians are enjoying a renaissance, even though physicians are still streaming into hospital systems. The share of physicians in large practices increased from 14.7% in 2018 to 17.2% in 2020, the largest 2-year change for this group, according to the American Medical Association.

“Physicians expect that large groups will treat them better than hospitals do,” says Robert Pearl, MD, former CEO of Permanente Medical Group, the nation’s largest physicians’ group. 

Compared with hospitals, “doctors would prefer working in a group practice, if all other things are equal,” says Dr. Pearl, who is now a professor at Stanford (Calif.) University Medical School.

Large group practices can include both multispecialty groups and single-specialty groups. Groups in specialties like urology, orthopedics, and oncology have been growing in recent years, according to Gregory Mertz, managing director of Physician Strategies Group in Virginia Beach, Va.

A group practice could also be an independent physicians association – a federation of small practices that share functions like negotiations with insurers and management. Physicians can also form larger groups for single purposes like running an accountable care organization.

Some large group practices can have a mix of partners and employees. In these groups, “some doctors either don’t want a partnership or aren’t offered one,” says Nathan Miller, CEO of the Medicus Firm, a physician recruitment company in Dallas. The AMA reports that about 10% of physicians are employees of large practices.

“Large groups like the Permanente Medical Group are not partnerships,” Dr. Pearl says. “They tend to be a corporation with a board of directors, and all the physicians are employees, but it’s a physician-led organization.”

Doctors in these groups can enjoy a great deal of control. While Permanente Medical Group is exclusively affiliated with Kaiser, which runs hospitals and an HMO, the group is an independent corporation run by its doctors, who are both shareholders and employees, Dr. Pearl says.

The Cleveland Clinic and Mayo Clinic are not medical groups in the strict sense of the word. They describe themselves as academic medical centers, but Dr. Pearl says, “Doctors have a tremendous amount of control there, particularly those in the most remunerative specialties.”

Pros of large groups 

Group practices are able to focus more on the physician participants’ needs and priorities, says Mr. Mertz. “In a hospital-based organization, physicians’ needs have to compete with the needs of the hospital. … In a large group, it can be easier to get policies changed and order equipment.”

However, for many physicians, their primary reason for joining a large group is having negotiating leverage with health insurance plans, and this leverage seems even more important today. It typically results in higher reimbursements, which could translate into higher pay. The higher practice income, however, could be negated by higher administrative overhead, which is endemic in large organizations.

Mr. Mertz says large groups also have the resources to recruit new doctors. Small practices, in contrast, often decide not to grow. The practice would at first need to guarantee the salary of a new partner, which could require existing partners to take a pay cut, which they often don’t want to do. “They’ll decide to ride the practice into the ground,” which means closing it down when they retire, he says.

Cons of large groups

One individual doctor may have relatively little input in decision-making in a large group, and strong leadership may be lacking. One study examining the pros and cons of large group practices found that lack of physician cooperation, investment, and leadership were the most frequently cited barriers in large groups.

Physicians in large groups can also divide into competing factions. Mr. Mertz says rifts are more likely to take place in multispecialty groups, where higher-reimbursed proceduralists resent having to financially support lower-reimbursed primary care physicians. But it’s rare that such rifts actually break up the practice, he says.
 

Private practice vs. employment

Even as more physicians enter large groups, physicians continue to flee private practice in general. In 2020, the AMA found that the number of physicians in private practices had dropped nearly 5 percentage points since 2018, the largest 2-year drop recorded by the AMA.

The hardest hit are small groups of 10 physicians or fewer, once the backbone of U.S. medicine. A 2020 survey found that 53.7% of physicians still work in small practices of 10 or fewer physicians, compared with 61.4% in 2012.

Private practices tend to be partnerships, but younger physicians, for their part, often don’t want to become a partner. In a 2016 survey, only 22% of medical residents surveyed said they anticipate owning a stake in a practice someday.

What’s good about private practice?

The obvious advantage of private practice is having control. Physician-owners can choose staff, oversee finances, and decide on the direction the practice should take. They don’t have to worry about being fired, because the partnership agreement virtually guarantees each doctor’s place in the group.

The atmosphere in a small practice is often more relaxed. “Private practices tend to offer a family-like environment,” Mr. Miller says. Owners of small practices tend to have lower burnout than large practices, a 2018 study found.

Unlike hospital-employed doctors, private practitioners get to keep their ancillary income. “Physicians own the equipment and receive income generated from ancillary services, not just professional fees,” says Mr. Miller.

What’s negative about private practice?

Since small groups have little negotiating power with private payers, they can’t get favorable reimbursement rates. And while partners are protected from being fired, the practice could still go bankrupt.

Running a private practice means putting on an entrepreneurial hat. To develop a strong practice, you need to learn about marketing, finance, IT, contract negotiations, and facility management. “Most young doctors have no interest in this work,” Mr. Mertz says.

Value-based contracting has added another disadvantage for small practices. “It can be harder for small, independent groups to compete,” says Mike Belkin, JD, a divisional vice president at Merritt Hawkins, a physician recruitment company based in Dallas. “They don’t have the data and integration of services that are necessary for this.”
 

Employment in hospital systems

More than one-third of all physicians worked for hospitals in 2018, and hospitals’ share has been growing since then. In 2020, for the first time, the AMA found that more than half of all physicians were employed, and employment is mainly a hospital phenomenon.

The trend shows no signs of stopping. In 2019 and 2020, hospitals and other corporate entities acquired 20,900 physician practices, representing 29,800 doctors. “This trend will continue,” Dr. Pearl says. “The bigger will get bigger. It’s all about market control. Everyone wants to be wider, more vertical, and more powerful.”

Pros of hospital employment 

“The advantages of hospital employment are mostly financial,” Mr. Mertz says. Unlike a private practice, “there’s no financial risk to hospital employment because you don’t own it. You won’t be on the tab for any losses.”

“Hospitals usually offer a highly competitive salary with less emphasis on production than in a private practice,” he says. New physicians are typically paid a guaranteed salary in the first 1-3 years of employment.

“You don’t have any management responsibilities, as you would in a practice,” Mr. Mertz says. “The hospital has a professional management team to handle the business side. Most young doctors have no interest in this work.”

“Employed physicians have a built-in referral network at a hospital,” Mr. Miller says. This is especially an advantage for new physicians, who don’t yet have a referral network of their own.”

Cons of hospital employment

Physicians employed by a hospital lack control. “You don’t decide the hours you work, the schedules you follow, and the physical facility you work in, and, for the most part, you don’t pick your staff,” Mr. Mertz says.

Like any big organization, hospitals are bureaucratic. “If you want to purchase a new piece of equipment, your request goes up the chain of command,” Mr. Mertz says. “Your purchase has to fit into the budget.” (This can be the case with large groups, too.)

Many employed doctors chafe under this lack of control. In an earlier survey by Medscape, 45% of employed respondents didn’t like having limited influence in decision-making, and 32% said they had less control over their work or schedule.

It’s no wonder that a large percentage of physicians would rather work in practices than hospitals. According to a 2021 Medicus Firm survey, 23% of physicians are interested in working in hospitals, while 40% would rather work either in multispecialty or single-specialty groups, Mr. Miller reports.
 

Doctors have differing views of hospital employment

New physicians are apt to dismiss any negatives about hospitals. “Lack of autonomy often matters less to younger physicians, who were trained in team-based models,” Mr. Belkin says.

Many young doctors actually like working in a large organization. “Young doctors out of residency are used to having everything at their fingertips – labs and testing is in-house,” Mr. Mertz says.

On the other hand, doctors who were previously self-employed – a group that makes up almost one-third of all hospital-employed doctors – can often be dissatisfied with employment. In a 2014 Medscape survey, 26% of previously self-employed doctors said job satisfaction had not improved with employment.

Mr. Mertz says these doctors remember what it was like to be in charge of a practice. “If you once owned a practice, you can always compare what’s going on now with that experience, and that can make you frustrated.”
 

Hospitals have higher turnover

It’s much easier to leave an organization when you don’t have an ownership stake. The annual physician turnover rate at hospitals is 28%, compared with 7% at medical groups, according to a 2019 report.

Mr. Belkin says changing jobs has become a way of life for many doctors. “Staying at a job for only a few years is no longer a red flag,” he says. “Physicians are exploring different options. They might try group practice and switch to hospitals or vice versa.”

Physicians are now part of a high-turnover culture: Once in a new job, many are already thinking about the next one. A 2018 survey found that 46% of doctors planned to leave their position within 3 years.
 

Private equity ownership of practice

Selling majority control of your practice to a private equity firm is a relatively new phenomenon and accounts for a small share of physicians – just 4% in 2020. This trend was originally limited to certain specialties, such as anesthesiology, emergency medicine, and dermatology, but now many others are courted.

The deals work like this: Physicians sell majority control of their practice to investors in return for shares in the private equity practice, and they become employees of that practice. The private equity firm then adds more physicians to the practice and invests in infrastructure with the intention of selling the practice at a large profit, which is then shared with the original physicians.

Pros of private equity

The original owners of the practice stand to make a substantial profit if they are willing to wait several years for the practice to be built up and sold. “If they are patient, they could earn a bonanza,” Mr. Belkin says.

Private equity investment helps the practice expand. “It’s an alternative to going to the bank and borrowing money,” Mr. Mertz says.

Cons of private equity

Physicians lose control of their practice. A client of Mr. Mertz’s briefly considered a private equity offer and turned it down. “The private equity firm would have veto power over what the doctors wanted to do,” he says.

Mr. Belkin says the selling physicians typically lose income after the sale. “Money they earned from ancillary services now goes to the practice,” Mr. Belkin says. The selling doctors could potentially take up to a 30% cut in their compensation, according to Coker Capital Advisors.

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

Large, physician-owned group practices are gaining ground as a popular form of practice, even as the number of physicians in solo and small practices declines, and employment maintains its appeal.

Ridofranz/Thinkstock

As physicians shift from owning private practices to employment in hospital systems, this countertrend is also taking place. Large group practices are growing in number, even as solo and small practices are in decline.

Do large, physician-owned groups bring benefits that beat employment? And how do large groups compare with smaller practices and new opportunities, such as private equity? You’ll find some answers here.
 

Working in large group practices

Large group practices with 50 or more physicians are enjoying a renaissance, even though physicians are still streaming into hospital systems. The share of physicians in large practices increased from 14.7% in 2018 to 17.2% in 2020, the largest 2-year change for this group, according to the American Medical Association.

“Physicians expect that large groups will treat them better than hospitals do,” says Robert Pearl, MD, former CEO of Permanente Medical Group, the nation’s largest physicians’ group. 

Compared with hospitals, “doctors would prefer working in a group practice, if all other things are equal,” says Dr. Pearl, who is now a professor at Stanford (Calif.) University Medical School.

Large group practices can include both multispecialty groups and single-specialty groups. Groups in specialties like urology, orthopedics, and oncology have been growing in recent years, according to Gregory Mertz, managing director of Physician Strategies Group in Virginia Beach, Va.

A group practice could also be an independent physicians association – a federation of small practices that share functions like negotiations with insurers and management. Physicians can also form larger groups for single purposes like running an accountable care organization.

Some large group practices can have a mix of partners and employees. In these groups, “some doctors either don’t want a partnership or aren’t offered one,” says Nathan Miller, CEO of the Medicus Firm, a physician recruitment company in Dallas. The AMA reports that about 10% of physicians are employees of large practices.

“Large groups like the Permanente Medical Group are not partnerships,” Dr. Pearl says. “They tend to be a corporation with a board of directors, and all the physicians are employees, but it’s a physician-led organization.”

Doctors in these groups can enjoy a great deal of control. While Permanente Medical Group is exclusively affiliated with Kaiser, which runs hospitals and an HMO, the group is an independent corporation run by its doctors, who are both shareholders and employees, Dr. Pearl says.

The Cleveland Clinic and Mayo Clinic are not medical groups in the strict sense of the word. They describe themselves as academic medical centers, but Dr. Pearl says, “Doctors have a tremendous amount of control there, particularly those in the most remunerative specialties.”

Pros of large groups 

Group practices are able to focus more on the physician participants’ needs and priorities, says Mr. Mertz. “In a hospital-based organization, physicians’ needs have to compete with the needs of the hospital. … In a large group, it can be easier to get policies changed and order equipment.”

However, for many physicians, their primary reason for joining a large group is having negotiating leverage with health insurance plans, and this leverage seems even more important today. It typically results in higher reimbursements, which could translate into higher pay. The higher practice income, however, could be negated by higher administrative overhead, which is endemic in large organizations.

Mr. Mertz says large groups also have the resources to recruit new doctors. Small practices, in contrast, often decide not to grow. The practice would at first need to guarantee the salary of a new partner, which could require existing partners to take a pay cut, which they often don’t want to do. “They’ll decide to ride the practice into the ground,” which means closing it down when they retire, he says.

Cons of large groups

One individual doctor may have relatively little input in decision-making in a large group, and strong leadership may be lacking. One study examining the pros and cons of large group practices found that lack of physician cooperation, investment, and leadership were the most frequently cited barriers in large groups.

Physicians in large groups can also divide into competing factions. Mr. Mertz says rifts are more likely to take place in multispecialty groups, where higher-reimbursed proceduralists resent having to financially support lower-reimbursed primary care physicians. But it’s rare that such rifts actually break up the practice, he says.
 

Private practice vs. employment

Even as more physicians enter large groups, physicians continue to flee private practice in general. In 2020, the AMA found that the number of physicians in private practices had dropped nearly 5 percentage points since 2018, the largest 2-year drop recorded by the AMA.

The hardest hit are small groups of 10 physicians or fewer, once the backbone of U.S. medicine. A 2020 survey found that 53.7% of physicians still work in small practices of 10 or fewer physicians, compared with 61.4% in 2012.

Private practices tend to be partnerships, but younger physicians, for their part, often don’t want to become a partner. In a 2016 survey, only 22% of medical residents surveyed said they anticipate owning a stake in a practice someday.

What’s good about private practice?

The obvious advantage of private practice is having control. Physician-owners can choose staff, oversee finances, and decide on the direction the practice should take. They don’t have to worry about being fired, because the partnership agreement virtually guarantees each doctor’s place in the group.

The atmosphere in a small practice is often more relaxed. “Private practices tend to offer a family-like environment,” Mr. Miller says. Owners of small practices tend to have lower burnout than large practices, a 2018 study found.

Unlike hospital-employed doctors, private practitioners get to keep their ancillary income. “Physicians own the equipment and receive income generated from ancillary services, not just professional fees,” says Mr. Miller.

What’s negative about private practice?

Since small groups have little negotiating power with private payers, they can’t get favorable reimbursement rates. And while partners are protected from being fired, the practice could still go bankrupt.

Running a private practice means putting on an entrepreneurial hat. To develop a strong practice, you need to learn about marketing, finance, IT, contract negotiations, and facility management. “Most young doctors have no interest in this work,” Mr. Mertz says.

Value-based contracting has added another disadvantage for small practices. “It can be harder for small, independent groups to compete,” says Mike Belkin, JD, a divisional vice president at Merritt Hawkins, a physician recruitment company based in Dallas. “They don’t have the data and integration of services that are necessary for this.”
 

Employment in hospital systems

More than one-third of all physicians worked for hospitals in 2018, and hospitals’ share has been growing since then. In 2020, for the first time, the AMA found that more than half of all physicians were employed, and employment is mainly a hospital phenomenon.

The trend shows no signs of stopping. In 2019 and 2020, hospitals and other corporate entities acquired 20,900 physician practices, representing 29,800 doctors. “This trend will continue,” Dr. Pearl says. “The bigger will get bigger. It’s all about market control. Everyone wants to be wider, more vertical, and more powerful.”

Pros of hospital employment 

“The advantages of hospital employment are mostly financial,” Mr. Mertz says. Unlike a private practice, “there’s no financial risk to hospital employment because you don’t own it. You won’t be on the tab for any losses.”

“Hospitals usually offer a highly competitive salary with less emphasis on production than in a private practice,” he says. New physicians are typically paid a guaranteed salary in the first 1-3 years of employment.

“You don’t have any management responsibilities, as you would in a practice,” Mr. Mertz says. “The hospital has a professional management team to handle the business side. Most young doctors have no interest in this work.”

“Employed physicians have a built-in referral network at a hospital,” Mr. Miller says. This is especially an advantage for new physicians, who don’t yet have a referral network of their own.”

Cons of hospital employment

Physicians employed by a hospital lack control. “You don’t decide the hours you work, the schedules you follow, and the physical facility you work in, and, for the most part, you don’t pick your staff,” Mr. Mertz says.

Like any big organization, hospitals are bureaucratic. “If you want to purchase a new piece of equipment, your request goes up the chain of command,” Mr. Mertz says. “Your purchase has to fit into the budget.” (This can be the case with large groups, too.)

Many employed doctors chafe under this lack of control. In an earlier survey by Medscape, 45% of employed respondents didn’t like having limited influence in decision-making, and 32% said they had less control over their work or schedule.

It’s no wonder that a large percentage of physicians would rather work in practices than hospitals. According to a 2021 Medicus Firm survey, 23% of physicians are interested in working in hospitals, while 40% would rather work either in multispecialty or single-specialty groups, Mr. Miller reports.
 

Doctors have differing views of hospital employment

New physicians are apt to dismiss any negatives about hospitals. “Lack of autonomy often matters less to younger physicians, who were trained in team-based models,” Mr. Belkin says.

Many young doctors actually like working in a large organization. “Young doctors out of residency are used to having everything at their fingertips – labs and testing is in-house,” Mr. Mertz says.

On the other hand, doctors who were previously self-employed – a group that makes up almost one-third of all hospital-employed doctors – can often be dissatisfied with employment. In a 2014 Medscape survey, 26% of previously self-employed doctors said job satisfaction had not improved with employment.

Mr. Mertz says these doctors remember what it was like to be in charge of a practice. “If you once owned a practice, you can always compare what’s going on now with that experience, and that can make you frustrated.”
 

Hospitals have higher turnover

It’s much easier to leave an organization when you don’t have an ownership stake. The annual physician turnover rate at hospitals is 28%, compared with 7% at medical groups, according to a 2019 report.

Mr. Belkin says changing jobs has become a way of life for many doctors. “Staying at a job for only a few years is no longer a red flag,” he says. “Physicians are exploring different options. They might try group practice and switch to hospitals or vice versa.”

Physicians are now part of a high-turnover culture: Once in a new job, many are already thinking about the next one. A 2018 survey found that 46% of doctors planned to leave their position within 3 years.
 

Private equity ownership of practice

Selling majority control of your practice to a private equity firm is a relatively new phenomenon and accounts for a small share of physicians – just 4% in 2020. This trend was originally limited to certain specialties, such as anesthesiology, emergency medicine, and dermatology, but now many others are courted.

The deals work like this: Physicians sell majority control of their practice to investors in return for shares in the private equity practice, and they become employees of that practice. The private equity firm then adds more physicians to the practice and invests in infrastructure with the intention of selling the practice at a large profit, which is then shared with the original physicians.

Pros of private equity

The original owners of the practice stand to make a substantial profit if they are willing to wait several years for the practice to be built up and sold. “If they are patient, they could earn a bonanza,” Mr. Belkin says.

Private equity investment helps the practice expand. “It’s an alternative to going to the bank and borrowing money,” Mr. Mertz says.

Cons of private equity

Physicians lose control of their practice. A client of Mr. Mertz’s briefly considered a private equity offer and turned it down. “The private equity firm would have veto power over what the doctors wanted to do,” he says.

Mr. Belkin says the selling physicians typically lose income after the sale. “Money they earned from ancillary services now goes to the practice,” Mr. Belkin says. The selling doctors could potentially take up to a 30% cut in their compensation, according to Coker Capital Advisors.

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

Large, physician-owned group practices are gaining ground as a popular form of practice, even as the number of physicians in solo and small practices declines, and employment maintains its appeal.

Ridofranz/Thinkstock

As physicians shift from owning private practices to employment in hospital systems, this countertrend is also taking place. Large group practices are growing in number, even as solo and small practices are in decline.

Do large, physician-owned groups bring benefits that beat employment? And how do large groups compare with smaller practices and new opportunities, such as private equity? You’ll find some answers here.
 

Working in large group practices

Large group practices with 50 or more physicians are enjoying a renaissance, even though physicians are still streaming into hospital systems. The share of physicians in large practices increased from 14.7% in 2018 to 17.2% in 2020, the largest 2-year change for this group, according to the American Medical Association.

“Physicians expect that large groups will treat them better than hospitals do,” says Robert Pearl, MD, former CEO of Permanente Medical Group, the nation’s largest physicians’ group. 

Compared with hospitals, “doctors would prefer working in a group practice, if all other things are equal,” says Dr. Pearl, who is now a professor at Stanford (Calif.) University Medical School.

Large group practices can include both multispecialty groups and single-specialty groups. Groups in specialties like urology, orthopedics, and oncology have been growing in recent years, according to Gregory Mertz, managing director of Physician Strategies Group in Virginia Beach, Va.

A group practice could also be an independent physicians association – a federation of small practices that share functions like negotiations with insurers and management. Physicians can also form larger groups for single purposes like running an accountable care organization.

Some large group practices can have a mix of partners and employees. In these groups, “some doctors either don’t want a partnership or aren’t offered one,” says Nathan Miller, CEO of the Medicus Firm, a physician recruitment company in Dallas. The AMA reports that about 10% of physicians are employees of large practices.

“Large groups like the Permanente Medical Group are not partnerships,” Dr. Pearl says. “They tend to be a corporation with a board of directors, and all the physicians are employees, but it’s a physician-led organization.”

Doctors in these groups can enjoy a great deal of control. While Permanente Medical Group is exclusively affiliated with Kaiser, which runs hospitals and an HMO, the group is an independent corporation run by its doctors, who are both shareholders and employees, Dr. Pearl says.

The Cleveland Clinic and Mayo Clinic are not medical groups in the strict sense of the word. They describe themselves as academic medical centers, but Dr. Pearl says, “Doctors have a tremendous amount of control there, particularly those in the most remunerative specialties.”

Pros of large groups 

Group practices are able to focus more on the physician participants’ needs and priorities, says Mr. Mertz. “In a hospital-based organization, physicians’ needs have to compete with the needs of the hospital. … In a large group, it can be easier to get policies changed and order equipment.”

However, for many physicians, their primary reason for joining a large group is having negotiating leverage with health insurance plans, and this leverage seems even more important today. It typically results in higher reimbursements, which could translate into higher pay. The higher practice income, however, could be negated by higher administrative overhead, which is endemic in large organizations.

Mr. Mertz says large groups also have the resources to recruit new doctors. Small practices, in contrast, often decide not to grow. The practice would at first need to guarantee the salary of a new partner, which could require existing partners to take a pay cut, which they often don’t want to do. “They’ll decide to ride the practice into the ground,” which means closing it down when they retire, he says.

Cons of large groups

One individual doctor may have relatively little input in decision-making in a large group, and strong leadership may be lacking. One study examining the pros and cons of large group practices found that lack of physician cooperation, investment, and leadership were the most frequently cited barriers in large groups.

Physicians in large groups can also divide into competing factions. Mr. Mertz says rifts are more likely to take place in multispecialty groups, where higher-reimbursed proceduralists resent having to financially support lower-reimbursed primary care physicians. But it’s rare that such rifts actually break up the practice, he says.
 

Private practice vs. employment

Even as more physicians enter large groups, physicians continue to flee private practice in general. In 2020, the AMA found that the number of physicians in private practices had dropped nearly 5 percentage points since 2018, the largest 2-year drop recorded by the AMA.

The hardest hit are small groups of 10 physicians or fewer, once the backbone of U.S. medicine. A 2020 survey found that 53.7% of physicians still work in small practices of 10 or fewer physicians, compared with 61.4% in 2012.

Private practices tend to be partnerships, but younger physicians, for their part, often don’t want to become a partner. In a 2016 survey, only 22% of medical residents surveyed said they anticipate owning a stake in a practice someday.

What’s good about private practice?

The obvious advantage of private practice is having control. Physician-owners can choose staff, oversee finances, and decide on the direction the practice should take. They don’t have to worry about being fired, because the partnership agreement virtually guarantees each doctor’s place in the group.

The atmosphere in a small practice is often more relaxed. “Private practices tend to offer a family-like environment,” Mr. Miller says. Owners of small practices tend to have lower burnout than large practices, a 2018 study found.

Unlike hospital-employed doctors, private practitioners get to keep their ancillary income. “Physicians own the equipment and receive income generated from ancillary services, not just professional fees,” says Mr. Miller.

What’s negative about private practice?

Since small groups have little negotiating power with private payers, they can’t get favorable reimbursement rates. And while partners are protected from being fired, the practice could still go bankrupt.

Running a private practice means putting on an entrepreneurial hat. To develop a strong practice, you need to learn about marketing, finance, IT, contract negotiations, and facility management. “Most young doctors have no interest in this work,” Mr. Mertz says.

Value-based contracting has added another disadvantage for small practices. “It can be harder for small, independent groups to compete,” says Mike Belkin, JD, a divisional vice president at Merritt Hawkins, a physician recruitment company based in Dallas. “They don’t have the data and integration of services that are necessary for this.”
 

Employment in hospital systems

More than one-third of all physicians worked for hospitals in 2018, and hospitals’ share has been growing since then. In 2020, for the first time, the AMA found that more than half of all physicians were employed, and employment is mainly a hospital phenomenon.

The trend shows no signs of stopping. In 2019 and 2020, hospitals and other corporate entities acquired 20,900 physician practices, representing 29,800 doctors. “This trend will continue,” Dr. Pearl says. “The bigger will get bigger. It’s all about market control. Everyone wants to be wider, more vertical, and more powerful.”

Pros of hospital employment 

“The advantages of hospital employment are mostly financial,” Mr. Mertz says. Unlike a private practice, “there’s no financial risk to hospital employment because you don’t own it. You won’t be on the tab for any losses.”

“Hospitals usually offer a highly competitive salary with less emphasis on production than in a private practice,” he says. New physicians are typically paid a guaranteed salary in the first 1-3 years of employment.

“You don’t have any management responsibilities, as you would in a practice,” Mr. Mertz says. “The hospital has a professional management team to handle the business side. Most young doctors have no interest in this work.”

“Employed physicians have a built-in referral network at a hospital,” Mr. Miller says. This is especially an advantage for new physicians, who don’t yet have a referral network of their own.”

Cons of hospital employment

Physicians employed by a hospital lack control. “You don’t decide the hours you work, the schedules you follow, and the physical facility you work in, and, for the most part, you don’t pick your staff,” Mr. Mertz says.

Like any big organization, hospitals are bureaucratic. “If you want to purchase a new piece of equipment, your request goes up the chain of command,” Mr. Mertz says. “Your purchase has to fit into the budget.” (This can be the case with large groups, too.)

Many employed doctors chafe under this lack of control. In an earlier survey by Medscape, 45% of employed respondents didn’t like having limited influence in decision-making, and 32% said they had less control over their work or schedule.

It’s no wonder that a large percentage of physicians would rather work in practices than hospitals. According to a 2021 Medicus Firm survey, 23% of physicians are interested in working in hospitals, while 40% would rather work either in multispecialty or single-specialty groups, Mr. Miller reports.
 

Doctors have differing views of hospital employment

New physicians are apt to dismiss any negatives about hospitals. “Lack of autonomy often matters less to younger physicians, who were trained in team-based models,” Mr. Belkin says.

Many young doctors actually like working in a large organization. “Young doctors out of residency are used to having everything at their fingertips – labs and testing is in-house,” Mr. Mertz says.

On the other hand, doctors who were previously self-employed – a group that makes up almost one-third of all hospital-employed doctors – can often be dissatisfied with employment. In a 2014 Medscape survey, 26% of previously self-employed doctors said job satisfaction had not improved with employment.

Mr. Mertz says these doctors remember what it was like to be in charge of a practice. “If you once owned a practice, you can always compare what’s going on now with that experience, and that can make you frustrated.”
 

Hospitals have higher turnover

It’s much easier to leave an organization when you don’t have an ownership stake. The annual physician turnover rate at hospitals is 28%, compared with 7% at medical groups, according to a 2019 report.

Mr. Belkin says changing jobs has become a way of life for many doctors. “Staying at a job for only a few years is no longer a red flag,” he says. “Physicians are exploring different options. They might try group practice and switch to hospitals or vice versa.”

Physicians are now part of a high-turnover culture: Once in a new job, many are already thinking about the next one. A 2018 survey found that 46% of doctors planned to leave their position within 3 years.
 

Private equity ownership of practice

Selling majority control of your practice to a private equity firm is a relatively new phenomenon and accounts for a small share of physicians – just 4% in 2020. This trend was originally limited to certain specialties, such as anesthesiology, emergency medicine, and dermatology, but now many others are courted.

The deals work like this: Physicians sell majority control of their practice to investors in return for shares in the private equity practice, and they become employees of that practice. The private equity firm then adds more physicians to the practice and invests in infrastructure with the intention of selling the practice at a large profit, which is then shared with the original physicians.

Pros of private equity

The original owners of the practice stand to make a substantial profit if they are willing to wait several years for the practice to be built up and sold. “If they are patient, they could earn a bonanza,” Mr. Belkin says.

Private equity investment helps the practice expand. “It’s an alternative to going to the bank and borrowing money,” Mr. Mertz says.

Cons of private equity

Physicians lose control of their practice. A client of Mr. Mertz’s briefly considered a private equity offer and turned it down. “The private equity firm would have veto power over what the doctors wanted to do,” he says.

Mr. Belkin says the selling physicians typically lose income after the sale. “Money they earned from ancillary services now goes to the practice,” Mr. Belkin says. The selling doctors could potentially take up to a 30% cut in their compensation, according to Coker Capital Advisors.

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

Recently, the National Osteoporosis Foundation (NOF) changed its name to the Bone Health and Osteoporosis Foundation (BHOF). Several years ago, in 2016 at my urging, this column was renamed from “Update on osteoporosis” to “Update on bone health.” I believe we were on the leading edge of this movement. As expressed in last year’s Update, our patients’ bone health must be emphasized more than it has been in the past.¹

Consider that localized breast cancer carries a 5-year survival rate of 99%.² Most of my patients are keenly aware that periodic competent breast imaging is the key to the earliest possible diagnosis. By contrast, in this country a hip fracture carries a mortality in the first year of 21%!³ Furthermore, approximately one-third of women who fracture their hip do not have osteoporosis.⁴ While the risk of hip fracture is greatest in women with osteoporosis, it is not absent in those without the condition. Finally, the role of muscle mass, strength, and performance in bone health is a rapidly emerging topic and one that constitutes the core of this year’s Update.

Muscle mass and strength play key role in bone health

de Villiers TJ, Goldstein SR. Update on bone health: the International Menopause Society white paper 2021. Climacteric. 2021;24:498-504. doi:10.1080/13697137.2021.1950967.

Recently, de Villiers and Goldstein offered an overview of osteoporosis.⁵ What is worthy of reporting here is the role of muscle in bone health.

The bone-muscle relationship

Most clinicians know that osteoporosis and osteopenia are well-defined conditions with known risks associated with fracture. According to a review of PubMed, the first article with the keyword “osteoporosis” was published in 1894; through May 2020, 93,335 articles used that keyword. “Osteoporosis” is derived from the Greek osteon (bone) and poros (little hole). Thus, osteoporosis means “porous bone.”

Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass, strength, and function, and the condition is associated with a risk of adverse outcomes that include physical disabilities, poor quality of life, and death.^6,7 “Sarcopenia” has its roots in the Greek words sarx (flesh) and penia (loss), and the term was coined in 1989.⁸ A PubMed review that included “sarcopenia” as the keyword revealed that the first article was published in 1993, with 12,068 articles published through May 2020.

Notably, muscle accounts for about 60% of the body’s protein. Muscle mass decreases with age, but younger patients with malnutrition, cachexia, or inflammatory diseases are also prone to decreased muscle mass. While osteoporosis has a well-accepted definition based on dual-energy x-ray absorptiometry (DXA) measurements, sarcopenia has no universally accepted definition, consensus diagnostic criteria, or treatment guidelines. In 2016, however, the International Classification of Diseases, Tenth Revision, Clinical Modification (CD-10-CM) finally recognized sarcopenia as a disease entity.

Currently, the most widely accepted definition comes from the European Working Group on Sarcopenia in Older People, which labeled presarcopenia as low muscle mass without impact on muscle strength or performance; sarcopenia as low muscle mass with either low muscle strength or low physical performance; and severe sarcopenia has all 3 criteria being present.⁹

When osteosarcopenia (osteoporosis or osteopenia combined with sarcopenia) exists, it can result in a threefold increase in risk of falls and a fourfold increase in fracture risk compared with women who have osteopenia or osteoporosis alone.¹⁰

Continue to: Denosumab decreased falls risk, improved sarcopenia measures vs comparator antiresorptives...

Denosumab decreased falls risk, improved sarcopenia measures vs comparator antiresorptives

El Miedany Y, El Gaafary M, Toth M, et al; Egyptian Academy of Bone Health, Metabolic Bone Diseases. Is there a potential dual effect of denosumab for treatment of osteoporosis and sarcopenia? Clin Rheumatol. 2021;40:4225-4232. doi: 10.1007/s10067-021 -05757-w.

Osteosarcopenia, the combination of osteoporosis or osteopenia with sarcopenia, has been shown to increase the overall rate of falls and fracture when compared with fall and fracture rates in women with osteopenia or osteoporosis alone.¹⁰ A study by El Miedany and colleagues examined whether denosumab treatment had a possible dual therapeutic effect on osteoporosis and sarcopenia.¹¹

Study details

The investigators looked at 135 patients diagnosed with postmenopausal osteoporosis and who were prescribed denosumab and compared them with a control group of 272 patients stratified into 2 subgroups: 136 were prescribed alendronate and 136 were prescribed zoledronate.

Assessments were performed for all participants for BMD (DXA), fall risk (falls risk assessment score [FRAS]), fracture risk (FRAX assessment tool), and sarcopenia measures. Reassessments were conducted after 5 years of denosumab or alendronate therapy, 3 years of zoledronate therapy, and 1 year after stopping the osteoporosis therapy.

The FRAS uses the clinical variables of history of falls in the last 12 months, impaired sight, weak hand grip, history of loss of balance in the last 12 months, and slowing of the walking speed/change in gait to yield a percent chance of sustaining a fall.¹² Sarcopenic measures include grip strength, timed up and go (TUG) mobility test, and gait speed. There were no significant demographic differences between the 3 groups.

Denosumab reduced risk of falls and positively affected muscle strength

On completion of the 5-year denosumab therapy, falls risk was significantly decreased (P = .001) and significant improvements were seen in all sarcopenia measures (P = .01). One year after denosumab was discontinued, a significant worsening of both falls risk and sarcopenia measures (P = .01) occurred. This was in contrast to results in both control groups (alendronate and zoledronate), in which there was an improvement, although less robust in gait speed and the TUG test (P = .05) but no improvement in risk of falls. Thus, the results of this study showed that denosumab not only improved bone mass but also reduced falls risk.

Compared with bisphosphonates, denosumab showed the highest significant positive effect on both physical performance and skeletal muscle strength. This is evidenced by improvement of the gait speed, TUG test, and 4-m walk test (P<.001) in the denosumab group versus in the alendronate and zoledronate group (P<.05).

These results agree with the outcomes of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis 6 months) trial, which revealed that not only did denosumab treatment reduce the risk of vertebral, nonvertebral, and hip fracture over 36 months, but also that the denosumab-treated group had fewer falls (4.5%) compared with the other groups (5.7%) (P = .02).¹³

Continue to: Estrogen’s role in bone health and its therapeutic potential in osteosarcopenia...

Estrogen’s role in bone health and its therapeutic potential in osteosarcopenia

Mandelli A, Tacconi E, Levinger I, et al. The role of estrogens in osteosarcopenia: from biology to potential dual therapeutic effects. Climacteric. 2021;1-7. doi: 10.1080/13697137.2021.1965118.

Osteosarcopenia is a particular term used to describe the coexistence of 2 pathologies, osteopenia/ osteoporosis and sarcopenia.¹⁴ Sarcopenia is characterized by a loss of muscle mass, strength, and performance. Numerous studies indicate that higher lean body mass is related to increased BMD and reduced fracture risk, especially in postmenopausal women.¹⁵

Menopause, muscle, and estrogen’s physiologic effects

Estrogens play a critical role in maintaining bone and muscle mass in women. Women experience a decline in musculoskeletal quantity and quality at the onset of menopause.¹⁶ Muscle mass and strength decrease rapidly after menopause, which suggests that degradation of muscle protein begins to exert a more significant effect due to a decrease in protein synthesis. Indeed, a reduced response to anabolic stimuli has been shown in postmenopausal women.¹⁷ Normalization of the protein synthesis response after restoring estrogen levels with estrogen therapy supports this hypothesis.¹⁸

In a meta-analysis to identify the role of estrogen therapy on muscle strength, the authors concluded that estrogens benefit muscle strength not by increasing the skeletal mass but by improving muscle quality and its ability to generate force.¹⁹ In addition, however, it has been demonstrated that exercise prevents and delays the onset of osteosarcopenia.²⁰

When should bone mass be measured in premenopausal women?

Conradie M, de Villiers T. Premenopausal osteoporosis. Climacteric. 2021:1-14. doi: 10.1080/13697137 .2021.1926974.

Most women’s clinicians are somewhat well acquainted with the increasing importance of preventing, diagnosing, and treating postmenopausal osteoporosis, which predisposes to fragility fracture and the morbidity and even mortality that brings. Increasingly, some younger women are asking for and receiving both bone mass measurements that may be inappropriately ordered and/or wrongly interpreted. Conradie and de Villiers provided an overview of premenopausal osteoporosis, containing important facts that all clinicians who care for women should be aware of.²¹

Indications for testing

BMD testing is only indicated in younger women in settings in which the result may influence management decisions, such as:

• a history of fragility fracture
• diseases associated with low bone mass, such as anorexia nervosa, hypogonadism, hyperparathyroidism, hyperthyroidism, celiac disease, irritable bowel disease, rheumatoid arthritis, lupus, renal disease, Marfan syndrome
• medications, such as glucocorticoids, aromatase inhibitors, premenopausal tamoxifen, excess thyroid hormone replacement, progesterone contraception
• excessive alcohol consumption, heavy smoking, vitamin D deficiency, calcium deficiency, occasionally veganism or vegetarianism.

BMD interpretation in premenopausal women does not use the T-scores developed for postmenopausal women in which standard deviations (SD) from the mean for a young reference population are employed. In that population, the normal range is up to -1.0 SD; osteopenia > -1.0 < -2.5 SD; and osteoporosis > -2.5 SD. Instead, in premenopausal patients, Z-scores, which compare the measured bone mass to an age- and gender-matched cohort, are employed. Z-scores > 2 SD below the matched population should be used rather than the T-scores that are already familiar to most clinicians.

Up to 90% of these premenopausal women with such skeletal fragility will display the secondary causes described above. ●

Recently, the National Osteoporosis Foundation (NOF) changed its name to the Bone Health and Osteoporosis Foundation (BHOF). Several years ago, in 2016 at my urging, this column was renamed from “Update on osteoporosis” to “Update on bone health.” I believe we were on the leading edge of this movement. As expressed in last year’s Update, our patients’ bone health must be emphasized more than it has been in the past.¹

Consider that localized breast cancer carries a 5-year survival rate of 99%.² Most of my patients are keenly aware that periodic competent breast imaging is the key to the earliest possible diagnosis. By contrast, in this country a hip fracture carries a mortality in the first year of 21%!³ Furthermore, approximately one-third of women who fracture their hip do not have osteoporosis.⁴ While the risk of hip fracture is greatest in women with osteoporosis, it is not absent in those without the condition. Finally, the role of muscle mass, strength, and performance in bone health is a rapidly emerging topic and one that constitutes the core of this year’s Update.

Muscle mass and strength play key role in bone health

de Villiers TJ, Goldstein SR. Update on bone health: the International Menopause Society white paper 2021. Climacteric. 2021;24:498-504. doi:10.1080/13697137.2021.1950967.

Recently, de Villiers and Goldstein offered an overview of osteoporosis.⁵ What is worthy of reporting here is the role of muscle in bone health.

The bone-muscle relationship

Most clinicians know that osteoporosis and osteopenia are well-defined conditions with known risks associated with fracture. According to a review of PubMed, the first article with the keyword “osteoporosis” was published in 1894; through May 2020, 93,335 articles used that keyword. “Osteoporosis” is derived from the Greek osteon (bone) and poros (little hole). Thus, osteoporosis means “porous bone.”

Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass, strength, and function, and the condition is associated with a risk of adverse outcomes that include physical disabilities, poor quality of life, and death.^6,7 “Sarcopenia” has its roots in the Greek words sarx (flesh) and penia (loss), and the term was coined in 1989.⁸ A PubMed review that included “sarcopenia” as the keyword revealed that the first article was published in 1993, with 12,068 articles published through May 2020.

Notably, muscle accounts for about 60% of the body’s protein. Muscle mass decreases with age, but younger patients with malnutrition, cachexia, or inflammatory diseases are also prone to decreased muscle mass. While osteoporosis has a well-accepted definition based on dual-energy x-ray absorptiometry (DXA) measurements, sarcopenia has no universally accepted definition, consensus diagnostic criteria, or treatment guidelines. In 2016, however, the International Classification of Diseases, Tenth Revision, Clinical Modification (CD-10-CM) finally recognized sarcopenia as a disease entity.

Currently, the most widely accepted definition comes from the European Working Group on Sarcopenia in Older People, which labeled presarcopenia as low muscle mass without impact on muscle strength or performance; sarcopenia as low muscle mass with either low muscle strength or low physical performance; and severe sarcopenia has all 3 criteria being present.⁹

When osteosarcopenia (osteoporosis or osteopenia combined with sarcopenia) exists, it can result in a threefold increase in risk of falls and a fourfold increase in fracture risk compared with women who have osteopenia or osteoporosis alone.¹⁰

Continue to: Denosumab decreased falls risk, improved sarcopenia measures vs comparator antiresorptives...

Denosumab decreased falls risk, improved sarcopenia measures vs comparator antiresorptives

El Miedany Y, El Gaafary M, Toth M, et al; Egyptian Academy of Bone Health, Metabolic Bone Diseases. Is there a potential dual effect of denosumab for treatment of osteoporosis and sarcopenia? Clin Rheumatol. 2021;40:4225-4232. doi: 10.1007/s10067-021 -05757-w.

Osteosarcopenia, the combination of osteoporosis or osteopenia with sarcopenia, has been shown to increase the overall rate of falls and fracture when compared with fall and fracture rates in women with osteopenia or osteoporosis alone.¹⁰ A study by El Miedany and colleagues examined whether denosumab treatment had a possible dual therapeutic effect on osteoporosis and sarcopenia.¹¹

Study details

The investigators looked at 135 patients diagnosed with postmenopausal osteoporosis and who were prescribed denosumab and compared them with a control group of 272 patients stratified into 2 subgroups: 136 were prescribed alendronate and 136 were prescribed zoledronate.

Assessments were performed for all participants for BMD (DXA), fall risk (falls risk assessment score [FRAS]), fracture risk (FRAX assessment tool), and sarcopenia measures. Reassessments were conducted after 5 years of denosumab or alendronate therapy, 3 years of zoledronate therapy, and 1 year after stopping the osteoporosis therapy.

The FRAS uses the clinical variables of history of falls in the last 12 months, impaired sight, weak hand grip, history of loss of balance in the last 12 months, and slowing of the walking speed/change in gait to yield a percent chance of sustaining a fall.¹² Sarcopenic measures include grip strength, timed up and go (TUG) mobility test, and gait speed. There were no significant demographic differences between the 3 groups.

Denosumab reduced risk of falls and positively affected muscle strength

On completion of the 5-year denosumab therapy, falls risk was significantly decreased (P = .001) and significant improvements were seen in all sarcopenia measures (P = .01). One year after denosumab was discontinued, a significant worsening of both falls risk and sarcopenia measures (P = .01) occurred. This was in contrast to results in both control groups (alendronate and zoledronate), in which there was an improvement, although less robust in gait speed and the TUG test (P = .05) but no improvement in risk of falls. Thus, the results of this study showed that denosumab not only improved bone mass but also reduced falls risk.

Compared with bisphosphonates, denosumab showed the highest significant positive effect on both physical performance and skeletal muscle strength. This is evidenced by improvement of the gait speed, TUG test, and 4-m walk test (P<.001) in the denosumab group versus in the alendronate and zoledronate group (P<.05).

These results agree with the outcomes of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis 6 months) trial, which revealed that not only did denosumab treatment reduce the risk of vertebral, nonvertebral, and hip fracture over 36 months, but also that the denosumab-treated group had fewer falls (4.5%) compared with the other groups (5.7%) (P = .02).¹³

Continue to: Estrogen’s role in bone health and its therapeutic potential in osteosarcopenia...

Estrogen’s role in bone health and its therapeutic potential in osteosarcopenia

Mandelli A, Tacconi E, Levinger I, et al. The role of estrogens in osteosarcopenia: from biology to potential dual therapeutic effects. Climacteric. 2021;1-7. doi: 10.1080/13697137.2021.1965118.

Osteosarcopenia is a particular term used to describe the coexistence of 2 pathologies, osteopenia/ osteoporosis and sarcopenia.¹⁴ Sarcopenia is characterized by a loss of muscle mass, strength, and performance. Numerous studies indicate that higher lean body mass is related to increased BMD and reduced fracture risk, especially in postmenopausal women.¹⁵

Menopause, muscle, and estrogen’s physiologic effects

Estrogens play a critical role in maintaining bone and muscle mass in women. Women experience a decline in musculoskeletal quantity and quality at the onset of menopause.¹⁶ Muscle mass and strength decrease rapidly after menopause, which suggests that degradation of muscle protein begins to exert a more significant effect due to a decrease in protein synthesis. Indeed, a reduced response to anabolic stimuli has been shown in postmenopausal women.¹⁷ Normalization of the protein synthesis response after restoring estrogen levels with estrogen therapy supports this hypothesis.¹⁸

In a meta-analysis to identify the role of estrogen therapy on muscle strength, the authors concluded that estrogens benefit muscle strength not by increasing the skeletal mass but by improving muscle quality and its ability to generate force.¹⁹ In addition, however, it has been demonstrated that exercise prevents and delays the onset of osteosarcopenia.²⁰

When should bone mass be measured in premenopausal women?

Conradie M, de Villiers T. Premenopausal osteoporosis. Climacteric. 2021:1-14. doi: 10.1080/13697137 .2021.1926974.

Most women’s clinicians are somewhat well acquainted with the increasing importance of preventing, diagnosing, and treating postmenopausal osteoporosis, which predisposes to fragility fracture and the morbidity and even mortality that brings. Increasingly, some younger women are asking for and receiving both bone mass measurements that may be inappropriately ordered and/or wrongly interpreted. Conradie and de Villiers provided an overview of premenopausal osteoporosis, containing important facts that all clinicians who care for women should be aware of.²¹

Indications for testing

BMD testing is only indicated in younger women in settings in which the result may influence management decisions, such as:

• a history of fragility fracture
• diseases associated with low bone mass, such as anorexia nervosa, hypogonadism, hyperparathyroidism, hyperthyroidism, celiac disease, irritable bowel disease, rheumatoid arthritis, lupus, renal disease, Marfan syndrome
• medications, such as glucocorticoids, aromatase inhibitors, premenopausal tamoxifen, excess thyroid hormone replacement, progesterone contraception
• excessive alcohol consumption, heavy smoking, vitamin D deficiency, calcium deficiency, occasionally veganism or vegetarianism.

BMD interpretation in premenopausal women does not use the T-scores developed for postmenopausal women in which standard deviations (SD) from the mean for a young reference population are employed. In that population, the normal range is up to -1.0 SD; osteopenia > -1.0 < -2.5 SD; and osteoporosis > -2.5 SD. Instead, in premenopausal patients, Z-scores, which compare the measured bone mass to an age- and gender-matched cohort, are employed. Z-scores > 2 SD below the matched population should be used rather than the T-scores that are already familiar to most clinicians.

Up to 90% of these premenopausal women with such skeletal fragility will display the secondary causes described above. ●

Recently, the National Osteoporosis Foundation (NOF) changed its name to the Bone Health and Osteoporosis Foundation (BHOF). Several years ago, in 2016 at my urging, this column was renamed from “Update on osteoporosis” to “Update on bone health.” I believe we were on the leading edge of this movement. As expressed in last year’s Update, our patients’ bone health must be emphasized more than it has been in the past.¹

Consider that localized breast cancer carries a 5-year survival rate of 99%.² Most of my patients are keenly aware that periodic competent breast imaging is the key to the earliest possible diagnosis. By contrast, in this country a hip fracture carries a mortality in the first year of 21%!³ Furthermore, approximately one-third of women who fracture their hip do not have osteoporosis.⁴ While the risk of hip fracture is greatest in women with osteoporosis, it is not absent in those without the condition. Finally, the role of muscle mass, strength, and performance in bone health is a rapidly emerging topic and one that constitutes the core of this year’s Update.

Muscle mass and strength play key role in bone health

de Villiers TJ, Goldstein SR. Update on bone health: the International Menopause Society white paper 2021. Climacteric. 2021;24:498-504. doi:10.1080/13697137.2021.1950967.

Recently, de Villiers and Goldstein offered an overview of osteoporosis.⁵ What is worthy of reporting here is the role of muscle in bone health.

The bone-muscle relationship

Most clinicians know that osteoporosis and osteopenia are well-defined conditions with known risks associated with fracture. According to a review of PubMed, the first article with the keyword “osteoporosis” was published in 1894; through May 2020, 93,335 articles used that keyword. “Osteoporosis” is derived from the Greek osteon (bone) and poros (little hole). Thus, osteoporosis means “porous bone.”

Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass, strength, and function, and the condition is associated with a risk of adverse outcomes that include physical disabilities, poor quality of life, and death.^6,7 “Sarcopenia” has its roots in the Greek words sarx (flesh) and penia (loss), and the term was coined in 1989.⁸ A PubMed review that included “sarcopenia” as the keyword revealed that the first article was published in 1993, with 12,068 articles published through May 2020.

Notably, muscle accounts for about 60% of the body’s protein. Muscle mass decreases with age, but younger patients with malnutrition, cachexia, or inflammatory diseases are also prone to decreased muscle mass. While osteoporosis has a well-accepted definition based on dual-energy x-ray absorptiometry (DXA) measurements, sarcopenia has no universally accepted definition, consensus diagnostic criteria, or treatment guidelines. In 2016, however, the International Classification of Diseases, Tenth Revision, Clinical Modification (CD-10-CM) finally recognized sarcopenia as a disease entity.

Currently, the most widely accepted definition comes from the European Working Group on Sarcopenia in Older People, which labeled presarcopenia as low muscle mass without impact on muscle strength or performance; sarcopenia as low muscle mass with either low muscle strength or low physical performance; and severe sarcopenia has all 3 criteria being present.⁹

When osteosarcopenia (osteoporosis or osteopenia combined with sarcopenia) exists, it can result in a threefold increase in risk of falls and a fourfold increase in fracture risk compared with women who have osteopenia or osteoporosis alone.¹⁰

Continue to: Denosumab decreased falls risk, improved sarcopenia measures vs comparator antiresorptives...

Denosumab decreased falls risk, improved sarcopenia measures vs comparator antiresorptives

El Miedany Y, El Gaafary M, Toth M, et al; Egyptian Academy of Bone Health, Metabolic Bone Diseases. Is there a potential dual effect of denosumab for treatment of osteoporosis and sarcopenia? Clin Rheumatol. 2021;40:4225-4232. doi: 10.1007/s10067-021 -05757-w.

Osteosarcopenia, the combination of osteoporosis or osteopenia with sarcopenia, has been shown to increase the overall rate of falls and fracture when compared with fall and fracture rates in women with osteopenia or osteoporosis alone.¹⁰ A study by El Miedany and colleagues examined whether denosumab treatment had a possible dual therapeutic effect on osteoporosis and sarcopenia.¹¹

Study details

The investigators looked at 135 patients diagnosed with postmenopausal osteoporosis and who were prescribed denosumab and compared them with a control group of 272 patients stratified into 2 subgroups: 136 were prescribed alendronate and 136 were prescribed zoledronate.

Assessments were performed for all participants for BMD (DXA), fall risk (falls risk assessment score [FRAS]), fracture risk (FRAX assessment tool), and sarcopenia measures. Reassessments were conducted after 5 years of denosumab or alendronate therapy, 3 years of zoledronate therapy, and 1 year after stopping the osteoporosis therapy.

The FRAS uses the clinical variables of history of falls in the last 12 months, impaired sight, weak hand grip, history of loss of balance in the last 12 months, and slowing of the walking speed/change in gait to yield a percent chance of sustaining a fall.¹² Sarcopenic measures include grip strength, timed up and go (TUG) mobility test, and gait speed. There were no significant demographic differences between the 3 groups.

Denosumab reduced risk of falls and positively affected muscle strength

On completion of the 5-year denosumab therapy, falls risk was significantly decreased (P = .001) and significant improvements were seen in all sarcopenia measures (P = .01). One year after denosumab was discontinued, a significant worsening of both falls risk and sarcopenia measures (P = .01) occurred. This was in contrast to results in both control groups (alendronate and zoledronate), in which there was an improvement, although less robust in gait speed and the TUG test (P = .05) but no improvement in risk of falls. Thus, the results of this study showed that denosumab not only improved bone mass but also reduced falls risk.

Compared with bisphosphonates, denosumab showed the highest significant positive effect on both physical performance and skeletal muscle strength. This is evidenced by improvement of the gait speed, TUG test, and 4-m walk test (P<.001) in the denosumab group versus in the alendronate and zoledronate group (P<.05).

These results agree with the outcomes of the FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis 6 months) trial, which revealed that not only did denosumab treatment reduce the risk of vertebral, nonvertebral, and hip fracture over 36 months, but also that the denosumab-treated group had fewer falls (4.5%) compared with the other groups (5.7%) (P = .02).¹³

Continue to: Estrogen’s role in bone health and its therapeutic potential in osteosarcopenia...

Estrogen’s role in bone health and its therapeutic potential in osteosarcopenia

Mandelli A, Tacconi E, Levinger I, et al. The role of estrogens in osteosarcopenia: from biology to potential dual therapeutic effects. Climacteric. 2021;1-7. doi: 10.1080/13697137.2021.1965118.

Osteosarcopenia is a particular term used to describe the coexistence of 2 pathologies, osteopenia/ osteoporosis and sarcopenia.¹⁴ Sarcopenia is characterized by a loss of muscle mass, strength, and performance. Numerous studies indicate that higher lean body mass is related to increased BMD and reduced fracture risk, especially in postmenopausal women.¹⁵

Menopause, muscle, and estrogen’s physiologic effects

Estrogens play a critical role in maintaining bone and muscle mass in women. Women experience a decline in musculoskeletal quantity and quality at the onset of menopause.¹⁶ Muscle mass and strength decrease rapidly after menopause, which suggests that degradation of muscle protein begins to exert a more significant effect due to a decrease in protein synthesis. Indeed, a reduced response to anabolic stimuli has been shown in postmenopausal women.¹⁷ Normalization of the protein synthesis response after restoring estrogen levels with estrogen therapy supports this hypothesis.¹⁸

In a meta-analysis to identify the role of estrogen therapy on muscle strength, the authors concluded that estrogens benefit muscle strength not by increasing the skeletal mass but by improving muscle quality and its ability to generate force.¹⁹ In addition, however, it has been demonstrated that exercise prevents and delays the onset of osteosarcopenia.²⁰

When should bone mass be measured in premenopausal women?

Conradie M, de Villiers T. Premenopausal osteoporosis. Climacteric. 2021:1-14. doi: 10.1080/13697137 .2021.1926974.

Most women’s clinicians are somewhat well acquainted with the increasing importance of preventing, diagnosing, and treating postmenopausal osteoporosis, which predisposes to fragility fracture and the morbidity and even mortality that brings. Increasingly, some younger women are asking for and receiving both bone mass measurements that may be inappropriately ordered and/or wrongly interpreted. Conradie and de Villiers provided an overview of premenopausal osteoporosis, containing important facts that all clinicians who care for women should be aware of.²¹

Indications for testing

BMD testing is only indicated in younger women in settings in which the result may influence management decisions, such as:

• a history of fragility fracture
• diseases associated with low bone mass, such as anorexia nervosa, hypogonadism, hyperparathyroidism, hyperthyroidism, celiac disease, irritable bowel disease, rheumatoid arthritis, lupus, renal disease, Marfan syndrome
• medications, such as glucocorticoids, aromatase inhibitors, premenopausal tamoxifen, excess thyroid hormone replacement, progesterone contraception
• excessive alcohol consumption, heavy smoking, vitamin D deficiency, calcium deficiency, occasionally veganism or vegetarianism.

BMD interpretation in premenopausal women does not use the T-scores developed for postmenopausal women in which standard deviations (SD) from the mean for a young reference population are employed. In that population, the normal range is up to -1.0 SD; osteopenia > -1.0 < -2.5 SD; and osteoporosis > -2.5 SD. Instead, in premenopausal patients, Z-scores, which compare the measured bone mass to an age- and gender-matched cohort, are employed. Z-scores > 2 SD below the matched population should be used rather than the T-scores that are already familiar to most clinicians.

Up to 90% of these premenopausal women with such skeletal fragility will display the secondary causes described above. ●

In her presentation at The North American Menopause Society (NAMS) 2021 annual meeting (September 22–25, 2021, in Washington, DC), Dr. Holly J. Pederson offered her expert perspectives on breast cancer prevention in at-risk women in “Chemoprevention for risk reduction: Women’s health clinicians have a role.” OBG Management talked with Dr. Pederson after the meeting to explore key points of the presentation.

Which patients would benefit from chemoprevention?

OBG Management: In your NAMS 2021 presentation on chemoprevention for cancer risk reduction, you make the point that for certain women, preventive medication can decrease the risk of breast cancer but is vastly underutilized. Which women specifically would benefit most from breast cancer risk-reducing medication?

Holly J. Pederson, MD: Obviously, women with significant family history are at risk. And approximately 10% of biopsies that are done for other reasons incidentally show atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS)—which are not precancers or cancers but are markers for the development of the disease—and they markedly increase risk. Atypical hyperplasia confers a 30% risk for developing breast cancer over the next 25 years, and LCIS is associated with up to a 2% per year risk. In this setting, preventive medication has been shown to cut risk by 56% to 86%; this is a targeted population that is often overlooked.

Mathematical risk models can be used to assess risk by assessing women’s risk factors. The United States Preventive Services Task Force (USPSTF) has set forth a threshold at which they believe the benefits outweigh the risks of preventive medications. That threshold is 3% or greater over the next 5 years using the Gail breast cancer risk assessment tool.¹ The American Society of Clinical Oncology (ASCO) uses the Tyrer-Cuzick breast cancer risk evaluation model with a threshold of 5% over the next 10 years.² In general, those are the situations in which chemoprevention is a no-brainer.

Certain genetic mutations also predispose to estrogen-sensitive breast cancer. While preventive medications specifically have not been studied in large groups of gene carriers, chemoprevention makes sense because these medications prevent estrogen-sensitive breast cancers that those patients are prone to. Examples would be patients with ATM and CHEK2 gene mutations, which are very common, and patients with BRCA2 and even BRCA1 variants in the postmenopausal years. Those are the big targets.

Risk assessment models

OBG Management: Do you have a preferred breast cancer risk assessment model that you use in your practice?

Dr. Pederson: Yes, I almost exclusively use the Tyrer-Cuzick risk model, version 8, which incorporates breast density. This model is intimidating to some practitioners initially, but once you get used to it, you can complete it very quickly.

The Gail model is very limited. It assesses only first-degree relatives, so you don’t get the paternal information at all, and you don’t use age at diagnosis, family structure, genetic testing, results of breast density, or body mass index (BMI). There are many limitations of the Gail model, but most people use it because it is so easy and they are familiar with it.

Possibly the best model is the CanRisk tool, which incorporates the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA), but it takes too much time to use in clinic; it’s too complicated. The Tyrer-Cuzick model is easy to use once you get used to it.

OBG Management: When would results of the Tyrer-Cuzick assessment necessitate referral to a specialist?

Dr. Pederson: Risk doesn’t always need to be formally calculated, which can be time-consuming. It’s one of those situations where most practitioners know it when they see it. Benign atypical biopsies, a strong family history, or, obviously, the presence of a genetic mutation are huge red flags.

If a practitioner has a nearby high-risk center where they can refer patients, that can be so useful, even for a one-time consultation to guide management. For example, with the virtual world now, I do a lot of consultations for patients and outline a plan, and then the referring practitioner can carry out the plan with confidence and then send the patient back periodically. There are so many more options now that previously did not exist for the busy ObGyn or primary care provider to rely on.

Continue to: Chemoprevention uptake in at-risk women...

OBG Management: How does the risk assessment result influence the uptake of chemoprevention? Are more women willing to take preventive medication?

Dr. Pederson: We really never practice medicine using numbers. We use clinical judgment, and we use relationships with patients in terms of developing confidence and trust. I think that the uptake that we exhibit in our center probably is more based on the patients’ perception that we are confident in our recommendations. I think that many practitioners simply are not comfortable with explaining medications, explaining and managing adverse effects, and using alternative medications. While the modeling helps, I think the personal expertise really makes the difference.

Going forward, the addition of the polygenic risk score to the mathematical risk models is going to make a big difference. Right now, the mathematical risk model is simply that: it takes the traditional risk factors that a patient has and spits out a number. But adding the patient’s genomic data—that is, a weighted summation of SNPs, or single nucleotide polymorphisms, now numbering over 300 for breast cancer—can explain more about their personalized risk, which is going to be more powerful in influencing a woman to take medication or not to take medication, in my opinion. Knowing their actual genomic risk will be a big step forward in individualized risk stratification and increased medication uptake as well as vigilance with high risk screening and attention to diet, exercise, and drinking alcohol in moderation.

OBG Management: What drugs can be used for breast cancer preventive therapy, and how do you select a drug based on patient factors?

Dr. Pederson: The only drug that can be used in the premenopausal setting is tamoxifen (TABLE 1). Women can’t take it if they are pregnant, planning to become pregnant, or if they don’t use a reliable form of birth control because it is teratogenic. Women also cannot take tamoxifen if they have had a history of blood clots, stroke, or transient ischemic attack; if they are on warfarin or estrogen preparations; or if they have had atypical endometrial biopsies or endometrial cancer. Those are the absolute contraindications for tamoxifen use.

Tamoxifen is generally very well tolerated in most women; some women experience hot flashes and night sweats that often will subside (or become tolerable) over the first 90 days. In addition, some women experience vaginal discharge rather than dryness, but it is not as bothersome to patients as dryness can be.

Tamoxifen can be used in the pre- or postmenopausal setting. In healthy premenopausal women, there’s no increased risk of the serious adverse effects that are seen with tamoxifen use in postmenopausal women, such as the 1% risk of blood clots and the 1% risk of endometrial cancer.

In postmenopausal women who still have their uterus, I’ll preferentially use raloxifene over tamoxifen. If they don’t have their uterus, tamoxifen is slightly more effective than the raloxifene, and I’ll use that.

Tamoxifen and raloxifene are both selective estrogen receptor modulators, or SERMs, which means that they stimulate receptors in some tissues, like bone, keeping bones strong, and block the receptors in other tissues, like the breast, reducing risk. And so you get kind of a two-for-one in terms of breast cancer risk reduction and osteoporosis prevention.

Another class of preventive drugs is the aromatase inhibitors (AIs). They block the enzyme aromatase, which converts androgens to estrogens peripherally; that is, the androgens that are produced primarily in the adrenal gland, but in part in postmenopausal ovaries.

In general, AIs are less well tolerated. There are generally more hot flashes and night sweats, and more vaginal dryness than with the SERMs. Anastrozole use is associated with arthralgias; and with exemestane use, there can be some hair loss (TABLE 2). Relative contraindications to SERMs become more important in the postmenopausal setting because of the increased frequency of both blood clots and uterine cancer in the postmenopausal years. I won’t give it to smokers. I won’t give tamoxifen to smokers in the premenopausal period either. With obese women, care must be taken because of the risk of blood clots with the SERMS, so then I’ll resort to the AIs. In the postmenopausal setting, you have to think a lot harder about the choices you use for preventive medication. Preferentially, I’ll use the SERMS if possible as they have fewer adverse effects.

OBG Management: What is the general duration of treatment with these risk-reducing drugs?

Dr. Pederson: All of them are recommended to be given for 5 years, but the MAP.3 trial, which studied exemestane compared with placebo, showed a 65% risk reduction with 3 years of therapy.³ So occasionally, we’ll use 3 years of therapy. Why the treatment recommendation is universally 5 years is unclear, given that the trial with that particular drug was done in 3 years. And with low-dose tamoxifen, the recommended duration is 3 years. That study was done in Italy with 5 mg daily for 3 years.⁴ In the United States we use 10 mg every other day for 3 years because the 5-mg tablet is not available here.

Continue to: Counseling points...

OBG Management: How do you counsel patients about the adverse effects of preventive medications, and how can they be managed?

Dr. Pederson: Patients’ fears about adverse effects are often worse than the adverse effects themselves. Women will fester over, Should I take it? Should I take it possibly for years? And then they take the medication and they tell me, “I don’t even notice that I’m taking it, and I know I’m being proactive.” The majority of patients who take these medications don’t have a lot of significant adverse effects.

Severe hot flashes can be managed in a number of ways, primarily and most effectively with certain antidepressants. Oxybutynin use is another good way to manage vasomotor symptoms. Sometimes we use local vaginal estrogen if a patient has vaginal dryness. In general, however, I would say at least 80% of my patients who take preventive medications do not require management of adverse side effects, that they are tolerable.

I counsel women this way, “Don’t think of this as a 5-year course of medication. Think of it as a 90-day trial, and let’s see how you do. If you hate it, then we don’t do it.” They often are pleasantly surprised that the medication is much easier to tolerate than they thought it would be.

OBG Management: What role does lifestyle modification play in conjunction with chemoprevention?

Dr. Pederson: It would be neat if a trial would directly compare lifestyle interventions with medications, because probably lifestyle change is as effective as medication is—but we don’t know that and probably will never have that data. We do know that alcohol consumption, every drink per day, increases risk by 10%. We know that obesity is responsible for 30% of breast cancers in this country, and that hormone replacement probably is overrated as a significant risk factor. Updated data from the Women’s Health Initiative study suggest that hormone replacement may actually reduce both breast cancer and cardiovascular risk in women in their 50s, but that’s in average-risk women and not in high-risk women, so we can’t generalize. We do recommend lifestyle measures including weight loss, exercise, and limiting alcohol consumption for all of our patients and certainly for our high-risk patients.

The only 2 things a woman can do to reduce the risk of triple negative breast cancer are to achieve and maintain ideal body weight and to breastfeed. The medications that I have mentioned don’t reduce the risk of triple negative breast cancer. Staying thin and breastfeeding do. It’s a problem in this country because at least 35% of all women and 58% of Black women are obese in America, and Black women tend to be prone to triple-negative breast cancer. That’s a real public health issue that we need to address. If we were going to focus on one thing, it would be focusing on obesity in terms of risk reduction.

Final thoughts

OBG Management: Would you like to add any other points about chemoprevention?

Dr. Pederson: I would like to direct attention to the American Heart Association scientific statement published at the end of 2020 that reported that hormone replacement in average-risk women reduced both cardiovascular events and overall mortality in women in their 50s by 30%.⁵ While that’s not directly related to what we are talking about, we need to weigh the pros and cons of estrogen versus estrogen blockade in women in terms of breast cancer risk management discussions. Part of shared decision making now needs to include cardiovascular risk factors and how estrogen is going to play into that.

In women with atypical hyperplasia or LCIS, they may benefit from the preventive medications we discussed. But in women with family history or in women with genetic mutations who have not had benign atypical biopsies, they may choose to consider estrogen during their 50s and perhaps take tamoxifen either beforehand or raloxifene afterward.

We need to look at patients holistically and consider all their risk factors together. We can’t look at one dimension alone.

OBG Management: Thank you for sharing your insights, Dr. Pederson. ●

In her presentation at The North American Menopause Society (NAMS) 2021 annual meeting (September 22–25, 2021, in Washington, DC), Dr. Holly J. Pederson offered her expert perspectives on breast cancer prevention in at-risk women in “Chemoprevention for risk reduction: Women’s health clinicians have a role.” OBG Management talked with Dr. Pederson after the meeting to explore key points of the presentation.

Which patients would benefit from chemoprevention?

OBG Management: In your NAMS 2021 presentation on chemoprevention for cancer risk reduction, you make the point that for certain women, preventive medication can decrease the risk of breast cancer but is vastly underutilized. Which women specifically would benefit most from breast cancer risk-reducing medication?

Holly J. Pederson, MD: Obviously, women with significant family history are at risk. And approximately 10% of biopsies that are done for other reasons incidentally show atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS)—which are not precancers or cancers but are markers for the development of the disease—and they markedly increase risk. Atypical hyperplasia confers a 30% risk for developing breast cancer over the next 25 years, and LCIS is associated with up to a 2% per year risk. In this setting, preventive medication has been shown to cut risk by 56% to 86%; this is a targeted population that is often overlooked.

Mathematical risk models can be used to assess risk by assessing women’s risk factors. The United States Preventive Services Task Force (USPSTF) has set forth a threshold at which they believe the benefits outweigh the risks of preventive medications. That threshold is 3% or greater over the next 5 years using the Gail breast cancer risk assessment tool.¹ The American Society of Clinical Oncology (ASCO) uses the Tyrer-Cuzick breast cancer risk evaluation model with a threshold of 5% over the next 10 years.² In general, those are the situations in which chemoprevention is a no-brainer.

Certain genetic mutations also predispose to estrogen-sensitive breast cancer. While preventive medications specifically have not been studied in large groups of gene carriers, chemoprevention makes sense because these medications prevent estrogen-sensitive breast cancers that those patients are prone to. Examples would be patients with ATM and CHEK2 gene mutations, which are very common, and patients with BRCA2 and even BRCA1 variants in the postmenopausal years. Those are the big targets.

Risk assessment models

OBG Management: Do you have a preferred breast cancer risk assessment model that you use in your practice?

Dr. Pederson: Yes, I almost exclusively use the Tyrer-Cuzick risk model, version 8, which incorporates breast density. This model is intimidating to some practitioners initially, but once you get used to it, you can complete it very quickly.

The Gail model is very limited. It assesses only first-degree relatives, so you don’t get the paternal information at all, and you don’t use age at diagnosis, family structure, genetic testing, results of breast density, or body mass index (BMI). There are many limitations of the Gail model, but most people use it because it is so easy and they are familiar with it.

Possibly the best model is the CanRisk tool, which incorporates the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA), but it takes too much time to use in clinic; it’s too complicated. The Tyrer-Cuzick model is easy to use once you get used to it.

OBG Management: When would results of the Tyrer-Cuzick assessment necessitate referral to a specialist?

Dr. Pederson: Risk doesn’t always need to be formally calculated, which can be time-consuming. It’s one of those situations where most practitioners know it when they see it. Benign atypical biopsies, a strong family history, or, obviously, the presence of a genetic mutation are huge red flags.

If a practitioner has a nearby high-risk center where they can refer patients, that can be so useful, even for a one-time consultation to guide management. For example, with the virtual world now, I do a lot of consultations for patients and outline a plan, and then the referring practitioner can carry out the plan with confidence and then send the patient back periodically. There are so many more options now that previously did not exist for the busy ObGyn or primary care provider to rely on.

Continue to: Chemoprevention uptake in at-risk women...

OBG Management: How does the risk assessment result influence the uptake of chemoprevention? Are more women willing to take preventive medication?

Dr. Pederson: We really never practice medicine using numbers. We use clinical judgment, and we use relationships with patients in terms of developing confidence and trust. I think that the uptake that we exhibit in our center probably is more based on the patients’ perception that we are confident in our recommendations. I think that many practitioners simply are not comfortable with explaining medications, explaining and managing adverse effects, and using alternative medications. While the modeling helps, I think the personal expertise really makes the difference.

Going forward, the addition of the polygenic risk score to the mathematical risk models is going to make a big difference. Right now, the mathematical risk model is simply that: it takes the traditional risk factors that a patient has and spits out a number. But adding the patient’s genomic data—that is, a weighted summation of SNPs, or single nucleotide polymorphisms, now numbering over 300 for breast cancer—can explain more about their personalized risk, which is going to be more powerful in influencing a woman to take medication or not to take medication, in my opinion. Knowing their actual genomic risk will be a big step forward in individualized risk stratification and increased medication uptake as well as vigilance with high risk screening and attention to diet, exercise, and drinking alcohol in moderation.

OBG Management: What drugs can be used for breast cancer preventive therapy, and how do you select a drug based on patient factors?

Dr. Pederson: The only drug that can be used in the premenopausal setting is tamoxifen (TABLE 1). Women can’t take it if they are pregnant, planning to become pregnant, or if they don’t use a reliable form of birth control because it is teratogenic. Women also cannot take tamoxifen if they have had a history of blood clots, stroke, or transient ischemic attack; if they are on warfarin or estrogen preparations; or if they have had atypical endometrial biopsies or endometrial cancer. Those are the absolute contraindications for tamoxifen use.

Tamoxifen is generally very well tolerated in most women; some women experience hot flashes and night sweats that often will subside (or become tolerable) over the first 90 days. In addition, some women experience vaginal discharge rather than dryness, but it is not as bothersome to patients as dryness can be.

Tamoxifen can be used in the pre- or postmenopausal setting. In healthy premenopausal women, there’s no increased risk of the serious adverse effects that are seen with tamoxifen use in postmenopausal women, such as the 1% risk of blood clots and the 1% risk of endometrial cancer.

In postmenopausal women who still have their uterus, I’ll preferentially use raloxifene over tamoxifen. If they don’t have their uterus, tamoxifen is slightly more effective than the raloxifene, and I’ll use that.

Tamoxifen and raloxifene are both selective estrogen receptor modulators, or SERMs, which means that they stimulate receptors in some tissues, like bone, keeping bones strong, and block the receptors in other tissues, like the breast, reducing risk. And so you get kind of a two-for-one in terms of breast cancer risk reduction and osteoporosis prevention.

Another class of preventive drugs is the aromatase inhibitors (AIs). They block the enzyme aromatase, which converts androgens to estrogens peripherally; that is, the androgens that are produced primarily in the adrenal gland, but in part in postmenopausal ovaries.

In general, AIs are less well tolerated. There are generally more hot flashes and night sweats, and more vaginal dryness than with the SERMs. Anastrozole use is associated with arthralgias; and with exemestane use, there can be some hair loss (TABLE 2). Relative contraindications to SERMs become more important in the postmenopausal setting because of the increased frequency of both blood clots and uterine cancer in the postmenopausal years. I won’t give it to smokers. I won’t give tamoxifen to smokers in the premenopausal period either. With obese women, care must be taken because of the risk of blood clots with the SERMS, so then I’ll resort to the AIs. In the postmenopausal setting, you have to think a lot harder about the choices you use for preventive medication. Preferentially, I’ll use the SERMS if possible as they have fewer adverse effects.

OBG Management: What is the general duration of treatment with these risk-reducing drugs?

Dr. Pederson: All of them are recommended to be given for 5 years, but the MAP.3 trial, which studied exemestane compared with placebo, showed a 65% risk reduction with 3 years of therapy.³ So occasionally, we’ll use 3 years of therapy. Why the treatment recommendation is universally 5 years is unclear, given that the trial with that particular drug was done in 3 years. And with low-dose tamoxifen, the recommended duration is 3 years. That study was done in Italy with 5 mg daily for 3 years.⁴ In the United States we use 10 mg every other day for 3 years because the 5-mg tablet is not available here.

Continue to: Counseling points...

OBG Management: How do you counsel patients about the adverse effects of preventive medications, and how can they be managed?

Dr. Pederson: Patients’ fears about adverse effects are often worse than the adverse effects themselves. Women will fester over, Should I take it? Should I take it possibly for years? And then they take the medication and they tell me, “I don’t even notice that I’m taking it, and I know I’m being proactive.” The majority of patients who take these medications don’t have a lot of significant adverse effects.

Severe hot flashes can be managed in a number of ways, primarily and most effectively with certain antidepressants. Oxybutynin use is another good way to manage vasomotor symptoms. Sometimes we use local vaginal estrogen if a patient has vaginal dryness. In general, however, I would say at least 80% of my patients who take preventive medications do not require management of adverse side effects, that they are tolerable.

I counsel women this way, “Don’t think of this as a 5-year course of medication. Think of it as a 90-day trial, and let’s see how you do. If you hate it, then we don’t do it.” They often are pleasantly surprised that the medication is much easier to tolerate than they thought it would be.

OBG Management: What role does lifestyle modification play in conjunction with chemoprevention?

Dr. Pederson: It would be neat if a trial would directly compare lifestyle interventions with medications, because probably lifestyle change is as effective as medication is—but we don’t know that and probably will never have that data. We do know that alcohol consumption, every drink per day, increases risk by 10%. We know that obesity is responsible for 30% of breast cancers in this country, and that hormone replacement probably is overrated as a significant risk factor. Updated data from the Women’s Health Initiative study suggest that hormone replacement may actually reduce both breast cancer and cardiovascular risk in women in their 50s, but that’s in average-risk women and not in high-risk women, so we can’t generalize. We do recommend lifestyle measures including weight loss, exercise, and limiting alcohol consumption for all of our patients and certainly for our high-risk patients.

The only 2 things a woman can do to reduce the risk of triple negative breast cancer are to achieve and maintain ideal body weight and to breastfeed. The medications that I have mentioned don’t reduce the risk of triple negative breast cancer. Staying thin and breastfeeding do. It’s a problem in this country because at least 35% of all women and 58% of Black women are obese in America, and Black women tend to be prone to triple-negative breast cancer. That’s a real public health issue that we need to address. If we were going to focus on one thing, it would be focusing on obesity in terms of risk reduction.

Final thoughts

OBG Management: Would you like to add any other points about chemoprevention?

Dr. Pederson: I would like to direct attention to the American Heart Association scientific statement published at the end of 2020 that reported that hormone replacement in average-risk women reduced both cardiovascular events and overall mortality in women in their 50s by 30%.⁵ While that’s not directly related to what we are talking about, we need to weigh the pros and cons of estrogen versus estrogen blockade in women in terms of breast cancer risk management discussions. Part of shared decision making now needs to include cardiovascular risk factors and how estrogen is going to play into that.

In women with atypical hyperplasia or LCIS, they may benefit from the preventive medications we discussed. But in women with family history or in women with genetic mutations who have not had benign atypical biopsies, they may choose to consider estrogen during their 50s and perhaps take tamoxifen either beforehand or raloxifene afterward.

We need to look at patients holistically and consider all their risk factors together. We can’t look at one dimension alone.

OBG Management: Thank you for sharing your insights, Dr. Pederson. ●

In her presentation at The North American Menopause Society (NAMS) 2021 annual meeting (September 22–25, 2021, in Washington, DC), Dr. Holly J. Pederson offered her expert perspectives on breast cancer prevention in at-risk women in “Chemoprevention for risk reduction: Women’s health clinicians have a role.” OBG Management talked with Dr. Pederson after the meeting to explore key points of the presentation.

Which patients would benefit from chemoprevention?

OBG Management: In your NAMS 2021 presentation on chemoprevention for cancer risk reduction, you make the point that for certain women, preventive medication can decrease the risk of breast cancer but is vastly underutilized. Which women specifically would benefit most from breast cancer risk-reducing medication?

Holly J. Pederson, MD: Obviously, women with significant family history are at risk. And approximately 10% of biopsies that are done for other reasons incidentally show atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS)—which are not precancers or cancers but are markers for the development of the disease—and they markedly increase risk. Atypical hyperplasia confers a 30% risk for developing breast cancer over the next 25 years, and LCIS is associated with up to a 2% per year risk. In this setting, preventive medication has been shown to cut risk by 56% to 86%; this is a targeted population that is often overlooked.

Mathematical risk models can be used to assess risk by assessing women’s risk factors. The United States Preventive Services Task Force (USPSTF) has set forth a threshold at which they believe the benefits outweigh the risks of preventive medications. That threshold is 3% or greater over the next 5 years using the Gail breast cancer risk assessment tool.¹ The American Society of Clinical Oncology (ASCO) uses the Tyrer-Cuzick breast cancer risk evaluation model with a threshold of 5% over the next 10 years.² In general, those are the situations in which chemoprevention is a no-brainer.

Certain genetic mutations also predispose to estrogen-sensitive breast cancer. While preventive medications specifically have not been studied in large groups of gene carriers, chemoprevention makes sense because these medications prevent estrogen-sensitive breast cancers that those patients are prone to. Examples would be patients with ATM and CHEK2 gene mutations, which are very common, and patients with BRCA2 and even BRCA1 variants in the postmenopausal years. Those are the big targets.

Risk assessment models

OBG Management: Do you have a preferred breast cancer risk assessment model that you use in your practice?

Dr. Pederson: Yes, I almost exclusively use the Tyrer-Cuzick risk model, version 8, which incorporates breast density. This model is intimidating to some practitioners initially, but once you get used to it, you can complete it very quickly.

The Gail model is very limited. It assesses only first-degree relatives, so you don’t get the paternal information at all, and you don’t use age at diagnosis, family structure, genetic testing, results of breast density, or body mass index (BMI). There are many limitations of the Gail model, but most people use it because it is so easy and they are familiar with it.

Possibly the best model is the CanRisk tool, which incorporates the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA), but it takes too much time to use in clinic; it’s too complicated. The Tyrer-Cuzick model is easy to use once you get used to it.

OBG Management: When would results of the Tyrer-Cuzick assessment necessitate referral to a specialist?

Dr. Pederson: Risk doesn’t always need to be formally calculated, which can be time-consuming. It’s one of those situations where most practitioners know it when they see it. Benign atypical biopsies, a strong family history, or, obviously, the presence of a genetic mutation are huge red flags.

If a practitioner has a nearby high-risk center where they can refer patients, that can be so useful, even for a one-time consultation to guide management. For example, with the virtual world now, I do a lot of consultations for patients and outline a plan, and then the referring practitioner can carry out the plan with confidence and then send the patient back periodically. There are so many more options now that previously did not exist for the busy ObGyn or primary care provider to rely on.

Continue to: Chemoprevention uptake in at-risk women...

OBG Management: How does the risk assessment result influence the uptake of chemoprevention? Are more women willing to take preventive medication?

Dr. Pederson: We really never practice medicine using numbers. We use clinical judgment, and we use relationships with patients in terms of developing confidence and trust. I think that the uptake that we exhibit in our center probably is more based on the patients’ perception that we are confident in our recommendations. I think that many practitioners simply are not comfortable with explaining medications, explaining and managing adverse effects, and using alternative medications. While the modeling helps, I think the personal expertise really makes the difference.

Going forward, the addition of the polygenic risk score to the mathematical risk models is going to make a big difference. Right now, the mathematical risk model is simply that: it takes the traditional risk factors that a patient has and spits out a number. But adding the patient’s genomic data—that is, a weighted summation of SNPs, or single nucleotide polymorphisms, now numbering over 300 for breast cancer—can explain more about their personalized risk, which is going to be more powerful in influencing a woman to take medication or not to take medication, in my opinion. Knowing their actual genomic risk will be a big step forward in individualized risk stratification and increased medication uptake as well as vigilance with high risk screening and attention to diet, exercise, and drinking alcohol in moderation.

OBG Management: What drugs can be used for breast cancer preventive therapy, and how do you select a drug based on patient factors?

Dr. Pederson: The only drug that can be used in the premenopausal setting is tamoxifen (TABLE 1). Women can’t take it if they are pregnant, planning to become pregnant, or if they don’t use a reliable form of birth control because it is teratogenic. Women also cannot take tamoxifen if they have had a history of blood clots, stroke, or transient ischemic attack; if they are on warfarin or estrogen preparations; or if they have had atypical endometrial biopsies or endometrial cancer. Those are the absolute contraindications for tamoxifen use.

Tamoxifen is generally very well tolerated in most women; some women experience hot flashes and night sweats that often will subside (or become tolerable) over the first 90 days. In addition, some women experience vaginal discharge rather than dryness, but it is not as bothersome to patients as dryness can be.

Tamoxifen can be used in the pre- or postmenopausal setting. In healthy premenopausal women, there’s no increased risk of the serious adverse effects that are seen with tamoxifen use in postmenopausal women, such as the 1% risk of blood clots and the 1% risk of endometrial cancer.

In postmenopausal women who still have their uterus, I’ll preferentially use raloxifene over tamoxifen. If they don’t have their uterus, tamoxifen is slightly more effective than the raloxifene, and I’ll use that.

Tamoxifen and raloxifene are both selective estrogen receptor modulators, or SERMs, which means that they stimulate receptors in some tissues, like bone, keeping bones strong, and block the receptors in other tissues, like the breast, reducing risk. And so you get kind of a two-for-one in terms of breast cancer risk reduction and osteoporosis prevention.

Another class of preventive drugs is the aromatase inhibitors (AIs). They block the enzyme aromatase, which converts androgens to estrogens peripherally; that is, the androgens that are produced primarily in the adrenal gland, but in part in postmenopausal ovaries.

In general, AIs are less well tolerated. There are generally more hot flashes and night sweats, and more vaginal dryness than with the SERMs. Anastrozole use is associated with arthralgias; and with exemestane use, there can be some hair loss (TABLE 2). Relative contraindications to SERMs become more important in the postmenopausal setting because of the increased frequency of both blood clots and uterine cancer in the postmenopausal years. I won’t give it to smokers. I won’t give tamoxifen to smokers in the premenopausal period either. With obese women, care must be taken because of the risk of blood clots with the SERMS, so then I’ll resort to the AIs. In the postmenopausal setting, you have to think a lot harder about the choices you use for preventive medication. Preferentially, I’ll use the SERMS if possible as they have fewer adverse effects.

OBG Management: What is the general duration of treatment with these risk-reducing drugs?

Dr. Pederson: All of them are recommended to be given for 5 years, but the MAP.3 trial, which studied exemestane compared with placebo, showed a 65% risk reduction with 3 years of therapy.³ So occasionally, we’ll use 3 years of therapy. Why the treatment recommendation is universally 5 years is unclear, given that the trial with that particular drug was done in 3 years. And with low-dose tamoxifen, the recommended duration is 3 years. That study was done in Italy with 5 mg daily for 3 years.⁴ In the United States we use 10 mg every other day for 3 years because the 5-mg tablet is not available here.

Continue to: Counseling points...

OBG Management: How do you counsel patients about the adverse effects of preventive medications, and how can they be managed?

Dr. Pederson: Patients’ fears about adverse effects are often worse than the adverse effects themselves. Women will fester over, Should I take it? Should I take it possibly for years? And then they take the medication and they tell me, “I don’t even notice that I’m taking it, and I know I’m being proactive.” The majority of patients who take these medications don’t have a lot of significant adverse effects.

Severe hot flashes can be managed in a number of ways, primarily and most effectively with certain antidepressants. Oxybutynin use is another good way to manage vasomotor symptoms. Sometimes we use local vaginal estrogen if a patient has vaginal dryness. In general, however, I would say at least 80% of my patients who take preventive medications do not require management of adverse side effects, that they are tolerable.

I counsel women this way, “Don’t think of this as a 5-year course of medication. Think of it as a 90-day trial, and let’s see how you do. If you hate it, then we don’t do it.” They often are pleasantly surprised that the medication is much easier to tolerate than they thought it would be.

OBG Management: What role does lifestyle modification play in conjunction with chemoprevention?

Dr. Pederson: It would be neat if a trial would directly compare lifestyle interventions with medications, because probably lifestyle change is as effective as medication is—but we don’t know that and probably will never have that data. We do know that alcohol consumption, every drink per day, increases risk by 10%. We know that obesity is responsible for 30% of breast cancers in this country, and that hormone replacement probably is overrated as a significant risk factor. Updated data from the Women’s Health Initiative study suggest that hormone replacement may actually reduce both breast cancer and cardiovascular risk in women in their 50s, but that’s in average-risk women and not in high-risk women, so we can’t generalize. We do recommend lifestyle measures including weight loss, exercise, and limiting alcohol consumption for all of our patients and certainly for our high-risk patients.

The only 2 things a woman can do to reduce the risk of triple negative breast cancer are to achieve and maintain ideal body weight and to breastfeed. The medications that I have mentioned don’t reduce the risk of triple negative breast cancer. Staying thin and breastfeeding do. It’s a problem in this country because at least 35% of all women and 58% of Black women are obese in America, and Black women tend to be prone to triple-negative breast cancer. That’s a real public health issue that we need to address. If we were going to focus on one thing, it would be focusing on obesity in terms of risk reduction.

Final thoughts

OBG Management: Would you like to add any other points about chemoprevention?

Dr. Pederson: I would like to direct attention to the American Heart Association scientific statement published at the end of 2020 that reported that hormone replacement in average-risk women reduced both cardiovascular events and overall mortality in women in their 50s by 30%.⁵ While that’s not directly related to what we are talking about, we need to weigh the pros and cons of estrogen versus estrogen blockade in women in terms of breast cancer risk management discussions. Part of shared decision making now needs to include cardiovascular risk factors and how estrogen is going to play into that.

In women with atypical hyperplasia or LCIS, they may benefit from the preventive medications we discussed. But in women with family history or in women with genetic mutations who have not had benign atypical biopsies, they may choose to consider estrogen during their 50s and perhaps take tamoxifen either beforehand or raloxifene afterward.

We need to look at patients holistically and consider all their risk factors together. We can’t look at one dimension alone.

OBG Management: Thank you for sharing your insights, Dr. Pederson. ●

CASE Woman with BRCA2 mutation

An 80-year-old woman presents for evaluation of newly diagnosed metastatic pancreatic adenocarcinoma. Her medical history is notable for breast cancer. Genetic testing of pancreatic tumor tissue detected a pathogenic variant in BRCA2. Family history revealed a history of melanoma as well as bladder, prostate, breast, and colon cancer. The patient subsequently underwent germline genetic testing with an 86-gene panel and a pathogenic mutation in BRCA2 was identified.

Watch a video of this patient and her clinician, Dr. Andrea Hagemann: https://www.youtube.com/watch?v=0x1jUG2u51c&t=21s.

Methods of genetic testing

It is estimated that 1 in 300 to 1 in 500 women in the United States carry a deleterious mutation in BRCA1 or BRCA2. This equates to between 250,000 and 415,000 women who are at high risk for breast and ovarian cancer.¹ Looking at all women with cancer, 20% with ovarian,² 10% with breast,³ 2% to 3% with endometrial,⁴ and 5% with colon cancer⁵ will have a germline mutation predisposing them to cancer. Identification of germline or somatic (tumor) mutations now inform treatment for patients with cancer. An equally important goal of germline genetic testing is cancer prevention. Cancer prevention strategies include risk-based screening for breast, colon, melanoma, and pancreatic cancer and prophylactic surgeries to reduce the risk of breast and ovarian cancer based on mutation type. Evidence-based screening guidelines by mutation type and absolute risk of associated cancers can be found on the National Comprehensive Cancer Network (NCCN).^6,7

Multiple strategies have been proposed to identify patients for germline genetic testing. Patients can be identified based on a detailed multigenerational family history. This strategy requires clinicians or genetic counselors to take and update family histories, to recognize when a patient requires referral for testing, and for such testing to be completed. Even then the generation of a detailed pedigree is not very sensitive or specific. Population-based screening for high-penetrance breast and ovarian cancer susceptibility genes, regardless of family history, also has been proposed.⁸ Such a strategy has become increasingly realistic with decreasing cost and increasing availability of genetic testing. However, it would require increased genetic counseling resources to feasibly and equitably reach the target population and to explain the results to those patients and their relatives.

An alternative is to test the enriched population of family members of a patient with cancer who has been found to carry a pathogenic variant in a clinically relevant cancer susceptibility gene. This type of testing is termed cascade genetic testing. Cascade testing in first-degree family members carries a 50% probability of detecting the same pathogenic mutation. A related testing model is traceback testing where genetic testing is performed on pathology or tumor registry specimens from deceased patients with cancer.⁹ This genetic testing information is then provided to the family. Traceback models of genetic testing are an active area of research but can introduce ethical dilemmas. The more widely accepted cascade testing starts with the testing of a living patient affected with cancer. A recent article demonstrated the feasibility of a cascade testing model. Using a multiple linear regression model, the authors determined that all carriers of pathogenic mutations in 18 clinically relevant cancer susceptibility genes in the United States could be identified in 9.9 years if there was a 70% cascade testing rate of first-, second- and third-degree relatives, compared to 59.5 years with no cascade testing.¹⁰

Gaps in practice

Identification of mutation carriers, either through screening triggered by family history or through testing of patients affected with cancer, represents a gap between guidelines and clinical practice. Current NCCN guidelines outline genetic testing criteria for hereditary breast and ovarian cancer syndrome and for hereditary colorectal cancer. Despite well-established criteria, a survey in the United States revealed that only 19% of primary care providers were able to accurately assess family history for BRCA1 and 2 testing.¹¹ Looking at patients who meet criteria for testing for Lynch syndrome, only 1 in 4 individuals have undergone genetic testing.¹² Among patients diagnosed with breast and ovarian cancer, current NCCN guidelines recommend germline genetic testing for all patients with epithelial ovarian cancer; emerging evidence suggests all patients with breast cancer should be offered germline genetic testing.^7,13 Large population-based studies have repeatedly demonstrated that testing rates fall short of this goal, with only 10% to 30% of patients undergoing genetic testing.^9,14

Among families with a known hereditary mutation, rates of cascade genetic testing are also low, ranging from 17% to 50%.^15-18 Evidence-based management guidelines, for both hereditary breast and ovarian cancer as well as Lynch syndrome, have been shown to reduce mortality.^19,20 Failure to identify patients who carry these genetic mutations equates to increased mortality for our patients.

Barriers to cascade genetic testing

Cascade genetic testing ideally would be performed on entire families. Actual practice is far from ideal, and barriers to cascade testing exist. Barriers encompass resistance on the part of the family and provider as well as environmental or system factors.

Family factors

Because of privacy laws, the responsibility of disclosure of genetic testing results to family members falls primarily to the patient. Proband education is critical to ensure disclosure amongst family members. Family dynamics and geographic distribution of family members can further complicate disclosure. Following disclosure, family member gender, education, and demographics as well as personal views, attitudes, and emotions affect whether a family member decides to undergo testing.²¹ Furthermore, insurance status and awareness of and access to specialty-specific care for the proband’s family members may influence cascade genetic testing rates.

Provider factors

Provider factors that affect cascade genetic testing include awareness of testing guidelines, interpretation of genetic testing results, and education and knowledge of specific mutations. For instance, providers must recognize that cascade testing is not appropriate for variants of uncertain significance. This can lead to unnecessary surveillance testing and prophylactic surgeries. Providers, however, must continue to follow patients and periodically update testing results as variants may be reclassified over time. Additionally, providers must be knowledgeable about the complex and nuanced nature of the screening guidelines for each mutation. The NCCN provides detailed recommendations by mutation.⁷ Patients may benefit from care with cancer specialists who are aware of the guidelines, particularly for moderate-penetrance genes like BRIP1 and PALB2, as discussions about the timing of risk-reducing surgery are more nuanced in this population. Finally, which providers are responsible for facilitating cascade testing may be unclear; oncologists and genetic counselors not primarily treating probands’ relatives may assume the proper information has been passed along to family members without a practical means to follow up, and primary care providers may assume it is being taken care of by the oncology provider.

Continue to: Environmental or system factors...

Environmental or system factors

Accessibility of genetic counseling and testing is a common barrier to cascade testing. Family members may be geographically remote and connecting them to counseling and testing can be challenging. Working with local genetic counselors can facilitate this process. Insurance coverage of testing is a common perceived barrier; however, many testing companies now provide cascade testing free of charge if within a certain window from the initial test. Despite this, patients often site cost as a barrier to undergoing testing. Concerns about insurance coverage are common after a positive result. The Genetic Information Nondiscrimination Act of 2008 prohibits discrimination against employees or insurance applicants because of genetic information. Life insurance or long-term care policies, however, can incorporate genetic testing information into policy rates, so patients should be recommended to consider purchasing life insurance prior to undergoing genetic testing. This is especially important if the person considering testing has not yet been diagnosed with cancer.

Implications of a positive result

Family members who receive a positive test result should be referred for genetic counseling and to the appropriate specialists for evidence-based screening and discussion for risk-reducing surgery (FIGURE).⁷ For mutations associated with hereditary breast and ovarian cancer, referral to breast and gynecologic surgeons with expertise in risk reducing surgery is critical as the risk of diagnosing an occult malignancy is approximately 1%.²² Surgical technique with a 2-cm margin on the infundibulopelvic ligament and pathologic evaluation with sectioning and extensive examination of the fimbriated end of the tubes (SEE-Fim technique) is recommended for mutation carriers. Additionally, evidence has emerged suggesting an increased risk of uterine serous cancer in BRCA1 carriers necessitating a discussion about risk-reducing hysterectomy in these patients.²³ Following risk reducing surgery, surgical menopause can have significant impacts on patients’ health and well-being. Treatment options including hormone replacement therapy can be considered.²⁴ To minimize recovery time burdens for patients, combination surgeries with breast, plastic, and gynecology specialties can be offered.

Patient resources: decision aids, websites

As genetic testing becomes more accessible and people are tested at younger ages, studies examining the balance of risk reduction and quality of life (QOL) are increasingly important. Fertility concerns, effects of early menopause, and the interrelatedness between decisions for breast and gynecologic risk reduction should all be considered in the counseling for surgical risk reduction. Patient decision aids can help mutation carriers navigate the complex information and decisions.²⁵ Websites specifically designed by advocacy groups can be useful adjuncts to in-office counseling (Facing Our Risk Empowered, FORCE; Facingourrisk.org).

Family letters

The American College of Obstetricians and Gynecologists recommends an ObGyn have a letter or documentation stating that the patient’s relative has a specific mutation before initiating cascade testing for an at-risk family member. The indicated test (such as BRCA1) should be ordered only after the patient has been counseled about potential outcomes and has expressly decided to be tested.²⁶ Letters, such as the example given in the American College of Obstetricians and Gynecologists practice bulletin,²⁶ are a key component of communication between oncology providers, probands, family members, and their primary care providers. ObGyn providers should work together with genetic counselors and gynecologic oncologists to determine the most efficient strategies in their communities.

Technology

Access to genetic testing and genetic counseling has been improved with the rise in telemedicine. Geographically remote patients can now access genetic counseling through medical center–based counselors as well as company-provided genetic counseling over the phone. Patients also can submit samples remotely without needing to be tested in a doctor’s office.

Databases from cancer centers that detail cascade genetic testing rates. As the preventive impact of cascade genetic testing becomes clearer, strategies to have recurrent discussions with cancer patients regarding their family members’ risk should be implemented. It is still unclear which providers—genetic counselors, gynecologic oncologists, medical oncologists, breast surgeons, ObGyns, to name a few—are primarily responsible for remembering to have these follow-up discussions, and despite advances, the burden still rests on the cancer patient themselves. Databases with automated follow-up surveys done every 6 to 12 months could provide some aid to busy providers in this regard.

Emerging research

If gynecologic risk-reducing surgery is chosen, clinical trial involvement should be encouraged. The Women Choosing Surgical Prevention (NCT02760849) in the United States and the TUBA study (NCT02321228) in the Netherlands were designed to compare menopause-related QOL between standard risk-reducing salpingo-oophorectomy (RRSO) and the innovative risk-reducing salpingectomy with delayed oophorectomy for mutation carriers. Results from the nonrandomized controlled TUBA trial suggest that patients have better menopause-related QOL after risk-reducing salpingectomy than after RRSO, regardless of hormone replacement therapy.²⁷ International collaboration is continuing to better understand oncologic safety. In the United States, the SOROCk trial (NCT04251052) is a noninferiority surgical choice study underway for BRCA1 mutation carriers aged 35 to 50, powered to determine oncologic outcome differences in addition to QOL outcomes between RRSO and delayed oophorectomy arms.

Returning to the case

The patient and her family underwent genetic counseling. The patient’s 2 daughters, each in their 50s, underwent cascade genetic testing and were found to carry the same pathogenic mutation in BRCA2. After counseling from both breast and gynecologic surgeons, they both elected to undergo risk reducing bilateral salpingo-oophorectomy with hysterectomy. Both now complete regular screening for breast cancer and melanoma with plans to start screening for pancreatic cancer. Both are currently cancer free.

Summary

Cascade genetic testing is an efficient strategy to identify mutation carriers for hereditary breast and ovarian cancer syndrome. Implementation of the best patient-centric care will require continued collaboration and communication across and within disciplines. ●

CASE Woman with BRCA2 mutation

An 80-year-old woman presents for evaluation of newly diagnosed metastatic pancreatic adenocarcinoma. Her medical history is notable for breast cancer. Genetic testing of pancreatic tumor tissue detected a pathogenic variant in BRCA2. Family history revealed a history of melanoma as well as bladder, prostate, breast, and colon cancer. The patient subsequently underwent germline genetic testing with an 86-gene panel and a pathogenic mutation in BRCA2 was identified.

Watch a video of this patient and her clinician, Dr. Andrea Hagemann: https://www.youtube.com/watch?v=0x1jUG2u51c&t=21s.

Methods of genetic testing

It is estimated that 1 in 300 to 1 in 500 women in the United States carry a deleterious mutation in BRCA1 or BRCA2. This equates to between 250,000 and 415,000 women who are at high risk for breast and ovarian cancer.¹ Looking at all women with cancer, 20% with ovarian,² 10% with breast,³ 2% to 3% with endometrial,⁴ and 5% with colon cancer⁵ will have a germline mutation predisposing them to cancer. Identification of germline or somatic (tumor) mutations now inform treatment for patients with cancer. An equally important goal of germline genetic testing is cancer prevention. Cancer prevention strategies include risk-based screening for breast, colon, melanoma, and pancreatic cancer and prophylactic surgeries to reduce the risk of breast and ovarian cancer based on mutation type. Evidence-based screening guidelines by mutation type and absolute risk of associated cancers can be found on the National Comprehensive Cancer Network (NCCN).^6,7

Multiple strategies have been proposed to identify patients for germline genetic testing. Patients can be identified based on a detailed multigenerational family history. This strategy requires clinicians or genetic counselors to take and update family histories, to recognize when a patient requires referral for testing, and for such testing to be completed. Even then the generation of a detailed pedigree is not very sensitive or specific. Population-based screening for high-penetrance breast and ovarian cancer susceptibility genes, regardless of family history, also has been proposed.⁸ Such a strategy has become increasingly realistic with decreasing cost and increasing availability of genetic testing. However, it would require increased genetic counseling resources to feasibly and equitably reach the target population and to explain the results to those patients and their relatives.

An alternative is to test the enriched population of family members of a patient with cancer who has been found to carry a pathogenic variant in a clinically relevant cancer susceptibility gene. This type of testing is termed cascade genetic testing. Cascade testing in first-degree family members carries a 50% probability of detecting the same pathogenic mutation. A related testing model is traceback testing where genetic testing is performed on pathology or tumor registry specimens from deceased patients with cancer.⁹ This genetic testing information is then provided to the family. Traceback models of genetic testing are an active area of research but can introduce ethical dilemmas. The more widely accepted cascade testing starts with the testing of a living patient affected with cancer. A recent article demonstrated the feasibility of a cascade testing model. Using a multiple linear regression model, the authors determined that all carriers of pathogenic mutations in 18 clinically relevant cancer susceptibility genes in the United States could be identified in 9.9 years if there was a 70% cascade testing rate of first-, second- and third-degree relatives, compared to 59.5 years with no cascade testing.¹⁰

Gaps in practice

Identification of mutation carriers, either through screening triggered by family history or through testing of patients affected with cancer, represents a gap between guidelines and clinical practice. Current NCCN guidelines outline genetic testing criteria for hereditary breast and ovarian cancer syndrome and for hereditary colorectal cancer. Despite well-established criteria, a survey in the United States revealed that only 19% of primary care providers were able to accurately assess family history for BRCA1 and 2 testing.¹¹ Looking at patients who meet criteria for testing for Lynch syndrome, only 1 in 4 individuals have undergone genetic testing.¹² Among patients diagnosed with breast and ovarian cancer, current NCCN guidelines recommend germline genetic testing for all patients with epithelial ovarian cancer; emerging evidence suggests all patients with breast cancer should be offered germline genetic testing.^7,13 Large population-based studies have repeatedly demonstrated that testing rates fall short of this goal, with only 10% to 30% of patients undergoing genetic testing.^9,14

Among families with a known hereditary mutation, rates of cascade genetic testing are also low, ranging from 17% to 50%.^15-18 Evidence-based management guidelines, for both hereditary breast and ovarian cancer as well as Lynch syndrome, have been shown to reduce mortality.^19,20 Failure to identify patients who carry these genetic mutations equates to increased mortality for our patients.

Barriers to cascade genetic testing

Cascade genetic testing ideally would be performed on entire families. Actual practice is far from ideal, and barriers to cascade testing exist. Barriers encompass resistance on the part of the family and provider as well as environmental or system factors.

Family factors

Because of privacy laws, the responsibility of disclosure of genetic testing results to family members falls primarily to the patient. Proband education is critical to ensure disclosure amongst family members. Family dynamics and geographic distribution of family members can further complicate disclosure. Following disclosure, family member gender, education, and demographics as well as personal views, attitudes, and emotions affect whether a family member decides to undergo testing.²¹ Furthermore, insurance status and awareness of and access to specialty-specific care for the proband’s family members may influence cascade genetic testing rates.

Provider factors

Provider factors that affect cascade genetic testing include awareness of testing guidelines, interpretation of genetic testing results, and education and knowledge of specific mutations. For instance, providers must recognize that cascade testing is not appropriate for variants of uncertain significance. This can lead to unnecessary surveillance testing and prophylactic surgeries. Providers, however, must continue to follow patients and periodically update testing results as variants may be reclassified over time. Additionally, providers must be knowledgeable about the complex and nuanced nature of the screening guidelines for each mutation. The NCCN provides detailed recommendations by mutation.⁷ Patients may benefit from care with cancer specialists who are aware of the guidelines, particularly for moderate-penetrance genes like BRIP1 and PALB2, as discussions about the timing of risk-reducing surgery are more nuanced in this population. Finally, which providers are responsible for facilitating cascade testing may be unclear; oncologists and genetic counselors not primarily treating probands’ relatives may assume the proper information has been passed along to family members without a practical means to follow up, and primary care providers may assume it is being taken care of by the oncology provider.

Continue to: Environmental or system factors...

Environmental or system factors

Accessibility of genetic counseling and testing is a common barrier to cascade testing. Family members may be geographically remote and connecting them to counseling and testing can be challenging. Working with local genetic counselors can facilitate this process. Insurance coverage of testing is a common perceived barrier; however, many testing companies now provide cascade testing free of charge if within a certain window from the initial test. Despite this, patients often site cost as a barrier to undergoing testing. Concerns about insurance coverage are common after a positive result. The Genetic Information Nondiscrimination Act of 2008 prohibits discrimination against employees or insurance applicants because of genetic information. Life insurance or long-term care policies, however, can incorporate genetic testing information into policy rates, so patients should be recommended to consider purchasing life insurance prior to undergoing genetic testing. This is especially important if the person considering testing has not yet been diagnosed with cancer.

Implications of a positive result

Family members who receive a positive test result should be referred for genetic counseling and to the appropriate specialists for evidence-based screening and discussion for risk-reducing surgery (FIGURE).⁷ For mutations associated with hereditary breast and ovarian cancer, referral to breast and gynecologic surgeons with expertise in risk reducing surgery is critical as the risk of diagnosing an occult malignancy is approximately 1%.²² Surgical technique with a 2-cm margin on the infundibulopelvic ligament and pathologic evaluation with sectioning and extensive examination of the fimbriated end of the tubes (SEE-Fim technique) is recommended for mutation carriers. Additionally, evidence has emerged suggesting an increased risk of uterine serous cancer in BRCA1 carriers necessitating a discussion about risk-reducing hysterectomy in these patients.²³ Following risk reducing surgery, surgical menopause can have significant impacts on patients’ health and well-being. Treatment options including hormone replacement therapy can be considered.²⁴ To minimize recovery time burdens for patients, combination surgeries with breast, plastic, and gynecology specialties can be offered.

Patient resources: decision aids, websites

As genetic testing becomes more accessible and people are tested at younger ages, studies examining the balance of risk reduction and quality of life (QOL) are increasingly important. Fertility concerns, effects of early menopause, and the interrelatedness between decisions for breast and gynecologic risk reduction should all be considered in the counseling for surgical risk reduction. Patient decision aids can help mutation carriers navigate the complex information and decisions.²⁵ Websites specifically designed by advocacy groups can be useful adjuncts to in-office counseling (Facing Our Risk Empowered, FORCE; Facingourrisk.org).

Family letters

The American College of Obstetricians and Gynecologists recommends an ObGyn have a letter or documentation stating that the patient’s relative has a specific mutation before initiating cascade testing for an at-risk family member. The indicated test (such as BRCA1) should be ordered only after the patient has been counseled about potential outcomes and has expressly decided to be tested.²⁶ Letters, such as the example given in the American College of Obstetricians and Gynecologists practice bulletin,²⁶ are a key component of communication between oncology providers, probands, family members, and their primary care providers. ObGyn providers should work together with genetic counselors and gynecologic oncologists to determine the most efficient strategies in their communities.

Technology

Access to genetic testing and genetic counseling has been improved with the rise in telemedicine. Geographically remote patients can now access genetic counseling through medical center–based counselors as well as company-provided genetic counseling over the phone. Patients also can submit samples remotely without needing to be tested in a doctor’s office.

Databases from cancer centers that detail cascade genetic testing rates. As the preventive impact of cascade genetic testing becomes clearer, strategies to have recurrent discussions with cancer patients regarding their family members’ risk should be implemented. It is still unclear which providers—genetic counselors, gynecologic oncologists, medical oncologists, breast surgeons, ObGyns, to name a few—are primarily responsible for remembering to have these follow-up discussions, and despite advances, the burden still rests on the cancer patient themselves. Databases with automated follow-up surveys done every 6 to 12 months could provide some aid to busy providers in this regard.

Emerging research

If gynecologic risk-reducing surgery is chosen, clinical trial involvement should be encouraged. The Women Choosing Surgical Prevention (NCT02760849) in the United States and the TUBA study (NCT02321228) in the Netherlands were designed to compare menopause-related QOL between standard risk-reducing salpingo-oophorectomy (RRSO) and the innovative risk-reducing salpingectomy with delayed oophorectomy for mutation carriers. Results from the nonrandomized controlled TUBA trial suggest that patients have better menopause-related QOL after risk-reducing salpingectomy than after RRSO, regardless of hormone replacement therapy.²⁷ International collaboration is continuing to better understand oncologic safety. In the United States, the SOROCk trial (NCT04251052) is a noninferiority surgical choice study underway for BRCA1 mutation carriers aged 35 to 50, powered to determine oncologic outcome differences in addition to QOL outcomes between RRSO and delayed oophorectomy arms.

Returning to the case

The patient and her family underwent genetic counseling. The patient’s 2 daughters, each in their 50s, underwent cascade genetic testing and were found to carry the same pathogenic mutation in BRCA2. After counseling from both breast and gynecologic surgeons, they both elected to undergo risk reducing bilateral salpingo-oophorectomy with hysterectomy. Both now complete regular screening for breast cancer and melanoma with plans to start screening for pancreatic cancer. Both are currently cancer free.

Summary

Cascade genetic testing is an efficient strategy to identify mutation carriers for hereditary breast and ovarian cancer syndrome. Implementation of the best patient-centric care will require continued collaboration and communication across and within disciplines. ●

CASE Woman with BRCA2 mutation

An 80-year-old woman presents for evaluation of newly diagnosed metastatic pancreatic adenocarcinoma. Her medical history is notable for breast cancer. Genetic testing of pancreatic tumor tissue detected a pathogenic variant in BRCA2. Family history revealed a history of melanoma as well as bladder, prostate, breast, and colon cancer. The patient subsequently underwent germline genetic testing with an 86-gene panel and a pathogenic mutation in BRCA2 was identified.

Watch a video of this patient and her clinician, Dr. Andrea Hagemann: https://www.youtube.com/watch?v=0x1jUG2u51c&t=21s.

Methods of genetic testing

It is estimated that 1 in 300 to 1 in 500 women in the United States carry a deleterious mutation in BRCA1 or BRCA2. This equates to between 250,000 and 415,000 women who are at high risk for breast and ovarian cancer.¹ Looking at all women with cancer, 20% with ovarian,² 10% with breast,³ 2% to 3% with endometrial,⁴ and 5% with colon cancer⁵ will have a germline mutation predisposing them to cancer. Identification of germline or somatic (tumor) mutations now inform treatment for patients with cancer. An equally important goal of germline genetic testing is cancer prevention. Cancer prevention strategies include risk-based screening for breast, colon, melanoma, and pancreatic cancer and prophylactic surgeries to reduce the risk of breast and ovarian cancer based on mutation type. Evidence-based screening guidelines by mutation type and absolute risk of associated cancers can be found on the National Comprehensive Cancer Network (NCCN).^6,7

Multiple strategies have been proposed to identify patients for germline genetic testing. Patients can be identified based on a detailed multigenerational family history. This strategy requires clinicians or genetic counselors to take and update family histories, to recognize when a patient requires referral for testing, and for such testing to be completed. Even then the generation of a detailed pedigree is not very sensitive or specific. Population-based screening for high-penetrance breast and ovarian cancer susceptibility genes, regardless of family history, also has been proposed.⁸ Such a strategy has become increasingly realistic with decreasing cost and increasing availability of genetic testing. However, it would require increased genetic counseling resources to feasibly and equitably reach the target population and to explain the results to those patients and their relatives.

An alternative is to test the enriched population of family members of a patient with cancer who has been found to carry a pathogenic variant in a clinically relevant cancer susceptibility gene. This type of testing is termed cascade genetic testing. Cascade testing in first-degree family members carries a 50% probability of detecting the same pathogenic mutation. A related testing model is traceback testing where genetic testing is performed on pathology or tumor registry specimens from deceased patients with cancer.⁹ This genetic testing information is then provided to the family. Traceback models of genetic testing are an active area of research but can introduce ethical dilemmas. The more widely accepted cascade testing starts with the testing of a living patient affected with cancer. A recent article demonstrated the feasibility of a cascade testing model. Using a multiple linear regression model, the authors determined that all carriers of pathogenic mutations in 18 clinically relevant cancer susceptibility genes in the United States could be identified in 9.9 years if there was a 70% cascade testing rate of first-, second- and third-degree relatives, compared to 59.5 years with no cascade testing.¹⁰

Gaps in practice

Identification of mutation carriers, either through screening triggered by family history or through testing of patients affected with cancer, represents a gap between guidelines and clinical practice. Current NCCN guidelines outline genetic testing criteria for hereditary breast and ovarian cancer syndrome and for hereditary colorectal cancer. Despite well-established criteria, a survey in the United States revealed that only 19% of primary care providers were able to accurately assess family history for BRCA1 and 2 testing.¹¹ Looking at patients who meet criteria for testing for Lynch syndrome, only 1 in 4 individuals have undergone genetic testing.¹² Among patients diagnosed with breast and ovarian cancer, current NCCN guidelines recommend germline genetic testing for all patients with epithelial ovarian cancer; emerging evidence suggests all patients with breast cancer should be offered germline genetic testing.^7,13 Large population-based studies have repeatedly demonstrated that testing rates fall short of this goal, with only 10% to 30% of patients undergoing genetic testing.^9,14

Among families with a known hereditary mutation, rates of cascade genetic testing are also low, ranging from 17% to 50%.^15-18 Evidence-based management guidelines, for both hereditary breast and ovarian cancer as well as Lynch syndrome, have been shown to reduce mortality.^19,20 Failure to identify patients who carry these genetic mutations equates to increased mortality for our patients.

Barriers to cascade genetic testing

Cascade genetic testing ideally would be performed on entire families. Actual practice is far from ideal, and barriers to cascade testing exist. Barriers encompass resistance on the part of the family and provider as well as environmental or system factors.

Family factors

Because of privacy laws, the responsibility of disclosure of genetic testing results to family members falls primarily to the patient. Proband education is critical to ensure disclosure amongst family members. Family dynamics and geographic distribution of family members can further complicate disclosure. Following disclosure, family member gender, education, and demographics as well as personal views, attitudes, and emotions affect whether a family member decides to undergo testing.²¹ Furthermore, insurance status and awareness of and access to specialty-specific care for the proband’s family members may influence cascade genetic testing rates.

Provider factors

Provider factors that affect cascade genetic testing include awareness of testing guidelines, interpretation of genetic testing results, and education and knowledge of specific mutations. For instance, providers must recognize that cascade testing is not appropriate for variants of uncertain significance. This can lead to unnecessary surveillance testing and prophylactic surgeries. Providers, however, must continue to follow patients and periodically update testing results as variants may be reclassified over time. Additionally, providers must be knowledgeable about the complex and nuanced nature of the screening guidelines for each mutation. The NCCN provides detailed recommendations by mutation.⁷ Patients may benefit from care with cancer specialists who are aware of the guidelines, particularly for moderate-penetrance genes like BRIP1 and PALB2, as discussions about the timing of risk-reducing surgery are more nuanced in this population. Finally, which providers are responsible for facilitating cascade testing may be unclear; oncologists and genetic counselors not primarily treating probands’ relatives may assume the proper information has been passed along to family members without a practical means to follow up, and primary care providers may assume it is being taken care of by the oncology provider.

Continue to: Environmental or system factors...

Environmental or system factors

Accessibility of genetic counseling and testing is a common barrier to cascade testing. Family members may be geographically remote and connecting them to counseling and testing can be challenging. Working with local genetic counselors can facilitate this process. Insurance coverage of testing is a common perceived barrier; however, many testing companies now provide cascade testing free of charge if within a certain window from the initial test. Despite this, patients often site cost as a barrier to undergoing testing. Concerns about insurance coverage are common after a positive result. The Genetic Information Nondiscrimination Act of 2008 prohibits discrimination against employees or insurance applicants because of genetic information. Life insurance or long-term care policies, however, can incorporate genetic testing information into policy rates, so patients should be recommended to consider purchasing life insurance prior to undergoing genetic testing. This is especially important if the person considering testing has not yet been diagnosed with cancer.

Implications of a positive result

Family members who receive a positive test result should be referred for genetic counseling and to the appropriate specialists for evidence-based screening and discussion for risk-reducing surgery (FIGURE).⁷ For mutations associated with hereditary breast and ovarian cancer, referral to breast and gynecologic surgeons with expertise in risk reducing surgery is critical as the risk of diagnosing an occult malignancy is approximately 1%.²² Surgical technique with a 2-cm margin on the infundibulopelvic ligament and pathologic evaluation with sectioning and extensive examination of the fimbriated end of the tubes (SEE-Fim technique) is recommended for mutation carriers. Additionally, evidence has emerged suggesting an increased risk of uterine serous cancer in BRCA1 carriers necessitating a discussion about risk-reducing hysterectomy in these patients.²³ Following risk reducing surgery, surgical menopause can have significant impacts on patients’ health and well-being. Treatment options including hormone replacement therapy can be considered.²⁴ To minimize recovery time burdens for patients, combination surgeries with breast, plastic, and gynecology specialties can be offered.

Patient resources: decision aids, websites

As genetic testing becomes more accessible and people are tested at younger ages, studies examining the balance of risk reduction and quality of life (QOL) are increasingly important. Fertility concerns, effects of early menopause, and the interrelatedness between decisions for breast and gynecologic risk reduction should all be considered in the counseling for surgical risk reduction. Patient decision aids can help mutation carriers navigate the complex information and decisions.²⁵ Websites specifically designed by advocacy groups can be useful adjuncts to in-office counseling (Facing Our Risk Empowered, FORCE; Facingourrisk.org).

Family letters

The American College of Obstetricians and Gynecologists recommends an ObGyn have a letter or documentation stating that the patient’s relative has a specific mutation before initiating cascade testing for an at-risk family member. The indicated test (such as BRCA1) should be ordered only after the patient has been counseled about potential outcomes and has expressly decided to be tested.²⁶ Letters, such as the example given in the American College of Obstetricians and Gynecologists practice bulletin,²⁶ are a key component of communication between oncology providers, probands, family members, and their primary care providers. ObGyn providers should work together with genetic counselors and gynecologic oncologists to determine the most efficient strategies in their communities.

Technology

Access to genetic testing and genetic counseling has been improved with the rise in telemedicine. Geographically remote patients can now access genetic counseling through medical center–based counselors as well as company-provided genetic counseling over the phone. Patients also can submit samples remotely without needing to be tested in a doctor’s office.

Databases from cancer centers that detail cascade genetic testing rates. As the preventive impact of cascade genetic testing becomes clearer, strategies to have recurrent discussions with cancer patients regarding their family members’ risk should be implemented. It is still unclear which providers—genetic counselors, gynecologic oncologists, medical oncologists, breast surgeons, ObGyns, to name a few—are primarily responsible for remembering to have these follow-up discussions, and despite advances, the burden still rests on the cancer patient themselves. Databases with automated follow-up surveys done every 6 to 12 months could provide some aid to busy providers in this regard.

Emerging research

If gynecologic risk-reducing surgery is chosen, clinical trial involvement should be encouraged. The Women Choosing Surgical Prevention (NCT02760849) in the United States and the TUBA study (NCT02321228) in the Netherlands were designed to compare menopause-related QOL between standard risk-reducing salpingo-oophorectomy (RRSO) and the innovative risk-reducing salpingectomy with delayed oophorectomy for mutation carriers. Results from the nonrandomized controlled TUBA trial suggest that patients have better menopause-related QOL after risk-reducing salpingectomy than after RRSO, regardless of hormone replacement therapy.²⁷ International collaboration is continuing to better understand oncologic safety. In the United States, the SOROCk trial (NCT04251052) is a noninferiority surgical choice study underway for BRCA1 mutation carriers aged 35 to 50, powered to determine oncologic outcome differences in addition to QOL outcomes between RRSO and delayed oophorectomy arms.

Returning to the case

The patient and her family underwent genetic counseling. The patient’s 2 daughters, each in their 50s, underwent cascade genetic testing and were found to carry the same pathogenic mutation in BRCA2. After counseling from both breast and gynecologic surgeons, they both elected to undergo risk reducing bilateral salpingo-oophorectomy with hysterectomy. Both now complete regular screening for breast cancer and melanoma with plans to start screening for pancreatic cancer. Both are currently cancer free.

Summary

Cascade genetic testing is an efficient strategy to identify mutation carriers for hereditary breast and ovarian cancer syndrome. Implementation of the best patient-centric care will require continued collaboration and communication across and within disciplines. ●

CASE Woman who has undergone recent cesarean delivery

A 23-year-old woman had a primary cesarean delivery 72 hours ago due to an arrest of dilation at 6 cm. She was in labor for 22 hours, and her membranes were ruptured for 18 hours. She had 10 internal vaginal examinations, and the duration of internal fetal monitoring was 12 hours; 24 hours after delivery, she developed a fever of 39°C, in association with lower abdominal pain and tenderness. She was presumptively treated for endometritis with cefepime; 48 hours after the initiation of antibiotics, she remains febrile and symptomatic.

• What are the most likely causes of her persistent fever?
• What should be the next steps in her evaluation?

Cesarean delivery background

Cesarean delivery is now the most common major operation performed in US hospitals. Cesarean delivery rates hover between 25% and 30% in most medical centers in the United States.¹ The most common postoperative complication of cesarean delivery is infection. Infection typically takes 1 of 3 forms: endometritis (organ space infection), wound infection (surgical site infection), and urinary tract infection (UTI).¹ This article will review the initial differential diagnosis, evaluation, and management of the patient with a postoperative fever and also will describe the appropriate assessment and treatment of the patient who has a persistent postoperative fever despite therapy. The article will also highlight key interventions that help to prevent postoperative infections.

Initial evaluation of the febrile patient

In the first 24 to 48 hours after cesarean delivery, the most common cause of fever is endometritis (organ space infection). This condition is a polymicrobial, mixed aerobic-anaerobic infection (FIGURE). The principal pathogens include anaerobic gram-positive cocci (Peptococcus and Peptostreptococcus species), aerobic gram-negative bacilli (primarily Escherichia coli, Klebsiella pneumoniae, and Proteus species), and aerobic gram-positive cocci (group B Streptococcus, Enterococcus, and Staphylococcus).¹

The major risk factors for postcesarean endometritis are extended duration of labor and ruptured membranes, multiple internal vaginal examinations, invasive fetal monitoring, and pre-existing colonization with group B Streptococcus and/or the organisms that cause bacterial vaginosis. Affected patients typically have a fever in the range of 38 to 39°C, tachycardia, mild tachypnea, lower abdominal pain and tenderness, and purulent lochia in some individuals.¹

Differential for postoperative fever

The initial differential diagnosis of postoperative fever is relatively limited (TABLE 1). In addition to endometritis, it includes extensive atelectasis, perhaps resulting from general anesthesia; lower respiratory tract infection, either viral influenza or bacterial pneumonia; and acute pyelonephritis. A simple infection of the bladder (cystitis or asymptomatic bacteriuria) should not cause a substantial temperature elevation and systemic symptoms.¹

Differentiation between these entities usually is possible based on physical examination and a few laboratory tests. The peripheral white blood cell count usually is elevated, and a left shift may be evident. If a respiratory tract infection is suspected, chest radiography is indicated. A urine culture should be obtained if acute pyelonephritis strongly is considered. Lower genital tract cultures are rarely of value, and uncontaminated upper tract cultures are difficult to obtain. I do not believe that blood cultures should be performed as a matter of routine. They are expensive, and the results are often not available until after the patient has cleared her infection and left the hospital. However, I would obtain blood cultures in patients who meet one of these criteria^1,2:

• They are immunocompromised (eg, HIV infection).
• They have a cardiac or vascular prosthesis and, thus, are at increased risk of complications related to bacteremia.
• They seem critically ill at the onset of evaluation.
• They fail to respond appropriately to initial therapy.

The cornerstone of therapy is broad spectrum antibiotics that target the multiple organisms responsible for endometritis.³ There are several single agents and several combination antibiotic regimens that provide excellent coverage against the usual pelvic pathogens (TABLE 2). I personally favor the generic combination regimen (clindamycin plus gentamicin) because it is relatively inexpensive and has been very well validated in multiple studies. In patients who have underlying renal dysfunction, aztreonam can be substituted for gentamicin.

Continue to: Persistent postoperative fever...

Resistant microorganism

The most common cause of a persistent fever after initiating antibiotic therapy is a resistant microorganism. There are potential gaps in coverage for the antibiotic regimens commonly used to treat postcesarean endometritis (TABLE 3).^1,4 Assuming there is no other obvious cause for treatment failure, I recommend that therapy be changed to the triple combination of metronidazole plus ampicillin plus gentamicin (or aztreonam). The first drug provides superb coverage against anaerobes; the second covers enterococci. Gentamicin or aztreonam cover virtually all aerobic Gram-negative bacilli likely to cause postcesarean infection. I prefer metronidazole rather than clindamycin in this regimen because, unlike clindamycin, it is less likely to trigger diarrhea when used in combination with ampicillin. The 3-drug regimen should be continued until the patient has been afebrile and asymptomatic for approximately 24 hours.^1,3,4

Wound infection

The second most common reason for a poor response to initial antibiotic therapy is a wound (surgical site) infection. Wound infections are caused by many of the same pelvic pathogens responsible for endometritis combined with skin flora, notably Streptococcus and Staphylococcus species, including methicillin-resistant Staphylococcus aureus (MRSA).^1,4

Wound infections typically take one of two forms. The first is an actual incisional abscess. The patient is febrile; the margins of the wound are warm, indurated, erythematous, and tender; and purulent material drains from the incision. In this situation, the wound should be opened widely to drain the purulent collection. The fascia should then be probed to be certain that dehiscence has not occurred. In addition, intravenous vancomycin (1 g every 12 h) should be included in the antibiotic regimen to ensure adequate coverage of hospital-acquired MRSA.^1,4

The second common presentation of a wound infection is cellulitis. The patient is febrile, and there is a spreading area of erythema, warmth, and exquisite tenderness extending from the edges of the incision; however, no purulent drainage is apparent. In this second scenario, the wound should not be opened, but intravenous vancomycin should be added to the treatment regimen.^1,3,4

A third and very rare form of wound infection is necrotizing fasciitis. In affected patients, the margins of the wound are darkened and necrotic rather than erythematous and indurated. Two other key physical findings are crepitance and loss of sensation along the margins of the wound. Necrotizing fasciitis is truly a life-threatening emergency and requires immediate and extensive debridement of the devitalized tissue, combined with broad spectrum therapy with antibiotics that provide excellent coverage against anaerobes, aerobic streptococci (particularly group A streptococci), and staphylococci. The requirement for debridement may be so extensive that a skin graft subsequently is necessary to close the defect.^1,4

Continue to: Unusual causes of persistent postoperative fever...

Unusual causes of persistent postoperative fever

If a resistant microorganism and wound infection can be excluded, the clinician then must begin a diligent search for “zebras” (ie, uncommon but potentially serious causes of persistent fever).^1,4 One possible cause is a pelvic abscess. These purulent collections typically form in the retrovesicle space as a result of infection of a hematoma that formed between the posterior bladder wall and the lower uterine segment, in the leaves of the broad ligament, or in the posterior cul-de-sac. The abscess may or may not be palpable. The patient’s peripheral white blood cell count usually is elevated, with a preponderance of neutrophils. The best imaging test for an abscess is a computed tomography (CT) scan. Abscesses require drainage, which usually can be accomplished by insertion of a percutaneous drain under ultrasonographic or CT guidance.

A second unusual cause of persistent fever is septic pelvic vein thrombophlebitis. The infected venous emboli usually are present in the ovarian veins, with the right side predominant. The patient’s peripheral white blood cell count usually is elevated, and the infected clots are best imaged by CT scan with contrast or magnetic resonance angiography. The appropriate treatment is continuation of broad-spectrum antibiotics and administration of therapeutic doses of parenteral anticoagulants such as enoxaparin or unfractionated heparin.

A third explanation for persistent fever is retained products of conception. This diagnosis is best made by ultrasonography. The placental fragments should be removed by sharp curettage.

A fourth consideration when evaluating the patient with persistent fever is an allergic drug reaction. In most instances, the increase in the patient’s temperature will correspond with administration of the offending antibiotic(s). Affected patients typically have an increased number of eosinophils in their peripheral white blood cell count. The appropriate management of drug fever is discontinuation of antibiotics.

A final and distinctly unusual consideration is recrudescence of a connective tissue disorder such as systemic lupus erythematosus. The best test to confirm this diagnosis is the serum complement assay, which will demonstrate a decreased serum concentration of complement, reflecting consumption of this serum protein during the inflammatory process. The correct management for this condition is administration of a short course of systemic glucocorticoids. TABLE 4 summarizes a simple, systematic plan for evaluation of the patient with a persistent postoperative fever.

Preventive measures

We all remember the simple but profound statement by Benjamin Franklin, “An ounce of prevention is worth a pound of cure.” That folksy adage rings true with respect to postoperative infection because this complication extends hospital stay, increases hospital expense, and causes considerable discomfort and inconvenience for the patient. Therefore, we would do well to prevent as many instances of postoperative infection as possible.

Endometritis

On the basis of well-designed, prospective, randomized trials (Level 1 evidence), 3 interventions have proven effective in reducing the frequency of postcesarean endometritis. The first is irrigation of the vaginal canal preoperatively with an iodophor solution.^5,6 The second is preoperative administration of systemic antibiotics.^7-9 The combination of cefazolin (2 g IV within 30 minutes of incision) plus azithromycin (500 mg IV over 1 hour prior to incision) is superior to cefazolin alone.^10,11 The third important preventive measure is removing the placenta by traction on the umbilical cord rather than by manual extraction.^12,13

Wound infection

Several interventions are of proven effectiveness in reducing the frequency of postcesarean wound (surgical site) infection. The first is removal of hair at the incision site by clipping rather than by shaving (Level 2 evidence).¹⁴ The second is cleansing of the skin with chlorhexidine rather than iodophor (Level 1 evidence).¹⁵ The third is closing of the deep subcutaneous layer of the incision if it exceeds 2 cm in depth (Level 1 evidence).^16,17 The fourth is closure of the skin with subcutaneous sutures rather than staples (Level 1 evidence).¹⁸ The monofilament suture poliglecaprone 25 is superior to the multifilament suture polyglactin 910 for this purpose (Level 1 evidence).¹⁹ Finally, in obese patients (body mass index >30 kg/m²), application of a negative pressure wound vacuum dressing may offer additional protection against infection (Level 1 evidence).²⁰ Such dressings are too expensive, however, to be used routinely in all patients.

Urinary tract infection

The most important measures for preventing postoperative UTIs are identifying and clearing asymptomatic bacteriuria prior to delivery, inserting the urinary catheter prior to surgery using strict sterile technique, and removing the catheter as soon as possible after surgery, ideally within 12 hours.^1,4

CASE Resolved

The 2 most likely causes for this patient’s poor response to initial therapy are resistant microorganism and wound infection. If a wound infection can be excluded by physical examination, the patient’s antibiotic regimen should be changed to metronidazole plus ampicillin plus gentamicin (or aztreonam). If an incisional abscess is identified, the incision should be opened and drained, and vancomycin should be added to the treatment regimen. If a wound cellulitis is evident, the incision should not be opened, but vancomycin should be added to the treatment regimen to enhance coverage against aerobic Streptococcus and Staphylococcus species. ●

CASE Woman who has undergone recent cesarean delivery

A 23-year-old woman had a primary cesarean delivery 72 hours ago due to an arrest of dilation at 6 cm. She was in labor for 22 hours, and her membranes were ruptured for 18 hours. She had 10 internal vaginal examinations, and the duration of internal fetal monitoring was 12 hours; 24 hours after delivery, she developed a fever of 39°C, in association with lower abdominal pain and tenderness. She was presumptively treated for endometritis with cefepime; 48 hours after the initiation of antibiotics, she remains febrile and symptomatic.

• What are the most likely causes of her persistent fever?
• What should be the next steps in her evaluation?

Cesarean delivery background

Cesarean delivery is now the most common major operation performed in US hospitals. Cesarean delivery rates hover between 25% and 30% in most medical centers in the United States.¹ The most common postoperative complication of cesarean delivery is infection. Infection typically takes 1 of 3 forms: endometritis (organ space infection), wound infection (surgical site infection), and urinary tract infection (UTI).¹ This article will review the initial differential diagnosis, evaluation, and management of the patient with a postoperative fever and also will describe the appropriate assessment and treatment of the patient who has a persistent postoperative fever despite therapy. The article will also highlight key interventions that help to prevent postoperative infections.

Initial evaluation of the febrile patient

In the first 24 to 48 hours after cesarean delivery, the most common cause of fever is endometritis (organ space infection). This condition is a polymicrobial, mixed aerobic-anaerobic infection (FIGURE). The principal pathogens include anaerobic gram-positive cocci (Peptococcus and Peptostreptococcus species), aerobic gram-negative bacilli (primarily Escherichia coli, Klebsiella pneumoniae, and Proteus species), and aerobic gram-positive cocci (group B Streptococcus, Enterococcus, and Staphylococcus).¹

The major risk factors for postcesarean endometritis are extended duration of labor and ruptured membranes, multiple internal vaginal examinations, invasive fetal monitoring, and pre-existing colonization with group B Streptococcus and/or the organisms that cause bacterial vaginosis. Affected patients typically have a fever in the range of 38 to 39°C, tachycardia, mild tachypnea, lower abdominal pain and tenderness, and purulent lochia in some individuals.¹

Differential for postoperative fever

The initial differential diagnosis of postoperative fever is relatively limited (TABLE 1). In addition to endometritis, it includes extensive atelectasis, perhaps resulting from general anesthesia; lower respiratory tract infection, either viral influenza or bacterial pneumonia; and acute pyelonephritis. A simple infection of the bladder (cystitis or asymptomatic bacteriuria) should not cause a substantial temperature elevation and systemic symptoms.¹

Differentiation between these entities usually is possible based on physical examination and a few laboratory tests. The peripheral white blood cell count usually is elevated, and a left shift may be evident. If a respiratory tract infection is suspected, chest radiography is indicated. A urine culture should be obtained if acute pyelonephritis strongly is considered. Lower genital tract cultures are rarely of value, and uncontaminated upper tract cultures are difficult to obtain. I do not believe that blood cultures should be performed as a matter of routine. They are expensive, and the results are often not available until after the patient has cleared her infection and left the hospital. However, I would obtain blood cultures in patients who meet one of these criteria^1,2:

• They are immunocompromised (eg, HIV infection).
• They have a cardiac or vascular prosthesis and, thus, are at increased risk of complications related to bacteremia.
• They seem critically ill at the onset of evaluation.
• They fail to respond appropriately to initial therapy.

The cornerstone of therapy is broad spectrum antibiotics that target the multiple organisms responsible for endometritis.³ There are several single agents and several combination antibiotic regimens that provide excellent coverage against the usual pelvic pathogens (TABLE 2). I personally favor the generic combination regimen (clindamycin plus gentamicin) because it is relatively inexpensive and has been very well validated in multiple studies. In patients who have underlying renal dysfunction, aztreonam can be substituted for gentamicin.

Continue to: Persistent postoperative fever...

Resistant microorganism

The most common cause of a persistent fever after initiating antibiotic therapy is a resistant microorganism. There are potential gaps in coverage for the antibiotic regimens commonly used to treat postcesarean endometritis (TABLE 3).^1,4 Assuming there is no other obvious cause for treatment failure, I recommend that therapy be changed to the triple combination of metronidazole plus ampicillin plus gentamicin (or aztreonam). The first drug provides superb coverage against anaerobes; the second covers enterococci. Gentamicin or aztreonam cover virtually all aerobic Gram-negative bacilli likely to cause postcesarean infection. I prefer metronidazole rather than clindamycin in this regimen because, unlike clindamycin, it is less likely to trigger diarrhea when used in combination with ampicillin. The 3-drug regimen should be continued until the patient has been afebrile and asymptomatic for approximately 24 hours.^1,3,4

Wound infection

The second most common reason for a poor response to initial antibiotic therapy is a wound (surgical site) infection. Wound infections are caused by many of the same pelvic pathogens responsible for endometritis combined with skin flora, notably Streptococcus and Staphylococcus species, including methicillin-resistant Staphylococcus aureus (MRSA).^1,4

Wound infections typically take one of two forms. The first is an actual incisional abscess. The patient is febrile; the margins of the wound are warm, indurated, erythematous, and tender; and purulent material drains from the incision. In this situation, the wound should be opened widely to drain the purulent collection. The fascia should then be probed to be certain that dehiscence has not occurred. In addition, intravenous vancomycin (1 g every 12 h) should be included in the antibiotic regimen to ensure adequate coverage of hospital-acquired MRSA.^1,4

The second common presentation of a wound infection is cellulitis. The patient is febrile, and there is a spreading area of erythema, warmth, and exquisite tenderness extending from the edges of the incision; however, no purulent drainage is apparent. In this second scenario, the wound should not be opened, but intravenous vancomycin should be added to the treatment regimen.^1,3,4

A third and very rare form of wound infection is necrotizing fasciitis. In affected patients, the margins of the wound are darkened and necrotic rather than erythematous and indurated. Two other key physical findings are crepitance and loss of sensation along the margins of the wound. Necrotizing fasciitis is truly a life-threatening emergency and requires immediate and extensive debridement of the devitalized tissue, combined with broad spectrum therapy with antibiotics that provide excellent coverage against anaerobes, aerobic streptococci (particularly group A streptococci), and staphylococci. The requirement for debridement may be so extensive that a skin graft subsequently is necessary to close the defect.^1,4

Continue to: Unusual causes of persistent postoperative fever...

Unusual causes of persistent postoperative fever

If a resistant microorganism and wound infection can be excluded, the clinician then must begin a diligent search for “zebras” (ie, uncommon but potentially serious causes of persistent fever).^1,4 One possible cause is a pelvic abscess. These purulent collections typically form in the retrovesicle space as a result of infection of a hematoma that formed between the posterior bladder wall and the lower uterine segment, in the leaves of the broad ligament, or in the posterior cul-de-sac. The abscess may or may not be palpable. The patient’s peripheral white blood cell count usually is elevated, with a preponderance of neutrophils. The best imaging test for an abscess is a computed tomography (CT) scan. Abscesses require drainage, which usually can be accomplished by insertion of a percutaneous drain under ultrasonographic or CT guidance.

A second unusual cause of persistent fever is septic pelvic vein thrombophlebitis. The infected venous emboli usually are present in the ovarian veins, with the right side predominant. The patient’s peripheral white blood cell count usually is elevated, and the infected clots are best imaged by CT scan with contrast or magnetic resonance angiography. The appropriate treatment is continuation of broad-spectrum antibiotics and administration of therapeutic doses of parenteral anticoagulants such as enoxaparin or unfractionated heparin.

A third explanation for persistent fever is retained products of conception. This diagnosis is best made by ultrasonography. The placental fragments should be removed by sharp curettage.

A fourth consideration when evaluating the patient with persistent fever is an allergic drug reaction. In most instances, the increase in the patient’s temperature will correspond with administration of the offending antibiotic(s). Affected patients typically have an increased number of eosinophils in their peripheral white blood cell count. The appropriate management of drug fever is discontinuation of antibiotics.

A final and distinctly unusual consideration is recrudescence of a connective tissue disorder such as systemic lupus erythematosus. The best test to confirm this diagnosis is the serum complement assay, which will demonstrate a decreased serum concentration of complement, reflecting consumption of this serum protein during the inflammatory process. The correct management for this condition is administration of a short course of systemic glucocorticoids. TABLE 4 summarizes a simple, systematic plan for evaluation of the patient with a persistent postoperative fever.

Preventive measures

We all remember the simple but profound statement by Benjamin Franklin, “An ounce of prevention is worth a pound of cure.” That folksy adage rings true with respect to postoperative infection because this complication extends hospital stay, increases hospital expense, and causes considerable discomfort and inconvenience for the patient. Therefore, we would do well to prevent as many instances of postoperative infection as possible.

Endometritis

On the basis of well-designed, prospective, randomized trials (Level 1 evidence), 3 interventions have proven effective in reducing the frequency of postcesarean endometritis. The first is irrigation of the vaginal canal preoperatively with an iodophor solution.^5,6 The second is preoperative administration of systemic antibiotics.^7-9 The combination of cefazolin (2 g IV within 30 minutes of incision) plus azithromycin (500 mg IV over 1 hour prior to incision) is superior to cefazolin alone.^10,11 The third important preventive measure is removing the placenta by traction on the umbilical cord rather than by manual extraction.^12,13

Wound infection

Several interventions are of proven effectiveness in reducing the frequency of postcesarean wound (surgical site) infection. The first is removal of hair at the incision site by clipping rather than by shaving (Level 2 evidence).¹⁴ The second is cleansing of the skin with chlorhexidine rather than iodophor (Level 1 evidence).¹⁵ The third is closing of the deep subcutaneous layer of the incision if it exceeds 2 cm in depth (Level 1 evidence).^16,17 The fourth is closure of the skin with subcutaneous sutures rather than staples (Level 1 evidence).¹⁸ The monofilament suture poliglecaprone 25 is superior to the multifilament suture polyglactin 910 for this purpose (Level 1 evidence).¹⁹ Finally, in obese patients (body mass index >30 kg/m²), application of a negative pressure wound vacuum dressing may offer additional protection against infection (Level 1 evidence).²⁰ Such dressings are too expensive, however, to be used routinely in all patients.

Urinary tract infection

The most important measures for preventing postoperative UTIs are identifying and clearing asymptomatic bacteriuria prior to delivery, inserting the urinary catheter prior to surgery using strict sterile technique, and removing the catheter as soon as possible after surgery, ideally within 12 hours.^1,4

CASE Resolved

The 2 most likely causes for this patient’s poor response to initial therapy are resistant microorganism and wound infection. If a wound infection can be excluded by physical examination, the patient’s antibiotic regimen should be changed to metronidazole plus ampicillin plus gentamicin (or aztreonam). If an incisional abscess is identified, the incision should be opened and drained, and vancomycin should be added to the treatment regimen. If a wound cellulitis is evident, the incision should not be opened, but vancomycin should be added to the treatment regimen to enhance coverage against aerobic Streptococcus and Staphylococcus species. ●

CASE Woman who has undergone recent cesarean delivery

A 23-year-old woman had a primary cesarean delivery 72 hours ago due to an arrest of dilation at 6 cm. She was in labor for 22 hours, and her membranes were ruptured for 18 hours. She had 10 internal vaginal examinations, and the duration of internal fetal monitoring was 12 hours; 24 hours after delivery, she developed a fever of 39°C, in association with lower abdominal pain and tenderness. She was presumptively treated for endometritis with cefepime; 48 hours after the initiation of antibiotics, she remains febrile and symptomatic.

• What are the most likely causes of her persistent fever?
• What should be the next steps in her evaluation?

Cesarean delivery background

Cesarean delivery is now the most common major operation performed in US hospitals. Cesarean delivery rates hover between 25% and 30% in most medical centers in the United States.¹ The most common postoperative complication of cesarean delivery is infection. Infection typically takes 1 of 3 forms: endometritis (organ space infection), wound infection (surgical site infection), and urinary tract infection (UTI).¹ This article will review the initial differential diagnosis, evaluation, and management of the patient with a postoperative fever and also will describe the appropriate assessment and treatment of the patient who has a persistent postoperative fever despite therapy. The article will also highlight key interventions that help to prevent postoperative infections.

Initial evaluation of the febrile patient

In the first 24 to 48 hours after cesarean delivery, the most common cause of fever is endometritis (organ space infection). This condition is a polymicrobial, mixed aerobic-anaerobic infection (FIGURE). The principal pathogens include anaerobic gram-positive cocci (Peptococcus and Peptostreptococcus species), aerobic gram-negative bacilli (primarily Escherichia coli, Klebsiella pneumoniae, and Proteus species), and aerobic gram-positive cocci (group B Streptococcus, Enterococcus, and Staphylococcus).¹

The major risk factors for postcesarean endometritis are extended duration of labor and ruptured membranes, multiple internal vaginal examinations, invasive fetal monitoring, and pre-existing colonization with group B Streptococcus and/or the organisms that cause bacterial vaginosis. Affected patients typically have a fever in the range of 38 to 39°C, tachycardia, mild tachypnea, lower abdominal pain and tenderness, and purulent lochia in some individuals.¹

Differential for postoperative fever

The initial differential diagnosis of postoperative fever is relatively limited (TABLE 1). In addition to endometritis, it includes extensive atelectasis, perhaps resulting from general anesthesia; lower respiratory tract infection, either viral influenza or bacterial pneumonia; and acute pyelonephritis. A simple infection of the bladder (cystitis or asymptomatic bacteriuria) should not cause a substantial temperature elevation and systemic symptoms.¹

Differentiation between these entities usually is possible based on physical examination and a few laboratory tests. The peripheral white blood cell count usually is elevated, and a left shift may be evident. If a respiratory tract infection is suspected, chest radiography is indicated. A urine culture should be obtained if acute pyelonephritis strongly is considered. Lower genital tract cultures are rarely of value, and uncontaminated upper tract cultures are difficult to obtain. I do not believe that blood cultures should be performed as a matter of routine. They are expensive, and the results are often not available until after the patient has cleared her infection and left the hospital. However, I would obtain blood cultures in patients who meet one of these criteria^1,2:

• They are immunocompromised (eg, HIV infection).
• They have a cardiac or vascular prosthesis and, thus, are at increased risk of complications related to bacteremia.
• They seem critically ill at the onset of evaluation.
• They fail to respond appropriately to initial therapy.

The cornerstone of therapy is broad spectrum antibiotics that target the multiple organisms responsible for endometritis.³ There are several single agents and several combination antibiotic regimens that provide excellent coverage against the usual pelvic pathogens (TABLE 2). I personally favor the generic combination regimen (clindamycin plus gentamicin) because it is relatively inexpensive and has been very well validated in multiple studies. In patients who have underlying renal dysfunction, aztreonam can be substituted for gentamicin.

Continue to: Persistent postoperative fever...

Resistant microorganism

The most common cause of a persistent fever after initiating antibiotic therapy is a resistant microorganism. There are potential gaps in coverage for the antibiotic regimens commonly used to treat postcesarean endometritis (TABLE 3).^1,4 Assuming there is no other obvious cause for treatment failure, I recommend that therapy be changed to the triple combination of metronidazole plus ampicillin plus gentamicin (or aztreonam). The first drug provides superb coverage against anaerobes; the second covers enterococci. Gentamicin or aztreonam cover virtually all aerobic Gram-negative bacilli likely to cause postcesarean infection. I prefer metronidazole rather than clindamycin in this regimen because, unlike clindamycin, it is less likely to trigger diarrhea when used in combination with ampicillin. The 3-drug regimen should be continued until the patient has been afebrile and asymptomatic for approximately 24 hours.^1,3,4

Wound infection

The second most common reason for a poor response to initial antibiotic therapy is a wound (surgical site) infection. Wound infections are caused by many of the same pelvic pathogens responsible for endometritis combined with skin flora, notably Streptococcus and Staphylococcus species, including methicillin-resistant Staphylococcus aureus (MRSA).^1,4

Wound infections typically take one of two forms. The first is an actual incisional abscess. The patient is febrile; the margins of the wound are warm, indurated, erythematous, and tender; and purulent material drains from the incision. In this situation, the wound should be opened widely to drain the purulent collection. The fascia should then be probed to be certain that dehiscence has not occurred. In addition, intravenous vancomycin (1 g every 12 h) should be included in the antibiotic regimen to ensure adequate coverage of hospital-acquired MRSA.^1,4

The second common presentation of a wound infection is cellulitis. The patient is febrile, and there is a spreading area of erythema, warmth, and exquisite tenderness extending from the edges of the incision; however, no purulent drainage is apparent. In this second scenario, the wound should not be opened, but intravenous vancomycin should be added to the treatment regimen.^1,3,4

A third and very rare form of wound infection is necrotizing fasciitis. In affected patients, the margins of the wound are darkened and necrotic rather than erythematous and indurated. Two other key physical findings are crepitance and loss of sensation along the margins of the wound. Necrotizing fasciitis is truly a life-threatening emergency and requires immediate and extensive debridement of the devitalized tissue, combined with broad spectrum therapy with antibiotics that provide excellent coverage against anaerobes, aerobic streptococci (particularly group A streptococci), and staphylococci. The requirement for debridement may be so extensive that a skin graft subsequently is necessary to close the defect.^1,4

Continue to: Unusual causes of persistent postoperative fever...

Unusual causes of persistent postoperative fever

If a resistant microorganism and wound infection can be excluded, the clinician then must begin a diligent search for “zebras” (ie, uncommon but potentially serious causes of persistent fever).^1,4 One possible cause is a pelvic abscess. These purulent collections typically form in the retrovesicle space as a result of infection of a hematoma that formed between the posterior bladder wall and the lower uterine segment, in the leaves of the broad ligament, or in the posterior cul-de-sac. The abscess may or may not be palpable. The patient’s peripheral white blood cell count usually is elevated, with a preponderance of neutrophils. The best imaging test for an abscess is a computed tomography (CT) scan. Abscesses require drainage, which usually can be accomplished by insertion of a percutaneous drain under ultrasonographic or CT guidance.

A second unusual cause of persistent fever is septic pelvic vein thrombophlebitis. The infected venous emboli usually are present in the ovarian veins, with the right side predominant. The patient’s peripheral white blood cell count usually is elevated, and the infected clots are best imaged by CT scan with contrast or magnetic resonance angiography. The appropriate treatment is continuation of broad-spectrum antibiotics and administration of therapeutic doses of parenteral anticoagulants such as enoxaparin or unfractionated heparin.

A third explanation for persistent fever is retained products of conception. This diagnosis is best made by ultrasonography. The placental fragments should be removed by sharp curettage.

A fourth consideration when evaluating the patient with persistent fever is an allergic drug reaction. In most instances, the increase in the patient’s temperature will correspond with administration of the offending antibiotic(s). Affected patients typically have an increased number of eosinophils in their peripheral white blood cell count. The appropriate management of drug fever is discontinuation of antibiotics.

A final and distinctly unusual consideration is recrudescence of a connective tissue disorder such as systemic lupus erythematosus. The best test to confirm this diagnosis is the serum complement assay, which will demonstrate a decreased serum concentration of complement, reflecting consumption of this serum protein during the inflammatory process. The correct management for this condition is administration of a short course of systemic glucocorticoids. TABLE 4 summarizes a simple, systematic plan for evaluation of the patient with a persistent postoperative fever.

Preventive measures

We all remember the simple but profound statement by Benjamin Franklin, “An ounce of prevention is worth a pound of cure.” That folksy adage rings true with respect to postoperative infection because this complication extends hospital stay, increases hospital expense, and causes considerable discomfort and inconvenience for the patient. Therefore, we would do well to prevent as many instances of postoperative infection as possible.

Endometritis

On the basis of well-designed, prospective, randomized trials (Level 1 evidence), 3 interventions have proven effective in reducing the frequency of postcesarean endometritis. The first is irrigation of the vaginal canal preoperatively with an iodophor solution.^5,6 The second is preoperative administration of systemic antibiotics.^7-9 The combination of cefazolin (2 g IV within 30 minutes of incision) plus azithromycin (500 mg IV over 1 hour prior to incision) is superior to cefazolin alone.^10,11 The third important preventive measure is removing the placenta by traction on the umbilical cord rather than by manual extraction.^12,13

Wound infection

Several interventions are of proven effectiveness in reducing the frequency of postcesarean wound (surgical site) infection. The first is removal of hair at the incision site by clipping rather than by shaving (Level 2 evidence).¹⁴ The second is cleansing of the skin with chlorhexidine rather than iodophor (Level 1 evidence).¹⁵ The third is closing of the deep subcutaneous layer of the incision if it exceeds 2 cm in depth (Level 1 evidence).^16,17 The fourth is closure of the skin with subcutaneous sutures rather than staples (Level 1 evidence).¹⁸ The monofilament suture poliglecaprone 25 is superior to the multifilament suture polyglactin 910 for this purpose (Level 1 evidence).¹⁹ Finally, in obese patients (body mass index >30 kg/m²), application of a negative pressure wound vacuum dressing may offer additional protection against infection (Level 1 evidence).²⁰ Such dressings are too expensive, however, to be used routinely in all patients.

Urinary tract infection

The most important measures for preventing postoperative UTIs are identifying and clearing asymptomatic bacteriuria prior to delivery, inserting the urinary catheter prior to surgery using strict sterile technique, and removing the catheter as soon as possible after surgery, ideally within 12 hours.^1,4

CASE Resolved

The 2 most likely causes for this patient’s poor response to initial therapy are resistant microorganism and wound infection. If a wound infection can be excluded by physical examination, the patient’s antibiotic regimen should be changed to metronidazole plus ampicillin plus gentamicin (or aztreonam). If an incisional abscess is identified, the incision should be opened and drained, and vancomycin should be added to the treatment regimen. If a wound cellulitis is evident, the incision should not be opened, but vancomycin should be added to the treatment regimen to enhance coverage against aerobic Streptococcus and Staphylococcus species. ●