CASE 1 Huge out-of-pocket cost makes patient forego treatment

Ms. M. is a 28-year-old patient who recently posted this on her Facebook page: “I went to the drugstore this morning to pick up a prescription, and as the pharmacist handed it to me she said, ‘That will be $180.00.’ And that’s after insurance coverage! Wow! I think I’ll pass!”

Our patients probably experience this type of situation more commonly than we know.

CASE 2 Catastrophic medical costs bankrupt family

A middle-class couple who had college degrees and full-time jobs with health insurance had twins at 24 weeks’ gestation. They accrued $450,000 in medical debt after exceeding the $2 million cap of their insurance policy. Having premature twins cost them everything. They liquidated their retirement and savings accounts, sold everything they had, and still ended up filing for bankruptcy.¹

Costs indeed matter to patients, and we have a professional responsibility to help our patients navigate the murky waters of health care so that they can maintain financial as well as physical health.

Rising costs, lower yield,and opportunities for change

Rising health care costs are unsustainable for both our patients and our society. Although the United States spends more on health care than any other developed country, our health outcomes are actually worse—ranking at or near the bottom in both prevalence and mortality for multiple diseases, risk factors, and injuries.²

Of the 171 countries included in a study by the United Nations Maternal Mortality Estimation Inter-Agency Group, the United States was 1 of 13 countries that had an increasing maternal mortality and the only developed nation with an increasing maternal mortality rate.³ This tells us that, as our country spends more on health care, our patients’ health is not improving. For individuals, medical bills are now the leading cause of personal bankruptcy in the United States, even for those who are insured.⁴

ObGyns play an important leadership role in the practice of cost-conscious health care, as 25% of hospitalizations in the United States are pregnancy related.^5,6 In addition, the wide scope of ObGyn practice reaches beyond pregnancy-related conditions and provides multiple opportunities to decrease the use of unnecessary tests and treatments.

The good news is that approximately 30% of health care costs are wasted on unnecessary care that could be eliminated without decreasing the quality of care.⁷

High-value change #1: Eliminate use of expensive products

Embarking on a high-value care improvement project, experts at Greenville Health System examined the cost of different topical pain medications for perineal pain after a vaginal delivery. They found that Epifoam (hydrocortisone acetate/pramoxine hydrochloride) was ordered 2,287 times over the course of a year.

The study intervention consisted of an educational grand rounds and discussion of a Cochrane review, which concluded there was no difference in pain relief with topical anesthetics compared with placebo.⁸ Less expensive options for pain relief were discussed, and the department agreed to remove Epifoam as a standing order.

After the intervention, Epifoam was ordered 228 times, a 90% reduction. Over the period of a year, this translated to a cost savings of $92,655 for the hospital, with reduced charges passed on to patients.⁹ Thus, a seemingly small individual cost ($45.00 per can of Epifoam) can add up to a substantial sum in a large health care system.

Continue to: High-value change #2: Stop ordering unnecessary lab work...

High-value change #2: Stop ordering unnecessary lab work

Another high-value change to consider: Examine each laboratory test order to understand if the test results will really alter the care of a patient. Providers vary, and ordering lab tests to “make sure” can add up as financial expense.

Best practices from the American College of Obstetricians and Gynecologists (ACOG) and other professional societies can help guide decision-making as we order lab tests. Think twice, for example, about whether every evaluation for preeclampsia requires a uric acid test, since ACOG does not endorse that as part of the diagnostic criteria. While a single uric acid test costs only $8.00 to $38.00 (according to Healthcare Bluebook), testing uric acid in many patients over the course of a year can add up to significant dollars.¹¹

High-value change #3: Consider care redesign

In addition to seeking opportunities to use more cost-effective products and reduce the use of unnecessary tests, “care redesign” is an innovative way to provide high-quality care (and increased patient satisfaction) at a lower cost for both the health care system and the patient. A prime example of care redesign is using telehealth to enhance prenatal care.

Several health systems around the country are piloting and implementing remote blood pressure monitoring, app-based prenatal education, and telehealth visits to enhance prenatal care.^12,13 Use of a home blood pressure monitor can reduce in-person visits for low-risk prenatal care and open up access for other patients. Additionally, allowing the patient to participate in her own care at home or work can eliminate drives to and waits in the office and reduce absence from work because of a doctor visit.

A systematic review of more than 60,000 women showed that low-risk women who attend 5 to 9 prenatal visits have the same outcomes as women who attend the standard schedule of 13 to 15 visits.¹⁴ Although patient satisfaction was higher with more visits, when a bidirectional app or a telehealth visit is offered as an option, then patient satisfaction is equivalent to that in the standard schedule group.¹² So why not expand the choice for patients?

The challenge of teaching high-value care: Medical education responds

In a 2010 article in the New England Journal of Medicine, Dr. Molly Cooke commented on medical education’s responsibility regarding cost consciousness in patient care, and she highlighted the importance of teaching medical students and residents about considering cost in treating patients.¹⁵ Similarly, the Accreditation Council for Graduate Medical Education asks residents to consider cost and stewardship of medical resources as one of its system-based practice competencies.¹⁶ In 2012, the Choosing Wisely campaign, initiated by the American Board of Internal Medicine Foundation, asked specialty society members to identify tests or procedures commonly used in their field whose necessity should be questioned and discussed.¹⁷ ACOG and other women’s health specialty societies participate in this campaign.

From an educational standpoint, ACOG’s Council on Resident Education in Obstetrics and Gynecology has developed a curriculum resource, “Cases in High Value Care,” that can be used by any women’s health department to start the conversation on high-value care.¹⁸ The web program encourages medical students and residents to submit clinical vignettes that demonstrate examples of low- and high-value care. These cases can be used for discussion and debate and can serve as high-value care performance improvement projects in your own department.

Other useful publications are available outside the ObGyn specialty. Consider the Society of Hospital Medicine’s article series in the Journal of Hospital Medicine, “Choosing Wisely: Things We Do for No Reason”and “Choosing Wisely: Next Steps in Improving Healthcare Value.”¹⁹ The former focuses on discussing practices (tests, procedures, supplies, and prescriptions) that may be poorly supported by evidence or are part of standard practice even though other less expensive, higher-value alternatives may be available. The latter highlights perspective pieces that describe health care value initiatives relating to the practice of hospital medicine.

Continue to: The bottom line...

The bottom line

ObGyns and other health care providers are concerned about providing high-value care to patients and are working toward improving performance in this area. We really do care about the health care–related financial burdens that confront Ms. M., the premature twins’ parents, and all our patients.

CASE 1 Huge out-of-pocket cost makes patient forego treatment

Ms. M. is a 28-year-old patient who recently posted this on her Facebook page: “I went to the drugstore this morning to pick up a prescription, and as the pharmacist handed it to me she said, ‘That will be $180.00.’ And that’s after insurance coverage! Wow! I think I’ll pass!”

Our patients probably experience this type of situation more commonly than we know.

CASE 2 Catastrophic medical costs bankrupt family

A middle-class couple who had college degrees and full-time jobs with health insurance had twins at 24 weeks’ gestation. They accrued $450,000 in medical debt after exceeding the $2 million cap of their insurance policy. Having premature twins cost them everything. They liquidated their retirement and savings accounts, sold everything they had, and still ended up filing for bankruptcy.¹

Costs indeed matter to patients, and we have a professional responsibility to help our patients navigate the murky waters of health care so that they can maintain financial as well as physical health.

Rising costs, lower yield,and opportunities for change

Rising health care costs are unsustainable for both our patients and our society. Although the United States spends more on health care than any other developed country, our health outcomes are actually worse—ranking at or near the bottom in both prevalence and mortality for multiple diseases, risk factors, and injuries.²

Of the 171 countries included in a study by the United Nations Maternal Mortality Estimation Inter-Agency Group, the United States was 1 of 13 countries that had an increasing maternal mortality and the only developed nation with an increasing maternal mortality rate.³ This tells us that, as our country spends more on health care, our patients’ health is not improving. For individuals, medical bills are now the leading cause of personal bankruptcy in the United States, even for those who are insured.⁴

ObGyns play an important leadership role in the practice of cost-conscious health care, as 25% of hospitalizations in the United States are pregnancy related.^5,6 In addition, the wide scope of ObGyn practice reaches beyond pregnancy-related conditions and provides multiple opportunities to decrease the use of unnecessary tests and treatments.

The good news is that approximately 30% of health care costs are wasted on unnecessary care that could be eliminated without decreasing the quality of care.⁷

High-value change #1: Eliminate use of expensive products

Embarking on a high-value care improvement project, experts at Greenville Health System examined the cost of different topical pain medications for perineal pain after a vaginal delivery. They found that Epifoam (hydrocortisone acetate/pramoxine hydrochloride) was ordered 2,287 times over the course of a year.

The study intervention consisted of an educational grand rounds and discussion of a Cochrane review, which concluded there was no difference in pain relief with topical anesthetics compared with placebo.⁸ Less expensive options for pain relief were discussed, and the department agreed to remove Epifoam as a standing order.

After the intervention, Epifoam was ordered 228 times, a 90% reduction. Over the period of a year, this translated to a cost savings of $92,655 for the hospital, with reduced charges passed on to patients.⁹ Thus, a seemingly small individual cost ($45.00 per can of Epifoam) can add up to a substantial sum in a large health care system.

Continue to: High-value change #2: Stop ordering unnecessary lab work...

High-value change #2: Stop ordering unnecessary lab work

Another high-value change to consider: Examine each laboratory test order to understand if the test results will really alter the care of a patient. Providers vary, and ordering lab tests to “make sure” can add up as financial expense.

Best practices from the American College of Obstetricians and Gynecologists (ACOG) and other professional societies can help guide decision-making as we order lab tests. Think twice, for example, about whether every evaluation for preeclampsia requires a uric acid test, since ACOG does not endorse that as part of the diagnostic criteria. While a single uric acid test costs only $8.00 to $38.00 (according to Healthcare Bluebook), testing uric acid in many patients over the course of a year can add up to significant dollars.¹¹

High-value change #3: Consider care redesign

In addition to seeking opportunities to use more cost-effective products and reduce the use of unnecessary tests, “care redesign” is an innovative way to provide high-quality care (and increased patient satisfaction) at a lower cost for both the health care system and the patient. A prime example of care redesign is using telehealth to enhance prenatal care.

Several health systems around the country are piloting and implementing remote blood pressure monitoring, app-based prenatal education, and telehealth visits to enhance prenatal care.^12,13 Use of a home blood pressure monitor can reduce in-person visits for low-risk prenatal care and open up access for other patients. Additionally, allowing the patient to participate in her own care at home or work can eliminate drives to and waits in the office and reduce absence from work because of a doctor visit.

A systematic review of more than 60,000 women showed that low-risk women who attend 5 to 9 prenatal visits have the same outcomes as women who attend the standard schedule of 13 to 15 visits.¹⁴ Although patient satisfaction was higher with more visits, when a bidirectional app or a telehealth visit is offered as an option, then patient satisfaction is equivalent to that in the standard schedule group.¹² So why not expand the choice for patients?

The challenge of teaching high-value care: Medical education responds

In a 2010 article in the New England Journal of Medicine, Dr. Molly Cooke commented on medical education’s responsibility regarding cost consciousness in patient care, and she highlighted the importance of teaching medical students and residents about considering cost in treating patients.¹⁵ Similarly, the Accreditation Council for Graduate Medical Education asks residents to consider cost and stewardship of medical resources as one of its system-based practice competencies.¹⁶ In 2012, the Choosing Wisely campaign, initiated by the American Board of Internal Medicine Foundation, asked specialty society members to identify tests or procedures commonly used in their field whose necessity should be questioned and discussed.¹⁷ ACOG and other women’s health specialty societies participate in this campaign.

From an educational standpoint, ACOG’s Council on Resident Education in Obstetrics and Gynecology has developed a curriculum resource, “Cases in High Value Care,” that can be used by any women’s health department to start the conversation on high-value care.¹⁸ The web program encourages medical students and residents to submit clinical vignettes that demonstrate examples of low- and high-value care. These cases can be used for discussion and debate and can serve as high-value care performance improvement projects in your own department.

Other useful publications are available outside the ObGyn specialty. Consider the Society of Hospital Medicine’s article series in the Journal of Hospital Medicine, “Choosing Wisely: Things We Do for No Reason”and “Choosing Wisely: Next Steps in Improving Healthcare Value.”¹⁹ The former focuses on discussing practices (tests, procedures, supplies, and prescriptions) that may be poorly supported by evidence or are part of standard practice even though other less expensive, higher-value alternatives may be available. The latter highlights perspective pieces that describe health care value initiatives relating to the practice of hospital medicine.

Continue to: The bottom line...

The bottom line

ObGyns and other health care providers are concerned about providing high-value care to patients and are working toward improving performance in this area. We really do care about the health care–related financial burdens that confront Ms. M., the premature twins’ parents, and all our patients.

CASE 1 Huge out-of-pocket cost makes patient forego treatment

Ms. M. is a 28-year-old patient who recently posted this on her Facebook page: “I went to the drugstore this morning to pick up a prescription, and as the pharmacist handed it to me she said, ‘That will be $180.00.’ And that’s after insurance coverage! Wow! I think I’ll pass!”

Our patients probably experience this type of situation more commonly than we know.

CASE 2 Catastrophic medical costs bankrupt family

A middle-class couple who had college degrees and full-time jobs with health insurance had twins at 24 weeks’ gestation. They accrued $450,000 in medical debt after exceeding the $2 million cap of their insurance policy. Having premature twins cost them everything. They liquidated their retirement and savings accounts, sold everything they had, and still ended up filing for bankruptcy.¹

Costs indeed matter to patients, and we have a professional responsibility to help our patients navigate the murky waters of health care so that they can maintain financial as well as physical health.

Rising costs, lower yield,and opportunities for change

Rising health care costs are unsustainable for both our patients and our society. Although the United States spends more on health care than any other developed country, our health outcomes are actually worse—ranking at or near the bottom in both prevalence and mortality for multiple diseases, risk factors, and injuries.²

Of the 171 countries included in a study by the United Nations Maternal Mortality Estimation Inter-Agency Group, the United States was 1 of 13 countries that had an increasing maternal mortality and the only developed nation with an increasing maternal mortality rate.³ This tells us that, as our country spends more on health care, our patients’ health is not improving. For individuals, medical bills are now the leading cause of personal bankruptcy in the United States, even for those who are insured.⁴

ObGyns play an important leadership role in the practice of cost-conscious health care, as 25% of hospitalizations in the United States are pregnancy related.^5,6 In addition, the wide scope of ObGyn practice reaches beyond pregnancy-related conditions and provides multiple opportunities to decrease the use of unnecessary tests and treatments.

The good news is that approximately 30% of health care costs are wasted on unnecessary care that could be eliminated without decreasing the quality of care.⁷

High-value change #1: Eliminate use of expensive products

Embarking on a high-value care improvement project, experts at Greenville Health System examined the cost of different topical pain medications for perineal pain after a vaginal delivery. They found that Epifoam (hydrocortisone acetate/pramoxine hydrochloride) was ordered 2,287 times over the course of a year.

The study intervention consisted of an educational grand rounds and discussion of a Cochrane review, which concluded there was no difference in pain relief with topical anesthetics compared with placebo.⁸ Less expensive options for pain relief were discussed, and the department agreed to remove Epifoam as a standing order.

After the intervention, Epifoam was ordered 228 times, a 90% reduction. Over the period of a year, this translated to a cost savings of $92,655 for the hospital, with reduced charges passed on to patients.⁹ Thus, a seemingly small individual cost ($45.00 per can of Epifoam) can add up to a substantial sum in a large health care system.

Continue to: High-value change #2: Stop ordering unnecessary lab work...

High-value change #2: Stop ordering unnecessary lab work

Another high-value change to consider: Examine each laboratory test order to understand if the test results will really alter the care of a patient. Providers vary, and ordering lab tests to “make sure” can add up as financial expense.

Best practices from the American College of Obstetricians and Gynecologists (ACOG) and other professional societies can help guide decision-making as we order lab tests. Think twice, for example, about whether every evaluation for preeclampsia requires a uric acid test, since ACOG does not endorse that as part of the diagnostic criteria. While a single uric acid test costs only $8.00 to $38.00 (according to Healthcare Bluebook), testing uric acid in many patients over the course of a year can add up to significant dollars.¹¹

High-value change #3: Consider care redesign

In addition to seeking opportunities to use more cost-effective products and reduce the use of unnecessary tests, “care redesign” is an innovative way to provide high-quality care (and increased patient satisfaction) at a lower cost for both the health care system and the patient. A prime example of care redesign is using telehealth to enhance prenatal care.

Several health systems around the country are piloting and implementing remote blood pressure monitoring, app-based prenatal education, and telehealth visits to enhance prenatal care.^12,13 Use of a home blood pressure monitor can reduce in-person visits for low-risk prenatal care and open up access for other patients. Additionally, allowing the patient to participate in her own care at home or work can eliminate drives to and waits in the office and reduce absence from work because of a doctor visit.

A systematic review of more than 60,000 women showed that low-risk women who attend 5 to 9 prenatal visits have the same outcomes as women who attend the standard schedule of 13 to 15 visits.¹⁴ Although patient satisfaction was higher with more visits, when a bidirectional app or a telehealth visit is offered as an option, then patient satisfaction is equivalent to that in the standard schedule group.¹² So why not expand the choice for patients?

The challenge of teaching high-value care: Medical education responds

In a 2010 article in the New England Journal of Medicine, Dr. Molly Cooke commented on medical education’s responsibility regarding cost consciousness in patient care, and she highlighted the importance of teaching medical students and residents about considering cost in treating patients.¹⁵ Similarly, the Accreditation Council for Graduate Medical Education asks residents to consider cost and stewardship of medical resources as one of its system-based practice competencies.¹⁶ In 2012, the Choosing Wisely campaign, initiated by the American Board of Internal Medicine Foundation, asked specialty society members to identify tests or procedures commonly used in their field whose necessity should be questioned and discussed.¹⁷ ACOG and other women’s health specialty societies participate in this campaign.

From an educational standpoint, ACOG’s Council on Resident Education in Obstetrics and Gynecology has developed a curriculum resource, “Cases in High Value Care,” that can be used by any women’s health department to start the conversation on high-value care.¹⁸ The web program encourages medical students and residents to submit clinical vignettes that demonstrate examples of low- and high-value care. These cases can be used for discussion and debate and can serve as high-value care performance improvement projects in your own department.

Other useful publications are available outside the ObGyn specialty. Consider the Society of Hospital Medicine’s article series in the Journal of Hospital Medicine, “Choosing Wisely: Things We Do for No Reason”and “Choosing Wisely: Next Steps in Improving Healthcare Value.”¹⁹ The former focuses on discussing practices (tests, procedures, supplies, and prescriptions) that may be poorly supported by evidence or are part of standard practice even though other less expensive, higher-value alternatives may be available. The latter highlights perspective pieces that describe health care value initiatives relating to the practice of hospital medicine.

Continue to: The bottom line...

The bottom line

ObGyns and other health care providers are concerned about providing high-value care to patients and are working toward improving performance in this area. We really do care about the health care–related financial burdens that confront Ms. M., the premature twins’ parents, and all our patients.

Breast cancer survivors entering menopause face the risk of several menopausal symptoms:

• Hot flashes, the most common symptom, occur in more than 75% of women during menopause and have the potential to persist for as long as 15 years.¹ That lengthy interval becomes a major issue for patients, especially when hot flashes are associated with other menopausal symptoms, including sleep disruption, difficulty concentrating, and emotional instability (crying, irritability).

• Painful intercourse and loss of interest in sexual activity often develop as a result of vaginal atrophy and dryness.

• Urinary tract symptoms include urgency and, compared to the patient’s history, more frequent infections.
• Bone loss is a concern for many women after breast cancer, especially if they are, or have been, on aromatase inhibitor therapy.

• Depression might be related to hormonal changes due to menopause or hormonal therapies, a consequence of merely having a diagnosis of cancer, or an adverse effect of chemotherapy.

In this brief review, I’ll examine options for treating symptoms of menopause by strategy—lifestyle modifications, over-the-counter treatments, and prescription drugs. Separately, I’ll look at options for managing genitourinary syndrome of menopause (GSM).

CASE 1

Rose is a 56-year-old woman who presents to clinic with a new breast mass, felt on breast self exam. The mass is about 1 cm, mobile, and firm. Diagnostic mammogram and ultrasound confirm a worrisome mass; biopsy returns positive with a 9-mm invasive, estrogen-receptor positive, ductal carcinoma with negative sentinel nodes at the time of lumpectomy. Radiation therapy was completed. She then met with oncology and decided against chemotherapy. Instead, she began an aromatase inhibitor 3 months ago. Bone density showed osteopenia. She presents to your office reporting frequent bothersome hot flashes and disrupted sleep.

Strategy #1: Lifestyle adaptations

First-line interventions for menopausal women who have had breast cancer usually involve taking a critical look at lifestyle and undertaking modifications that can alleviate discomfort. Because overall health is important for women who have had breast cancer, you should, across the spectrum of patients, encourage them to:

• increase physical activity
• reduce body weight by approximately 10% (if overweight or obese)
• reduce alcohol consumption
• stop smoking
• ensure adequate intake of calcium (1,200 mg, preferably by diet)
• optimize the level of vitamin D, including by increasing intake of fresh fish, eggs, and numerous other fortified foods.

The value of nondrug therapy for hot flashes is difficult to prove. Certain lifestyle changes are sensible, even if not evidence-based, and will help some women (but not others). We suggest that patients try lowering the temperature in the home (65–68˚ at night); running a fan; wearing clothing that can be removed in layers; and avoiding triggers such as spicy food, alcohol, cigarettes, and hot drinks. Hypnosis and cognitive behavioral therapy (CBT) have been shown to help in clinical trials. Measures with benefit and minimal risks, but effectiveness not established, include acupuncture (sham worked as well as traditional), exercise, yoga, paced respiration, relaxation training, and mindfulness-based stress reduction.

Continue to: Strategy #2: OTC compounds...

Strategy #2: OTC compounds

Over-the-counter products—from soy products to black cohosh to flax seed, and including dong quai, evening primrose oil, maca, omegas, pollen extract, ginseng, and red clover,² or several compounds formulated in combination—have not been proven to be of more benefit for relieving symptoms of menopause than placebo in randomized trials, and thus might or might not be effective in a given patient. S-equol, a metabolite of a soy isoflavone taken by women who are non-equol producers, is available under the trade name Equelle and has shown some benefit. Note: There is concern that supplements that contain estrogen-like compounds, like soy products, might actually increase the risk of breast cancer. Dietary soy is not felt to be a concern.

Ask questions about the severity of a patient’s hot flashes. When a patient reports hot flashes, and is requesting help to relieve her discomfort, inquire 1) how often she has hot flashes, 2) how severe they are, and 3) how bothered she is by them (not all women are equally troubled, of course). The patient’s answers to these questions will help you decide which treatment option to offer, based on evidence and your experience.

CASE 1 Continued

Rose tried black cohosh OTC without improvement. She was interested in hypnosis but did not find it effective for her. She returned 3 months later stating that she is miserable, exhausted, not getting enough sleep, and her hot flashes and night sweats are affecting both her work and her relationship.

Strategy #3: Prescription medication

When addressing hot flashes, consider whether they occur more at night or during the day, or do not follow a day–night pattern. For women whose hot flashes occur mostly at night, and might therefore make sleeping difficult and cause fatigue and irritability, gabapentin, taken approximately 1 hour before bed, can be helpful. If tolerated without excessive somnolence the next day, the dose can be increased at night or additional doses provided during the day depending on hot flash response. For women who have hot flashes day and night, we often prescribe a low-dose antidepressant from the selective serotonin-reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) class.

When prescribing an antidepressant, we make a distinction between breast cancer patients who are taking tamoxifen and those who are not, to avoid cytochrome P450 2D6 inhibitors in women taking tamoxifen.³ Better choices for women taking tamoxifen include desvenlafaxine, venlafaxine, escitalopram, or gabapentin or pregabalin.

For women with breast cancer who are taking an aromatase inhibitor, and who are also experiencing mood changes with their hot flashes, we often choose a trial of a low-dose antidepressant, either an SSRI or SNRI. One drug is approved by the US Food and Drug Administration (FDA) for the treatment of hot flashes (but not for mood disorder). This is low-dose salt of paroxetine, 7.5 mg/d, which has the advantage of exerting no adverse effect on libido or weight (but is sometimes difficult to obtain because it is a branded product that might not be covered, or not covered fully, by a given patient’s insurance plan). Other antidepressants can be used in doses lower than needed for depression, with more rapid onset of effect on hot flashes, often within 2 weeks.

Last, transdermal clonidine, an antihypertensive, also has been found to relieve hot flashes.

Continue to: Not a recommended strategy: Systemic hormone therapy

Not a recommended strategy: Systemic hormone therapy

Although hormone therapy is, in general, the gold standard for alleviating hot flashes, it is contraindicated in most women with breast cancer.⁴ At our institution, we avoid systemic hormone therapy for hot flashes in almost all breast cancer patients.

CASE 2

Sarah first presented with hot flashes that improved while taking escitalopram 10 mg. Her night sweats persisted, however. Gabapentin 300 mg was added to take nightly. With this regimen, she finally felt that she was coping better. Six months later, she reported that she and her long-term partner had not been able to resume vaginal intercourse post–breast cancer treatment because of pain.

The challenge of managing GSM

What if your patient says, “Doctor, I’m really doing OK with my hot flashes, but sex has become painful. I don’t have any interest. I have vaginal dryness, and it’s affecting my quality of life”?

Studies have shown that GSM affects up to 50% of women, and even more than that among women who have had breast cancer.⁵ The condition interferes with sexual intimacy, disrupts quality of life, and can sour a partnership—significant quality-of-life concerns for breast cancer survivors.

For mild symptoms, encourage patients to apply a lubricant just before intercourse or a vaginal moisturizer twice weekly; moisturizers improve vaginal pH, too. These treatments do not fix the problem of a lack of superficial cells due to estrogen loss, however; to accomplish that, consider prescribing low-dose vaginal estrogen therapy or intravaginal dehydroepiandrosterone (DHEA). This strategy is felt to be safe for many breast cancer survivors, as systemic absorption of estrogen is minimal if dosed low, keeping levels in the postmenopausal range.

The American College of Obstetricians and Gynecologists (ACOG), the North American Menopause Society (NAMS), and the Endocrine Society agree that vaginal estrogen therapy may be a good option for many women with breast cancer for whom moisturizers and lubricants are inadequate.⁶ Delivery options include vaginal creams, tablets, suppositories used 2 or 3 times per week, or the low-dose vaginal estrogen ring, replaced every 3 months. We are concerned about using vaginal estrogen in women who have had aromatase inhibitor (AI) therapy; their estrogen levels are so low that absorbing even a small amount might make a difference in terms of effectiveness of AI. For women who need more than lubricants or vaginal moisturizers, particularly those taking anti-estrogen therapy (aromatase therapy), the use of low-dose vaginal hormones may be considered on an individual basis, but should include the oncologist in decision making.^1,3

Beyond low-dose vaginal estrogen therapies, there are additional options that can be considered but with less supporting data for treating GSM in women with breast cancer.

Oral ospemifene, a selective estrogen-receptor modulator (SERM; Osphena), might be neutral or even protective in its effect on the breast, as demonstrated in preclinical trials.⁷ In human trials, the drug is approved only for painful intercourse, not for loss of libido, and has not been tested in breast cancer patients.

Intravaginal DHEA (Prasterone), has been on the market for almost 1 year. The drug is approved for treating painful intercourse, but it also reverses vaginal atrophy and alleviates urinary symptoms. Because DHEA is a prohormone, it is converted to estrogen and androgen in the vagina. Again, absorption appears minimal. Intravaginal DHEA does not have the US Food and Drug Administration (FDA) black-box warning that vaginal estrogen products do, but it is accompanied by a warning that it has not been tested in women with breast cancer.

Tissue selective estrogen receptor modulator is a conjugated estrogen combined with a third-generation SERM bazedoxifene, which treats hot flashes and reverses vaginal atrophy. This new systemic agent is probably neutral on the breast (at least that is the finding in clinical trials at 2 years⁸); again, however, it has not been tested in patients with breast cancer.

Continue to: Nonhormone therapies...

Nonhormone therapies

Topical lidocaine for insertional dyspareunia has been studied in postmenopausal women with breast cancer with severe GSM, dyspareunia, increased sexual distress scores, or abnormal sexual function with improvement seen using 4% aqueous lidocaine versus saline applied with a cotton ball to the vestibule for 3 minutes before vaginal penetration.⁹

Vaginal laser therapy has the potential to ameliorate distressing GSM without the need for local hormone intervention; however, placebo or active-controlled trials and long-term safety follow-up are needed.⁵

Treatment begins with a conversation

Most importantly, we need to listen to our patients in discomfort because of their menopausal symptoms. Consider proceeding along these lines: “You’ve been treated for breast cancer; now, let’s look at the medical issues that are affecting your quality of life. Are you depressed? Are you having hot flashes? Are you getting enough sleep? Have you stopped having sex or not restarted after your breast cancer treatment? Are you having painful sex or avoiding sex due to fear of pain? Let’s discuss options and work with your oncologist to try to relieve your symptoms and make your life better.”

First-line therapy for the treatment of menopausal symptoms in women with a history of breast cancer should start with lifestyle changes and nonhormone therapies. For GSM, lubricants and vaginal moisturizers should be tried first and may be effective. Reassure patients that there are many treatment options, even though not all of them have been well-tested in breast cancer patients, and that new modalities are under investigation and review (see “Newly arrived and on the horizon,”). Become familiar with published data on the safety and effectiveness of the range of available treatments; guide patients through the process of finding what works best for them; and invite their oncologist into the therapeutic partnership. If you do not feel comfortable with these issues in women who are breast cancer survivors, find a menopause specialist to help, available by zip code at Find a Provider, http://www.menopause.org.

Breast cancer survivors entering menopause face the risk of several menopausal symptoms:

• Hot flashes, the most common symptom, occur in more than 75% of women during menopause and have the potential to persist for as long as 15 years.¹ That lengthy interval becomes a major issue for patients, especially when hot flashes are associated with other menopausal symptoms, including sleep disruption, difficulty concentrating, and emotional instability (crying, irritability).

• Painful intercourse and loss of interest in sexual activity often develop as a result of vaginal atrophy and dryness.

• Urinary tract symptoms include urgency and, compared to the patient’s history, more frequent infections.
• Bone loss is a concern for many women after breast cancer, especially if they are, or have been, on aromatase inhibitor therapy.

• Depression might be related to hormonal changes due to menopause or hormonal therapies, a consequence of merely having a diagnosis of cancer, or an adverse effect of chemotherapy.

In this brief review, I’ll examine options for treating symptoms of menopause by strategy—lifestyle modifications, over-the-counter treatments, and prescription drugs. Separately, I’ll look at options for managing genitourinary syndrome of menopause (GSM).

CASE 1

Rose is a 56-year-old woman who presents to clinic with a new breast mass, felt on breast self exam. The mass is about 1 cm, mobile, and firm. Diagnostic mammogram and ultrasound confirm a worrisome mass; biopsy returns positive with a 9-mm invasive, estrogen-receptor positive, ductal carcinoma with negative sentinel nodes at the time of lumpectomy. Radiation therapy was completed. She then met with oncology and decided against chemotherapy. Instead, she began an aromatase inhibitor 3 months ago. Bone density showed osteopenia. She presents to your office reporting frequent bothersome hot flashes and disrupted sleep.

Strategy #1: Lifestyle adaptations

First-line interventions for menopausal women who have had breast cancer usually involve taking a critical look at lifestyle and undertaking modifications that can alleviate discomfort. Because overall health is important for women who have had breast cancer, you should, across the spectrum of patients, encourage them to:

• increase physical activity
• reduce body weight by approximately 10% (if overweight or obese)
• reduce alcohol consumption
• stop smoking
• ensure adequate intake of calcium (1,200 mg, preferably by diet)
• optimize the level of vitamin D, including by increasing intake of fresh fish, eggs, and numerous other fortified foods.

The value of nondrug therapy for hot flashes is difficult to prove. Certain lifestyle changes are sensible, even if not evidence-based, and will help some women (but not others). We suggest that patients try lowering the temperature in the home (65–68˚ at night); running a fan; wearing clothing that can be removed in layers; and avoiding triggers such as spicy food, alcohol, cigarettes, and hot drinks. Hypnosis and cognitive behavioral therapy (CBT) have been shown to help in clinical trials. Measures with benefit and minimal risks, but effectiveness not established, include acupuncture (sham worked as well as traditional), exercise, yoga, paced respiration, relaxation training, and mindfulness-based stress reduction.

Continue to: Strategy #2: OTC compounds...

Strategy #2: OTC compounds

Over-the-counter products—from soy products to black cohosh to flax seed, and including dong quai, evening primrose oil, maca, omegas, pollen extract, ginseng, and red clover,² or several compounds formulated in combination—have not been proven to be of more benefit for relieving symptoms of menopause than placebo in randomized trials, and thus might or might not be effective in a given patient. S-equol, a metabolite of a soy isoflavone taken by women who are non-equol producers, is available under the trade name Equelle and has shown some benefit. Note: There is concern that supplements that contain estrogen-like compounds, like soy products, might actually increase the risk of breast cancer. Dietary soy is not felt to be a concern.

Ask questions about the severity of a patient’s hot flashes. When a patient reports hot flashes, and is requesting help to relieve her discomfort, inquire 1) how often she has hot flashes, 2) how severe they are, and 3) how bothered she is by them (not all women are equally troubled, of course). The patient’s answers to these questions will help you decide which treatment option to offer, based on evidence and your experience.

CASE 1 Continued

Rose tried black cohosh OTC without improvement. She was interested in hypnosis but did not find it effective for her. She returned 3 months later stating that she is miserable, exhausted, not getting enough sleep, and her hot flashes and night sweats are affecting both her work and her relationship.

Strategy #3: Prescription medication

When addressing hot flashes, consider whether they occur more at night or during the day, or do not follow a day–night pattern. For women whose hot flashes occur mostly at night, and might therefore make sleeping difficult and cause fatigue and irritability, gabapentin, taken approximately 1 hour before bed, can be helpful. If tolerated without excessive somnolence the next day, the dose can be increased at night or additional doses provided during the day depending on hot flash response. For women who have hot flashes day and night, we often prescribe a low-dose antidepressant from the selective serotonin-reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) class.

When prescribing an antidepressant, we make a distinction between breast cancer patients who are taking tamoxifen and those who are not, to avoid cytochrome P450 2D6 inhibitors in women taking tamoxifen.³ Better choices for women taking tamoxifen include desvenlafaxine, venlafaxine, escitalopram, or gabapentin or pregabalin.

For women with breast cancer who are taking an aromatase inhibitor, and who are also experiencing mood changes with their hot flashes, we often choose a trial of a low-dose antidepressant, either an SSRI or SNRI. One drug is approved by the US Food and Drug Administration (FDA) for the treatment of hot flashes (but not for mood disorder). This is low-dose salt of paroxetine, 7.5 mg/d, which has the advantage of exerting no adverse effect on libido or weight (but is sometimes difficult to obtain because it is a branded product that might not be covered, or not covered fully, by a given patient’s insurance plan). Other antidepressants can be used in doses lower than needed for depression, with more rapid onset of effect on hot flashes, often within 2 weeks.

Last, transdermal clonidine, an antihypertensive, also has been found to relieve hot flashes.

Continue to: Not a recommended strategy: Systemic hormone therapy

Not a recommended strategy: Systemic hormone therapy

Although hormone therapy is, in general, the gold standard for alleviating hot flashes, it is contraindicated in most women with breast cancer.⁴ At our institution, we avoid systemic hormone therapy for hot flashes in almost all breast cancer patients.

CASE 2

Sarah first presented with hot flashes that improved while taking escitalopram 10 mg. Her night sweats persisted, however. Gabapentin 300 mg was added to take nightly. With this regimen, she finally felt that she was coping better. Six months later, she reported that she and her long-term partner had not been able to resume vaginal intercourse post–breast cancer treatment because of pain.

The challenge of managing GSM

What if your patient says, “Doctor, I’m really doing OK with my hot flashes, but sex has become painful. I don’t have any interest. I have vaginal dryness, and it’s affecting my quality of life”?

Studies have shown that GSM affects up to 50% of women, and even more than that among women who have had breast cancer.⁵ The condition interferes with sexual intimacy, disrupts quality of life, and can sour a partnership—significant quality-of-life concerns for breast cancer survivors.

For mild symptoms, encourage patients to apply a lubricant just before intercourse or a vaginal moisturizer twice weekly; moisturizers improve vaginal pH, too. These treatments do not fix the problem of a lack of superficial cells due to estrogen loss, however; to accomplish that, consider prescribing low-dose vaginal estrogen therapy or intravaginal dehydroepiandrosterone (DHEA). This strategy is felt to be safe for many breast cancer survivors, as systemic absorption of estrogen is minimal if dosed low, keeping levels in the postmenopausal range.

The American College of Obstetricians and Gynecologists (ACOG), the North American Menopause Society (NAMS), and the Endocrine Society agree that vaginal estrogen therapy may be a good option for many women with breast cancer for whom moisturizers and lubricants are inadequate.⁶ Delivery options include vaginal creams, tablets, suppositories used 2 or 3 times per week, or the low-dose vaginal estrogen ring, replaced every 3 months. We are concerned about using vaginal estrogen in women who have had aromatase inhibitor (AI) therapy; their estrogen levels are so low that absorbing even a small amount might make a difference in terms of effectiveness of AI. For women who need more than lubricants or vaginal moisturizers, particularly those taking anti-estrogen therapy (aromatase therapy), the use of low-dose vaginal hormones may be considered on an individual basis, but should include the oncologist in decision making.^1,3

Beyond low-dose vaginal estrogen therapies, there are additional options that can be considered but with less supporting data for treating GSM in women with breast cancer.

Oral ospemifene, a selective estrogen-receptor modulator (SERM; Osphena), might be neutral or even protective in its effect on the breast, as demonstrated in preclinical trials.⁷ In human trials, the drug is approved only for painful intercourse, not for loss of libido, and has not been tested in breast cancer patients.

Intravaginal DHEA (Prasterone), has been on the market for almost 1 year. The drug is approved for treating painful intercourse, but it also reverses vaginal atrophy and alleviates urinary symptoms. Because DHEA is a prohormone, it is converted to estrogen and androgen in the vagina. Again, absorption appears minimal. Intravaginal DHEA does not have the US Food and Drug Administration (FDA) black-box warning that vaginal estrogen products do, but it is accompanied by a warning that it has not been tested in women with breast cancer.

Tissue selective estrogen receptor modulator is a conjugated estrogen combined with a third-generation SERM bazedoxifene, which treats hot flashes and reverses vaginal atrophy. This new systemic agent is probably neutral on the breast (at least that is the finding in clinical trials at 2 years⁸); again, however, it has not been tested in patients with breast cancer.

Continue to: Nonhormone therapies...

Nonhormone therapies

Topical lidocaine for insertional dyspareunia has been studied in postmenopausal women with breast cancer with severe GSM, dyspareunia, increased sexual distress scores, or abnormal sexual function with improvement seen using 4% aqueous lidocaine versus saline applied with a cotton ball to the vestibule for 3 minutes before vaginal penetration.⁹

Vaginal laser therapy has the potential to ameliorate distressing GSM without the need for local hormone intervention; however, placebo or active-controlled trials and long-term safety follow-up are needed.⁵

Treatment begins with a conversation

Most importantly, we need to listen to our patients in discomfort because of their menopausal symptoms. Consider proceeding along these lines: “You’ve been treated for breast cancer; now, let’s look at the medical issues that are affecting your quality of life. Are you depressed? Are you having hot flashes? Are you getting enough sleep? Have you stopped having sex or not restarted after your breast cancer treatment? Are you having painful sex or avoiding sex due to fear of pain? Let’s discuss options and work with your oncologist to try to relieve your symptoms and make your life better.”

First-line therapy for the treatment of menopausal symptoms in women with a history of breast cancer should start with lifestyle changes and nonhormone therapies. For GSM, lubricants and vaginal moisturizers should be tried first and may be effective. Reassure patients that there are many treatment options, even though not all of them have been well-tested in breast cancer patients, and that new modalities are under investigation and review (see “Newly arrived and on the horizon,”). Become familiar with published data on the safety and effectiveness of the range of available treatments; guide patients through the process of finding what works best for them; and invite their oncologist into the therapeutic partnership. If you do not feel comfortable with these issues in women who are breast cancer survivors, find a menopause specialist to help, available by zip code at Find a Provider, http://www.menopause.org.

Breast cancer survivors entering menopause face the risk of several menopausal symptoms:

• Hot flashes, the most common symptom, occur in more than 75% of women during menopause and have the potential to persist for as long as 15 years.¹ That lengthy interval becomes a major issue for patients, especially when hot flashes are associated with other menopausal symptoms, including sleep disruption, difficulty concentrating, and emotional instability (crying, irritability).

• Painful intercourse and loss of interest in sexual activity often develop as a result of vaginal atrophy and dryness.

• Urinary tract symptoms include urgency and, compared to the patient’s history, more frequent infections.
• Bone loss is a concern for many women after breast cancer, especially if they are, or have been, on aromatase inhibitor therapy.

• Depression might be related to hormonal changes due to menopause or hormonal therapies, a consequence of merely having a diagnosis of cancer, or an adverse effect of chemotherapy.

In this brief review, I’ll examine options for treating symptoms of menopause by strategy—lifestyle modifications, over-the-counter treatments, and prescription drugs. Separately, I’ll look at options for managing genitourinary syndrome of menopause (GSM).

CASE 1

Rose is a 56-year-old woman who presents to clinic with a new breast mass, felt on breast self exam. The mass is about 1 cm, mobile, and firm. Diagnostic mammogram and ultrasound confirm a worrisome mass; biopsy returns positive with a 9-mm invasive, estrogen-receptor positive, ductal carcinoma with negative sentinel nodes at the time of lumpectomy. Radiation therapy was completed. She then met with oncology and decided against chemotherapy. Instead, she began an aromatase inhibitor 3 months ago. Bone density showed osteopenia. She presents to your office reporting frequent bothersome hot flashes and disrupted sleep.

Strategy #1: Lifestyle adaptations

First-line interventions for menopausal women who have had breast cancer usually involve taking a critical look at lifestyle and undertaking modifications that can alleviate discomfort. Because overall health is important for women who have had breast cancer, you should, across the spectrum of patients, encourage them to:

• increase physical activity
• reduce body weight by approximately 10% (if overweight or obese)
• reduce alcohol consumption
• stop smoking
• ensure adequate intake of calcium (1,200 mg, preferably by diet)
• optimize the level of vitamin D, including by increasing intake of fresh fish, eggs, and numerous other fortified foods.

The value of nondrug therapy for hot flashes is difficult to prove. Certain lifestyle changes are sensible, even if not evidence-based, and will help some women (but not others). We suggest that patients try lowering the temperature in the home (65–68˚ at night); running a fan; wearing clothing that can be removed in layers; and avoiding triggers such as spicy food, alcohol, cigarettes, and hot drinks. Hypnosis and cognitive behavioral therapy (CBT) have been shown to help in clinical trials. Measures with benefit and minimal risks, but effectiveness not established, include acupuncture (sham worked as well as traditional), exercise, yoga, paced respiration, relaxation training, and mindfulness-based stress reduction.

Continue to: Strategy #2: OTC compounds...

Strategy #2: OTC compounds

Over-the-counter products—from soy products to black cohosh to flax seed, and including dong quai, evening primrose oil, maca, omegas, pollen extract, ginseng, and red clover,² or several compounds formulated in combination—have not been proven to be of more benefit for relieving symptoms of menopause than placebo in randomized trials, and thus might or might not be effective in a given patient. S-equol, a metabolite of a soy isoflavone taken by women who are non-equol producers, is available under the trade name Equelle and has shown some benefit. Note: There is concern that supplements that contain estrogen-like compounds, like soy products, might actually increase the risk of breast cancer. Dietary soy is not felt to be a concern.

Ask questions about the severity of a patient’s hot flashes. When a patient reports hot flashes, and is requesting help to relieve her discomfort, inquire 1) how often she has hot flashes, 2) how severe they are, and 3) how bothered she is by them (not all women are equally troubled, of course). The patient’s answers to these questions will help you decide which treatment option to offer, based on evidence and your experience.

CASE 1 Continued

Rose tried black cohosh OTC without improvement. She was interested in hypnosis but did not find it effective for her. She returned 3 months later stating that she is miserable, exhausted, not getting enough sleep, and her hot flashes and night sweats are affecting both her work and her relationship.

Strategy #3: Prescription medication

When addressing hot flashes, consider whether they occur more at night or during the day, or do not follow a day–night pattern. For women whose hot flashes occur mostly at night, and might therefore make sleeping difficult and cause fatigue and irritability, gabapentin, taken approximately 1 hour before bed, can be helpful. If tolerated without excessive somnolence the next day, the dose can be increased at night or additional doses provided during the day depending on hot flash response. For women who have hot flashes day and night, we often prescribe a low-dose antidepressant from the selective serotonin-reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) class.

When prescribing an antidepressant, we make a distinction between breast cancer patients who are taking tamoxifen and those who are not, to avoid cytochrome P450 2D6 inhibitors in women taking tamoxifen.³ Better choices for women taking tamoxifen include desvenlafaxine, venlafaxine, escitalopram, or gabapentin or pregabalin.

For women with breast cancer who are taking an aromatase inhibitor, and who are also experiencing mood changes with their hot flashes, we often choose a trial of a low-dose antidepressant, either an SSRI or SNRI. One drug is approved by the US Food and Drug Administration (FDA) for the treatment of hot flashes (but not for mood disorder). This is low-dose salt of paroxetine, 7.5 mg/d, which has the advantage of exerting no adverse effect on libido or weight (but is sometimes difficult to obtain because it is a branded product that might not be covered, or not covered fully, by a given patient’s insurance plan). Other antidepressants can be used in doses lower than needed for depression, with more rapid onset of effect on hot flashes, often within 2 weeks.

Last, transdermal clonidine, an antihypertensive, also has been found to relieve hot flashes.

Continue to: Not a recommended strategy: Systemic hormone therapy

Not a recommended strategy: Systemic hormone therapy

Although hormone therapy is, in general, the gold standard for alleviating hot flashes, it is contraindicated in most women with breast cancer.⁴ At our institution, we avoid systemic hormone therapy for hot flashes in almost all breast cancer patients.

CASE 2

Sarah first presented with hot flashes that improved while taking escitalopram 10 mg. Her night sweats persisted, however. Gabapentin 300 mg was added to take nightly. With this regimen, she finally felt that she was coping better. Six months later, she reported that she and her long-term partner had not been able to resume vaginal intercourse post–breast cancer treatment because of pain.

The challenge of managing GSM

What if your patient says, “Doctor, I’m really doing OK with my hot flashes, but sex has become painful. I don’t have any interest. I have vaginal dryness, and it’s affecting my quality of life”?

Studies have shown that GSM affects up to 50% of women, and even more than that among women who have had breast cancer.⁵ The condition interferes with sexual intimacy, disrupts quality of life, and can sour a partnership—significant quality-of-life concerns for breast cancer survivors.

For mild symptoms, encourage patients to apply a lubricant just before intercourse or a vaginal moisturizer twice weekly; moisturizers improve vaginal pH, too. These treatments do not fix the problem of a lack of superficial cells due to estrogen loss, however; to accomplish that, consider prescribing low-dose vaginal estrogen therapy or intravaginal dehydroepiandrosterone (DHEA). This strategy is felt to be safe for many breast cancer survivors, as systemic absorption of estrogen is minimal if dosed low, keeping levels in the postmenopausal range.

The American College of Obstetricians and Gynecologists (ACOG), the North American Menopause Society (NAMS), and the Endocrine Society agree that vaginal estrogen therapy may be a good option for many women with breast cancer for whom moisturizers and lubricants are inadequate.⁶ Delivery options include vaginal creams, tablets, suppositories used 2 or 3 times per week, or the low-dose vaginal estrogen ring, replaced every 3 months. We are concerned about using vaginal estrogen in women who have had aromatase inhibitor (AI) therapy; their estrogen levels are so low that absorbing even a small amount might make a difference in terms of effectiveness of AI. For women who need more than lubricants or vaginal moisturizers, particularly those taking anti-estrogen therapy (aromatase therapy), the use of low-dose vaginal hormones may be considered on an individual basis, but should include the oncologist in decision making.^1,3

Beyond low-dose vaginal estrogen therapies, there are additional options that can be considered but with less supporting data for treating GSM in women with breast cancer.

Oral ospemifene, a selective estrogen-receptor modulator (SERM; Osphena), might be neutral or even protective in its effect on the breast, as demonstrated in preclinical trials.⁷ In human trials, the drug is approved only for painful intercourse, not for loss of libido, and has not been tested in breast cancer patients.

Intravaginal DHEA (Prasterone), has been on the market for almost 1 year. The drug is approved for treating painful intercourse, but it also reverses vaginal atrophy and alleviates urinary symptoms. Because DHEA is a prohormone, it is converted to estrogen and androgen in the vagina. Again, absorption appears minimal. Intravaginal DHEA does not have the US Food and Drug Administration (FDA) black-box warning that vaginal estrogen products do, but it is accompanied by a warning that it has not been tested in women with breast cancer.

Tissue selective estrogen receptor modulator is a conjugated estrogen combined with a third-generation SERM bazedoxifene, which treats hot flashes and reverses vaginal atrophy. This new systemic agent is probably neutral on the breast (at least that is the finding in clinical trials at 2 years⁸); again, however, it has not been tested in patients with breast cancer.

Continue to: Nonhormone therapies...

Nonhormone therapies

Topical lidocaine for insertional dyspareunia has been studied in postmenopausal women with breast cancer with severe GSM, dyspareunia, increased sexual distress scores, or abnormal sexual function with improvement seen using 4% aqueous lidocaine versus saline applied with a cotton ball to the vestibule for 3 minutes before vaginal penetration.⁹

Vaginal laser therapy has the potential to ameliorate distressing GSM without the need for local hormone intervention; however, placebo or active-controlled trials and long-term safety follow-up are needed.⁵

Treatment begins with a conversation

Most importantly, we need to listen to our patients in discomfort because of their menopausal symptoms. Consider proceeding along these lines: “You’ve been treated for breast cancer; now, let’s look at the medical issues that are affecting your quality of life. Are you depressed? Are you having hot flashes? Are you getting enough sleep? Have you stopped having sex or not restarted after your breast cancer treatment? Are you having painful sex or avoiding sex due to fear of pain? Let’s discuss options and work with your oncologist to try to relieve your symptoms and make your life better.”

First-line therapy for the treatment of menopausal symptoms in women with a history of breast cancer should start with lifestyle changes and nonhormone therapies. For GSM, lubricants and vaginal moisturizers should be tried first and may be effective. Reassure patients that there are many treatment options, even though not all of them have been well-tested in breast cancer patients, and that new modalities are under investigation and review (see “Newly arrived and on the horizon,”). Become familiar with published data on the safety and effectiveness of the range of available treatments; guide patients through the process of finding what works best for them; and invite their oncologist into the therapeutic partnership. If you do not feel comfortable with these issues in women who are breast cancer survivors, find a menopause specialist to help, available by zip code at Find a Provider, http://www.menopause.org.

Cancer pharmaceutical manufacturers are making profits that more than cover their research and development costs, calling into question the need for these products to carry a high price tag, limiting access.

Mathier/Thinkstock

“Based on a risk-adjusted R&D cost of $794 million [$219 million to $2.8 billion], by the end of 2017, $1 (risk-adjusted) invested for R&D of the 99 drugs had generated a median of $14.50 (range, $3.30-$55.10) in sales income for the originator companies” wrote Kiu Tay-Teo, PhD, of the World Health Organization, Geneva, Switzerland, and colleagues. The report is in JAMA Network Open.

“Assuming the upper threshold R&D cost of [$2.8 billion], rituximab, trastuzumab, bevacizumab, pegfilgrastim, and imatinib have brought in for the originator companies, $33.20, $31.20, $29.50, $22.60, and $22.60, respectively, for every risk adjusted dollar that went into their R&D.”

The study authors looked at all cancer drugs approved by the Food and Drug Administration from 1989 to 2017 (156 total) and narrowed the analysis down to the 99 products that had sales data on more than half of the years since being approved.

The analysis shows that compared with the risk-adjusted R&D cost of $794 million (with a range of $219 million to $2.8 billion) per medicine, by the end of 2017, the median cumulative sales income was $14.50 (range, $3.30-$55.10) per dollar invested for R&D. “Median time to fully recover the maximum possible risk-adjusted cost of R&D [$2.8 billion] was 5 years (range, 2-10 years; n = 56),” the authors stated.

“By the end of 2017, the cumulative sales of 73 cancer drugs (73.7%) included in the analysis had fully recovered the median R&D costs of $794 million,” Dr. Tay-Teo and colleagues reported.

The authors argue that such high prices and high profits, while far exceeding even the upper bound of R&D costs, could also be hindering access to drugs.

“The high incomes and supernormal returns would be less worrying if patients were able to access cancer drugs at affordable prices,” Dr. Tay-Teo and colleagues stated. “However, the existing evidence suggests otherwise: Access to cancer drugs globally remains low and the number of cancer drugs with annual costs at least in the tens of thousands is increasing fast. The resulting expenditure effects have compelled insurance schemes to exclude patients from coverage, restrict access, or impose high out-of-pocket costs.”

They suggest that for these reasons, the high price tags on cancer drugs is reducing patient access worldwide.

The analysis was limited to the information on sales and R&D costs that was made public by manufacturers in annual reports and did not estimate cumulative profits due to lack of information on year-over-year variations on production costs of cancer drugs.

[email protected]

SOURCE: Kiu Tay-Teo, PhD, et al. JAMA Netw Open. doi: 10.1001/jamanetworkopen.2018.6875.

Cancer pharmaceutical manufacturers are making profits that more than cover their research and development costs, calling into question the need for these products to carry a high price tag, limiting access.

Mathier/Thinkstock

“Based on a risk-adjusted R&D cost of $794 million [$219 million to $2.8 billion], by the end of 2017, $1 (risk-adjusted) invested for R&D of the 99 drugs had generated a median of $14.50 (range, $3.30-$55.10) in sales income for the originator companies” wrote Kiu Tay-Teo, PhD, of the World Health Organization, Geneva, Switzerland, and colleagues. The report is in JAMA Network Open.

“Assuming the upper threshold R&D cost of [$2.8 billion], rituximab, trastuzumab, bevacizumab, pegfilgrastim, and imatinib have brought in for the originator companies, $33.20, $31.20, $29.50, $22.60, and $22.60, respectively, for every risk adjusted dollar that went into their R&D.”

The study authors looked at all cancer drugs approved by the Food and Drug Administration from 1989 to 2017 (156 total) and narrowed the analysis down to the 99 products that had sales data on more than half of the years since being approved.

The analysis shows that compared with the risk-adjusted R&D cost of $794 million (with a range of $219 million to $2.8 billion) per medicine, by the end of 2017, the median cumulative sales income was $14.50 (range, $3.30-$55.10) per dollar invested for R&D. “Median time to fully recover the maximum possible risk-adjusted cost of R&D [$2.8 billion] was 5 years (range, 2-10 years; n = 56),” the authors stated.

“By the end of 2017, the cumulative sales of 73 cancer drugs (73.7%) included in the analysis had fully recovered the median R&D costs of $794 million,” Dr. Tay-Teo and colleagues reported.

The authors argue that such high prices and high profits, while far exceeding even the upper bound of R&D costs, could also be hindering access to drugs.

“The high incomes and supernormal returns would be less worrying if patients were able to access cancer drugs at affordable prices,” Dr. Tay-Teo and colleagues stated. “However, the existing evidence suggests otherwise: Access to cancer drugs globally remains low and the number of cancer drugs with annual costs at least in the tens of thousands is increasing fast. The resulting expenditure effects have compelled insurance schemes to exclude patients from coverage, restrict access, or impose high out-of-pocket costs.”

They suggest that for these reasons, the high price tags on cancer drugs is reducing patient access worldwide.

The analysis was limited to the information on sales and R&D costs that was made public by manufacturers in annual reports and did not estimate cumulative profits due to lack of information on year-over-year variations on production costs of cancer drugs.

[email protected]

SOURCE: Kiu Tay-Teo, PhD, et al. JAMA Netw Open. doi: 10.1001/jamanetworkopen.2018.6875.

Cancer pharmaceutical manufacturers are making profits that more than cover their research and development costs, calling into question the need for these products to carry a high price tag, limiting access.

Mathier/Thinkstock

“Based on a risk-adjusted R&D cost of $794 million [$219 million to $2.8 billion], by the end of 2017, $1 (risk-adjusted) invested for R&D of the 99 drugs had generated a median of $14.50 (range, $3.30-$55.10) in sales income for the originator companies” wrote Kiu Tay-Teo, PhD, of the World Health Organization, Geneva, Switzerland, and colleagues. The report is in JAMA Network Open.

“Assuming the upper threshold R&D cost of [$2.8 billion], rituximab, trastuzumab, bevacizumab, pegfilgrastim, and imatinib have brought in for the originator companies, $33.20, $31.20, $29.50, $22.60, and $22.60, respectively, for every risk adjusted dollar that went into their R&D.”

The study authors looked at all cancer drugs approved by the Food and Drug Administration from 1989 to 2017 (156 total) and narrowed the analysis down to the 99 products that had sales data on more than half of the years since being approved.

The analysis shows that compared with the risk-adjusted R&D cost of $794 million (with a range of $219 million to $2.8 billion) per medicine, by the end of 2017, the median cumulative sales income was $14.50 (range, $3.30-$55.10) per dollar invested for R&D. “Median time to fully recover the maximum possible risk-adjusted cost of R&D [$2.8 billion] was 5 years (range, 2-10 years; n = 56),” the authors stated.

“By the end of 2017, the cumulative sales of 73 cancer drugs (73.7%) included in the analysis had fully recovered the median R&D costs of $794 million,” Dr. Tay-Teo and colleagues reported.

The authors argue that such high prices and high profits, while far exceeding even the upper bound of R&D costs, could also be hindering access to drugs.

“The high incomes and supernormal returns would be less worrying if patients were able to access cancer drugs at affordable prices,” Dr. Tay-Teo and colleagues stated. “However, the existing evidence suggests otherwise: Access to cancer drugs globally remains low and the number of cancer drugs with annual costs at least in the tens of thousands is increasing fast. The resulting expenditure effects have compelled insurance schemes to exclude patients from coverage, restrict access, or impose high out-of-pocket costs.”

They suggest that for these reasons, the high price tags on cancer drugs is reducing patient access worldwide.

The analysis was limited to the information on sales and R&D costs that was made public by manufacturers in annual reports and did not estimate cumulative profits due to lack of information on year-over-year variations on production costs of cancer drugs.

[email protected]

SOURCE: Kiu Tay-Teo, PhD, et al. JAMA Netw Open. doi: 10.1001/jamanetworkopen.2018.6875.

The Diagnosis: Basal Cell Nevus Syndrome

Given the patient’s history of numerous basal cell carcinomas (BCCs), odontogenic keratocysts, palmar pits, and a nonhealing ulcer, the clinical presentation was highly suggestive of interdigital BCC in the setting of basal cell nevus syndrome (BCNS). A shave biopsy was performed revealing islands of basaloid cells with peripheral palisading and a retraction artifact surrounded by fibromyxoid stroma, consistent with nodular and infiltrative BCC (Figure 1).

Basal cell nevus syndrome (also known as Gorlin syndrome) is a rare neurocutaneous syndrome that manifests with multiple BCCs; palmar and plantar pits (Figure 2); central nervous system tumors; and skeletal anomalies including jaw cysts, macrocephaly, frontal bossing, and bifid ribs.¹ It is an autosomal-dominant condition caused by mutations in the PTCH1 gene, a tumor suppressor gene involved in the Hedgehog signaling pathway.² Basal cell carcinoma is the most distinctive feature of BCNS, causing notable morbidity. Tumors typically present between puberty and 35 years of age, and patients can have anywhere from a few to thousands of tumors. They rarely become locally aggressive; however, with radiation therapy, proliferation and local invasion may occur within a few years. Therefore, radiotherapy should be avoided in these patients.¹

Although the most common sites for BCCs in BCNS are the head, neck, and back, there is a higher rate of occurrence on sun-protected areas in BCNS compared to the general population.³ Our patient presented with interdigital BCC of the foot, which is an extremely rare occurrence. PubMed and Ovid searches using the terms basal cell carcinoma, BCC, foot, interdigital, and nonmelanoma skin cancer revealed only 3 cases of interdigital BCC of the foot. One case was associated with prior surgical trauma, the second presented as a junctional nevus, and the third did not appear to have any associated inciting factors.^4-6 Dermatologists need to have a low threshold for biopsy for any unusual nonhealing lesions, especially in the setting of BCNS. Basal cell carcinomas in BCNS cannot be histologically differentiated from sporadic BCCs, and management largely depends on the size, location, recurrence, and number of lesions. Treatment methods range from topical agents to Mohs micrographic surgery.¹

Nonhealing lesions of the foot may give an initial clinical impression of infection overlying peripheral vascular disease or diabetes mellitus with the possibility of associated osteomyelitis. Our patient had no clinical history to suggest peripheral vascular disease or diabetes mellitus, and he had palpable dorsalis pedis pulses as well as a normal neurologic examination. Clinicians also may consider fungal infection in the differential diagnosis. Erosio interdigitalis blastomycetica is a superficial yeast infection described as a well-defined, red, shiny plaque found in chronically wet areas, usually affecting the third or fourth interdigital spaces of the fingers.⁷ However, the lack of improvement with antibiotics and antifungals argued against bacterial or fungal infection in our patient. Although BCC also is a common feature of Bazex Dupré-Christol syndrome, it also is characterized by follicular atrophoderma, milia, hypohidrosis, and hypotrichosis,⁸ which were not evident in our patient. Pseudomonas hot foot syndrome is characterized by painful, plantar, erythematous nodules after exposure to ontaminated water that typically is self-limited but does respond to antibiotics for Pseudomonas.⁹

Our patient underwent Mohs micrographic surgery with a complex repair utilizing a full-thickness skin graft. There were no signs of recurrence at 3-month follow-up, and he was counseled on the importance of sun-protective behaviors along with regular dermatologic follow-up.

The Diagnosis: Basal Cell Nevus Syndrome

Given the patient’s history of numerous basal cell carcinomas (BCCs), odontogenic keratocysts, palmar pits, and a nonhealing ulcer, the clinical presentation was highly suggestive of interdigital BCC in the setting of basal cell nevus syndrome (BCNS). A shave biopsy was performed revealing islands of basaloid cells with peripheral palisading and a retraction artifact surrounded by fibromyxoid stroma, consistent with nodular and infiltrative BCC (Figure 1).

Basal cell nevus syndrome (also known as Gorlin syndrome) is a rare neurocutaneous syndrome that manifests with multiple BCCs; palmar and plantar pits (Figure 2); central nervous system tumors; and skeletal anomalies including jaw cysts, macrocephaly, frontal bossing, and bifid ribs.¹ It is an autosomal-dominant condition caused by mutations in the PTCH1 gene, a tumor suppressor gene involved in the Hedgehog signaling pathway.² Basal cell carcinoma is the most distinctive feature of BCNS, causing notable morbidity. Tumors typically present between puberty and 35 years of age, and patients can have anywhere from a few to thousands of tumors. They rarely become locally aggressive; however, with radiation therapy, proliferation and local invasion may occur within a few years. Therefore, radiotherapy should be avoided in these patients.¹

Although the most common sites for BCCs in BCNS are the head, neck, and back, there is a higher rate of occurrence on sun-protected areas in BCNS compared to the general population.³ Our patient presented with interdigital BCC of the foot, which is an extremely rare occurrence. PubMed and Ovid searches using the terms basal cell carcinoma, BCC, foot, interdigital, and nonmelanoma skin cancer revealed only 3 cases of interdigital BCC of the foot. One case was associated with prior surgical trauma, the second presented as a junctional nevus, and the third did not appear to have any associated inciting factors.^4-6 Dermatologists need to have a low threshold for biopsy for any unusual nonhealing lesions, especially in the setting of BCNS. Basal cell carcinomas in BCNS cannot be histologically differentiated from sporadic BCCs, and management largely depends on the size, location, recurrence, and number of lesions. Treatment methods range from topical agents to Mohs micrographic surgery.¹

Nonhealing lesions of the foot may give an initial clinical impression of infection overlying peripheral vascular disease or diabetes mellitus with the possibility of associated osteomyelitis. Our patient had no clinical history to suggest peripheral vascular disease or diabetes mellitus, and he had palpable dorsalis pedis pulses as well as a normal neurologic examination. Clinicians also may consider fungal infection in the differential diagnosis. Erosio interdigitalis blastomycetica is a superficial yeast infection described as a well-defined, red, shiny plaque found in chronically wet areas, usually affecting the third or fourth interdigital spaces of the fingers.⁷ However, the lack of improvement with antibiotics and antifungals argued against bacterial or fungal infection in our patient. Although BCC also is a common feature of Bazex Dupré-Christol syndrome, it also is characterized by follicular atrophoderma, milia, hypohidrosis, and hypotrichosis,⁸ which were not evident in our patient. Pseudomonas hot foot syndrome is characterized by painful, plantar, erythematous nodules after exposure to ontaminated water that typically is self-limited but does respond to antibiotics for Pseudomonas.⁹

Our patient underwent Mohs micrographic surgery with a complex repair utilizing a full-thickness skin graft. There were no signs of recurrence at 3-month follow-up, and he was counseled on the importance of sun-protective behaviors along with regular dermatologic follow-up.

The Diagnosis: Basal Cell Nevus Syndrome

Given the patient’s history of numerous basal cell carcinomas (BCCs), odontogenic keratocysts, palmar pits, and a nonhealing ulcer, the clinical presentation was highly suggestive of interdigital BCC in the setting of basal cell nevus syndrome (BCNS). A shave biopsy was performed revealing islands of basaloid cells with peripheral palisading and a retraction artifact surrounded by fibromyxoid stroma, consistent with nodular and infiltrative BCC (Figure 1).

Basal cell nevus syndrome (also known as Gorlin syndrome) is a rare neurocutaneous syndrome that manifests with multiple BCCs; palmar and plantar pits (Figure 2); central nervous system tumors; and skeletal anomalies including jaw cysts, macrocephaly, frontal bossing, and bifid ribs.¹ It is an autosomal-dominant condition caused by mutations in the PTCH1 gene, a tumor suppressor gene involved in the Hedgehog signaling pathway.² Basal cell carcinoma is the most distinctive feature of BCNS, causing notable morbidity. Tumors typically present between puberty and 35 years of age, and patients can have anywhere from a few to thousands of tumors. They rarely become locally aggressive; however, with radiation therapy, proliferation and local invasion may occur within a few years. Therefore, radiotherapy should be avoided in these patients.¹

Although the most common sites for BCCs in BCNS are the head, neck, and back, there is a higher rate of occurrence on sun-protected areas in BCNS compared to the general population.³ Our patient presented with interdigital BCC of the foot, which is an extremely rare occurrence. PubMed and Ovid searches using the terms basal cell carcinoma, BCC, foot, interdigital, and nonmelanoma skin cancer revealed only 3 cases of interdigital BCC of the foot. One case was associated with prior surgical trauma, the second presented as a junctional nevus, and the third did not appear to have any associated inciting factors.^4-6 Dermatologists need to have a low threshold for biopsy for any unusual nonhealing lesions, especially in the setting of BCNS. Basal cell carcinomas in BCNS cannot be histologically differentiated from sporadic BCCs, and management largely depends on the size, location, recurrence, and number of lesions. Treatment methods range from topical agents to Mohs micrographic surgery.¹

Nonhealing lesions of the foot may give an initial clinical impression of infection overlying peripheral vascular disease or diabetes mellitus with the possibility of associated osteomyelitis. Our patient had no clinical history to suggest peripheral vascular disease or diabetes mellitus, and he had palpable dorsalis pedis pulses as well as a normal neurologic examination. Clinicians also may consider fungal infection in the differential diagnosis. Erosio interdigitalis blastomycetica is a superficial yeast infection described as a well-defined, red, shiny plaque found in chronically wet areas, usually affecting the third or fourth interdigital spaces of the fingers.⁷ However, the lack of improvement with antibiotics and antifungals argued against bacterial or fungal infection in our patient. Although BCC also is a common feature of Bazex Dupré-Christol syndrome, it also is characterized by follicular atrophoderma, milia, hypohidrosis, and hypotrichosis,⁸ which were not evident in our patient. Pseudomonas hot foot syndrome is characterized by painful, plantar, erythematous nodules after exposure to ontaminated water that typically is self-limited but does respond to antibiotics for Pseudomonas.⁹

Our patient underwent Mohs micrographic surgery with a complex repair utilizing a full-thickness skin graft. There were no signs of recurrence at 3-month follow-up, and he was counseled on the importance of sun-protective behaviors along with regular dermatologic follow-up.

The US Food and Drug Administration (FDA) recently extended the approval for Gardasil 9 (to prevent HPV-associated cancers, cancer precursors, and genital lesions) to men and women aged 27 to 45.¹ In this editorial, we discuss the evolution of the HPV vaccine since its initial approval more than 10 years ago, the benefits of primary prevention with the HPV vaccine, and the case for the FDA’s recent extension of coverage to older men and women.

The evolution of the HPV vaccine

Since recognition in the 1980s and 90s that high-risk strains of HPV, notably HPV types 16 and 18, were linked to cervical cancer, there have been exciting advances in detection and prevention of high-risk HPV infection. About 70% of cervical cancers are attributable to these 2 oncogenic types.² The first vaccine licensed, Gardasil (Merck), was approved in 2006 for girls and women aged 9 through 26 to prevent HPV-related diseases caused by types 6, 11, 16, and 18.³ The vaccine was effective for prevention of cervical cancer; genital warts; and grades 2 and 3 of cervical, vulvar, and vaginal intraepithelial neoplasia. In 2008, prevention of vulvar and vaginal cancers was added to the indication. By 2009, prevention of genital warts was added, and use in males aged 9 to 15 was approved. By 2010 sufficient data were accumulated to document prevention of anal cancer and anal intraepithelial neoplasia in men and women, and this indication was added.

In 2014 Gardasil 9 was approved to extend coverage to an additional 5 oncogenic HPV types (31, 33, 45, 52, and 58), now covering an additional 20% of cervical cancers, and in 2015 Gardasil 9 indications were expanded to include boys and men 9 to 26 years of age. Immunogenicity studies were performed to infer effectiveness of a 2-dose regimen in boys and girls aged 9 to 14 years, which was recommended by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) in late 2016.⁴

Until October 2018, Gardasil 9 was indicated for prevention of genital warts, cervical, vaginal, vulvar and anal cancers and cancer precursors for males and females aged 9 to 26 years. In October the FDA extended approval of the 3-dose vaccine regimen to men and women up to age 45.

HPV vaccine uptake

HPV vaccination has been underutilized in the United States. In 2017, a disappointing 49% of adolescents were up to date on vaccination, and 66% had received at least one dose.⁵ In rural areas the vaccination rates are 11 points lower than in urban regions.⁶ The CDC notes an increasing number of HPV-associated cancers—from 30,000 per year in 1999 to 43,000 per year in 2015—due mostly to increases in oral and anal carcinomas. Vaccination with Gardasil 9 could prevent 90% of those cases.⁷

Non-US successes. HPV vaccine uptake in Australia provides an excellent opportunity to study the impact of universally available, school-based vaccinations. In 2007 Australia implemented a program of free HPV vaccination distributed through schools. Boys and girls aged 12 and 13 were targeted that year, with catch-up vaccinations for those aged 13 to 18 in 2007-2009 in schools and for those aged 18 to 26 reached in the community.⁸ 

Continue to: Ali and colleagues studied the... 

Ali and colleagues studied the preprogram and postprogram incidence of genital warts.⁹ About 83% received at least 1 dose of vaccine, and 73% of the eligible population completed the 3-dose regimen. There was a significant reduction in warts in both men and women younger than age 21 from 2007 to 2011 (12.1% to 2.2% in men and 11.5% to 0.85% in women). In the 21 to 30 age group there were similar reductions. This study demonstrates that with universal access and public implementation, the rates of HPV-associated disease can be reduced dramatically.

Data informing expanded vaccination ages

Will vaccination of an older population, with presumably many of whom sexually active and at risk for prior exposure to multiple HPV types, have a reasonable impact on lowering HPV-associated cancers? Are HPV-detected lesions in 27- to 45-year-old women the result of reactivation of latent HPV infection, or are they related to new-onset exposure? The FDA reviewed data from 3 studies of HPV vaccination in women aged 27 to 45. The first enrolled women who were naïve to oncogenic HPV types and provided all 3 doses of quadrivalent vaccine were followed for 4 years, along with a comparison group of nonvaccinated women. The second study allowed the nonvaccinated group to receive vaccine in year 4. Both groups were followed up to 10 years with the relevant outcome defined as cumulative incidence of HPV 6/11/16/18-related CIN and condyloma. The third study looked at the same outcomes in a set of all women—whether HPV high-risk naïve or not—after receiving vaccine and followed more than 10 years.⁷ This last study is most relevant to ObGyns, as it is closest to how we would consider vaccinating our patients.

The study findings are reassuring: A large proportion of HPV infections in women between 27 and 45 are the result of new exposure/infection. A study of 420 online daters aged 25 to 65 showed an annual incidence of high-risk HPV types in vaginal swabs of 25.4%, of which 64% were likely new acquisitions.¹⁰ The 2013-2014 National Health and Nutrition Examination Survey of 1,757 men aged 18 to 59 estimated approximately 45% had genital HPV infection. There was a bimodal distribution of disease with peaks at 28 to 32 and a larger second peak at 58 to 59 years of age.¹¹ Bottom line: Men and women older than age 26 who are sexually active likely acquire new HPV infections with oncogenic types. Exposure to high-risk HPV types prior to vaccination—as we would expect in the real-world setting—did not eliminate the substantial benefit of immunization.

Based on these study results, and extrapolation to the 9-valent vaccine, the FDA extended the approval of Gardasil 9 to men and women from age 9 to 45. The indications and usage will remain the same: for prevention of cervical, vulvar, vaginal, and anal cancer and genital warts as well as precancerous or dysplastic lesions of the cervix, vulva, vagina, and anus related to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

Continue to: Impact of the new... 

Impact of the new indication on HPV-related disease

As described above, widespread vaccination of young girls and boys is going to have major impact on HPV-related disease, including precancer and cancer. Because there is evidence that older women and men are at risk for new HPV infection,¹⁰ there likely will be some benefit from vaccination of adults. It is difficult, however, to extrapolate the degree to which adult vaccination will impact HPV-related disease. This is because we do not fully understand the rates at which new HPV infection in the cervices of older women will progress to high-grade dysplasia or cancer. Further, the pathophysiology of HPV-related cancers at other anogenital sites and new oral-pharyngeal infection is poorly understood in comparison with our knowledge of the natural history of high-risk HPV infection in younger women. That said, because of the outstanding efficacy of HPV vaccination and the low-risk profile, even if the actual impact on prevention of cancer or morbidity from dysplasia is relatively low, adult vaccination benefits outweigh the limited risks.

It may be that increased vaccination and awareness of vaccination for adults may enhance the adherence and acceptance of widespread vaccination of boys and girls. Adult vaccination could create a cultural shift toward HPV vaccination acceptance when adult parents and loved ones of vaccine-age boys and girls have been vaccinated themselves.

Current and future insurance coverage

The Affordable Care Act, otherwise known as Obamacare, mandates coverage for all immunizations recommended by the ACIP. HPV vaccination up to age 26 is fully covered, without copay or deductible. The ACIP did consider extension of the indications for HPV vaccination to men and women up to age 45 at their October 2018 meeting. They are tasked with considering not only safety and efficacy but also the cost effectiveness of implementing vaccination. They continue to study the costs and potential benefits of extending HPV vaccination to age 45. Their recommendations may be determined at the February 2019 meeting—or even later in 2019. The American College of Obstetricians and Gynecologists (ACOG) relies upon ACIP for practice guidance. Once the ACIP has made a determination, and if new guidelines are published in the Morbidity and Mortality Weekly Report, insurance coverage and ACOG guidance will be updated.

How should we react and change practice based on this new indication?

Given the information reviewed by the FDA, ObGyns will want to discuss the availability of Gardasil 9 with our patients between ages 27 and 45 who have not been previously immunized.

Especially for our patients with exposure to multiple or new sexual partners, immunization against oncogenic HPV viral types is effective in providing protection from cancer precursors and cancers of the cervix, vulva, vagina, and anus—and of course from genital warts. They should understand that, until formal recommendations are published by the ACIP, they are likely to be responsible for the cost of the vaccination series. These conversations will also remind our patients to immunize their teens against HPV. The more conversation we have regarding the benefits of vaccination against high-risk HPV types, the more likely we are to be able to achieve the impressive results seen in Australia.

The US Food and Drug Administration (FDA) recently extended the approval for Gardasil 9 (to prevent HPV-associated cancers, cancer precursors, and genital lesions) to men and women aged 27 to 45.¹ In this editorial, we discuss the evolution of the HPV vaccine since its initial approval more than 10 years ago, the benefits of primary prevention with the HPV vaccine, and the case for the FDA’s recent extension of coverage to older men and women.

The evolution of the HPV vaccine

Since recognition in the 1980s and 90s that high-risk strains of HPV, notably HPV types 16 and 18, were linked to cervical cancer, there have been exciting advances in detection and prevention of high-risk HPV infection. About 70% of cervical cancers are attributable to these 2 oncogenic types.² The first vaccine licensed, Gardasil (Merck), was approved in 2006 for girls and women aged 9 through 26 to prevent HPV-related diseases caused by types 6, 11, 16, and 18.³ The vaccine was effective for prevention of cervical cancer; genital warts; and grades 2 and 3 of cervical, vulvar, and vaginal intraepithelial neoplasia. In 2008, prevention of vulvar and vaginal cancers was added to the indication. By 2009, prevention of genital warts was added, and use in males aged 9 to 15 was approved. By 2010 sufficient data were accumulated to document prevention of anal cancer and anal intraepithelial neoplasia in men and women, and this indication was added.

In 2014 Gardasil 9 was approved to extend coverage to an additional 5 oncogenic HPV types (31, 33, 45, 52, and 58), now covering an additional 20% of cervical cancers, and in 2015 Gardasil 9 indications were expanded to include boys and men 9 to 26 years of age. Immunogenicity studies were performed to infer effectiveness of a 2-dose regimen in boys and girls aged 9 to 14 years, which was recommended by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) in late 2016.⁴

Until October 2018, Gardasil 9 was indicated for prevention of genital warts, cervical, vaginal, vulvar and anal cancers and cancer precursors for males and females aged 9 to 26 years. In October the FDA extended approval of the 3-dose vaccine regimen to men and women up to age 45.

HPV vaccine uptake

HPV vaccination has been underutilized in the United States. In 2017, a disappointing 49% of adolescents were up to date on vaccination, and 66% had received at least one dose.⁵ In rural areas the vaccination rates are 11 points lower than in urban regions.⁶ The CDC notes an increasing number of HPV-associated cancers—from 30,000 per year in 1999 to 43,000 per year in 2015—due mostly to increases in oral and anal carcinomas. Vaccination with Gardasil 9 could prevent 90% of those cases.⁷

Non-US successes. HPV vaccine uptake in Australia provides an excellent opportunity to study the impact of universally available, school-based vaccinations. In 2007 Australia implemented a program of free HPV vaccination distributed through schools. Boys and girls aged 12 and 13 were targeted that year, with catch-up vaccinations for those aged 13 to 18 in 2007-2009 in schools and for those aged 18 to 26 reached in the community.⁸ 

Continue to: Ali and colleagues studied the... 

Ali and colleagues studied the preprogram and postprogram incidence of genital warts.⁹ About 83% received at least 1 dose of vaccine, and 73% of the eligible population completed the 3-dose regimen. There was a significant reduction in warts in both men and women younger than age 21 from 2007 to 2011 (12.1% to 2.2% in men and 11.5% to 0.85% in women). In the 21 to 30 age group there were similar reductions. This study demonstrates that with universal access and public implementation, the rates of HPV-associated disease can be reduced dramatically.

Data informing expanded vaccination ages

Will vaccination of an older population, with presumably many of whom sexually active and at risk for prior exposure to multiple HPV types, have a reasonable impact on lowering HPV-associated cancers? Are HPV-detected lesions in 27- to 45-year-old women the result of reactivation of latent HPV infection, or are they related to new-onset exposure? The FDA reviewed data from 3 studies of HPV vaccination in women aged 27 to 45. The first enrolled women who were naïve to oncogenic HPV types and provided all 3 doses of quadrivalent vaccine were followed for 4 years, along with a comparison group of nonvaccinated women. The second study allowed the nonvaccinated group to receive vaccine in year 4. Both groups were followed up to 10 years with the relevant outcome defined as cumulative incidence of HPV 6/11/16/18-related CIN and condyloma. The third study looked at the same outcomes in a set of all women—whether HPV high-risk naïve or not—after receiving vaccine and followed more than 10 years.⁷ This last study is most relevant to ObGyns, as it is closest to how we would consider vaccinating our patients.

The study findings are reassuring: A large proportion of HPV infections in women between 27 and 45 are the result of new exposure/infection. A study of 420 online daters aged 25 to 65 showed an annual incidence of high-risk HPV types in vaginal swabs of 25.4%, of which 64% were likely new acquisitions.¹⁰ The 2013-2014 National Health and Nutrition Examination Survey of 1,757 men aged 18 to 59 estimated approximately 45% had genital HPV infection. There was a bimodal distribution of disease with peaks at 28 to 32 and a larger second peak at 58 to 59 years of age.¹¹ Bottom line: Men and women older than age 26 who are sexually active likely acquire new HPV infections with oncogenic types. Exposure to high-risk HPV types prior to vaccination—as we would expect in the real-world setting—did not eliminate the substantial benefit of immunization.

Based on these study results, and extrapolation to the 9-valent vaccine, the FDA extended the approval of Gardasil 9 to men and women from age 9 to 45. The indications and usage will remain the same: for prevention of cervical, vulvar, vaginal, and anal cancer and genital warts as well as precancerous or dysplastic lesions of the cervix, vulva, vagina, and anus related to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

Continue to: Impact of the new... 

Impact of the new indication on HPV-related disease

As described above, widespread vaccination of young girls and boys is going to have major impact on HPV-related disease, including precancer and cancer. Because there is evidence that older women and men are at risk for new HPV infection,¹⁰ there likely will be some benefit from vaccination of adults. It is difficult, however, to extrapolate the degree to which adult vaccination will impact HPV-related disease. This is because we do not fully understand the rates at which new HPV infection in the cervices of older women will progress to high-grade dysplasia or cancer. Further, the pathophysiology of HPV-related cancers at other anogenital sites and new oral-pharyngeal infection is poorly understood in comparison with our knowledge of the natural history of high-risk HPV infection in younger women. That said, because of the outstanding efficacy of HPV vaccination and the low-risk profile, even if the actual impact on prevention of cancer or morbidity from dysplasia is relatively low, adult vaccination benefits outweigh the limited risks.

It may be that increased vaccination and awareness of vaccination for adults may enhance the adherence and acceptance of widespread vaccination of boys and girls. Adult vaccination could create a cultural shift toward HPV vaccination acceptance when adult parents and loved ones of vaccine-age boys and girls have been vaccinated themselves.

Current and future insurance coverage

The Affordable Care Act, otherwise known as Obamacare, mandates coverage for all immunizations recommended by the ACIP. HPV vaccination up to age 26 is fully covered, without copay or deductible. The ACIP did consider extension of the indications for HPV vaccination to men and women up to age 45 at their October 2018 meeting. They are tasked with considering not only safety and efficacy but also the cost effectiveness of implementing vaccination. They continue to study the costs and potential benefits of extending HPV vaccination to age 45. Their recommendations may be determined at the February 2019 meeting—or even later in 2019. The American College of Obstetricians and Gynecologists (ACOG) relies upon ACIP for practice guidance. Once the ACIP has made a determination, and if new guidelines are published in the Morbidity and Mortality Weekly Report, insurance coverage and ACOG guidance will be updated.

How should we react and change practice based on this new indication?

Given the information reviewed by the FDA, ObGyns will want to discuss the availability of Gardasil 9 with our patients between ages 27 and 45 who have not been previously immunized.

Especially for our patients with exposure to multiple or new sexual partners, immunization against oncogenic HPV viral types is effective in providing protection from cancer precursors and cancers of the cervix, vulva, vagina, and anus—and of course from genital warts. They should understand that, until formal recommendations are published by the ACIP, they are likely to be responsible for the cost of the vaccination series. These conversations will also remind our patients to immunize their teens against HPV. The more conversation we have regarding the benefits of vaccination against high-risk HPV types, the more likely we are to be able to achieve the impressive results seen in Australia.

The US Food and Drug Administration (FDA) recently extended the approval for Gardasil 9 (to prevent HPV-associated cancers, cancer precursors, and genital lesions) to men and women aged 27 to 45.¹ In this editorial, we discuss the evolution of the HPV vaccine since its initial approval more than 10 years ago, the benefits of primary prevention with the HPV vaccine, and the case for the FDA’s recent extension of coverage to older men and women.

The evolution of the HPV vaccine

Since recognition in the 1980s and 90s that high-risk strains of HPV, notably HPV types 16 and 18, were linked to cervical cancer, there have been exciting advances in detection and prevention of high-risk HPV infection. About 70% of cervical cancers are attributable to these 2 oncogenic types.² The first vaccine licensed, Gardasil (Merck), was approved in 2006 for girls and women aged 9 through 26 to prevent HPV-related diseases caused by types 6, 11, 16, and 18.³ The vaccine was effective for prevention of cervical cancer; genital warts; and grades 2 and 3 of cervical, vulvar, and vaginal intraepithelial neoplasia. In 2008, prevention of vulvar and vaginal cancers was added to the indication. By 2009, prevention of genital warts was added, and use in males aged 9 to 15 was approved. By 2010 sufficient data were accumulated to document prevention of anal cancer and anal intraepithelial neoplasia in men and women, and this indication was added.

In 2014 Gardasil 9 was approved to extend coverage to an additional 5 oncogenic HPV types (31, 33, 45, 52, and 58), now covering an additional 20% of cervical cancers, and in 2015 Gardasil 9 indications were expanded to include boys and men 9 to 26 years of age. Immunogenicity studies were performed to infer effectiveness of a 2-dose regimen in boys and girls aged 9 to 14 years, which was recommended by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) in late 2016.⁴

Until October 2018, Gardasil 9 was indicated for prevention of genital warts, cervical, vaginal, vulvar and anal cancers and cancer precursors for males and females aged 9 to 26 years. In October the FDA extended approval of the 3-dose vaccine regimen to men and women up to age 45.

HPV vaccine uptake

HPV vaccination has been underutilized in the United States. In 2017, a disappointing 49% of adolescents were up to date on vaccination, and 66% had received at least one dose.⁵ In rural areas the vaccination rates are 11 points lower than in urban regions.⁶ The CDC notes an increasing number of HPV-associated cancers—from 30,000 per year in 1999 to 43,000 per year in 2015—due mostly to increases in oral and anal carcinomas. Vaccination with Gardasil 9 could prevent 90% of those cases.⁷

Non-US successes. HPV vaccine uptake in Australia provides an excellent opportunity to study the impact of universally available, school-based vaccinations. In 2007 Australia implemented a program of free HPV vaccination distributed through schools. Boys and girls aged 12 and 13 were targeted that year, with catch-up vaccinations for those aged 13 to 18 in 2007-2009 in schools and for those aged 18 to 26 reached in the community.⁸ 

Continue to: Ali and colleagues studied the... 

Ali and colleagues studied the preprogram and postprogram incidence of genital warts.⁹ About 83% received at least 1 dose of vaccine, and 73% of the eligible population completed the 3-dose regimen. There was a significant reduction in warts in both men and women younger than age 21 from 2007 to 2011 (12.1% to 2.2% in men and 11.5% to 0.85% in women). In the 21 to 30 age group there were similar reductions. This study demonstrates that with universal access and public implementation, the rates of HPV-associated disease can be reduced dramatically.

Data informing expanded vaccination ages

Will vaccination of an older population, with presumably many of whom sexually active and at risk for prior exposure to multiple HPV types, have a reasonable impact on lowering HPV-associated cancers? Are HPV-detected lesions in 27- to 45-year-old women the result of reactivation of latent HPV infection, or are they related to new-onset exposure? The FDA reviewed data from 3 studies of HPV vaccination in women aged 27 to 45. The first enrolled women who were naïve to oncogenic HPV types and provided all 3 doses of quadrivalent vaccine were followed for 4 years, along with a comparison group of nonvaccinated women. The second study allowed the nonvaccinated group to receive vaccine in year 4. Both groups were followed up to 10 years with the relevant outcome defined as cumulative incidence of HPV 6/11/16/18-related CIN and condyloma. The third study looked at the same outcomes in a set of all women—whether HPV high-risk naïve or not—after receiving vaccine and followed more than 10 years.⁷ This last study is most relevant to ObGyns, as it is closest to how we would consider vaccinating our patients.

The study findings are reassuring: A large proportion of HPV infections in women between 27 and 45 are the result of new exposure/infection. A study of 420 online daters aged 25 to 65 showed an annual incidence of high-risk HPV types in vaginal swabs of 25.4%, of which 64% were likely new acquisitions.¹⁰ The 2013-2014 National Health and Nutrition Examination Survey of 1,757 men aged 18 to 59 estimated approximately 45% had genital HPV infection. There was a bimodal distribution of disease with peaks at 28 to 32 and a larger second peak at 58 to 59 years of age.¹¹ Bottom line: Men and women older than age 26 who are sexually active likely acquire new HPV infections with oncogenic types. Exposure to high-risk HPV types prior to vaccination—as we would expect in the real-world setting—did not eliminate the substantial benefit of immunization.

Based on these study results, and extrapolation to the 9-valent vaccine, the FDA extended the approval of Gardasil 9 to men and women from age 9 to 45. The indications and usage will remain the same: for prevention of cervical, vulvar, vaginal, and anal cancer and genital warts as well as precancerous or dysplastic lesions of the cervix, vulva, vagina, and anus related to HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58.

Continue to: Impact of the new... 

Impact of the new indication on HPV-related disease

As described above, widespread vaccination of young girls and boys is going to have major impact on HPV-related disease, including precancer and cancer. Because there is evidence that older women and men are at risk for new HPV infection,¹⁰ there likely will be some benefit from vaccination of adults. It is difficult, however, to extrapolate the degree to which adult vaccination will impact HPV-related disease. This is because we do not fully understand the rates at which new HPV infection in the cervices of older women will progress to high-grade dysplasia or cancer. Further, the pathophysiology of HPV-related cancers at other anogenital sites and new oral-pharyngeal infection is poorly understood in comparison with our knowledge of the natural history of high-risk HPV infection in younger women. That said, because of the outstanding efficacy of HPV vaccination and the low-risk profile, even if the actual impact on prevention of cancer or morbidity from dysplasia is relatively low, adult vaccination benefits outweigh the limited risks.

It may be that increased vaccination and awareness of vaccination for adults may enhance the adherence and acceptance of widespread vaccination of boys and girls. Adult vaccination could create a cultural shift toward HPV vaccination acceptance when adult parents and loved ones of vaccine-age boys and girls have been vaccinated themselves.

Current and future insurance coverage

The Affordable Care Act, otherwise known as Obamacare, mandates coverage for all immunizations recommended by the ACIP. HPV vaccination up to age 26 is fully covered, without copay or deductible. The ACIP did consider extension of the indications for HPV vaccination to men and women up to age 45 at their October 2018 meeting. They are tasked with considering not only safety and efficacy but also the cost effectiveness of implementing vaccination. They continue to study the costs and potential benefits of extending HPV vaccination to age 45. Their recommendations may be determined at the February 2019 meeting—or even later in 2019. The American College of Obstetricians and Gynecologists (ACOG) relies upon ACIP for practice guidance. Once the ACIP has made a determination, and if new guidelines are published in the Morbidity and Mortality Weekly Report, insurance coverage and ACOG guidance will be updated.

How should we react and change practice based on this new indication?

Given the information reviewed by the FDA, ObGyns will want to discuss the availability of Gardasil 9 with our patients between ages 27 and 45 who have not been previously immunized.

Especially for our patients with exposure to multiple or new sexual partners, immunization against oncogenic HPV viral types is effective in providing protection from cancer precursors and cancers of the cervix, vulva, vagina, and anus—and of course from genital warts. They should understand that, until formal recommendations are published by the ACIP, they are likely to be responsible for the cost of the vaccination series. These conversations will also remind our patients to immunize their teens against HPV. The more conversation we have regarding the benefits of vaccination against high-risk HPV types, the more likely we are to be able to achieve the impressive results seen in Australia.

Individuals going to rabies-endemic countries should have a pretrip consultation with a travel health specialist, say authors of a case report describing the death of a woman who sustained a bite from a rabid puppy during a 2017 yoga retreat in rural India.

copyright/Dr. Daniel P. Perl/CDC

Preexposure prophylaxis is warranted, especially for individuals expected to be in those countries for long durations, those planning to go to remote areas, or if they plan activities that may put them at risk for rabies exposure, the authors wrote in Morbidity and Mortality Weekly Report.

“In the case of the yoga retreat tour, given the extended length of the tour and the rural and community activities involved, pretravel rabies vaccination should have been considered,” said Julia Murphy, DVM, a veterinarian with the Virginia Department of Health, and her coauthors in the recently published report.

The case also underscores the importance of prompt rabies diagnosis, according to Dr. Murphy and her colleagues: 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis and were treated at a cost of nearly a quarter million dollars.

The Virginia woman described in the case report was aged 65 years and had no preexisting health conditions. She had spent more than 2 months on a yoga retreat tour in India and was bitten by a puppy near her hotel in Rishikesh in northern India, according to results of a public health investigation.

That retreat ended on April 7, 2017, according to the report, and on May 3, 2017, the woman started to have pain and paresthesia in her right arm during gardening.

On May 6, she sought care at an urgent care facility, resulting in a diagnosis of carpal tunnel syndrome and a prescription for an NSAID.

The next day, she was evaluated at a hospital for anxiety, insomnia, shortness of breath, and difficulty swallowing water and was given lorazepam for a presumed panic attack. She was discharged and, in her car, experienced claustrophobia and shortness of breath. She returned to the hospital’s ED, received more lorazepam, and was again discharged.

The day after that, she was transported by ambulance to another hospital with increased anxiety, shortness of breath, chest discomfort, and progressive paresthesia; she was found to have elevated cardiac enzymes and underwent emergency cardiac catheterization, which revealed normal arteries.

That evening, the patient became “progressively agitated and combative,” according to the report, and was found to be gasping for air while trying to drink water. When family were questioned about animal exposures, the woman’s husband indicated that she had been bitten on the right hand by a puppy during the yoga retreat, about 6 weeks before the symptoms started.

Once a diagnosis of rabies was confirmed, the woman was started on aggressive treatment but eventually died, according to Dr. Murphy and her coauthors, which made this patient the ninth person in the United States to die from rabies exposure while overseas since 2008. Canine rabies has been eliminated in the United States because of the strict vaccination laws.

“These events underscore the importance of obtaining a thorough pretravel health consultation, particularly when visiting countries with high incidence of emerging or zoonotic pathogens, to ensure awareness of health risks and appropriate pretravel and postexposure health care actions,” they concluded in their report.

Dr. Murphy and her coauthors reported no potential conflicts of interest related to the case report.

SOURCE: Murphy J et al. MMWR Morb Mortal Wkly Rep. 2019 Jan 4;67(5152):1410-4.

Individuals going to rabies-endemic countries should have a pretrip consultation with a travel health specialist, say authors of a case report describing the death of a woman who sustained a bite from a rabid puppy during a 2017 yoga retreat in rural India.

copyright/Dr. Daniel P. Perl/CDC

Preexposure prophylaxis is warranted, especially for individuals expected to be in those countries for long durations, those planning to go to remote areas, or if they plan activities that may put them at risk for rabies exposure, the authors wrote in Morbidity and Mortality Weekly Report.

“In the case of the yoga retreat tour, given the extended length of the tour and the rural and community activities involved, pretravel rabies vaccination should have been considered,” said Julia Murphy, DVM, a veterinarian with the Virginia Department of Health, and her coauthors in the recently published report.

The case also underscores the importance of prompt rabies diagnosis, according to Dr. Murphy and her colleagues: 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis and were treated at a cost of nearly a quarter million dollars.

The Virginia woman described in the case report was aged 65 years and had no preexisting health conditions. She had spent more than 2 months on a yoga retreat tour in India and was bitten by a puppy near her hotel in Rishikesh in northern India, according to results of a public health investigation.

That retreat ended on April 7, 2017, according to the report, and on May 3, 2017, the woman started to have pain and paresthesia in her right arm during gardening.

On May 6, she sought care at an urgent care facility, resulting in a diagnosis of carpal tunnel syndrome and a prescription for an NSAID.

The next day, she was evaluated at a hospital for anxiety, insomnia, shortness of breath, and difficulty swallowing water and was given lorazepam for a presumed panic attack. She was discharged and, in her car, experienced claustrophobia and shortness of breath. She returned to the hospital’s ED, received more lorazepam, and was again discharged.

The day after that, she was transported by ambulance to another hospital with increased anxiety, shortness of breath, chest discomfort, and progressive paresthesia; she was found to have elevated cardiac enzymes and underwent emergency cardiac catheterization, which revealed normal arteries.

That evening, the patient became “progressively agitated and combative,” according to the report, and was found to be gasping for air while trying to drink water. When family were questioned about animal exposures, the woman’s husband indicated that she had been bitten on the right hand by a puppy during the yoga retreat, about 6 weeks before the symptoms started.

Once a diagnosis of rabies was confirmed, the woman was started on aggressive treatment but eventually died, according to Dr. Murphy and her coauthors, which made this patient the ninth person in the United States to die from rabies exposure while overseas since 2008. Canine rabies has been eliminated in the United States because of the strict vaccination laws.

“These events underscore the importance of obtaining a thorough pretravel health consultation, particularly when visiting countries with high incidence of emerging or zoonotic pathogens, to ensure awareness of health risks and appropriate pretravel and postexposure health care actions,” they concluded in their report.

Dr. Murphy and her coauthors reported no potential conflicts of interest related to the case report.

SOURCE: Murphy J et al. MMWR Morb Mortal Wkly Rep. 2019 Jan 4;67(5152):1410-4.

Individuals going to rabies-endemic countries should have a pretrip consultation with a travel health specialist, say authors of a case report describing the death of a woman who sustained a bite from a rabid puppy during a 2017 yoga retreat in rural India.

copyright/Dr. Daniel P. Perl/CDC

Preexposure prophylaxis is warranted, especially for individuals expected to be in those countries for long durations, those planning to go to remote areas, or if they plan activities that may put them at risk for rabies exposure, the authors wrote in Morbidity and Mortality Weekly Report.

“In the case of the yoga retreat tour, given the extended length of the tour and the rural and community activities involved, pretravel rabies vaccination should have been considered,” said Julia Murphy, DVM, a veterinarian with the Virginia Department of Health, and her coauthors in the recently published report.

The case also underscores the importance of prompt rabies diagnosis, according to Dr. Murphy and her colleagues: 250 health care workers were assessed for exposure to the patient, 72 (29%) of whom were advised to initiate postexposure prophylaxis and were treated at a cost of nearly a quarter million dollars.

The Virginia woman described in the case report was aged 65 years and had no preexisting health conditions. She had spent more than 2 months on a yoga retreat tour in India and was bitten by a puppy near her hotel in Rishikesh in northern India, according to results of a public health investigation.

That retreat ended on April 7, 2017, according to the report, and on May 3, 2017, the woman started to have pain and paresthesia in her right arm during gardening.

On May 6, she sought care at an urgent care facility, resulting in a diagnosis of carpal tunnel syndrome and a prescription for an NSAID.

The next day, she was evaluated at a hospital for anxiety, insomnia, shortness of breath, and difficulty swallowing water and was given lorazepam for a presumed panic attack. She was discharged and, in her car, experienced claustrophobia and shortness of breath. She returned to the hospital’s ED, received more lorazepam, and was again discharged.

The day after that, she was transported by ambulance to another hospital with increased anxiety, shortness of breath, chest discomfort, and progressive paresthesia; she was found to have elevated cardiac enzymes and underwent emergency cardiac catheterization, which revealed normal arteries.

That evening, the patient became “progressively agitated and combative,” according to the report, and was found to be gasping for air while trying to drink water. When family were questioned about animal exposures, the woman’s husband indicated that she had been bitten on the right hand by a puppy during the yoga retreat, about 6 weeks before the symptoms started.

Once a diagnosis of rabies was confirmed, the woman was started on aggressive treatment but eventually died, according to Dr. Murphy and her coauthors, which made this patient the ninth person in the United States to die from rabies exposure while overseas since 2008. Canine rabies has been eliminated in the United States because of the strict vaccination laws.

“These events underscore the importance of obtaining a thorough pretravel health consultation, particularly when visiting countries with high incidence of emerging or zoonotic pathogens, to ensure awareness of health risks and appropriate pretravel and postexposure health care actions,” they concluded in their report.

Dr. Murphy and her coauthors reported no potential conflicts of interest related to the case report.

SOURCE: Murphy J et al. MMWR Morb Mortal Wkly Rep. 2019 Jan 4;67(5152):1410-4.

PARIS – Women with active atopic dermatitis during pregnancy and their physicians can find reassurance in the Danish national experience over an 18-year period, which showed no increased risk of pregnancy and birth problems other than modestly increased risks of premature rupture of membranes and neonatal staphylococcal septicemia, according to Jacob P. Thyssen, MD, PhD.

Bruce Jancin/MDedge News

At a session of the European Task Force of Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology, he presented a case control study of 10,668 births to Danish women with atopic dermatitis (AD) during 1997-2014. They were matched 1:10 by age, parity, and birth year to mothers without AD.

The risk of premature rupture of membranes was 15% higher in mothers with AD. And while the increased relative risk of neonatal staphylococcal septicemia was more substantial – a 145% increase – this was in fact a rare complication, observed Dr. Thyssen, a dermatologist at the University of Copenhagen.

There was no significant difference between women with or without AD in rates of preeclampsia, prematurity, pregnancy-induced hypertension, placenta previa, placental abruption, neonatal nonstaphylococcal septicemia, or other complications. The two groups had a similar number of visits to physicians and midwives during pregnancy.

Moreover, although the body mass index was similar in women with or without AD, the risk of gestational diabetes in women with the disease was significantly reduced by 21%; their risk of having a large-for-gestational-age baby with a birth weight of 4,500 g or more was also significantly lower than in controls.

Women received less treatment for AD during their pregnancy than they did beforehand. While pregnant, their disease was managed predominantly with topical corticosteroids and UV therapy. There was very little use of superpotent topical steroids, topical calcineurin inhibitors, or immunosuppressants, although 10% of pregnant women received systemic corticosteroids for their AD.

Dr. Thyssen reported serving as a scientific adviser and paid speaker for Leo Pharma, Roche, Eli Lilly, and Sanofi-Genzyme, although this study was conducted without commercial support.

[email protected]

PARIS – Women with active atopic dermatitis during pregnancy and their physicians can find reassurance in the Danish national experience over an 18-year period, which showed no increased risk of pregnancy and birth problems other than modestly increased risks of premature rupture of membranes and neonatal staphylococcal septicemia, according to Jacob P. Thyssen, MD, PhD.

Bruce Jancin/MDedge News

At a session of the European Task Force of Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology, he presented a case control study of 10,668 births to Danish women with atopic dermatitis (AD) during 1997-2014. They were matched 1:10 by age, parity, and birth year to mothers without AD.

The risk of premature rupture of membranes was 15% higher in mothers with AD. And while the increased relative risk of neonatal staphylococcal septicemia was more substantial – a 145% increase – this was in fact a rare complication, observed Dr. Thyssen, a dermatologist at the University of Copenhagen.

There was no significant difference between women with or without AD in rates of preeclampsia, prematurity, pregnancy-induced hypertension, placenta previa, placental abruption, neonatal nonstaphylococcal septicemia, or other complications. The two groups had a similar number of visits to physicians and midwives during pregnancy.

Moreover, although the body mass index was similar in women with or without AD, the risk of gestational diabetes in women with the disease was significantly reduced by 21%; their risk of having a large-for-gestational-age baby with a birth weight of 4,500 g or more was also significantly lower than in controls.

Women received less treatment for AD during their pregnancy than they did beforehand. While pregnant, their disease was managed predominantly with topical corticosteroids and UV therapy. There was very little use of superpotent topical steroids, topical calcineurin inhibitors, or immunosuppressants, although 10% of pregnant women received systemic corticosteroids for their AD.

Dr. Thyssen reported serving as a scientific adviser and paid speaker for Leo Pharma, Roche, Eli Lilly, and Sanofi-Genzyme, although this study was conducted without commercial support.

[email protected]

PARIS – Women with active atopic dermatitis during pregnancy and their physicians can find reassurance in the Danish national experience over an 18-year period, which showed no increased risk of pregnancy and birth problems other than modestly increased risks of premature rupture of membranes and neonatal staphylococcal septicemia, according to Jacob P. Thyssen, MD, PhD.

Bruce Jancin/MDedge News

At a session of the European Task Force of Atopic Dermatitis held in conjunction with the annual congress of the European Academy of Dermatology and Venereology, he presented a case control study of 10,668 births to Danish women with atopic dermatitis (AD) during 1997-2014. They were matched 1:10 by age, parity, and birth year to mothers without AD.

The risk of premature rupture of membranes was 15% higher in mothers with AD. And while the increased relative risk of neonatal staphylococcal septicemia was more substantial – a 145% increase – this was in fact a rare complication, observed Dr. Thyssen, a dermatologist at the University of Copenhagen.

There was no significant difference between women with or without AD in rates of preeclampsia, prematurity, pregnancy-induced hypertension, placenta previa, placental abruption, neonatal nonstaphylococcal septicemia, or other complications. The two groups had a similar number of visits to physicians and midwives during pregnancy.

Moreover, although the body mass index was similar in women with or without AD, the risk of gestational diabetes in women with the disease was significantly reduced by 21%; their risk of having a large-for-gestational-age baby with a birth weight of 4,500 g or more was also significantly lower than in controls.

Women received less treatment for AD during their pregnancy than they did beforehand. While pregnant, their disease was managed predominantly with topical corticosteroids and UV therapy. There was very little use of superpotent topical steroids, topical calcineurin inhibitors, or immunosuppressants, although 10% of pregnant women received systemic corticosteroids for their AD.

Dr. Thyssen reported serving as a scientific adviser and paid speaker for Leo Pharma, Roche, Eli Lilly, and Sanofi-Genzyme, although this study was conducted without commercial support.

[email protected]

PARIS – Difelikefalin, an investigational peripheral kappa opioid receptor agonist, significantly reduced moderate to severe chronic itching while achieving across-the-board clinically meaningful improvements in quality of life measures in patients with hemodialysis-associated pruritus in a phase 2 study, Frédérique Menzaghi, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

At present there is no approved medication in the United States or Europe for the often intense itching associated with chronic kidney disease. Off-label treatments have limited efficacy.

Dr. Menzaghi is senior vice president for research and development at Cara Therapeutics, which is developing difelikefalin.

More than half – 60% to 70% – of patients on hemodialysis for end-stage renal disease experience chronic pruritus, as do a smaller proportion of individuals with chronic kidney disease (CKD) not requiring dialysis. CKD-associated pruritus is a day-and-night itch that makes life miserable for affected patients. Not only must they endure the predictable complications of skin excoriation, including impetigo, ulcerations, papules, and prurigo nodularis, but they also experience sleep disruption, depressed mood, and a 10%-20% increased mortality risk compared with CKD patients without pruritus.

Difelikefalin is a potent and selective peripheral kappa opioid receptor agonist that doesn’t activate mu or delta opioid receptors. It’s a synthetic drug that mimics endogenous dynorphin. Its key attribute is that it doesn’t cross the blood/brain barrier, so it doesn’t pose a risk for adverse events caused by activation of central opioid receptors. Difelikefalin has two mechanisms of action in CKD-associated pruritus: an antipruritic effect due to inhibition of ion channels responsible for afferent peripheral nerve activity; and an anti-inflammatory effect mediated by activation of kappa opioid receptors expressed by immune system cells, according to Dr. Menzaghi.

She reported on 174 hemodialysis patients with moderate to severe CKD-associated pruritus who were randomized to a double-blind, phase 2, dose-ranging study featuring an intravenous bolus of difelikefalin at 0.5, 1.0, or 1.5 mcg/kg or placebo given immediately after each of the thrice-weekly hemodialysis sessions for 8 weeks.

An oral formulation of difelikefalin is also under investigation for treatment of CKD-associated pruritus. The IV version is being developed for hemodialysis patients because difelikefalin is renally excreted.

“We’re taking advantage of the fact that their kidneys aren’t working. The drug stays in the system until the next dialysis because it can’t be eliminated. It’s quite convenient for these patients,” she explained.

The primary endpoint in the phase 2 study was change from baseline through week 8 in the weekly average of a patient’s daily self-rated 0-10 worst itching intensity numeric rating scale (NRS) scores. All participants had to have a baseline NRS score of at least 4, considered the lower threshold for moderate itch. In fact, the mean baseline score was 6.7-7.1 in the four study arms.
 

The results

Sixty-four percent of patients on difelikefalin 0.5 mcg/kg – the most effective dose – experienced at least a 3-point reduction, compared with 29% of placebo-treated controls. And a 4-point or greater reduction in NRS from baseline was documented in 51% of patients on difelikefalin at 0.5 mcg/kg, compared with 24% of controls.

Although a 4-point difference is widely considered to represent clinically meaningful improvement in atopic dermatitis studies, Dr. Menzaghi said psychometric analyses of the difelikefalin trial data indicated that a 3-point or greater improvement in NRS score was associated with clinically meaningful change.

“Our data suggest that a 4-point change may not be generalizable to all conditions,” she said.

Hemodialysis patients with severe baseline itch typically improved to moderate itch on difelikefalin, while those with baseline moderate itch – that is, an NRS of 4-6 – dropped down to mild or no itch while on the drug.

“But that’s just a number. The question is, is that really clinically meaningful?” Dr. Menzaghi noted.

The answer, she continued, is yes. A high correlation was seen between reduction in itch intensity and improvement in quality of life. Scores on the 5-D Itch Scale and Skindex-10 improved two- to threefold more in the difelikefalin 0.5-mcg group than in controls. So did scores on the 12-item Medical Outcomes Study Sleep Scale assessing sleep restlessness, awakening during sleep, and trouble falling asleep.

“We think these results suggest that peripheral kappa opioid receptors play an integral role in the modulation of itch signals and represent a primary target for the development of antipruritic agents,” said Dr. Menzaghi.

Indeed, a phase 3 randomized trial of difelikefalin 0.5 mcg/kg versus placebo in 350 hemodialysis patients with CKD-associated itch is ongoing in the United States, Europe, Australia, and Korea. Also ongoing is a phase 2 U.S. study of oral difelikefalin in patients with CKD-associated pruritus, many of whom are not on hemodialysis. In January, the company announced that enrollment in a phase 3 U.S. study of difelikefalin injection (0.5 mcg/kg) in hemodialysis patients with moderate to severe CKD-associated pruritus had been completed. The trials are funded by Cara Therapeutics.

[email protected]

SOURCE: Menzaghi F. EADV Congress, Abstract FC0.4.7.

PARIS – Difelikefalin, an investigational peripheral kappa opioid receptor agonist, significantly reduced moderate to severe chronic itching while achieving across-the-board clinically meaningful improvements in quality of life measures in patients with hemodialysis-associated pruritus in a phase 2 study, Frédérique Menzaghi, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

At present there is no approved medication in the United States or Europe for the often intense itching associated with chronic kidney disease. Off-label treatments have limited efficacy.

Dr. Menzaghi is senior vice president for research and development at Cara Therapeutics, which is developing difelikefalin.

More than half – 60% to 70% – of patients on hemodialysis for end-stage renal disease experience chronic pruritus, as do a smaller proportion of individuals with chronic kidney disease (CKD) not requiring dialysis. CKD-associated pruritus is a day-and-night itch that makes life miserable for affected patients. Not only must they endure the predictable complications of skin excoriation, including impetigo, ulcerations, papules, and prurigo nodularis, but they also experience sleep disruption, depressed mood, and a 10%-20% increased mortality risk compared with CKD patients without pruritus.

Difelikefalin is a potent and selective peripheral kappa opioid receptor agonist that doesn’t activate mu or delta opioid receptors. It’s a synthetic drug that mimics endogenous dynorphin. Its key attribute is that it doesn’t cross the blood/brain barrier, so it doesn’t pose a risk for adverse events caused by activation of central opioid receptors. Difelikefalin has two mechanisms of action in CKD-associated pruritus: an antipruritic effect due to inhibition of ion channels responsible for afferent peripheral nerve activity; and an anti-inflammatory effect mediated by activation of kappa opioid receptors expressed by immune system cells, according to Dr. Menzaghi.

She reported on 174 hemodialysis patients with moderate to severe CKD-associated pruritus who were randomized to a double-blind, phase 2, dose-ranging study featuring an intravenous bolus of difelikefalin at 0.5, 1.0, or 1.5 mcg/kg or placebo given immediately after each of the thrice-weekly hemodialysis sessions for 8 weeks.

An oral formulation of difelikefalin is also under investigation for treatment of CKD-associated pruritus. The IV version is being developed for hemodialysis patients because difelikefalin is renally excreted.

“We’re taking advantage of the fact that their kidneys aren’t working. The drug stays in the system until the next dialysis because it can’t be eliminated. It’s quite convenient for these patients,” she explained.

The primary endpoint in the phase 2 study was change from baseline through week 8 in the weekly average of a patient’s daily self-rated 0-10 worst itching intensity numeric rating scale (NRS) scores. All participants had to have a baseline NRS score of at least 4, considered the lower threshold for moderate itch. In fact, the mean baseline score was 6.7-7.1 in the four study arms.
 

The results

Sixty-four percent of patients on difelikefalin 0.5 mcg/kg – the most effective dose – experienced at least a 3-point reduction, compared with 29% of placebo-treated controls. And a 4-point or greater reduction in NRS from baseline was documented in 51% of patients on difelikefalin at 0.5 mcg/kg, compared with 24% of controls.

Although a 4-point difference is widely considered to represent clinically meaningful improvement in atopic dermatitis studies, Dr. Menzaghi said psychometric analyses of the difelikefalin trial data indicated that a 3-point or greater improvement in NRS score was associated with clinically meaningful change.

“Our data suggest that a 4-point change may not be generalizable to all conditions,” she said.

Hemodialysis patients with severe baseline itch typically improved to moderate itch on difelikefalin, while those with baseline moderate itch – that is, an NRS of 4-6 – dropped down to mild or no itch while on the drug.

“But that’s just a number. The question is, is that really clinically meaningful?” Dr. Menzaghi noted.

The answer, she continued, is yes. A high correlation was seen between reduction in itch intensity and improvement in quality of life. Scores on the 5-D Itch Scale and Skindex-10 improved two- to threefold more in the difelikefalin 0.5-mcg group than in controls. So did scores on the 12-item Medical Outcomes Study Sleep Scale assessing sleep restlessness, awakening during sleep, and trouble falling asleep.

“We think these results suggest that peripheral kappa opioid receptors play an integral role in the modulation of itch signals and represent a primary target for the development of antipruritic agents,” said Dr. Menzaghi.

Indeed, a phase 3 randomized trial of difelikefalin 0.5 mcg/kg versus placebo in 350 hemodialysis patients with CKD-associated itch is ongoing in the United States, Europe, Australia, and Korea. Also ongoing is a phase 2 U.S. study of oral difelikefalin in patients with CKD-associated pruritus, many of whom are not on hemodialysis. In January, the company announced that enrollment in a phase 3 U.S. study of difelikefalin injection (0.5 mcg/kg) in hemodialysis patients with moderate to severe CKD-associated pruritus had been completed. The trials are funded by Cara Therapeutics.

[email protected]

SOURCE: Menzaghi F. EADV Congress, Abstract FC0.4.7.

PARIS – Difelikefalin, an investigational peripheral kappa opioid receptor agonist, significantly reduced moderate to severe chronic itching while achieving across-the-board clinically meaningful improvements in quality of life measures in patients with hemodialysis-associated pruritus in a phase 2 study, Frédérique Menzaghi, PhD, reported at the annual congress of the European Academy of Dermatology and Venereology.

Bruce Jancin/MDedge News

At present there is no approved medication in the United States or Europe for the often intense itching associated with chronic kidney disease. Off-label treatments have limited efficacy.

Dr. Menzaghi is senior vice president for research and development at Cara Therapeutics, which is developing difelikefalin.

More than half – 60% to 70% – of patients on hemodialysis for end-stage renal disease experience chronic pruritus, as do a smaller proportion of individuals with chronic kidney disease (CKD) not requiring dialysis. CKD-associated pruritus is a day-and-night itch that makes life miserable for affected patients. Not only must they endure the predictable complications of skin excoriation, including impetigo, ulcerations, papules, and prurigo nodularis, but they also experience sleep disruption, depressed mood, and a 10%-20% increased mortality risk compared with CKD patients without pruritus.

Difelikefalin is a potent and selective peripheral kappa opioid receptor agonist that doesn’t activate mu or delta opioid receptors. It’s a synthetic drug that mimics endogenous dynorphin. Its key attribute is that it doesn’t cross the blood/brain barrier, so it doesn’t pose a risk for adverse events caused by activation of central opioid receptors. Difelikefalin has two mechanisms of action in CKD-associated pruritus: an antipruritic effect due to inhibition of ion channels responsible for afferent peripheral nerve activity; and an anti-inflammatory effect mediated by activation of kappa opioid receptors expressed by immune system cells, according to Dr. Menzaghi.

She reported on 174 hemodialysis patients with moderate to severe CKD-associated pruritus who were randomized to a double-blind, phase 2, dose-ranging study featuring an intravenous bolus of difelikefalin at 0.5, 1.0, or 1.5 mcg/kg or placebo given immediately after each of the thrice-weekly hemodialysis sessions for 8 weeks.

An oral formulation of difelikefalin is also under investigation for treatment of CKD-associated pruritus. The IV version is being developed for hemodialysis patients because difelikefalin is renally excreted.

“We’re taking advantage of the fact that their kidneys aren’t working. The drug stays in the system until the next dialysis because it can’t be eliminated. It’s quite convenient for these patients,” she explained.

The primary endpoint in the phase 2 study was change from baseline through week 8 in the weekly average of a patient’s daily self-rated 0-10 worst itching intensity numeric rating scale (NRS) scores. All participants had to have a baseline NRS score of at least 4, considered the lower threshold for moderate itch. In fact, the mean baseline score was 6.7-7.1 in the four study arms.
 

The results

Sixty-four percent of patients on difelikefalin 0.5 mcg/kg – the most effective dose – experienced at least a 3-point reduction, compared with 29% of placebo-treated controls. And a 4-point or greater reduction in NRS from baseline was documented in 51% of patients on difelikefalin at 0.5 mcg/kg, compared with 24% of controls.

Although a 4-point difference is widely considered to represent clinically meaningful improvement in atopic dermatitis studies, Dr. Menzaghi said psychometric analyses of the difelikefalin trial data indicated that a 3-point or greater improvement in NRS score was associated with clinically meaningful change.

“Our data suggest that a 4-point change may not be generalizable to all conditions,” she said.

Hemodialysis patients with severe baseline itch typically improved to moderate itch on difelikefalin, while those with baseline moderate itch – that is, an NRS of 4-6 – dropped down to mild or no itch while on the drug.

“But that’s just a number. The question is, is that really clinically meaningful?” Dr. Menzaghi noted.

The answer, she continued, is yes. A high correlation was seen between reduction in itch intensity and improvement in quality of life. Scores on the 5-D Itch Scale and Skindex-10 improved two- to threefold more in the difelikefalin 0.5-mcg group than in controls. So did scores on the 12-item Medical Outcomes Study Sleep Scale assessing sleep restlessness, awakening during sleep, and trouble falling asleep.

“We think these results suggest that peripheral kappa opioid receptors play an integral role in the modulation of itch signals and represent a primary target for the development of antipruritic agents,” said Dr. Menzaghi.

Indeed, a phase 3 randomized trial of difelikefalin 0.5 mcg/kg versus placebo in 350 hemodialysis patients with CKD-associated itch is ongoing in the United States, Europe, Australia, and Korea. Also ongoing is a phase 2 U.S. study of oral difelikefalin in patients with CKD-associated pruritus, many of whom are not on hemodialysis. In January, the company announced that enrollment in a phase 3 U.S. study of difelikefalin injection (0.5 mcg/kg) in hemodialysis patients with moderate to severe CKD-associated pruritus had been completed. The trials are funded by Cara Therapeutics.

[email protected]

SOURCE: Menzaghi F. EADV Congress, Abstract FC0.4.7.

Making art is not only life enriching—it can help reduce stress and anxiety, provide emotional release, relieve depression, and boost self-esteem. That is why art therapy has been a valuable part of VA mental health services since 1945. Plein air painting—painting outdoors “in the fresh air”—gives an added dimension to that. It can be both calming and energizing, offers challenges not found in a studio setting, teaches observation, and can lead to rewarding social interactions and connections. Not least, there is the benefit of being surrounded by nature.

The publishers and editor of Plein Air magazine wanted to introduce more veterans to the pleasures and benefits of outdoor painting, so they created the Plein Air Force Veterans Squad. Dennis Tyson, Commander of the Veterans Squad, says the goal is to “[s]how our gratitude to veterans by teaching them painting, allowing them to enjoy the benefits and stress reduction that come with painting outdoors.” The program seeks to enlist painters from around the nation to visit veterans’ groups, do demonstrations, and offer free lessons. The guiding principle, Tyson says, is that cost should not prevent any veteran from participating, so lessons and supplies are free or low-cost.

The program runs 2 websites. PleinAirForce.com gives existing plein air painters “missions” and tools to spread the word about plein air painting. That site provides scripts, posters, and guidance on promoting speaking engagements. A main purpose is to drive veterans and others interested in learning to the second website, PaintOutside.com, “so we can give them encouragement, free lessons, tips and tools to start painting.” PaintOutside.com also offers a directory of artists who teach, and a directory of “painting buddies.”

In addition to the websites, interested veterans can get more information at www.facebook.com/pleinairmagazine.

Making art is not only life enriching—it can help reduce stress and anxiety, provide emotional release, relieve depression, and boost self-esteem. That is why art therapy has been a valuable part of VA mental health services since 1945. Plein air painting—painting outdoors “in the fresh air”—gives an added dimension to that. It can be both calming and energizing, offers challenges not found in a studio setting, teaches observation, and can lead to rewarding social interactions and connections. Not least, there is the benefit of being surrounded by nature.

The publishers and editor of Plein Air magazine wanted to introduce more veterans to the pleasures and benefits of outdoor painting, so they created the Plein Air Force Veterans Squad. Dennis Tyson, Commander of the Veterans Squad, says the goal is to “[s]how our gratitude to veterans by teaching them painting, allowing them to enjoy the benefits and stress reduction that come with painting outdoors.” The program seeks to enlist painters from around the nation to visit veterans’ groups, do demonstrations, and offer free lessons. The guiding principle, Tyson says, is that cost should not prevent any veteran from participating, so lessons and supplies are free or low-cost.

The program runs 2 websites. PleinAirForce.com gives existing plein air painters “missions” and tools to spread the word about plein air painting. That site provides scripts, posters, and guidance on promoting speaking engagements. A main purpose is to drive veterans and others interested in learning to the second website, PaintOutside.com, “so we can give them encouragement, free lessons, tips and tools to start painting.” PaintOutside.com also offers a directory of artists who teach, and a directory of “painting buddies.”

In addition to the websites, interested veterans can get more information at www.facebook.com/pleinairmagazine.

Making art is not only life enriching—it can help reduce stress and anxiety, provide emotional release, relieve depression, and boost self-esteem. That is why art therapy has been a valuable part of VA mental health services since 1945. Plein air painting—painting outdoors “in the fresh air”—gives an added dimension to that. It can be both calming and energizing, offers challenges not found in a studio setting, teaches observation, and can lead to rewarding social interactions and connections. Not least, there is the benefit of being surrounded by nature.

The publishers and editor of Plein Air magazine wanted to introduce more veterans to the pleasures and benefits of outdoor painting, so they created the Plein Air Force Veterans Squad. Dennis Tyson, Commander of the Veterans Squad, says the goal is to “[s]how our gratitude to veterans by teaching them painting, allowing them to enjoy the benefits and stress reduction that come with painting outdoors.” The program seeks to enlist painters from around the nation to visit veterans’ groups, do demonstrations, and offer free lessons. The guiding principle, Tyson says, is that cost should not prevent any veteran from participating, so lessons and supplies are free or low-cost.

The program runs 2 websites. PleinAirForce.com gives existing plein air painters “missions” and tools to spread the word about plein air painting. That site provides scripts, posters, and guidance on promoting speaking engagements. A main purpose is to drive veterans and others interested in learning to the second website, PaintOutside.com, “so we can give them encouragement, free lessons, tips and tools to start painting.” PaintOutside.com also offers a directory of artists who teach, and a directory of “painting buddies.”

In addition to the websites, interested veterans can get more information at www.facebook.com/pleinairmagazine.

Among white women, obesity is positively associated with depressive symptoms across all income levels. However, among black women, no such associations are found – regardless of income. Meanwhile, among men, the link between obesity and depression appears strong for black men with high household incomes, a cross-sectional analysis of 12,220 adults suggests.

“This work underscores the importance of disentangling the association of race and [socioeconomic status] to gain a better understanding of how each operates to impact health outcomes,” wrote Caryn N. Bell, PhD, and her associates. The report is in Preventive Medicine.

The study comprised 3,755 black subjects, 55.5% of whom were women, and 8,465 white subjects, 51.8% of whom were women. They completed a detailed questionnaire as part of the 2007-2014 National Health and Nutrition Examination Survey and had a physical exam. Depressive symptoms were measured by the Patient Health Questionnaire-9 (PHQ-9), and obesity was defined as a body mass index of 30 kg/m² or higher. About 1% of both black and white subjects had severe depressive symptoms, meaning a PHQ-9 score ranging from 20 to 27 points.

A greater percentage of black participants were obese (47.3% vs. 34.4%), and black participants were less likely to live in a household earning $100,000 per year or more (10.9% vs. 28.3%). Black participants were a bit younger (mean age 44.8 years vs. 49.2 years), and less likely to be currently married, college graduates, insured, and physically active. A higher percentage reported fair to poor health (23.9% vs. 14.6%). The differences were statistically significant.

For white women, the association between obesity and depression held across all income levels. For black women, this association was not found at any income level. For black men, the link between obesity and depression was limited to those with a household income of $100,000 or more (odds ratio, 4.65; 95% confidence interval, 1.48-14.59). And for white men, the association was limited to those with a household income of $35,000-$74,999 (OR, 1.44; 95% CI, 1.02-2.03).

The effect of race on obesity and depression has been well studied – it’s known, for instance, that the association between obesity and depression is strongest among white women – but the role of income as a modifier has not been well addressed, wrote Dr. Bell, an assistant professor in the department of African American studies at the University of Maryland, College Park, and her associates.

“Though major life-time depression is less prevalent among African Americans, those who are obese should be screened for depression at similar rates as whites, particularly high-income African American men,” Dr. Bell and her associates wrote.

As for explanations, the authors suggested that strong, antiobesity stigma “may be present among white women at all income levels,” and may drive depression regardless of how much they make.

The prevalence of depressive symptoms at specific income levels among men suggests that something other than stigma is at work. Depression among obese, middle-income white men might be tied to “an unmeasured factor like subjective social status.” Meanwhile, obese black men with high household incomes “have less income and wealth than their white counterparts” because “of various forms of structural racism. ... This may be manifested with higher rates of depression through obesity-related factors like unhealthy coping behaviors and stress,” the investigators said.

Dr. Bell and her associates cited a few limitations. One is that the study looked only at those factors among black and white people. “Results could differ with other ethnic groups,” they wrote. In addition, income was self-reported, and three-way interactions – which are tough to interpret – were used. Nevertheless, they said, the study results have key public health implications.

The study had no financial disclosures, and the investigators reported having no conflicts of interest.

[email protected]

SOURCE: Bell CN et al. Prev Med. 2018 Dec 3. doi: 10.1016/j.ypmed.2018.11.024.

Among white women, obesity is positively associated with depressive symptoms across all income levels. However, among black women, no such associations are found – regardless of income. Meanwhile, among men, the link between obesity and depression appears strong for black men with high household incomes, a cross-sectional analysis of 12,220 adults suggests.

“This work underscores the importance of disentangling the association of race and [socioeconomic status] to gain a better understanding of how each operates to impact health outcomes,” wrote Caryn N. Bell, PhD, and her associates. The report is in Preventive Medicine.

The study comprised 3,755 black subjects, 55.5% of whom were women, and 8,465 white subjects, 51.8% of whom were women. They completed a detailed questionnaire as part of the 2007-2014 National Health and Nutrition Examination Survey and had a physical exam. Depressive symptoms were measured by the Patient Health Questionnaire-9 (PHQ-9), and obesity was defined as a body mass index of 30 kg/m² or higher. About 1% of both black and white subjects had severe depressive symptoms, meaning a PHQ-9 score ranging from 20 to 27 points.

A greater percentage of black participants were obese (47.3% vs. 34.4%), and black participants were less likely to live in a household earning $100,000 per year or more (10.9% vs. 28.3%). Black participants were a bit younger (mean age 44.8 years vs. 49.2 years), and less likely to be currently married, college graduates, insured, and physically active. A higher percentage reported fair to poor health (23.9% vs. 14.6%). The differences were statistically significant.

For white women, the association between obesity and depression held across all income levels. For black women, this association was not found at any income level. For black men, the link between obesity and depression was limited to those with a household income of $100,000 or more (odds ratio, 4.65; 95% confidence interval, 1.48-14.59). And for white men, the association was limited to those with a household income of $35,000-$74,999 (OR, 1.44; 95% CI, 1.02-2.03).

The effect of race on obesity and depression has been well studied – it’s known, for instance, that the association between obesity and depression is strongest among white women – but the role of income as a modifier has not been well addressed, wrote Dr. Bell, an assistant professor in the department of African American studies at the University of Maryland, College Park, and her associates.

“Though major life-time depression is less prevalent among African Americans, those who are obese should be screened for depression at similar rates as whites, particularly high-income African American men,” Dr. Bell and her associates wrote.

As for explanations, the authors suggested that strong, antiobesity stigma “may be present among white women at all income levels,” and may drive depression regardless of how much they make.

The prevalence of depressive symptoms at specific income levels among men suggests that something other than stigma is at work. Depression among obese, middle-income white men might be tied to “an unmeasured factor like subjective social status.” Meanwhile, obese black men with high household incomes “have less income and wealth than their white counterparts” because “of various forms of structural racism. ... This may be manifested with higher rates of depression through obesity-related factors like unhealthy coping behaviors and stress,” the investigators said.

Dr. Bell and her associates cited a few limitations. One is that the study looked only at those factors among black and white people. “Results could differ with other ethnic groups,” they wrote. In addition, income was self-reported, and three-way interactions – which are tough to interpret – were used. Nevertheless, they said, the study results have key public health implications.

The study had no financial disclosures, and the investigators reported having no conflicts of interest.

[email protected]

SOURCE: Bell CN et al. Prev Med. 2018 Dec 3. doi: 10.1016/j.ypmed.2018.11.024.

Among white women, obesity is positively associated with depressive symptoms across all income levels. However, among black women, no such associations are found – regardless of income. Meanwhile, among men, the link between obesity and depression appears strong for black men with high household incomes, a cross-sectional analysis of 12,220 adults suggests.

“This work underscores the importance of disentangling the association of race and [socioeconomic status] to gain a better understanding of how each operates to impact health outcomes,” wrote Caryn N. Bell, PhD, and her associates. The report is in Preventive Medicine.

The study comprised 3,755 black subjects, 55.5% of whom were women, and 8,465 white subjects, 51.8% of whom were women. They completed a detailed questionnaire as part of the 2007-2014 National Health and Nutrition Examination Survey and had a physical exam. Depressive symptoms were measured by the Patient Health Questionnaire-9 (PHQ-9), and obesity was defined as a body mass index of 30 kg/m² or higher. About 1% of both black and white subjects had severe depressive symptoms, meaning a PHQ-9 score ranging from 20 to 27 points.

A greater percentage of black participants were obese (47.3% vs. 34.4%), and black participants were less likely to live in a household earning $100,000 per year or more (10.9% vs. 28.3%). Black participants were a bit younger (mean age 44.8 years vs. 49.2 years), and less likely to be currently married, college graduates, insured, and physically active. A higher percentage reported fair to poor health (23.9% vs. 14.6%). The differences were statistically significant.

For white women, the association between obesity and depression held across all income levels. For black women, this association was not found at any income level. For black men, the link between obesity and depression was limited to those with a household income of $100,000 or more (odds ratio, 4.65; 95% confidence interval, 1.48-14.59). And for white men, the association was limited to those with a household income of $35,000-$74,999 (OR, 1.44; 95% CI, 1.02-2.03).

The effect of race on obesity and depression has been well studied – it’s known, for instance, that the association between obesity and depression is strongest among white women – but the role of income as a modifier has not been well addressed, wrote Dr. Bell, an assistant professor in the department of African American studies at the University of Maryland, College Park, and her associates.

“Though major life-time depression is less prevalent among African Americans, those who are obese should be screened for depression at similar rates as whites, particularly high-income African American men,” Dr. Bell and her associates wrote.

As for explanations, the authors suggested that strong, antiobesity stigma “may be present among white women at all income levels,” and may drive depression regardless of how much they make.

The prevalence of depressive symptoms at specific income levels among men suggests that something other than stigma is at work. Depression among obese, middle-income white men might be tied to “an unmeasured factor like subjective social status.” Meanwhile, obese black men with high household incomes “have less income and wealth than their white counterparts” because “of various forms of structural racism. ... This may be manifested with higher rates of depression through obesity-related factors like unhealthy coping behaviors and stress,” the investigators said.

Dr. Bell and her associates cited a few limitations. One is that the study looked only at those factors among black and white people. “Results could differ with other ethnic groups,” they wrote. In addition, income was self-reported, and three-way interactions – which are tough to interpret – were used. Nevertheless, they said, the study results have key public health implications.

The study had no financial disclosures, and the investigators reported having no conflicts of interest.

[email protected]

SOURCE: Bell CN et al. Prev Med. 2018 Dec 3. doi: 10.1016/j.ypmed.2018.11.024.