The term genitourinary syndrome of menopause (GSM) refers to the bothersome symptoms and physical findings associated with estrogen deficiency that involve the labia, vestibular tissue, clitoris, vagina, urethra, and bladder.¹ GSM is associated with genital irritation, dryness, and burning; urinary symptoms including urgency, dysuria, and recurrent urinary tract infections; and sexual symptoms including vaginal dryness and pain. Vulvovaginal atrophy (VVA) represents a component of GSM.

GSM is highly prevalent, affecting more than three-quarters of menopausal women. In contrast to menopausal vasomotor symptoms, which often are most severe and frequent in recently menopausal women, GSM commonly presents years following menopause. Unfortunately, VVA symptoms may have a substantial negative impact on women’s quality of life.

In this 2020 Menopause Update, I review a large observational study that provides reassurance to clinicians and patients regarding the safety of the best-studied prescription treatment for GSM—vaginal estrogen. Because some women should not use vaginal estrogen and others choose not to use it, nonhormonal management of GSM is important. Dr. JoAnn Pinkerton provides details on a randomized clinical trial that compared the use of fractionated CO2 laser therapy with vaginal estrogen for the treatment of GSM. In addition, Dr. JoAnn Manson discusses recent studies that found lower health risks with vaginal estrogen use compared with systemic estrogen therapy.

Diagnosing GSM

GSM can be diagnosed presumptively based on a characteristic history in a menopausal patient. Performing a pelvic examination, however, allows clinicians to exclude other conditions that may present with similar symptoms, such as lichen sclerosus, Candida infection, and malignancy.

During inspection of the external genitalia, the clinician may note loss of the fat pad in the labia majora and mons as well as a reduction in labia minora pigmentation and tissue. The urethral meatus often becomes erythematous and prominent. If vaginal or introital narrowing is present, use of a pediatric (ultrathin) speculum reduces patient discomfort. The vaginal mucosa may appear smooth due to loss of rugation; it also may appear shiny and dry. Bleeding (friability) on contact with a spatula or cotton-tipped swab may occur. In addition, the vaginal fornices may become attenuated, leaving the cervix flush with the vaginal apex.

GSM can be diagnosed without laboratory assessment. However, vaginal pH, if measured, is characteristically higher than 5.0; microscopic wet prep often reveals many white blood cells, immature epithelial cells (large nuclei), and reduced or absent lactobacilli.²

Nonhormonal management of GSM

Water, silicone-based, and oil-based lubricants reduce the friction and discomfort associated with sexual activity. By contrast, vaginal moisturizers act longer than lubricants and can be applied several times weekly or daily. Natural oils, including olive and coconut oil, may be useful both as lubricants and as moisturizers. Aqueous lidocaine 4%, applied to vestibular tissue with cotton balls prior to penetration, reduces dyspareunia in women with GSM.³

Vaginal estrogen therapy

When nonhormonal management does not sufficiently reduce GSM symptoms, use of low-dose vaginal estrogen enhances thickness and elasticity of genital tissue and improves vaginal blood flow. Vaginal estrogen creams, tablets, an insert, and a ring are marketed in the United States. Although clinical improvement may be apparent within several weeks of initiating vaginal estrogen, the full benefit of treatment becomes apparent after 2 to 3 months.³

Despite the availability and effectiveness of low-dose vaginal estrogen, fears regarding the safety of menopausal hormone therapy have resulted in the underutilization of vaginal estrogen.^4,5 Unfortunately, the package labeling for low-dose vaginal estrogen can exacerbate these fears.

Continue to: Nurses’ Health Study report...

Nurses’ Health Study report provides reassurance on long-term safety of vaginal estrogen

Bhupathiraju SN, Grodstein F, Stampfer MJ, et al. Vaginal estrogen use and chronic disease risk in the Nurses’ Health Study. Menopause. 2018;26:603-610

Bhupathiraju and colleagues published a report from the long-running Nurses’ Health prospective cohort  study on the health outcomes associated with the use of vaginal estrogen.

Recap of the study

Starting  in  1982, participants  in  the  Nurses’Health  Study were asked to report their use of vaginal estrogen via a validated questionnaire. For the years 1982 to 2012, investigators analyzed  data from 896 and 52,901 women who had and had not used vaginal estrogen, respectively. The mean duration of vaginal estrogen use was 36 months.

In an analysis adjusted for numerous  factors, the investigators observed no statistically significant differences in risk for cardiovascular outcomes (myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism) or invasive cancers (colorectal, endometrial, ovarian, or breast).

Findings uphold safety of vaginal estrogen

This landmark study provides reassurance that 3 years of use of vaginal estrogen does not increase the risk of cardiovascular events or invasive breast cancer, findings that hopefully will allow clinicians and women to feel comfortable regarding the safety of vaginal estrogen. A study of vaginal estrogen from the Women’s Health Initiative provided similar reassurance. Recent research supports guidance from The North American Menopause Society and the American College of Obstetricians and Gynecologists that vaginal estrogen can be used indefinitely, if indicated, and that use of concomitant progestin is not recommended in women who use vaginal estrogen and have an intact uterus.^6,7

I agree with the authors, who point out that since treatment of GSM may need to be continued long term (even indefinitely), it would be helpful to have data that assessed the safety of longer-duration use of vaginal estrogen.

How CO2 fractionated vaginal laser therapy compares with vaginal estrogen for relief of GSM symptoms

Paraiso MF, Ferrando CA, Sokol ER, et al. A randomized clinical trial comparing vaginal laser therapy to vaginal estrogen therapy in women with genitourinary syndrome of menopause: the VeLVET trial. Menopause. 2020;27:50-56.

Up to 50% to 60% of postmenopausal women experience GSM symptoms. However, many fewer receive treatment, either because they do not understand that the symptoms are related to menopause or they are not aware that safe and effective treatment is available. Sadly, many women are not asked about their symptoms or are embarrassed to tell providers.

GSM affects relationships and quality of life. Vaginal lubricants or moisturizers may provide relief. US Food and Drug Administration (FDA)–approved therapies include low-dose vaginal estrogen, available as a vaginal tablet, cream, suppository, and ring; intravaginal dehydroepiandrosterone (DHEA); and oral ospemifene, a selective estrogen replacement modulator. If women have an estrogen-sensitive breast or uterine cancer, an oncologist should be involved in decisions about vaginal hormonal therapy.

Energy-based devices such as vaginal lasers appear to induce wound healing; stimulate collagen and elastin fiber formation through increased storage of glycogen; and activate fibroblasts, which leads to increased extracellular matrix and restoration of vaginal pH.

These lasers are FDA approved for use in gynecology but not specifically for the treatment of GSM. In July 2016, the FDA issued a safety alert that energy-based devices, while approved for use in gynecology, have not been approved or adequately tested for menopausal vaginal conditions, and safety concerns include reports of vaginal burns.⁸ Lacking are publications of adequately powered randomized, sham-con-trolled trials to determine if laser therapy works better for women with GSM than placebos, moisturizers, or vaginal hormone therapies.

Recently, investigators conducted a multicenter, randomized, single-blinded trial of vaginal laser therapy and estrogen cream for treatment of GSM.

Continue to: Details of the study...

Details of the study

Paraiso and colleagues aimed to compare the 6-month efficacy and safety of fractionated CO2 vaginal laser therapy with that of estrogen vaginal cream for the treatment of vaginal dryness/GSM.

Participants randomly assigned to the estrogen therapy arm applied conjugated estrogen cream 0.5 g vaginally daily for 14 days, followed by twice weekly application for 24 weeks (a low-dose vaginal estrogen therapy). Participants randomly assigned to laser therapy underwent 3 vaginal treatments at a minimum of 6 weeks apart.

Sixty-nine women were enrolled in the trial before enrollment was closed because the FDA required that the sponsor obtain and maintain an investigational device exemption. Of 62 women who completed 6 months’ treatment, 30 received 3 laser treatments and 32 received estrogen cream.

The primary outcome compared subjective improvement in vaginal dryness using the visual analog scale (VAS) between the 2 groups at 6 months. Secondary outcomes included comparisons of the vaginal health index (VHI) and vaginal maturation index (VMI), the effect of GSM on quality of life, the effect of treatment on sexual function and urinary symptoms, and patient satisfaction.

Study findings

Efficacy. Laser therapy and estrogen therapy were found to be similarly effective except on the VMI, which favored estrogen. On patient global impression, 85.8% of laser-treated women rated their improvement as ‘‘better or much better’’ and 78.5% reported being either ‘‘satisfied or very satisfied,’’ compared with 70% and 73.3%, respectively, in the estrogen group, a statistically nonsignificant difference.

On linear regression, the investigators found a nonsignificant mean difference in female sexual function index scores. While VMI scores remained higher in the estrogen-treated group (adjusted P = .02), baseline and 6-month follow-up VMI data were available for only 34 participants (16 laser treated, 18 estrogen treated).

Regarding long-term effectiveness, 20% to 25% of the women in the laser-treated group needed further treatment after 1 year while the estrogen cream continued to work as long as it was used as prescribed.

Adverse effects. The incidence of vaginal bleeding was similar in the 2 groups: 6.7% in the laser group and 6.3% in the estrogen group. In the laser therapy group, 3% expe-rienced vaginal pain, discharge, and bladder infections, while in the estrogen cream group, 3% reported breast tenderness, migraine headaches, and abdominal cramping.

Takeaways. This small randomized, open-label (not blinded) trial provides pilot data on the effectiveness of vaginal CO2 laser compared with vaginal estrogen in treating vaginal atrophy, quality-of-life symptoms, sexual function, and urinary symptoms. Adverse events were minimal. Patient global impression of improvement and satisfaction improved for both vaginal laser and vaginal estrogen therapy.

Continue to: Study strengths and limitations...

Study strengths and limitations

To show noninferiority of vaginal laser therapy to vaginal estrogen, 196 study participants were needed. However, after 38% had been enrolled, the FDA sent a warning letter to the Foundation for Female Health Awareness, which required obtainment of an investigational device exemption for the laser and addition of a sham treatment arm.⁹ Instead of redesigning the trial and reconsenting the participants, the investigators closed the study, and analysis was performed only on the 62 participants who completed the study; vaginal maturation was assessed only in 34 participants.

The study lacked a placebo or sham control, which increases the risk of bias, while small numbers limit the strength of the findings. Longer-term evaluation of the effects of laser therapy beyond 6 months is needed to allow assessment of the effects of scarring on vaginal health, sexual function, and urinary issues.

Discussing therapy with patients

Despite this study’s preliminary findings, and until more robust data are available, providers should discuss the benefits and risks of all available treatment options for vaginal symptoms, including over-the-counter lubricants, vaginal moisturizers, FDA-approved vaginal hormone therapies (such as vaginal estrogen and intravaginal dehydroepiandrosterone), and systemic therapies, such as hormone therapy and ospemifene, to determine the best treatment for the individual woman with GSM.

In a healthy postmenopausal woman with bothersome GSM symptoms not responsive to lubricants and moisturizers, I recommend FDA-approved vaginal therapies as first-line treatment if there are no contraindications. For women with breast cancer, I involve their oncologist. If a patient asks about vaginal laser treatment, I share that vaginal energy-based therapies, such as the vaginal laser, have not been approved for menopausal vaginal concerns. In addition to the possibility of adverse events or unsuccessful treatment, there are significant out-of-pocket costs and the potential need for ongoing therapy after the initial 3 laser treatments.

The term genitourinary syndrome of menopause (GSM) refers to the bothersome symptoms and physical findings associated with estrogen deficiency that involve the labia, vestibular tissue, clitoris, vagina, urethra, and bladder.¹ GSM is associated with genital irritation, dryness, and burning; urinary symptoms including urgency, dysuria, and recurrent urinary tract infections; and sexual symptoms including vaginal dryness and pain. Vulvovaginal atrophy (VVA) represents a component of GSM.

GSM is highly prevalent, affecting more than three-quarters of menopausal women. In contrast to menopausal vasomotor symptoms, which often are most severe and frequent in recently menopausal women, GSM commonly presents years following menopause. Unfortunately, VVA symptoms may have a substantial negative impact on women’s quality of life.

In this 2020 Menopause Update, I review a large observational study that provides reassurance to clinicians and patients regarding the safety of the best-studied prescription treatment for GSM—vaginal estrogen. Because some women should not use vaginal estrogen and others choose not to use it, nonhormonal management of GSM is important. Dr. JoAnn Pinkerton provides details on a randomized clinical trial that compared the use of fractionated CO2 laser therapy with vaginal estrogen for the treatment of GSM. In addition, Dr. JoAnn Manson discusses recent studies that found lower health risks with vaginal estrogen use compared with systemic estrogen therapy.

Diagnosing GSM

GSM can be diagnosed presumptively based on a characteristic history in a menopausal patient. Performing a pelvic examination, however, allows clinicians to exclude other conditions that may present with similar symptoms, such as lichen sclerosus, Candida infection, and malignancy.

During inspection of the external genitalia, the clinician may note loss of the fat pad in the labia majora and mons as well as a reduction in labia minora pigmentation and tissue. The urethral meatus often becomes erythematous and prominent. If vaginal or introital narrowing is present, use of a pediatric (ultrathin) speculum reduces patient discomfort. The vaginal mucosa may appear smooth due to loss of rugation; it also may appear shiny and dry. Bleeding (friability) on contact with a spatula or cotton-tipped swab may occur. In addition, the vaginal fornices may become attenuated, leaving the cervix flush with the vaginal apex.

GSM can be diagnosed without laboratory assessment. However, vaginal pH, if measured, is characteristically higher than 5.0; microscopic wet prep often reveals many white blood cells, immature epithelial cells (large nuclei), and reduced or absent lactobacilli.²

Nonhormonal management of GSM

Water, silicone-based, and oil-based lubricants reduce the friction and discomfort associated with sexual activity. By contrast, vaginal moisturizers act longer than lubricants and can be applied several times weekly or daily. Natural oils, including olive and coconut oil, may be useful both as lubricants and as moisturizers. Aqueous lidocaine 4%, applied to vestibular tissue with cotton balls prior to penetration, reduces dyspareunia in women with GSM.³

Vaginal estrogen therapy

When nonhormonal management does not sufficiently reduce GSM symptoms, use of low-dose vaginal estrogen enhances thickness and elasticity of genital tissue and improves vaginal blood flow. Vaginal estrogen creams, tablets, an insert, and a ring are marketed in the United States. Although clinical improvement may be apparent within several weeks of initiating vaginal estrogen, the full benefit of treatment becomes apparent after 2 to 3 months.³

Despite the availability and effectiveness of low-dose vaginal estrogen, fears regarding the safety of menopausal hormone therapy have resulted in the underutilization of vaginal estrogen.^4,5 Unfortunately, the package labeling for low-dose vaginal estrogen can exacerbate these fears.

Continue to: Nurses’ Health Study report...

Nurses’ Health Study report provides reassurance on long-term safety of vaginal estrogen

Bhupathiraju SN, Grodstein F, Stampfer MJ, et al. Vaginal estrogen use and chronic disease risk in the Nurses’ Health Study. Menopause. 2018;26:603-610

Bhupathiraju and colleagues published a report from the long-running Nurses’ Health prospective cohort  study on the health outcomes associated with the use of vaginal estrogen.

Recap of the study

Starting  in  1982, participants  in  the  Nurses’Health  Study were asked to report their use of vaginal estrogen via a validated questionnaire. For the years 1982 to 2012, investigators analyzed  data from 896 and 52,901 women who had and had not used vaginal estrogen, respectively. The mean duration of vaginal estrogen use was 36 months.

In an analysis adjusted for numerous  factors, the investigators observed no statistically significant differences in risk for cardiovascular outcomes (myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism) or invasive cancers (colorectal, endometrial, ovarian, or breast).

Findings uphold safety of vaginal estrogen

This landmark study provides reassurance that 3 years of use of vaginal estrogen does not increase the risk of cardiovascular events or invasive breast cancer, findings that hopefully will allow clinicians and women to feel comfortable regarding the safety of vaginal estrogen. A study of vaginal estrogen from the Women’s Health Initiative provided similar reassurance. Recent research supports guidance from The North American Menopause Society and the American College of Obstetricians and Gynecologists that vaginal estrogen can be used indefinitely, if indicated, and that use of concomitant progestin is not recommended in women who use vaginal estrogen and have an intact uterus.^6,7

I agree with the authors, who point out that since treatment of GSM may need to be continued long term (even indefinitely), it would be helpful to have data that assessed the safety of longer-duration use of vaginal estrogen.

How CO2 fractionated vaginal laser therapy compares with vaginal estrogen for relief of GSM symptoms

Paraiso MF, Ferrando CA, Sokol ER, et al. A randomized clinical trial comparing vaginal laser therapy to vaginal estrogen therapy in women with genitourinary syndrome of menopause: the VeLVET trial. Menopause. 2020;27:50-56.

Up to 50% to 60% of postmenopausal women experience GSM symptoms. However, many fewer receive treatment, either because they do not understand that the symptoms are related to menopause or they are not aware that safe and effective treatment is available. Sadly, many women are not asked about their symptoms or are embarrassed to tell providers.

GSM affects relationships and quality of life. Vaginal lubricants or moisturizers may provide relief. US Food and Drug Administration (FDA)–approved therapies include low-dose vaginal estrogen, available as a vaginal tablet, cream, suppository, and ring; intravaginal dehydroepiandrosterone (DHEA); and oral ospemifene, a selective estrogen replacement modulator. If women have an estrogen-sensitive breast or uterine cancer, an oncologist should be involved in decisions about vaginal hormonal therapy.

Energy-based devices such as vaginal lasers appear to induce wound healing; stimulate collagen and elastin fiber formation through increased storage of glycogen; and activate fibroblasts, which leads to increased extracellular matrix and restoration of vaginal pH.

These lasers are FDA approved for use in gynecology but not specifically for the treatment of GSM. In July 2016, the FDA issued a safety alert that energy-based devices, while approved for use in gynecology, have not been approved or adequately tested for menopausal vaginal conditions, and safety concerns include reports of vaginal burns.⁸ Lacking are publications of adequately powered randomized, sham-con-trolled trials to determine if laser therapy works better for women with GSM than placebos, moisturizers, or vaginal hormone therapies.

Recently, investigators conducted a multicenter, randomized, single-blinded trial of vaginal laser therapy and estrogen cream for treatment of GSM.

Continue to: Details of the study...

Details of the study

Paraiso and colleagues aimed to compare the 6-month efficacy and safety of fractionated CO2 vaginal laser therapy with that of estrogen vaginal cream for the treatment of vaginal dryness/GSM.

Participants randomly assigned to the estrogen therapy arm applied conjugated estrogen cream 0.5 g vaginally daily for 14 days, followed by twice weekly application for 24 weeks (a low-dose vaginal estrogen therapy). Participants randomly assigned to laser therapy underwent 3 vaginal treatments at a minimum of 6 weeks apart.

Sixty-nine women were enrolled in the trial before enrollment was closed because the FDA required that the sponsor obtain and maintain an investigational device exemption. Of 62 women who completed 6 months’ treatment, 30 received 3 laser treatments and 32 received estrogen cream.

The primary outcome compared subjective improvement in vaginal dryness using the visual analog scale (VAS) between the 2 groups at 6 months. Secondary outcomes included comparisons of the vaginal health index (VHI) and vaginal maturation index (VMI), the effect of GSM on quality of life, the effect of treatment on sexual function and urinary symptoms, and patient satisfaction.

Study findings

Efficacy. Laser therapy and estrogen therapy were found to be similarly effective except on the VMI, which favored estrogen. On patient global impression, 85.8% of laser-treated women rated their improvement as ‘‘better or much better’’ and 78.5% reported being either ‘‘satisfied or very satisfied,’’ compared with 70% and 73.3%, respectively, in the estrogen group, a statistically nonsignificant difference.

On linear regression, the investigators found a nonsignificant mean difference in female sexual function index scores. While VMI scores remained higher in the estrogen-treated group (adjusted P = .02), baseline and 6-month follow-up VMI data were available for only 34 participants (16 laser treated, 18 estrogen treated).

Regarding long-term effectiveness, 20% to 25% of the women in the laser-treated group needed further treatment after 1 year while the estrogen cream continued to work as long as it was used as prescribed.

Adverse effects. The incidence of vaginal bleeding was similar in the 2 groups: 6.7% in the laser group and 6.3% in the estrogen group. In the laser therapy group, 3% expe-rienced vaginal pain, discharge, and bladder infections, while in the estrogen cream group, 3% reported breast tenderness, migraine headaches, and abdominal cramping.

Takeaways. This small randomized, open-label (not blinded) trial provides pilot data on the effectiveness of vaginal CO2 laser compared with vaginal estrogen in treating vaginal atrophy, quality-of-life symptoms, sexual function, and urinary symptoms. Adverse events were minimal. Patient global impression of improvement and satisfaction improved for both vaginal laser and vaginal estrogen therapy.

Continue to: Study strengths and limitations...

Study strengths and limitations

To show noninferiority of vaginal laser therapy to vaginal estrogen, 196 study participants were needed. However, after 38% had been enrolled, the FDA sent a warning letter to the Foundation for Female Health Awareness, which required obtainment of an investigational device exemption for the laser and addition of a sham treatment arm.⁹ Instead of redesigning the trial and reconsenting the participants, the investigators closed the study, and analysis was performed only on the 62 participants who completed the study; vaginal maturation was assessed only in 34 participants.

The study lacked a placebo or sham control, which increases the risk of bias, while small numbers limit the strength of the findings. Longer-term evaluation of the effects of laser therapy beyond 6 months is needed to allow assessment of the effects of scarring on vaginal health, sexual function, and urinary issues.

Discussing therapy with patients

Despite this study’s preliminary findings, and until more robust data are available, providers should discuss the benefits and risks of all available treatment options for vaginal symptoms, including over-the-counter lubricants, vaginal moisturizers, FDA-approved vaginal hormone therapies (such as vaginal estrogen and intravaginal dehydroepiandrosterone), and systemic therapies, such as hormone therapy and ospemifene, to determine the best treatment for the individual woman with GSM.

In a healthy postmenopausal woman with bothersome GSM symptoms not responsive to lubricants and moisturizers, I recommend FDA-approved vaginal therapies as first-line treatment if there are no contraindications. For women with breast cancer, I involve their oncologist. If a patient asks about vaginal laser treatment, I share that vaginal energy-based therapies, such as the vaginal laser, have not been approved for menopausal vaginal concerns. In addition to the possibility of adverse events or unsuccessful treatment, there are significant out-of-pocket costs and the potential need for ongoing therapy after the initial 3 laser treatments.

The term genitourinary syndrome of menopause (GSM) refers to the bothersome symptoms and physical findings associated with estrogen deficiency that involve the labia, vestibular tissue, clitoris, vagina, urethra, and bladder.¹ GSM is associated with genital irritation, dryness, and burning; urinary symptoms including urgency, dysuria, and recurrent urinary tract infections; and sexual symptoms including vaginal dryness and pain. Vulvovaginal atrophy (VVA) represents a component of GSM.

GSM is highly prevalent, affecting more than three-quarters of menopausal women. In contrast to menopausal vasomotor symptoms, which often are most severe and frequent in recently menopausal women, GSM commonly presents years following menopause. Unfortunately, VVA symptoms may have a substantial negative impact on women’s quality of life.

In this 2020 Menopause Update, I review a large observational study that provides reassurance to clinicians and patients regarding the safety of the best-studied prescription treatment for GSM—vaginal estrogen. Because some women should not use vaginal estrogen and others choose not to use it, nonhormonal management of GSM is important. Dr. JoAnn Pinkerton provides details on a randomized clinical trial that compared the use of fractionated CO2 laser therapy with vaginal estrogen for the treatment of GSM. In addition, Dr. JoAnn Manson discusses recent studies that found lower health risks with vaginal estrogen use compared with systemic estrogen therapy.

Diagnosing GSM

GSM can be diagnosed presumptively based on a characteristic history in a menopausal patient. Performing a pelvic examination, however, allows clinicians to exclude other conditions that may present with similar symptoms, such as lichen sclerosus, Candida infection, and malignancy.

During inspection of the external genitalia, the clinician may note loss of the fat pad in the labia majora and mons as well as a reduction in labia minora pigmentation and tissue. The urethral meatus often becomes erythematous and prominent. If vaginal or introital narrowing is present, use of a pediatric (ultrathin) speculum reduces patient discomfort. The vaginal mucosa may appear smooth due to loss of rugation; it also may appear shiny and dry. Bleeding (friability) on contact with a spatula or cotton-tipped swab may occur. In addition, the vaginal fornices may become attenuated, leaving the cervix flush with the vaginal apex.

GSM can be diagnosed without laboratory assessment. However, vaginal pH, if measured, is characteristically higher than 5.0; microscopic wet prep often reveals many white blood cells, immature epithelial cells (large nuclei), and reduced or absent lactobacilli.²

Nonhormonal management of GSM

Water, silicone-based, and oil-based lubricants reduce the friction and discomfort associated with sexual activity. By contrast, vaginal moisturizers act longer than lubricants and can be applied several times weekly or daily. Natural oils, including olive and coconut oil, may be useful both as lubricants and as moisturizers. Aqueous lidocaine 4%, applied to vestibular tissue with cotton balls prior to penetration, reduces dyspareunia in women with GSM.³

Vaginal estrogen therapy

When nonhormonal management does not sufficiently reduce GSM symptoms, use of low-dose vaginal estrogen enhances thickness and elasticity of genital tissue and improves vaginal blood flow. Vaginal estrogen creams, tablets, an insert, and a ring are marketed in the United States. Although clinical improvement may be apparent within several weeks of initiating vaginal estrogen, the full benefit of treatment becomes apparent after 2 to 3 months.³

Despite the availability and effectiveness of low-dose vaginal estrogen, fears regarding the safety of menopausal hormone therapy have resulted in the underutilization of vaginal estrogen.^4,5 Unfortunately, the package labeling for low-dose vaginal estrogen can exacerbate these fears.

Continue to: Nurses’ Health Study report...

Nurses’ Health Study report provides reassurance on long-term safety of vaginal estrogen

Bhupathiraju SN, Grodstein F, Stampfer MJ, et al. Vaginal estrogen use and chronic disease risk in the Nurses’ Health Study. Menopause. 2018;26:603-610

Bhupathiraju and colleagues published a report from the long-running Nurses’ Health prospective cohort  study on the health outcomes associated with the use of vaginal estrogen.

Recap of the study

Starting  in  1982, participants  in  the  Nurses’Health  Study were asked to report their use of vaginal estrogen via a validated questionnaire. For the years 1982 to 2012, investigators analyzed  data from 896 and 52,901 women who had and had not used vaginal estrogen, respectively. The mean duration of vaginal estrogen use was 36 months.

In an analysis adjusted for numerous  factors, the investigators observed no statistically significant differences in risk for cardiovascular outcomes (myocardial infarction, stroke, deep vein thrombosis, and pulmonary embolism) or invasive cancers (colorectal, endometrial, ovarian, or breast).

Findings uphold safety of vaginal estrogen

This landmark study provides reassurance that 3 years of use of vaginal estrogen does not increase the risk of cardiovascular events or invasive breast cancer, findings that hopefully will allow clinicians and women to feel comfortable regarding the safety of vaginal estrogen. A study of vaginal estrogen from the Women’s Health Initiative provided similar reassurance. Recent research supports guidance from The North American Menopause Society and the American College of Obstetricians and Gynecologists that vaginal estrogen can be used indefinitely, if indicated, and that use of concomitant progestin is not recommended in women who use vaginal estrogen and have an intact uterus.^6,7

I agree with the authors, who point out that since treatment of GSM may need to be continued long term (even indefinitely), it would be helpful to have data that assessed the safety of longer-duration use of vaginal estrogen.

How CO2 fractionated vaginal laser therapy compares with vaginal estrogen for relief of GSM symptoms

Paraiso MF, Ferrando CA, Sokol ER, et al. A randomized clinical trial comparing vaginal laser therapy to vaginal estrogen therapy in women with genitourinary syndrome of menopause: the VeLVET trial. Menopause. 2020;27:50-56.

Up to 50% to 60% of postmenopausal women experience GSM symptoms. However, many fewer receive treatment, either because they do not understand that the symptoms are related to menopause or they are not aware that safe and effective treatment is available. Sadly, many women are not asked about their symptoms or are embarrassed to tell providers.

GSM affects relationships and quality of life. Vaginal lubricants or moisturizers may provide relief. US Food and Drug Administration (FDA)–approved therapies include low-dose vaginal estrogen, available as a vaginal tablet, cream, suppository, and ring; intravaginal dehydroepiandrosterone (DHEA); and oral ospemifene, a selective estrogen replacement modulator. If women have an estrogen-sensitive breast or uterine cancer, an oncologist should be involved in decisions about vaginal hormonal therapy.

Energy-based devices such as vaginal lasers appear to induce wound healing; stimulate collagen and elastin fiber formation through increased storage of glycogen; and activate fibroblasts, which leads to increased extracellular matrix and restoration of vaginal pH.

These lasers are FDA approved for use in gynecology but not specifically for the treatment of GSM. In July 2016, the FDA issued a safety alert that energy-based devices, while approved for use in gynecology, have not been approved or adequately tested for menopausal vaginal conditions, and safety concerns include reports of vaginal burns.⁸ Lacking are publications of adequately powered randomized, sham-con-trolled trials to determine if laser therapy works better for women with GSM than placebos, moisturizers, or vaginal hormone therapies.

Recently, investigators conducted a multicenter, randomized, single-blinded trial of vaginal laser therapy and estrogen cream for treatment of GSM.

Continue to: Details of the study...

Details of the study

Paraiso and colleagues aimed to compare the 6-month efficacy and safety of fractionated CO2 vaginal laser therapy with that of estrogen vaginal cream for the treatment of vaginal dryness/GSM.

Participants randomly assigned to the estrogen therapy arm applied conjugated estrogen cream 0.5 g vaginally daily for 14 days, followed by twice weekly application for 24 weeks (a low-dose vaginal estrogen therapy). Participants randomly assigned to laser therapy underwent 3 vaginal treatments at a minimum of 6 weeks apart.

Sixty-nine women were enrolled in the trial before enrollment was closed because the FDA required that the sponsor obtain and maintain an investigational device exemption. Of 62 women who completed 6 months’ treatment, 30 received 3 laser treatments and 32 received estrogen cream.

The primary outcome compared subjective improvement in vaginal dryness using the visual analog scale (VAS) between the 2 groups at 6 months. Secondary outcomes included comparisons of the vaginal health index (VHI) and vaginal maturation index (VMI), the effect of GSM on quality of life, the effect of treatment on sexual function and urinary symptoms, and patient satisfaction.

Study findings

Efficacy. Laser therapy and estrogen therapy were found to be similarly effective except on the VMI, which favored estrogen. On patient global impression, 85.8% of laser-treated women rated their improvement as ‘‘better or much better’’ and 78.5% reported being either ‘‘satisfied or very satisfied,’’ compared with 70% and 73.3%, respectively, in the estrogen group, a statistically nonsignificant difference.

On linear regression, the investigators found a nonsignificant mean difference in female sexual function index scores. While VMI scores remained higher in the estrogen-treated group (adjusted P = .02), baseline and 6-month follow-up VMI data were available for only 34 participants (16 laser treated, 18 estrogen treated).

Regarding long-term effectiveness, 20% to 25% of the women in the laser-treated group needed further treatment after 1 year while the estrogen cream continued to work as long as it was used as prescribed.

Adverse effects. The incidence of vaginal bleeding was similar in the 2 groups: 6.7% in the laser group and 6.3% in the estrogen group. In the laser therapy group, 3% expe-rienced vaginal pain, discharge, and bladder infections, while in the estrogen cream group, 3% reported breast tenderness, migraine headaches, and abdominal cramping.

Takeaways. This small randomized, open-label (not blinded) trial provides pilot data on the effectiveness of vaginal CO2 laser compared with vaginal estrogen in treating vaginal atrophy, quality-of-life symptoms, sexual function, and urinary symptoms. Adverse events were minimal. Patient global impression of improvement and satisfaction improved for both vaginal laser and vaginal estrogen therapy.

Continue to: Study strengths and limitations...

Study strengths and limitations

To show noninferiority of vaginal laser therapy to vaginal estrogen, 196 study participants were needed. However, after 38% had been enrolled, the FDA sent a warning letter to the Foundation for Female Health Awareness, which required obtainment of an investigational device exemption for the laser and addition of a sham treatment arm.⁹ Instead of redesigning the trial and reconsenting the participants, the investigators closed the study, and analysis was performed only on the 62 participants who completed the study; vaginal maturation was assessed only in 34 participants.

The study lacked a placebo or sham control, which increases the risk of bias, while small numbers limit the strength of the findings. Longer-term evaluation of the effects of laser therapy beyond 6 months is needed to allow assessment of the effects of scarring on vaginal health, sexual function, and urinary issues.

Discussing therapy with patients

Despite this study’s preliminary findings, and until more robust data are available, providers should discuss the benefits and risks of all available treatment options for vaginal symptoms, including over-the-counter lubricants, vaginal moisturizers, FDA-approved vaginal hormone therapies (such as vaginal estrogen and intravaginal dehydroepiandrosterone), and systemic therapies, such as hormone therapy and ospemifene, to determine the best treatment for the individual woman with GSM.

In a healthy postmenopausal woman with bothersome GSM symptoms not responsive to lubricants and moisturizers, I recommend FDA-approved vaginal therapies as first-line treatment if there are no contraindications. For women with breast cancer, I involve their oncologist. If a patient asks about vaginal laser treatment, I share that vaginal energy-based therapies, such as the vaginal laser, have not been approved for menopausal vaginal concerns. In addition to the possibility of adverse events or unsuccessful treatment, there are significant out-of-pocket costs and the potential need for ongoing therapy after the initial 3 laser treatments.

The 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors Consensus Guidelines, which represent a consensus of nearly 20 professional organizations and patient advocates, are a culmination of almost 10 years of research.¹ With the last version issued in 2012,² these latest guidelines offer the most recent recommendations regarding safely triaging women with abnormal cervical cancer screening results.

According to the consensus, research has shown that risk-based management allows clinicians to better discriminate women who will likely develop precancer from those who can safely continue with routine screening. As you will hear from guidelines coauthor Dr. Warner Huh, one of the most important differences between these guidelines and the 2012 version is a new emphasis on the principle of “equal management for equal risk.” Essentially, this insures that all women who have the same amount of risk for progression to precancer or cancer are managed the same.

The guidelines were once again published in the Journal of Lower Genital Tract Disease, and the tables they reference are publicly available. Additionally, ASCCP is developing a new management guidelines app to facilitate the use of the guidelines on smartphones and computers. With the publicly available risk tables, and the ASCCP navigation app, the guidelines will more easily accommodate updates as new information and technology become available.

OBG Management: The latest ASCCP guidelines, published in April, represent a “paradigm shift” from results to risk-based guidelines. Can you explain what this means and why the shift was undertaken?

Warner K. Huh, MD: Yes, the shift occurred because we needed to focus less on algorithms and more on risk. We started promulgating a concept of “equal management for equal risk” back in 2012. What this means is that if we have a method to look up a risk score based on relevant test results and other pieces of information, then all patients with that score should be managed in the same manner. We wanted that to be the underlying principle.

Focusing on risk tables also makes it easier to incorporate any future technologies used for risk estimation without having to rebuild algorithms from scratch. ASCCP is developing a new management guidelines app to streamline navigation of the guidelines. This app makes them easier for clinicians to use; they simply plug in certain variables from the patient’s history and receive 1 of 5 outputs: treatment, colposcopy, or surveillance at 1, 3, or 5 years.

The only drawbacks, if you view them as such, are that the clinician must plug in all the variables, and then must sit back and trust in what we have done. Clinicians have to trust that the system works and will simplify the clinical decision making.

We spent a lot of time determining what the risk thresholds should be. Some may argue they are arbitrary, but the decisions were data-driven, and carefully, thoughtfully vetted; we deliberated about whether the cut points actually made sense clinically to a practicing clinician base. The clinical action thresholds refer to a specific percentage below which a woman falls into one bucket and above which she falls into another bucket.

The other element that is unique about the guidelines is that instead of looking at the patient’s current screening result in isolation, the user sees it along with the prior one because prior history dictates subsequent risk.

It’s important that clinicians understand why this system is so markedly different from what we have done previously, and why risk-based guidelines make infinitely more sense than algorithmic ones. It’s because: 1) they can be easier to use; 2) they incorporate new data more efficiently and effectively than algorithm-based guidelines; and 3) they can incorporate future technologies seamlessly rather than having to create yet another algorithm.

Continue to: OBG Management : What do clinicians need in order to execute the guidelines?...

OBG Management: What do clinicians need in order to execute the guidelines?

Dr. Huh: Nothing. All of the information needed—the guidelines article and risk tables—are publicly available. However, to make navigation of the guidelines easier, the plan is for the app that I mentioned. I have the app on my phone and am actively beta testing it now. We’re planning on creating a web-based application as well, that will allow users to access the Internet and their electronic health record system so that they can plug in information directly from patient charts. The web-based app will be similar to the web-based Breast Cancer Surveillance Consortium’s Risk Calculator (https://tools.bcsc-scc.org/BC5yearRisk/calculator.htm). You will pull it up, plug in the requested information, including the patient’s age; their Pap smear and genotyping results; and their previous screening history.

OBG Management: When will the app be available for users?

Dr. Huh: It will be available for release on June 8.

OBG Management: Were HPV vaccination levels incorporated into the new guidelines?

OBG Management: Have recommendations regarding colposcopy changed?

Dr. Huh: Not really. About 3 years ago, we created basic colposcopy guidelines—the ASCCP Colposcopy Standards—so everything about colposcopy references back to those guidelines. Those colposcopy standards covered terminology and risk-based colposcopy, which actually aligns beautifully with these guidelines.

OBG Management: To narrow in on some changes from the prior guidelines, can colposcopy be deferred in certain patients?

Dr. Huh: Yes. Not everyone who has an abnormal screening test needs to come back for colposcopy.

OBG Management: How has guidance for expedited treatment or treatment without colposcopic biopsy changed?

Dr. Huh: This was heavily debated within not only the treatment group that I co-chaired with Richard Guido, MD, but also within the entire steering committee. The recommendation is that if the patient has an immediate risk of CIN 3 that is >60%, the patient should go straight to treatment without a colposcopic biopsy. The main reason for this is that you do not want to biopsy a patient and then lose them to follow-up.

When a woman has >60% immediate risk of CIN 3, we are fairly certain that colposcopy is not going to change management ultimately, so we recommend that patients receive treatment right away. We have already been doing this for 15 to 20 years, so this is not a new concept. It is just more formally codified here by assigning a percentage to the risk. Those who have between 25% and 60% immediate risk of CIN 3 should receive immediate colposcopy. We realize that not all clinicians have the ability to do this, so if clinicians can’t treat immediately, we recommend they do whatever they can to prevent losing the patient to follow-up.

OBG Management: How should a positive primary HPV screening test be managed?

Dr. Huh: If a woman has a positive primary HPV screening test, genotyping should be performed. If genotyping reveals HPV 16 or 18, then the patient should proceed to colposcopy. If genotyping reveals other forms of HPV, reflex cytology or a Pap smear should follow. ●

The 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors Consensus Guidelines, which represent a consensus of nearly 20 professional organizations and patient advocates, are a culmination of almost 10 years of research.¹ With the last version issued in 2012,² these latest guidelines offer the most recent recommendations regarding safely triaging women with abnormal cervical cancer screening results.

According to the consensus, research has shown that risk-based management allows clinicians to better discriminate women who will likely develop precancer from those who can safely continue with routine screening. As you will hear from guidelines coauthor Dr. Warner Huh, one of the most important differences between these guidelines and the 2012 version is a new emphasis on the principle of “equal management for equal risk.” Essentially, this insures that all women who have the same amount of risk for progression to precancer or cancer are managed the same.

The guidelines were once again published in the Journal of Lower Genital Tract Disease, and the tables they reference are publicly available. Additionally, ASCCP is developing a new management guidelines app to facilitate the use of the guidelines on smartphones and computers. With the publicly available risk tables, and the ASCCP navigation app, the guidelines will more easily accommodate updates as new information and technology become available.

OBG Management: The latest ASCCP guidelines, published in April, represent a “paradigm shift” from results to risk-based guidelines. Can you explain what this means and why the shift was undertaken?

Warner K. Huh, MD: Yes, the shift occurred because we needed to focus less on algorithms and more on risk. We started promulgating a concept of “equal management for equal risk” back in 2012. What this means is that if we have a method to look up a risk score based on relevant test results and other pieces of information, then all patients with that score should be managed in the same manner. We wanted that to be the underlying principle.

Focusing on risk tables also makes it easier to incorporate any future technologies used for risk estimation without having to rebuild algorithms from scratch. ASCCP is developing a new management guidelines app to streamline navigation of the guidelines. This app makes them easier for clinicians to use; they simply plug in certain variables from the patient’s history and receive 1 of 5 outputs: treatment, colposcopy, or surveillance at 1, 3, or 5 years.

The only drawbacks, if you view them as such, are that the clinician must plug in all the variables, and then must sit back and trust in what we have done. Clinicians have to trust that the system works and will simplify the clinical decision making.

We spent a lot of time determining what the risk thresholds should be. Some may argue they are arbitrary, but the decisions were data-driven, and carefully, thoughtfully vetted; we deliberated about whether the cut points actually made sense clinically to a practicing clinician base. The clinical action thresholds refer to a specific percentage below which a woman falls into one bucket and above which she falls into another bucket.

The other element that is unique about the guidelines is that instead of looking at the patient’s current screening result in isolation, the user sees it along with the prior one because prior history dictates subsequent risk.

It’s important that clinicians understand why this system is so markedly different from what we have done previously, and why risk-based guidelines make infinitely more sense than algorithmic ones. It’s because: 1) they can be easier to use; 2) they incorporate new data more efficiently and effectively than algorithm-based guidelines; and 3) they can incorporate future technologies seamlessly rather than having to create yet another algorithm.

Continue to: OBG Management : What do clinicians need in order to execute the guidelines?...

OBG Management: What do clinicians need in order to execute the guidelines?

Dr. Huh: Nothing. All of the information needed—the guidelines article and risk tables—are publicly available. However, to make navigation of the guidelines easier, the plan is for the app that I mentioned. I have the app on my phone and am actively beta testing it now. We’re planning on creating a web-based application as well, that will allow users to access the Internet and their electronic health record system so that they can plug in information directly from patient charts. The web-based app will be similar to the web-based Breast Cancer Surveillance Consortium’s Risk Calculator (https://tools.bcsc-scc.org/BC5yearRisk/calculator.htm). You will pull it up, plug in the requested information, including the patient’s age; their Pap smear and genotyping results; and their previous screening history.

OBG Management: When will the app be available for users?

Dr. Huh: It will be available for release on June 8.

OBG Management: Were HPV vaccination levels incorporated into the new guidelines?

OBG Management: Have recommendations regarding colposcopy changed?

Dr. Huh: Not really. About 3 years ago, we created basic colposcopy guidelines—the ASCCP Colposcopy Standards—so everything about colposcopy references back to those guidelines. Those colposcopy standards covered terminology and risk-based colposcopy, which actually aligns beautifully with these guidelines.

OBG Management: To narrow in on some changes from the prior guidelines, can colposcopy be deferred in certain patients?

Dr. Huh: Yes. Not everyone who has an abnormal screening test needs to come back for colposcopy.

OBG Management: How has guidance for expedited treatment or treatment without colposcopic biopsy changed?

Dr. Huh: This was heavily debated within not only the treatment group that I co-chaired with Richard Guido, MD, but also within the entire steering committee. The recommendation is that if the patient has an immediate risk of CIN 3 that is >60%, the patient should go straight to treatment without a colposcopic biopsy. The main reason for this is that you do not want to biopsy a patient and then lose them to follow-up.

When a woman has >60% immediate risk of CIN 3, we are fairly certain that colposcopy is not going to change management ultimately, so we recommend that patients receive treatment right away. We have already been doing this for 15 to 20 years, so this is not a new concept. It is just more formally codified here by assigning a percentage to the risk. Those who have between 25% and 60% immediate risk of CIN 3 should receive immediate colposcopy. We realize that not all clinicians have the ability to do this, so if clinicians can’t treat immediately, we recommend they do whatever they can to prevent losing the patient to follow-up.

OBG Management: How should a positive primary HPV screening test be managed?

Dr. Huh: If a woman has a positive primary HPV screening test, genotyping should be performed. If genotyping reveals HPV 16 or 18, then the patient should proceed to colposcopy. If genotyping reveals other forms of HPV, reflex cytology or a Pap smear should follow. ●

The 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors Consensus Guidelines, which represent a consensus of nearly 20 professional organizations and patient advocates, are a culmination of almost 10 years of research.¹ With the last version issued in 2012,² these latest guidelines offer the most recent recommendations regarding safely triaging women with abnormal cervical cancer screening results.

According to the consensus, research has shown that risk-based management allows clinicians to better discriminate women who will likely develop precancer from those who can safely continue with routine screening. As you will hear from guidelines coauthor Dr. Warner Huh, one of the most important differences between these guidelines and the 2012 version is a new emphasis on the principle of “equal management for equal risk.” Essentially, this insures that all women who have the same amount of risk for progression to precancer or cancer are managed the same.

The guidelines were once again published in the Journal of Lower Genital Tract Disease, and the tables they reference are publicly available. Additionally, ASCCP is developing a new management guidelines app to facilitate the use of the guidelines on smartphones and computers. With the publicly available risk tables, and the ASCCP navigation app, the guidelines will more easily accommodate updates as new information and technology become available.

OBG Management: The latest ASCCP guidelines, published in April, represent a “paradigm shift” from results to risk-based guidelines. Can you explain what this means and why the shift was undertaken?

Warner K. Huh, MD: Yes, the shift occurred because we needed to focus less on algorithms and more on risk. We started promulgating a concept of “equal management for equal risk” back in 2012. What this means is that if we have a method to look up a risk score based on relevant test results and other pieces of information, then all patients with that score should be managed in the same manner. We wanted that to be the underlying principle.

Focusing on risk tables also makes it easier to incorporate any future technologies used for risk estimation without having to rebuild algorithms from scratch. ASCCP is developing a new management guidelines app to streamline navigation of the guidelines. This app makes them easier for clinicians to use; they simply plug in certain variables from the patient’s history and receive 1 of 5 outputs: treatment, colposcopy, or surveillance at 1, 3, or 5 years.

The only drawbacks, if you view them as such, are that the clinician must plug in all the variables, and then must sit back and trust in what we have done. Clinicians have to trust that the system works and will simplify the clinical decision making.

We spent a lot of time determining what the risk thresholds should be. Some may argue they are arbitrary, but the decisions were data-driven, and carefully, thoughtfully vetted; we deliberated about whether the cut points actually made sense clinically to a practicing clinician base. The clinical action thresholds refer to a specific percentage below which a woman falls into one bucket and above which she falls into another bucket.

The other element that is unique about the guidelines is that instead of looking at the patient’s current screening result in isolation, the user sees it along with the prior one because prior history dictates subsequent risk.

It’s important that clinicians understand why this system is so markedly different from what we have done previously, and why risk-based guidelines make infinitely more sense than algorithmic ones. It’s because: 1) they can be easier to use; 2) they incorporate new data more efficiently and effectively than algorithm-based guidelines; and 3) they can incorporate future technologies seamlessly rather than having to create yet another algorithm.

Continue to: OBG Management : What do clinicians need in order to execute the guidelines?...

OBG Management: What do clinicians need in order to execute the guidelines?

Dr. Huh: Nothing. All of the information needed—the guidelines article and risk tables—are publicly available. However, to make navigation of the guidelines easier, the plan is for the app that I mentioned. I have the app on my phone and am actively beta testing it now. We’re planning on creating a web-based application as well, that will allow users to access the Internet and their electronic health record system so that they can plug in information directly from patient charts. The web-based app will be similar to the web-based Breast Cancer Surveillance Consortium’s Risk Calculator (https://tools.bcsc-scc.org/BC5yearRisk/calculator.htm). You will pull it up, plug in the requested information, including the patient’s age; their Pap smear and genotyping results; and their previous screening history.

OBG Management: When will the app be available for users?

Dr. Huh: It will be available for release on June 8.

OBG Management: Were HPV vaccination levels incorporated into the new guidelines?

OBG Management: Have recommendations regarding colposcopy changed?

Dr. Huh: Not really. About 3 years ago, we created basic colposcopy guidelines—the ASCCP Colposcopy Standards—so everything about colposcopy references back to those guidelines. Those colposcopy standards covered terminology and risk-based colposcopy, which actually aligns beautifully with these guidelines.

OBG Management: To narrow in on some changes from the prior guidelines, can colposcopy be deferred in certain patients?

Dr. Huh: Yes. Not everyone who has an abnormal screening test needs to come back for colposcopy.

OBG Management: How has guidance for expedited treatment or treatment without colposcopic biopsy changed?

Dr. Huh: This was heavily debated within not only the treatment group that I co-chaired with Richard Guido, MD, but also within the entire steering committee. The recommendation is that if the patient has an immediate risk of CIN 3 that is >60%, the patient should go straight to treatment without a colposcopic biopsy. The main reason for this is that you do not want to biopsy a patient and then lose them to follow-up.

When a woman has >60% immediate risk of CIN 3, we are fairly certain that colposcopy is not going to change management ultimately, so we recommend that patients receive treatment right away. We have already been doing this for 15 to 20 years, so this is not a new concept. It is just more formally codified here by assigning a percentage to the risk. Those who have between 25% and 60% immediate risk of CIN 3 should receive immediate colposcopy. We realize that not all clinicians have the ability to do this, so if clinicians can’t treat immediately, we recommend they do whatever they can to prevent losing the patient to follow-up.

OBG Management: How should a positive primary HPV screening test be managed?

Dr. Huh: If a woman has a positive primary HPV screening test, genotyping should be performed. If genotyping reveals HPV 16 or 18, then the patient should proceed to colposcopy. If genotyping reveals other forms of HPV, reflex cytology or a Pap smear should follow. ●

Although pelvic examinations may only last a few minutes, the examination is scary and uncomfortable for many patients. To help minimize fear and discomfort, the exam should take place in a comfortable and professional environment. The clinician should provide appropriate gowns, private facilities for undressing, sensitively use draping, and clearly explain the components of the examination. Trained professional chaperones play an important role in intimate physical examinations, including:

• providing reassurance to the patient of the professional integrity of the intimate examination
• supporting and educating the patient during the examination
• increasing the efficiency of the clinician during a procedure
• acting as a witness should a misunderstanding with the patient arise.

Major medical professional societies have issued guidance to clinicians on the use of a chaperone during intimate physical examinations. Professional society guidance ranges from endorsing joint decision-making between physician and patient on the presence of a chaperone to more proscriptive guidance that emphasizes the importance of a chaperone at every intimate physical examination.

Examples of professional societies’ guidance that supports joint decision-making between physician and patient about the presence of a chaperone include:

• American Medical Association: “Adopt a policy that patients are free to request a chaperone and ensure that the policy is communicated to patients. Always honor a patient’s request to have a chaperone.”¹
• Society of Obstetricians and Gynaecologists of Canada: “It is a reasonable and acceptable practice to perform a physical examination, including breast and pelvic examination without the presence of a third person in the room unless the woman or health care provider indicates a desire for a third party to be present.” “If the health care provider chooses to have a third person present during all examinations, the health care provider should explain this policy to the woman.”²
• American College of Physicians: “Care and respect should guide the performance of the physical examination. The location and degree of privacy should be appropriate for the examination being performed, with chaperone services as an option. An appropriate setting and sufficient time should be allocated to encourage exploration of aspects of the patient’s life pertinent to health, including habits, relationships, sexuality, vocation, culture, religion, and spirituality.”³

By contrast, the following professional society guidance strongly recommends the presence of a chaperone for every intimate physical examination:

• United States Veterans Administration: “A female chaperone must be in the examination room during breast and pelvic exams…this includes procedures such as urodynamic testing or treatments such as pelvic floor physical therapy.”⁴
• Royal College of Obstetricians and Gynaecologists: “The presence of a chaperone is considered essential for every pelvic examination. Verbal consent should be obtained in the presence of the chaperone who is to be present during the examination and recorded in the notes. If the patient declines the presence of a chaperone, the doctor should explain that a chaperone is also required to help in many cases and then attempt to arrange for the chaperone to be standing nearby within earshot. The reasons for declining a chaperone and alternative arrangements offered should be documented. Consent should also be specific to whether the intended examination is vaginal, rectal or both. Communication skills are essential in conducting intimate examinations.”⁵
• American College Health Association (ACHA): “It is ACHA’s recommendation that, as part of institutional policy, a chaperone be provided for every sensitive medical examination and procedure.”⁶

Continue to: New guidance from ACOG on trained chaperones...

New guidance from ACOG on trained chaperones

The American College of Obstetricians and Gynecologists (ACOG) recently issued a committee opinion recommending “that a chaperone be present for all breast, genital, and rectal examinations. The need for a chaperone is irrespective of the sex or gender of the person performing the examination and applies to examinations performed in the outpatient and inpatient settings, including labor and delivery, as well as during diagnostic studies such as transvaginal ultrasonography and urodynamic testing.”⁷

This new proscriptive guidance will significantly change practice for the many obstetrician-gynecologists who do not routinely have a chaperone present during intimate examinations. The policy provides exceptions to the presence of a chaperone in cases of medical emergencies and if the patient declines a chaperone. ACOG recommends that when a patient declines a chaperone the clinician should educate the patient that a “chaperone is an integral part of the clinical team whose role includes assisting with the examination and protecting the patient and the physician. Any concerns the patient has regarding the presence of a chaperone should be elicited and addressed if feasible. If, after counseling, the patient refuses the chaperone, this decision should be respected and documented in the medical record.”⁷ ACOG discourages the use of family members, medical students, and residents as chaperones.

Training of chaperones

Chaperones are health care professionals who should be trained for their specific role. Chaperones need to protect patient privacy and the confidentiality of health information. Chaperones should be trained to recognize the components of a professional intimate examination and to identify variances from standard practice. In many ambulatory practices, medical assistants perform the role of chaperone. The American Association of Medical Assistants (AAMA) offers national certification for medical assistants through an examination developed by the National Board of Medical Examiners. To be eligible for AAMA certification an individual must complete at least two semesters of medical assisting education that includes courses in anatomy, physiology, pharmacology, and relevant mathematics.

Reporting variances that occur during an intimate examination

Best practices are evolving on how to deal with the rare event of a chaperone witnessing a physician perform an intimate examination that is outside of standard professional practice. Chaperones may be reluctant to report a variance because physicians are in a powerful position, and the accuracy of their report will be challenged, threatening the chaperone’s employment. Processes for encouraging all team members to report concerns must be clearly explained to the chaperone and other members of the health care team. Clinicians should be aware that deviations from standard practice will be reported and investigated. Medical practices must develop a reporting system that ensures the reporting individual will be protected from retaliation.

In addition, the chaperone needs to know to whom they should report a variance. In large multispecialty medical practices, chaperones often can report concerns to nursing leaders or human resources. In small ambulatory practices, chaperones may be advised to report concerns about a physician to the practice manager or medical director. Regardless, every practice should have the best process for reporting a concern. In turn, the practice leaders who are responsible for investigating reports of concerning behavior should have a defined process for confidentially interviewing the chaperone, clinician, and patient.

Even when a chaperone is present for intimate examinations, problems can arise if the chaperone is not trained to recognize variances from standard practice or does not have a clear means for reporting variances and when the practice does not have a process for investigating reported variances.

Sadly, misconduct has been documented among priests, ministers, sports coaches, professors, scout masters, and clinicians. Trusted professionals are in positions of power in relation to their clients, patients, and students. Physicians and nurses are held in high esteem and trust by patients. To preserve the trust of the public we must treat all people with dignity and respect their autonomy. The presence of a chaperone during intimate examinations may help us fulfill Hippocrates’ edict, “First, do no harm.” ●

Although pelvic examinations may only last a few minutes, the examination is scary and uncomfortable for many patients. To help minimize fear and discomfort, the exam should take place in a comfortable and professional environment. The clinician should provide appropriate gowns, private facilities for undressing, sensitively use draping, and clearly explain the components of the examination. Trained professional chaperones play an important role in intimate physical examinations, including:

• providing reassurance to the patient of the professional integrity of the intimate examination
• supporting and educating the patient during the examination
• increasing the efficiency of the clinician during a procedure
• acting as a witness should a misunderstanding with the patient arise.

Major medical professional societies have issued guidance to clinicians on the use of a chaperone during intimate physical examinations. Professional society guidance ranges from endorsing joint decision-making between physician and patient on the presence of a chaperone to more proscriptive guidance that emphasizes the importance of a chaperone at every intimate physical examination.

Examples of professional societies’ guidance that supports joint decision-making between physician and patient about the presence of a chaperone include:

• American Medical Association: “Adopt a policy that patients are free to request a chaperone and ensure that the policy is communicated to patients. Always honor a patient’s request to have a chaperone.”¹
• Society of Obstetricians and Gynaecologists of Canada: “It is a reasonable and acceptable practice to perform a physical examination, including breast and pelvic examination without the presence of a third person in the room unless the woman or health care provider indicates a desire for a third party to be present.” “If the health care provider chooses to have a third person present during all examinations, the health care provider should explain this policy to the woman.”²
• American College of Physicians: “Care and respect should guide the performance of the physical examination. The location and degree of privacy should be appropriate for the examination being performed, with chaperone services as an option. An appropriate setting and sufficient time should be allocated to encourage exploration of aspects of the patient’s life pertinent to health, including habits, relationships, sexuality, vocation, culture, religion, and spirituality.”³

By contrast, the following professional society guidance strongly recommends the presence of a chaperone for every intimate physical examination:

• United States Veterans Administration: “A female chaperone must be in the examination room during breast and pelvic exams…this includes procedures such as urodynamic testing or treatments such as pelvic floor physical therapy.”⁴
• Royal College of Obstetricians and Gynaecologists: “The presence of a chaperone is considered essential for every pelvic examination. Verbal consent should be obtained in the presence of the chaperone who is to be present during the examination and recorded in the notes. If the patient declines the presence of a chaperone, the doctor should explain that a chaperone is also required to help in many cases and then attempt to arrange for the chaperone to be standing nearby within earshot. The reasons for declining a chaperone and alternative arrangements offered should be documented. Consent should also be specific to whether the intended examination is vaginal, rectal or both. Communication skills are essential in conducting intimate examinations.”⁵
• American College Health Association (ACHA): “It is ACHA’s recommendation that, as part of institutional policy, a chaperone be provided for every sensitive medical examination and procedure.”⁶

Continue to: New guidance from ACOG on trained chaperones...

New guidance from ACOG on trained chaperones

The American College of Obstetricians and Gynecologists (ACOG) recently issued a committee opinion recommending “that a chaperone be present for all breast, genital, and rectal examinations. The need for a chaperone is irrespective of the sex or gender of the person performing the examination and applies to examinations performed in the outpatient and inpatient settings, including labor and delivery, as well as during diagnostic studies such as transvaginal ultrasonography and urodynamic testing.”⁷

This new proscriptive guidance will significantly change practice for the many obstetrician-gynecologists who do not routinely have a chaperone present during intimate examinations. The policy provides exceptions to the presence of a chaperone in cases of medical emergencies and if the patient declines a chaperone. ACOG recommends that when a patient declines a chaperone the clinician should educate the patient that a “chaperone is an integral part of the clinical team whose role includes assisting with the examination and protecting the patient and the physician. Any concerns the patient has regarding the presence of a chaperone should be elicited and addressed if feasible. If, after counseling, the patient refuses the chaperone, this decision should be respected and documented in the medical record.”⁷ ACOG discourages the use of family members, medical students, and residents as chaperones.

Training of chaperones

Chaperones are health care professionals who should be trained for their specific role. Chaperones need to protect patient privacy and the confidentiality of health information. Chaperones should be trained to recognize the components of a professional intimate examination and to identify variances from standard practice. In many ambulatory practices, medical assistants perform the role of chaperone. The American Association of Medical Assistants (AAMA) offers national certification for medical assistants through an examination developed by the National Board of Medical Examiners. To be eligible for AAMA certification an individual must complete at least two semesters of medical assisting education that includes courses in anatomy, physiology, pharmacology, and relevant mathematics.

Reporting variances that occur during an intimate examination

Best practices are evolving on how to deal with the rare event of a chaperone witnessing a physician perform an intimate examination that is outside of standard professional practice. Chaperones may be reluctant to report a variance because physicians are in a powerful position, and the accuracy of their report will be challenged, threatening the chaperone’s employment. Processes for encouraging all team members to report concerns must be clearly explained to the chaperone and other members of the health care team. Clinicians should be aware that deviations from standard practice will be reported and investigated. Medical practices must develop a reporting system that ensures the reporting individual will be protected from retaliation.

In addition, the chaperone needs to know to whom they should report a variance. In large multispecialty medical practices, chaperones often can report concerns to nursing leaders or human resources. In small ambulatory practices, chaperones may be advised to report concerns about a physician to the practice manager or medical director. Regardless, every practice should have the best process for reporting a concern. In turn, the practice leaders who are responsible for investigating reports of concerning behavior should have a defined process for confidentially interviewing the chaperone, clinician, and patient.

Even when a chaperone is present for intimate examinations, problems can arise if the chaperone is not trained to recognize variances from standard practice or does not have a clear means for reporting variances and when the practice does not have a process for investigating reported variances.

Sadly, misconduct has been documented among priests, ministers, sports coaches, professors, scout masters, and clinicians. Trusted professionals are in positions of power in relation to their clients, patients, and students. Physicians and nurses are held in high esteem and trust by patients. To preserve the trust of the public we must treat all people with dignity and respect their autonomy. The presence of a chaperone during intimate examinations may help us fulfill Hippocrates’ edict, “First, do no harm.” ●

Although pelvic examinations may only last a few minutes, the examination is scary and uncomfortable for many patients. To help minimize fear and discomfort, the exam should take place in a comfortable and professional environment. The clinician should provide appropriate gowns, private facilities for undressing, sensitively use draping, and clearly explain the components of the examination. Trained professional chaperones play an important role in intimate physical examinations, including:

• providing reassurance to the patient of the professional integrity of the intimate examination
• supporting and educating the patient during the examination
• increasing the efficiency of the clinician during a procedure
• acting as a witness should a misunderstanding with the patient arise.

Major medical professional societies have issued guidance to clinicians on the use of a chaperone during intimate physical examinations. Professional society guidance ranges from endorsing joint decision-making between physician and patient on the presence of a chaperone to more proscriptive guidance that emphasizes the importance of a chaperone at every intimate physical examination.

Examples of professional societies’ guidance that supports joint decision-making between physician and patient about the presence of a chaperone include:

• American Medical Association: “Adopt a policy that patients are free to request a chaperone and ensure that the policy is communicated to patients. Always honor a patient’s request to have a chaperone.”¹
• Society of Obstetricians and Gynaecologists of Canada: “It is a reasonable and acceptable practice to perform a physical examination, including breast and pelvic examination without the presence of a third person in the room unless the woman or health care provider indicates a desire for a third party to be present.” “If the health care provider chooses to have a third person present during all examinations, the health care provider should explain this policy to the woman.”²
• American College of Physicians: “Care and respect should guide the performance of the physical examination. The location and degree of privacy should be appropriate for the examination being performed, with chaperone services as an option. An appropriate setting and sufficient time should be allocated to encourage exploration of aspects of the patient’s life pertinent to health, including habits, relationships, sexuality, vocation, culture, religion, and spirituality.”³

By contrast, the following professional society guidance strongly recommends the presence of a chaperone for every intimate physical examination:

• United States Veterans Administration: “A female chaperone must be in the examination room during breast and pelvic exams…this includes procedures such as urodynamic testing or treatments such as pelvic floor physical therapy.”⁴
• Royal College of Obstetricians and Gynaecologists: “The presence of a chaperone is considered essential for every pelvic examination. Verbal consent should be obtained in the presence of the chaperone who is to be present during the examination and recorded in the notes. If the patient declines the presence of a chaperone, the doctor should explain that a chaperone is also required to help in many cases and then attempt to arrange for the chaperone to be standing nearby within earshot. The reasons for declining a chaperone and alternative arrangements offered should be documented. Consent should also be specific to whether the intended examination is vaginal, rectal or both. Communication skills are essential in conducting intimate examinations.”⁵
• American College Health Association (ACHA): “It is ACHA’s recommendation that, as part of institutional policy, a chaperone be provided for every sensitive medical examination and procedure.”⁶

Continue to: New guidance from ACOG on trained chaperones...

New guidance from ACOG on trained chaperones

The American College of Obstetricians and Gynecologists (ACOG) recently issued a committee opinion recommending “that a chaperone be present for all breast, genital, and rectal examinations. The need for a chaperone is irrespective of the sex or gender of the person performing the examination and applies to examinations performed in the outpatient and inpatient settings, including labor and delivery, as well as during diagnostic studies such as transvaginal ultrasonography and urodynamic testing.”⁷

This new proscriptive guidance will significantly change practice for the many obstetrician-gynecologists who do not routinely have a chaperone present during intimate examinations. The policy provides exceptions to the presence of a chaperone in cases of medical emergencies and if the patient declines a chaperone. ACOG recommends that when a patient declines a chaperone the clinician should educate the patient that a “chaperone is an integral part of the clinical team whose role includes assisting with the examination and protecting the patient and the physician. Any concerns the patient has regarding the presence of a chaperone should be elicited and addressed if feasible. If, after counseling, the patient refuses the chaperone, this decision should be respected and documented in the medical record.”⁷ ACOG discourages the use of family members, medical students, and residents as chaperones.

Training of chaperones

Chaperones are health care professionals who should be trained for their specific role. Chaperones need to protect patient privacy and the confidentiality of health information. Chaperones should be trained to recognize the components of a professional intimate examination and to identify variances from standard practice. In many ambulatory practices, medical assistants perform the role of chaperone. The American Association of Medical Assistants (AAMA) offers national certification for medical assistants through an examination developed by the National Board of Medical Examiners. To be eligible for AAMA certification an individual must complete at least two semesters of medical assisting education that includes courses in anatomy, physiology, pharmacology, and relevant mathematics.

Reporting variances that occur during an intimate examination

Best practices are evolving on how to deal with the rare event of a chaperone witnessing a physician perform an intimate examination that is outside of standard professional practice. Chaperones may be reluctant to report a variance because physicians are in a powerful position, and the accuracy of their report will be challenged, threatening the chaperone’s employment. Processes for encouraging all team members to report concerns must be clearly explained to the chaperone and other members of the health care team. Clinicians should be aware that deviations from standard practice will be reported and investigated. Medical practices must develop a reporting system that ensures the reporting individual will be protected from retaliation.

In addition, the chaperone needs to know to whom they should report a variance. In large multispecialty medical practices, chaperones often can report concerns to nursing leaders or human resources. In small ambulatory practices, chaperones may be advised to report concerns about a physician to the practice manager or medical director. Regardless, every practice should have the best process for reporting a concern. In turn, the practice leaders who are responsible for investigating reports of concerning behavior should have a defined process for confidentially interviewing the chaperone, clinician, and patient.

Even when a chaperone is present for intimate examinations, problems can arise if the chaperone is not trained to recognize variances from standard practice or does not have a clear means for reporting variances and when the practice does not have a process for investigating reported variances.

Sadly, misconduct has been documented among priests, ministers, sports coaches, professors, scout masters, and clinicians. Trusted professionals are in positions of power in relation to their clients, patients, and students. Physicians and nurses are held in high esteem and trust by patients. To preserve the trust of the public we must treat all people with dignity and respect their autonomy. The presence of a chaperone during intimate examinations may help us fulfill Hippocrates’ edict, “First, do no harm.” ●

I am not an elite athlete. Never have been, never will be. But as I contemplated how to support my colleagues at my hospital during the COVID-19 pandemic—knowing that we face more weeks of social distancing, probable virus outbreaks as business opens up, and myriad changes in how we will practice medicine—I wondered how Olympic athletes focus their mental and physical stamina to respond to the challenges of competition.

In this article, I offer some pointers, gleaned from techniques used by exceptional athletes, on how we can maintain our stamina during the COVID-19 marathon.

Tinseltown/Shutterstock

Train your mind

Elite athletes understand that what will take them to the top of their sport is less about their physical gifts (all elite athletes have superior athletic talent) and more about how they train their minds to achieve their goals. As basketball great Kareem Abdul-Jabbar said, “Your mind is what makes everything else work.” Not surprisingly, athletes who train to be mentally “tough” have a better chance to reach the podium.

One definition of mental toughness is the “ability to perform toward the upper range of your talent and skill” regardless of external circumstances.¹ Mental toughness involves an unshakable self-belief, resilience, motivation, focus, and ability to perform under pressure and manage physical and emotional pain.

Like me, most of you probably are not elite athletes, but you can train your mind to be tougher and increase your stamina using some of the following techniques.

Think positively

Do you find yourself dealing with an inner monologue of fear, self-doubt, and feelings of worthlessness? That is the Obnoxious Roommate in your head as described in a HuffPost article and based on the pioneering work of psychiatrist Aaron Beck, MD, the father of cognitive-behavioral therapy.^2,3 Such thoughts negatively affect one’s sense of self-efficacy, which is the mental state of believing that you can meet the challenges you face. Elite athletes pay particular attention to their self-talk and replace negative thoughts with positive ones. These may include affirmations of your strengths or cue words that pump you up or help you manage your nerves.

To begin this practice, first observe what you are telling yourself. You may be saying, “I can’t do this. This is too hard.” This is an important step because you may have lived with the Obnoxious Roommate for so long that these thoughts are automatic and seem like a part of you. If, however, you first observe the thought and acknowledge it, you can begin to replace negative thoughts with supportive ones: “This is hard, but I can do this. I am intelligent, strong, capable, and ready.” While practice and repetition are required, thinking positively eventually will become a habit of self-support. Elite athletes know that to reach the top, they need to become their own best friend.⁴

Continue to: Use visualization...

Use visualization

Elite athletes visualize their events in such meticulous detail that they can actually feel their feet on the track, their muscles tensing, the starter pistol going off, the roar of the crowd. Research shows that the part of the brain that is activated in a race is also activated when one visualizes the race. It is as though the race is happening in real time.⁵ Physicians could use this approach to visualize the day ahead, picturing the procedures in detail and the clinical encounters going well.

In the current crisis, we frequently need a way to calm down quickly. One suggestion is to find a quiet space and sit for a few minutes, allowing the chair to support you. Then imagine a beautiful, calm, soothing place. Relax there and take in that feeling. Or, imagine a past achievement when you felt good about yourself. See yourself in that moment, remember how you felt, and take it in.

Plan for setbacks

All elite athletes have setbacks: Marathon runners hit a wall, golfers hit into the rough. But they don’t spin out of control at setbacks. They expect them, and they have practiced skills to restore their confidence and re-center themselves.⁶ For example, some athletes calm themselves by performing a ritualized series of movements. Others use a specific phrase (that positive self-talk again!) that reminds them of their goals or skills, while others play specific songs on their media player, or in their head, to return to their center.

Another technique is to use deep, rhythmic, diaphragmatic breathing for about 30 seconds to bring yourself back to your body.

The point is to have a plan in place to respond to setbacks in a positive manner and get back on track. Don’t waste time on self-criticism.

Continue to: Manage stress...

Manage stress

Not all stress is negative. Everyone has a “sweet spot,” a level of activation from which we operate best.¹ If we go too far over that level, though, we can panic. If we aren’t stressed enough, it is hard to get going at all.

If you need to be pumped up to function at your best, try playing music that energizes you. If you work best when you are calm, take deep breaths and attend to the exhalation while you engage in positive self-talk.

Another way to manage stress levels during the COVID-19 pandemic is to employ the ESCAPE mnemonic:

• Exercise. Research shows that regular aerobic exercise is a potent stress reliever; it raises endorphin levels, provides a general sense of well-being, and improves immune function.⁷ If you exercise regularly, do everything possible to keep doing so. If you do not have an exercise routine, try taking walks. Get out into the fresh air, pay attention to your surroundings, and work to be present in your body as you move.
• Sleep. Getting adequate sleep, 7 to 9 hours a night for most people, is important for maintaining physical and emotional health.⁸ Elite athletes pay particular attention to sleep because they know that their bodies need to recharge. The COVID-19 crisis has affected sleep for many, and we need to consciously attend to sleep hygiene. This includes limiting use of screen time to no more than 2 hours before bed. As well, limit your intake of the news and definitely avoid it right before bedtime. Take a warm shower, drink a cup of herbal tea, or read a less-than-stimulating journal article. Make sure your bedroom is cool and dark. Keep a regular bedtime and wake up at a regular time.
• Connect. Despite the current need for physical distancing, do not neglect your need to connect to those you love and care about. Whatever modality works for you—telephone, e-mail, video conferencing—if you feel lonely, reach out. Friends and families are concerned about us, and it makes them feel useful to support us. Allow that.
• Appreciate/cultivate gratitude. Look for causes for celebration in your life, whether that is your family, friends, or that you have a job and a home. Perhaps it is the cleaner air or the beauty of nature. Whatever you are grateful for, acknowledge it, perhaps by writing it down in a journal. Remembering these things can serve as an antidote to the stress created by the COVID-19 crisis.
• Play. Seek out things that make you laugh.⁹ Find your inner goofiness. Get creative and paint, sing, garden, golf, play an instrument, dance, do puzzles, or play games. We need to remember the pleasures in life when times are dark. Find whatever feels like joy.
• Exhale. If you have a meditation practice continue to do it. If not, consider starting. Try yoga as a way to center yourself in your body. Elite athletes use meditation and yoga to harness their minds and bodies to feel more in control.¹⁰ When so many things feel out of our control and unpredictable, it can be immensely soothing to connect to yourself in this way and realize you can reliably relax.

Self-care is a necessity

While we are in a marathon not of our choosing, we can use the techniques of elite athletes to think positively, visualize scenarios to achieve our goals or to simply relax, plan for setbacks so that we can bounce back, and manage stress productively. Self-care is paramount as we continue to care for others. Let’s not neglect ourselves, and we will cross the finish line together. ●

I am not an elite athlete. Never have been, never will be. But as I contemplated how to support my colleagues at my hospital during the COVID-19 pandemic—knowing that we face more weeks of social distancing, probable virus outbreaks as business opens up, and myriad changes in how we will practice medicine—I wondered how Olympic athletes focus their mental and physical stamina to respond to the challenges of competition.

In this article, I offer some pointers, gleaned from techniques used by exceptional athletes, on how we can maintain our stamina during the COVID-19 marathon.

Tinseltown/Shutterstock

Train your mind

Elite athletes understand that what will take them to the top of their sport is less about their physical gifts (all elite athletes have superior athletic talent) and more about how they train their minds to achieve their goals. As basketball great Kareem Abdul-Jabbar said, “Your mind is what makes everything else work.” Not surprisingly, athletes who train to be mentally “tough” have a better chance to reach the podium.

One definition of mental toughness is the “ability to perform toward the upper range of your talent and skill” regardless of external circumstances.¹ Mental toughness involves an unshakable self-belief, resilience, motivation, focus, and ability to perform under pressure and manage physical and emotional pain.

Like me, most of you probably are not elite athletes, but you can train your mind to be tougher and increase your stamina using some of the following techniques.

Think positively

Do you find yourself dealing with an inner monologue of fear, self-doubt, and feelings of worthlessness? That is the Obnoxious Roommate in your head as described in a HuffPost article and based on the pioneering work of psychiatrist Aaron Beck, MD, the father of cognitive-behavioral therapy.^2,3 Such thoughts negatively affect one’s sense of self-efficacy, which is the mental state of believing that you can meet the challenges you face. Elite athletes pay particular attention to their self-talk and replace negative thoughts with positive ones. These may include affirmations of your strengths or cue words that pump you up or help you manage your nerves.

To begin this practice, first observe what you are telling yourself. You may be saying, “I can’t do this. This is too hard.” This is an important step because you may have lived with the Obnoxious Roommate for so long that these thoughts are automatic and seem like a part of you. If, however, you first observe the thought and acknowledge it, you can begin to replace negative thoughts with supportive ones: “This is hard, but I can do this. I am intelligent, strong, capable, and ready.” While practice and repetition are required, thinking positively eventually will become a habit of self-support. Elite athletes know that to reach the top, they need to become their own best friend.⁴

Continue to: Use visualization...

Use visualization

Elite athletes visualize their events in such meticulous detail that they can actually feel their feet on the track, their muscles tensing, the starter pistol going off, the roar of the crowd. Research shows that the part of the brain that is activated in a race is also activated when one visualizes the race. It is as though the race is happening in real time.⁵ Physicians could use this approach to visualize the day ahead, picturing the procedures in detail and the clinical encounters going well.

In the current crisis, we frequently need a way to calm down quickly. One suggestion is to find a quiet space and sit for a few minutes, allowing the chair to support you. Then imagine a beautiful, calm, soothing place. Relax there and take in that feeling. Or, imagine a past achievement when you felt good about yourself. See yourself in that moment, remember how you felt, and take it in.

Plan for setbacks

All elite athletes have setbacks: Marathon runners hit a wall, golfers hit into the rough. But they don’t spin out of control at setbacks. They expect them, and they have practiced skills to restore their confidence and re-center themselves.⁶ For example, some athletes calm themselves by performing a ritualized series of movements. Others use a specific phrase (that positive self-talk again!) that reminds them of their goals or skills, while others play specific songs on their media player, or in their head, to return to their center.

Another technique is to use deep, rhythmic, diaphragmatic breathing for about 30 seconds to bring yourself back to your body.

The point is to have a plan in place to respond to setbacks in a positive manner and get back on track. Don’t waste time on self-criticism.

Continue to: Manage stress...

Manage stress

Not all stress is negative. Everyone has a “sweet spot,” a level of activation from which we operate best.¹ If we go too far over that level, though, we can panic. If we aren’t stressed enough, it is hard to get going at all.

If you need to be pumped up to function at your best, try playing music that energizes you. If you work best when you are calm, take deep breaths and attend to the exhalation while you engage in positive self-talk.

Another way to manage stress levels during the COVID-19 pandemic is to employ the ESCAPE mnemonic:

• Exercise. Research shows that regular aerobic exercise is a potent stress reliever; it raises endorphin levels, provides a general sense of well-being, and improves immune function.⁷ If you exercise regularly, do everything possible to keep doing so. If you do not have an exercise routine, try taking walks. Get out into the fresh air, pay attention to your surroundings, and work to be present in your body as you move.
• Sleep. Getting adequate sleep, 7 to 9 hours a night for most people, is important for maintaining physical and emotional health.⁸ Elite athletes pay particular attention to sleep because they know that their bodies need to recharge. The COVID-19 crisis has affected sleep for many, and we need to consciously attend to sleep hygiene. This includes limiting use of screen time to no more than 2 hours before bed. As well, limit your intake of the news and definitely avoid it right before bedtime. Take a warm shower, drink a cup of herbal tea, or read a less-than-stimulating journal article. Make sure your bedroom is cool and dark. Keep a regular bedtime and wake up at a regular time.
• Connect. Despite the current need for physical distancing, do not neglect your need to connect to those you love and care about. Whatever modality works for you—telephone, e-mail, video conferencing—if you feel lonely, reach out. Friends and families are concerned about us, and it makes them feel useful to support us. Allow that.
• Appreciate/cultivate gratitude. Look for causes for celebration in your life, whether that is your family, friends, or that you have a job and a home. Perhaps it is the cleaner air or the beauty of nature. Whatever you are grateful for, acknowledge it, perhaps by writing it down in a journal. Remembering these things can serve as an antidote to the stress created by the COVID-19 crisis.
• Play. Seek out things that make you laugh.⁹ Find your inner goofiness. Get creative and paint, sing, garden, golf, play an instrument, dance, do puzzles, or play games. We need to remember the pleasures in life when times are dark. Find whatever feels like joy.
• Exhale. If you have a meditation practice continue to do it. If not, consider starting. Try yoga as a way to center yourself in your body. Elite athletes use meditation and yoga to harness their minds and bodies to feel more in control.¹⁰ When so many things feel out of our control and unpredictable, it can be immensely soothing to connect to yourself in this way and realize you can reliably relax.

Self-care is a necessity

While we are in a marathon not of our choosing, we can use the techniques of elite athletes to think positively, visualize scenarios to achieve our goals or to simply relax, plan for setbacks so that we can bounce back, and manage stress productively. Self-care is paramount as we continue to care for others. Let’s not neglect ourselves, and we will cross the finish line together. ●

I am not an elite athlete. Never have been, never will be. But as I contemplated how to support my colleagues at my hospital during the COVID-19 pandemic—knowing that we face more weeks of social distancing, probable virus outbreaks as business opens up, and myriad changes in how we will practice medicine—I wondered how Olympic athletes focus their mental and physical stamina to respond to the challenges of competition.

In this article, I offer some pointers, gleaned from techniques used by exceptional athletes, on how we can maintain our stamina during the COVID-19 marathon.

Tinseltown/Shutterstock

Train your mind

Elite athletes understand that what will take them to the top of their sport is less about their physical gifts (all elite athletes have superior athletic talent) and more about how they train their minds to achieve their goals. As basketball great Kareem Abdul-Jabbar said, “Your mind is what makes everything else work.” Not surprisingly, athletes who train to be mentally “tough” have a better chance to reach the podium.

One definition of mental toughness is the “ability to perform toward the upper range of your talent and skill” regardless of external circumstances.¹ Mental toughness involves an unshakable self-belief, resilience, motivation, focus, and ability to perform under pressure and manage physical and emotional pain.

Like me, most of you probably are not elite athletes, but you can train your mind to be tougher and increase your stamina using some of the following techniques.

Think positively

Do you find yourself dealing with an inner monologue of fear, self-doubt, and feelings of worthlessness? That is the Obnoxious Roommate in your head as described in a HuffPost article and based on the pioneering work of psychiatrist Aaron Beck, MD, the father of cognitive-behavioral therapy.^2,3 Such thoughts negatively affect one’s sense of self-efficacy, which is the mental state of believing that you can meet the challenges you face. Elite athletes pay particular attention to their self-talk and replace negative thoughts with positive ones. These may include affirmations of your strengths or cue words that pump you up or help you manage your nerves.

To begin this practice, first observe what you are telling yourself. You may be saying, “I can’t do this. This is too hard.” This is an important step because you may have lived with the Obnoxious Roommate for so long that these thoughts are automatic and seem like a part of you. If, however, you first observe the thought and acknowledge it, you can begin to replace negative thoughts with supportive ones: “This is hard, but I can do this. I am intelligent, strong, capable, and ready.” While practice and repetition are required, thinking positively eventually will become a habit of self-support. Elite athletes know that to reach the top, they need to become their own best friend.⁴

Continue to: Use visualization...

Use visualization

Elite athletes visualize their events in such meticulous detail that they can actually feel their feet on the track, their muscles tensing, the starter pistol going off, the roar of the crowd. Research shows that the part of the brain that is activated in a race is also activated when one visualizes the race. It is as though the race is happening in real time.⁵ Physicians could use this approach to visualize the day ahead, picturing the procedures in detail and the clinical encounters going well.

In the current crisis, we frequently need a way to calm down quickly. One suggestion is to find a quiet space and sit for a few minutes, allowing the chair to support you. Then imagine a beautiful, calm, soothing place. Relax there and take in that feeling. Or, imagine a past achievement when you felt good about yourself. See yourself in that moment, remember how you felt, and take it in.

Plan for setbacks

All elite athletes have setbacks: Marathon runners hit a wall, golfers hit into the rough. But they don’t spin out of control at setbacks. They expect them, and they have practiced skills to restore their confidence and re-center themselves.⁶ For example, some athletes calm themselves by performing a ritualized series of movements. Others use a specific phrase (that positive self-talk again!) that reminds them of their goals or skills, while others play specific songs on their media player, or in their head, to return to their center.

Another technique is to use deep, rhythmic, diaphragmatic breathing for about 30 seconds to bring yourself back to your body.

The point is to have a plan in place to respond to setbacks in a positive manner and get back on track. Don’t waste time on self-criticism.

Continue to: Manage stress...

Manage stress

Not all stress is negative. Everyone has a “sweet spot,” a level of activation from which we operate best.¹ If we go too far over that level, though, we can panic. If we aren’t stressed enough, it is hard to get going at all.

If you need to be pumped up to function at your best, try playing music that energizes you. If you work best when you are calm, take deep breaths and attend to the exhalation while you engage in positive self-talk.

Another way to manage stress levels during the COVID-19 pandemic is to employ the ESCAPE mnemonic:

• Exercise. Research shows that regular aerobic exercise is a potent stress reliever; it raises endorphin levels, provides a general sense of well-being, and improves immune function.⁷ If you exercise regularly, do everything possible to keep doing so. If you do not have an exercise routine, try taking walks. Get out into the fresh air, pay attention to your surroundings, and work to be present in your body as you move.
• Sleep. Getting adequate sleep, 7 to 9 hours a night for most people, is important for maintaining physical and emotional health.⁸ Elite athletes pay particular attention to sleep because they know that their bodies need to recharge. The COVID-19 crisis has affected sleep for many, and we need to consciously attend to sleep hygiene. This includes limiting use of screen time to no more than 2 hours before bed. As well, limit your intake of the news and definitely avoid it right before bedtime. Take a warm shower, drink a cup of herbal tea, or read a less-than-stimulating journal article. Make sure your bedroom is cool and dark. Keep a regular bedtime and wake up at a regular time.
• Connect. Despite the current need for physical distancing, do not neglect your need to connect to those you love and care about. Whatever modality works for you—telephone, e-mail, video conferencing—if you feel lonely, reach out. Friends and families are concerned about us, and it makes them feel useful to support us. Allow that.
• Appreciate/cultivate gratitude. Look for causes for celebration in your life, whether that is your family, friends, or that you have a job and a home. Perhaps it is the cleaner air or the beauty of nature. Whatever you are grateful for, acknowledge it, perhaps by writing it down in a journal. Remembering these things can serve as an antidote to the stress created by the COVID-19 crisis.
• Play. Seek out things that make you laugh.⁹ Find your inner goofiness. Get creative and paint, sing, garden, golf, play an instrument, dance, do puzzles, or play games. We need to remember the pleasures in life when times are dark. Find whatever feels like joy.
• Exhale. If you have a meditation practice continue to do it. If not, consider starting. Try yoga as a way to center yourself in your body. Elite athletes use meditation and yoga to harness their minds and bodies to feel more in control.¹⁰ When so many things feel out of our control and unpredictable, it can be immensely soothing to connect to yourself in this way and realize you can reliably relax.

Self-care is a necessity

While we are in a marathon not of our choosing, we can use the techniques of elite athletes to think positively, visualize scenarios to achieve our goals or to simply relax, plan for setbacks so that we can bounce back, and manage stress productively. Self-care is paramount as we continue to care for others. Let’s not neglect ourselves, and we will cross the finish line together. ●

Background: A small proportion of patients accounts for a large proportion of hospital use and readmissions. As hospitals and hospitalists focus efforts to improve transitions of care, there is a paucity of data that incorporates patients’ perspectives into the design of these programs.

A research coordinator conducted one-on-one semistructured interviews. Each interview was recorded, transcribed, and then coded using a team-based approach; 26 patients completed the interview process. From the analysis, four major themes emerged: Major medical problems were universal but high hospital use onset varied; participants noted that fluctuations in their course were often related to social, economic, and psychological stressors; onset and progression of episodes seemed uncontrollable and unpredictable; participants preferred to avoid hospitalization and sought care when attempts at self-management failed. The major limitation of this study was the small sample size located at one medical center, creating a data pool that is potentially not generalizable to other medical centers. These findings, however, are an important reminder to focus our interventions with patients’ needs and perceptions in mind.

Bottom line: Frequently hospitalized patients have insights into factors contributing to their high hospital use. Engaging patients in this discussion can enable us to create sustainable patient-centered programs that avoid rehospitalization.

Citation: O’Leary KJ et al. Frequently hospitalized patients’ perceptions of factors contributing to high hospital use. J Hosp Med. 2019 Mar 20;14:e1-6.

Dr. Richardson is a hospitalist at Duke University Health System.

Background: A small proportion of patients accounts for a large proportion of hospital use and readmissions. As hospitals and hospitalists focus efforts to improve transitions of care, there is a paucity of data that incorporates patients’ perspectives into the design of these programs.

A research coordinator conducted one-on-one semistructured interviews. Each interview was recorded, transcribed, and then coded using a team-based approach; 26 patients completed the interview process. From the analysis, four major themes emerged: Major medical problems were universal but high hospital use onset varied; participants noted that fluctuations in their course were often related to social, economic, and psychological stressors; onset and progression of episodes seemed uncontrollable and unpredictable; participants preferred to avoid hospitalization and sought care when attempts at self-management failed. The major limitation of this study was the small sample size located at one medical center, creating a data pool that is potentially not generalizable to other medical centers. These findings, however, are an important reminder to focus our interventions with patients’ needs and perceptions in mind.

Bottom line: Frequently hospitalized patients have insights into factors contributing to their high hospital use. Engaging patients in this discussion can enable us to create sustainable patient-centered programs that avoid rehospitalization.

Citation: O’Leary KJ et al. Frequently hospitalized patients’ perceptions of factors contributing to high hospital use. J Hosp Med. 2019 Mar 20;14:e1-6.

Dr. Richardson is a hospitalist at Duke University Health System.

Background: A small proportion of patients accounts for a large proportion of hospital use and readmissions. As hospitals and hospitalists focus efforts to improve transitions of care, there is a paucity of data that incorporates patients’ perspectives into the design of these programs.

A research coordinator conducted one-on-one semistructured interviews. Each interview was recorded, transcribed, and then coded using a team-based approach; 26 patients completed the interview process. From the analysis, four major themes emerged: Major medical problems were universal but high hospital use onset varied; participants noted that fluctuations in their course were often related to social, economic, and psychological stressors; onset and progression of episodes seemed uncontrollable and unpredictable; participants preferred to avoid hospitalization and sought care when attempts at self-management failed. The major limitation of this study was the small sample size located at one medical center, creating a data pool that is potentially not generalizable to other medical centers. These findings, however, are an important reminder to focus our interventions with patients’ needs and perceptions in mind.

Bottom line: Frequently hospitalized patients have insights into factors contributing to their high hospital use. Engaging patients in this discussion can enable us to create sustainable patient-centered programs that avoid rehospitalization.

Citation: O’Leary KJ et al. Frequently hospitalized patients’ perceptions of factors contributing to high hospital use. J Hosp Med. 2019 Mar 20;14:e1-6.

Dr. Richardson is a hospitalist at Duke University Health System.

COVID-19 infection is associated with a high risk for mortality in heart transplant (HT) recipients, a new case series suggests.

Investigators looked at data on 28 patients with a confirmed diagnosis of COVID-19 who received a HT between March 1, 2020, and April 24, 2020 and found a case-fatality rate of 25%.

“The high case fatality in our case series should alert physicians to the vulnerability of heart transplant recipients during the COVID-19 pandemic,” senior author Nir Uriel, MD, MSc, professor of medicine at Columbia University, New York, said in an interview.

“These patients require extra precautions to prevent the development of infection,” said Dr. Uriel, who is also a cardiologist at New York Presbyterian/Columbia University Irving Medical Center.

The study was published online May 13 in JAMA Cardiology.
 

Similar presentation

HT recipients can have several comorbidities after the procedure, including hypertension, diabetes, cardiac allograft vasculopathy, and ongoing immunosuppression, all of which can place them at risk for infection and adverse outcomes with COVID-19 infection, the authors wrote.

The researchers therefore embarked on a case series looking at 28 HT recipients with COVID-19 infection (median age, 64.0 years; interquartile range, 53.5-70.5; 79% male) to “describe the outcomes of recipients of HT who are chronically immunosuppressed and develop COVID-19 and raise important questions about the role of the immune system in the process.”

The median time from HT to study period was 8.6 (IQR, 4.2-14.5) years. Most patients had numerous comorbidities.

Medscape.com

No protective effect

Twenty-two patients (79%) required admission to the hospital, seven of whom (25%) required admission to the ICU and mechanical ventilation.

Despite the presence of immunosuppressive therapy, all patients had significant elevation of inflammatory biomarkers (median peak high-sensitivity C-reactive protein [hs-CRP], 11.83 mg/dL; IQR, 7.44-19.26; median peak interleukin [IL]-6, 105 pg/mL; IQR, 38-296).

Three-quarters had myocardial injury, with a median high-sensitivity troponin T of 0.055 (0.0205 - 0.1345) ng/mL.

Treatments of COVID-19 included hydroxychloroquine (18 patients; 78%), high-dose corticosteroids (eight patients; 47%), and IL-6 receptor antagonists (six patients; 26%).

Moreover, during hospitalization, mycophenolate mofetil was discontinued in most (70%) patients, and one-quarter had a reduction in their calcineurin inhibitor dose.

“Heart transplant recipients generally require more intense immunosuppressive therapy than most other solid organ transplant recipients, and this high baseline immunosuppression increases their propensity to develop infections and their likelihood of experiencing severe manifestations of infections,” Dr. Uriel commented.

“With COVID-19, in which the body’s inflammatory reaction appears to play a role in disease severity, there has been a question of whether immunosuppression may offer a protective effect,” he continued.

“This case series suggests that this is not the case, although this would need to be confirmed in larger studies,” he said.
 

Low threshold

Among the 22 patients who were admitted to the hospital, half were discharged home and four (18%) were still hospitalized at the end of the study.

Of the seven patients who died, two died at the study center, and five died in an outside institution.

“In the HT population, social distancing (or isolation), strict use of masks when in public, proper handwashing, and sanitization of surfaces are of paramount importance in the prevention of COVID-19 infection,” Dr. Uriel stated.

“In addition, we have restricted these patients’ contact with the hospital as much as possible during the pandemic,” he said.

However, “there should be a low threshold to hospitalize heart transplant patients who develop infection with COVID-19. Furthermore, in our series, outcomes were better for patients hospitalized at the transplant center; therefore, strong consideration should be given to transferring HT patients when hospitalized at another hospital,” he added.

The authors emphasized that COVID-19 patients “will require ongoing monitoring in the recovery phase, as an immunosuppression regimen is reintroduced and the consequences to the allograft itself become apparent.”
 

Vulnerable population

Commenting on the study, Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston, suggested that “in epidemiological terms, [the findings] might not look as bad as the way they are reflected in the paper.”

Given that Columbia is “one of the larger heart transplant centers in the U.S., following probably 1,000 patients, having only 22 out of perhaps thousands whom they transplanted or are actively following would actually represent a low serious infection rate,” said Dr. Mehra, who is also the executive director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, also in Boston.

“We must not forget to emphasize that, when assessing these case fatality rates, we must look at the entire population at risk, not only the handful that we were able to observe,” explained Dr. Mehra, who was not involved with the study.

Moreover, the patients were “older and had comorbidities, with poor underlying kidney function and other complications, and underlying coronary artery disease in the transplanted heart,” so “it would not surprise me that they had such a high fatality rate, since they had a high degree of vulnerability,” he said.

Dr. Mehra, who is also the editor-in-chief of the Journal of Heart and Lung Transplantation, said that the journal has received manuscripts still in the review process that suggest different fatality rates than those found in the current case series.

However, he acknowledged that, because these are patients with serious vulnerability due to underlying heart disease, “you can’t be lackadaisical and need to do everything to decrease this vulnerability.”

The authors noted that, although their study did not show a protective effect from immunosuppression against COVID-19, further studies are needed to assess each individual immunosuppressive agent and provide a definitive answer.

The study was supported by a grant to one of the investigators from the National Heart, Lung, and Blood Institute. Dr. Uriel reports no relevant financial relationships. The other authors’ disclosures are listed in the publication. Dr. Mehra reports no relevant financial relationships.

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

COVID-19 infection is associated with a high risk for mortality in heart transplant (HT) recipients, a new case series suggests.

Investigators looked at data on 28 patients with a confirmed diagnosis of COVID-19 who received a HT between March 1, 2020, and April 24, 2020 and found a case-fatality rate of 25%.

“The high case fatality in our case series should alert physicians to the vulnerability of heart transplant recipients during the COVID-19 pandemic,” senior author Nir Uriel, MD, MSc, professor of medicine at Columbia University, New York, said in an interview.

“These patients require extra precautions to prevent the development of infection,” said Dr. Uriel, who is also a cardiologist at New York Presbyterian/Columbia University Irving Medical Center.

The study was published online May 13 in JAMA Cardiology.
 

Similar presentation

HT recipients can have several comorbidities after the procedure, including hypertension, diabetes, cardiac allograft vasculopathy, and ongoing immunosuppression, all of which can place them at risk for infection and adverse outcomes with COVID-19 infection, the authors wrote.

The researchers therefore embarked on a case series looking at 28 HT recipients with COVID-19 infection (median age, 64.0 years; interquartile range, 53.5-70.5; 79% male) to “describe the outcomes of recipients of HT who are chronically immunosuppressed and develop COVID-19 and raise important questions about the role of the immune system in the process.”

The median time from HT to study period was 8.6 (IQR, 4.2-14.5) years. Most patients had numerous comorbidities.

Medscape.com

No protective effect

Twenty-two patients (79%) required admission to the hospital, seven of whom (25%) required admission to the ICU and mechanical ventilation.

Despite the presence of immunosuppressive therapy, all patients had significant elevation of inflammatory biomarkers (median peak high-sensitivity C-reactive protein [hs-CRP], 11.83 mg/dL; IQR, 7.44-19.26; median peak interleukin [IL]-6, 105 pg/mL; IQR, 38-296).

Three-quarters had myocardial injury, with a median high-sensitivity troponin T of 0.055 (0.0205 - 0.1345) ng/mL.

Treatments of COVID-19 included hydroxychloroquine (18 patients; 78%), high-dose corticosteroids (eight patients; 47%), and IL-6 receptor antagonists (six patients; 26%).

Moreover, during hospitalization, mycophenolate mofetil was discontinued in most (70%) patients, and one-quarter had a reduction in their calcineurin inhibitor dose.

“Heart transplant recipients generally require more intense immunosuppressive therapy than most other solid organ transplant recipients, and this high baseline immunosuppression increases their propensity to develop infections and their likelihood of experiencing severe manifestations of infections,” Dr. Uriel commented.

“With COVID-19, in which the body’s inflammatory reaction appears to play a role in disease severity, there has been a question of whether immunosuppression may offer a protective effect,” he continued.

“This case series suggests that this is not the case, although this would need to be confirmed in larger studies,” he said.
 

Low threshold

Among the 22 patients who were admitted to the hospital, half were discharged home and four (18%) were still hospitalized at the end of the study.

Of the seven patients who died, two died at the study center, and five died in an outside institution.

“In the HT population, social distancing (or isolation), strict use of masks when in public, proper handwashing, and sanitization of surfaces are of paramount importance in the prevention of COVID-19 infection,” Dr. Uriel stated.

“In addition, we have restricted these patients’ contact with the hospital as much as possible during the pandemic,” he said.

However, “there should be a low threshold to hospitalize heart transplant patients who develop infection with COVID-19. Furthermore, in our series, outcomes were better for patients hospitalized at the transplant center; therefore, strong consideration should be given to transferring HT patients when hospitalized at another hospital,” he added.

The authors emphasized that COVID-19 patients “will require ongoing monitoring in the recovery phase, as an immunosuppression regimen is reintroduced and the consequences to the allograft itself become apparent.”
 

Vulnerable population

Commenting on the study, Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston, suggested that “in epidemiological terms, [the findings] might not look as bad as the way they are reflected in the paper.”

Given that Columbia is “one of the larger heart transplant centers in the U.S., following probably 1,000 patients, having only 22 out of perhaps thousands whom they transplanted or are actively following would actually represent a low serious infection rate,” said Dr. Mehra, who is also the executive director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, also in Boston.

“We must not forget to emphasize that, when assessing these case fatality rates, we must look at the entire population at risk, not only the handful that we were able to observe,” explained Dr. Mehra, who was not involved with the study.

Moreover, the patients were “older and had comorbidities, with poor underlying kidney function and other complications, and underlying coronary artery disease in the transplanted heart,” so “it would not surprise me that they had such a high fatality rate, since they had a high degree of vulnerability,” he said.

Dr. Mehra, who is also the editor-in-chief of the Journal of Heart and Lung Transplantation, said that the journal has received manuscripts still in the review process that suggest different fatality rates than those found in the current case series.

However, he acknowledged that, because these are patients with serious vulnerability due to underlying heart disease, “you can’t be lackadaisical and need to do everything to decrease this vulnerability.”

The authors noted that, although their study did not show a protective effect from immunosuppression against COVID-19, further studies are needed to assess each individual immunosuppressive agent and provide a definitive answer.

The study was supported by a grant to one of the investigators from the National Heart, Lung, and Blood Institute. Dr. Uriel reports no relevant financial relationships. The other authors’ disclosures are listed in the publication. Dr. Mehra reports no relevant financial relationships.

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

COVID-19 infection is associated with a high risk for mortality in heart transplant (HT) recipients, a new case series suggests.

Investigators looked at data on 28 patients with a confirmed diagnosis of COVID-19 who received a HT between March 1, 2020, and April 24, 2020 and found a case-fatality rate of 25%.

“The high case fatality in our case series should alert physicians to the vulnerability of heart transplant recipients during the COVID-19 pandemic,” senior author Nir Uriel, MD, MSc, professor of medicine at Columbia University, New York, said in an interview.

“These patients require extra precautions to prevent the development of infection,” said Dr. Uriel, who is also a cardiologist at New York Presbyterian/Columbia University Irving Medical Center.

The study was published online May 13 in JAMA Cardiology.
 

Similar presentation

HT recipients can have several comorbidities after the procedure, including hypertension, diabetes, cardiac allograft vasculopathy, and ongoing immunosuppression, all of which can place them at risk for infection and adverse outcomes with COVID-19 infection, the authors wrote.

The researchers therefore embarked on a case series looking at 28 HT recipients with COVID-19 infection (median age, 64.0 years; interquartile range, 53.5-70.5; 79% male) to “describe the outcomes of recipients of HT who are chronically immunosuppressed and develop COVID-19 and raise important questions about the role of the immune system in the process.”

The median time from HT to study period was 8.6 (IQR, 4.2-14.5) years. Most patients had numerous comorbidities.

Medscape.com

No protective effect

Twenty-two patients (79%) required admission to the hospital, seven of whom (25%) required admission to the ICU and mechanical ventilation.

Despite the presence of immunosuppressive therapy, all patients had significant elevation of inflammatory biomarkers (median peak high-sensitivity C-reactive protein [hs-CRP], 11.83 mg/dL; IQR, 7.44-19.26; median peak interleukin [IL]-6, 105 pg/mL; IQR, 38-296).

Three-quarters had myocardial injury, with a median high-sensitivity troponin T of 0.055 (0.0205 - 0.1345) ng/mL.

Treatments of COVID-19 included hydroxychloroquine (18 patients; 78%), high-dose corticosteroids (eight patients; 47%), and IL-6 receptor antagonists (six patients; 26%).

Moreover, during hospitalization, mycophenolate mofetil was discontinued in most (70%) patients, and one-quarter had a reduction in their calcineurin inhibitor dose.

“Heart transplant recipients generally require more intense immunosuppressive therapy than most other solid organ transplant recipients, and this high baseline immunosuppression increases their propensity to develop infections and their likelihood of experiencing severe manifestations of infections,” Dr. Uriel commented.

“With COVID-19, in which the body’s inflammatory reaction appears to play a role in disease severity, there has been a question of whether immunosuppression may offer a protective effect,” he continued.

“This case series suggests that this is not the case, although this would need to be confirmed in larger studies,” he said.
 

Low threshold

Among the 22 patients who were admitted to the hospital, half were discharged home and four (18%) were still hospitalized at the end of the study.

Of the seven patients who died, two died at the study center, and five died in an outside institution.

“In the HT population, social distancing (or isolation), strict use of masks when in public, proper handwashing, and sanitization of surfaces are of paramount importance in the prevention of COVID-19 infection,” Dr. Uriel stated.

“In addition, we have restricted these patients’ contact with the hospital as much as possible during the pandemic,” he said.

However, “there should be a low threshold to hospitalize heart transplant patients who develop infection with COVID-19. Furthermore, in our series, outcomes were better for patients hospitalized at the transplant center; therefore, strong consideration should be given to transferring HT patients when hospitalized at another hospital,” he added.

The authors emphasized that COVID-19 patients “will require ongoing monitoring in the recovery phase, as an immunosuppression regimen is reintroduced and the consequences to the allograft itself become apparent.”
 

Vulnerable population

Commenting on the study, Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston, suggested that “in epidemiological terms, [the findings] might not look as bad as the way they are reflected in the paper.”

Given that Columbia is “one of the larger heart transplant centers in the U.S., following probably 1,000 patients, having only 22 out of perhaps thousands whom they transplanted or are actively following would actually represent a low serious infection rate,” said Dr. Mehra, who is also the executive director of the Center for Advanced Heart Disease at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, also in Boston.

“We must not forget to emphasize that, when assessing these case fatality rates, we must look at the entire population at risk, not only the handful that we were able to observe,” explained Dr. Mehra, who was not involved with the study.

Moreover, the patients were “older and had comorbidities, with poor underlying kidney function and other complications, and underlying coronary artery disease in the transplanted heart,” so “it would not surprise me that they had such a high fatality rate, since they had a high degree of vulnerability,” he said.

Dr. Mehra, who is also the editor-in-chief of the Journal of Heart and Lung Transplantation, said that the journal has received manuscripts still in the review process that suggest different fatality rates than those found in the current case series.

However, he acknowledged that, because these are patients with serious vulnerability due to underlying heart disease, “you can’t be lackadaisical and need to do everything to decrease this vulnerability.”

The authors noted that, although their study did not show a protective effect from immunosuppression against COVID-19, further studies are needed to assess each individual immunosuppressive agent and provide a definitive answer.

The study was supported by a grant to one of the investigators from the National Heart, Lung, and Blood Institute. Dr. Uriel reports no relevant financial relationships. The other authors’ disclosures are listed in the publication. Dr. Mehra reports no relevant financial relationships.

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

The patient was given a diagnosis of chondrodermatitis nodularis helicis (CNH), an inflammation of the cartilage and overlying skin causing a painful nodule of the helix. These lesions typically have a more prominent nodular component and a central ulceration or firm scale. They are thought to be due to chronic pressure on the ear.

There is a slight male predominance of CNH and onset is usually gradual. Patients often experience pain when sleeping on the affected side. The tenderness usually can be reproduced clinically by pressing on the lesion. The ears also are a high-risk area for actinic keratoses (AK) and nonmelanoma skin cancer (NMSC); if there is doubt about the diagnosis, a biopsy may be warranted to rule out AK or NMSC. In this patient, a shave biopsy was performed.

Various treatment regimens are available for CNH. The least invasive treatment approach is to use a “cut out” foam or a special donut-shaped pillow to protect the area from further pressure. By protecting from pressure and irritation, the lesion resolves in 57% to 92% of cases in clinical studies. Intralesional injection with 0.2 mL of 10 mg/mL triamcinolone acetonide is a simple in-office procedure that frequently helps the pain and may be curative; although, repeat injections may be necessary. Excision of the overlying skin and the affected cartilage is a more aggressive treatment with high success rates. More recently, treatment with topical nitroglycerin patches or photodynamic therapy have been described in small trials.

After confirming by a shave biopsy that the lesion was not cancerous, the patient returned for an elliptical excision of the lesion. A dermal curette was used to remove the rough abnormal inflammation of the underlying cartilage, and the elliptical wound was sutured with a linear closure.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

The patient was given a diagnosis of chondrodermatitis nodularis helicis (CNH), an inflammation of the cartilage and overlying skin causing a painful nodule of the helix. These lesions typically have a more prominent nodular component and a central ulceration or firm scale. They are thought to be due to chronic pressure on the ear.

There is a slight male predominance of CNH and onset is usually gradual. Patients often experience pain when sleeping on the affected side. The tenderness usually can be reproduced clinically by pressing on the lesion. The ears also are a high-risk area for actinic keratoses (AK) and nonmelanoma skin cancer (NMSC); if there is doubt about the diagnosis, a biopsy may be warranted to rule out AK or NMSC. In this patient, a shave biopsy was performed.

Various treatment regimens are available for CNH. The least invasive treatment approach is to use a “cut out” foam or a special donut-shaped pillow to protect the area from further pressure. By protecting from pressure and irritation, the lesion resolves in 57% to 92% of cases in clinical studies. Intralesional injection with 0.2 mL of 10 mg/mL triamcinolone acetonide is a simple in-office procedure that frequently helps the pain and may be curative; although, repeat injections may be necessary. Excision of the overlying skin and the affected cartilage is a more aggressive treatment with high success rates. More recently, treatment with topical nitroglycerin patches or photodynamic therapy have been described in small trials.

After confirming by a shave biopsy that the lesion was not cancerous, the patient returned for an elliptical excision of the lesion. A dermal curette was used to remove the rough abnormal inflammation of the underlying cartilage, and the elliptical wound was sutured with a linear closure.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

The patient was given a diagnosis of chondrodermatitis nodularis helicis (CNH), an inflammation of the cartilage and overlying skin causing a painful nodule of the helix. These lesions typically have a more prominent nodular component and a central ulceration or firm scale. They are thought to be due to chronic pressure on the ear.

There is a slight male predominance of CNH and onset is usually gradual. Patients often experience pain when sleeping on the affected side. The tenderness usually can be reproduced clinically by pressing on the lesion. The ears also are a high-risk area for actinic keratoses (AK) and nonmelanoma skin cancer (NMSC); if there is doubt about the diagnosis, a biopsy may be warranted to rule out AK or NMSC. In this patient, a shave biopsy was performed.

Various treatment regimens are available for CNH. The least invasive treatment approach is to use a “cut out” foam or a special donut-shaped pillow to protect the area from further pressure. By protecting from pressure and irritation, the lesion resolves in 57% to 92% of cases in clinical studies. Intralesional injection with 0.2 mL of 10 mg/mL triamcinolone acetonide is a simple in-office procedure that frequently helps the pain and may be curative; although, repeat injections may be necessary. Excision of the overlying skin and the affected cartilage is a more aggressive treatment with high success rates. More recently, treatment with topical nitroglycerin patches or photodynamic therapy have been described in small trials.

After confirming by a shave biopsy that the lesion was not cancerous, the patient returned for an elliptical excision of the lesion. A dermal curette was used to remove the rough abnormal inflammation of the underlying cartilage, and the elliptical wound was sutured with a linear closure.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

Adding durvalumab to first-line pemetrexed and cisplatin improved survival in patients with unresectable malignant pleural mesothelioma (MPM) in a phase 2 trial, compared with historical controls who received only pemetrexed and cisplatin.

The median overall survival was 20.4 months in patients who received durvalumab plus pemetrexed-cisplatin. This is significantly longer than the median overall survival of 12.1 months (P = .0014) observed with pemetrexed-cisplatin in a prior phase 3 study (J Clin Oncol. 2003 Jul 15;21[14]:2636-44).

The new phase 2 results are “promising,” said lead investigator Patrick Forde, MBBCh, director of the thoracic cancer clinical research program at Johns Hopkins University in Baltimore.

He presented the results as part of the American Society of Clinical Oncology virtual scientific program.

Dr. Forde noted that a phase 3 trial directly comparing pemetrexed-cisplatin plus durvalumab to pemetrexed-cisplatin will begin recruiting this year. The trial is a collaboration between U.S. investigators and Australian researchers who reported their own phase 2 results with durvalumab plus pemetrexed-cisplatin in 2018 (J Thorac Oncol. 2018 Oct;13[10]:S338-339).
 

Study details

Dr. Forde’s phase 2 study enrolled 55 patients with treatment-naive, unresectable MPM. Their median age was 68 years (range, 35-83 years), and 45 (82%) were men. All had an Eastern Cooperative Oncology Group performance status of 0-1.

Epithelioid mesothelioma was the histologic subtype in three-quarters of patients. “It was a fairly typical mesothelioma population,” Dr. Forde said.

The patients received durvalumab at 1,120 mg plus pemetrexed at 500 mg/m² and cisplatin at 75 mg/m² every 3 weeks for up to six cycles. Carboplatin was substituted when cisplatin was contraindicated or patients developed toxicities.

All but one patient had stable or responding disease on radiography and went on to durvalumab maintenance, also given at 1,120 mg every 3 weeks, for up to 1 year from study entry.
 

Results

Dr. Forde said this study had 90% power to detect a 58% improvement in median overall survival, from the 12.1 months seen in historical controls to 19 months, which was the goal of this study.

It was a positive study, he said, as the median overall survival was 20.4 months (P = .0014).

The overall survival rate was 87.2% at 6 months, 70.4% at 12 months, and 44.2% at 24 months. The progression-free survival rate was 69.1% at 6 months, 16.4% at 12 months, and 10.9% at 24 months.

The overall response rate was 56.4%, which comprised 31 partial responses. Forty percent of patients (n = 22) had stable disease. One patient had progressive disease, and one was not evaluable (1.8% each).

To help with future patient selection, the researchers looked for baseline biomarkers that predicted response. Tumor PD-L1 expression, tumor mutation burden, and other potential candidates haven’t worked out so far, but the work continues, Dr. Forde said.

He noted that many of the adverse events in this trial are those typically seen with platinum-based chemotherapy.

Grade 3/4 treatment-emergent adverse events included anemia (n = 14), fatigue (n = 4), decreased appetite (n = 1), and hypomagnesemia (n = 1).

The most common grade 1/2 adverse events of special interest were hypothyroidism (n = 7), rash (n = 5), pruritus (n = 3), AST elevation (n = 3), and hyperthyroidism (n = 3).
 

Putting the results in context

Given the role of inflammation in MPM, durvalumab is among several immunotherapies under investigation for the disease.

A phase 3 French trial showed MPM patients had a median overall survival of 18.8 months with pemetrexed-cisplatin plus bevacizumab versus 16.1 months with pemetrexed-cisplatin only (Lancet. 2016 Apr 2;387[10026]:1405-1414).

The higher overall survival in the French study’s pemetrexed-cisplatin arm, compared with the 2003 trial results, is likely due to the use of modern second-line options, said Marjorie Zauderer, MD, codirector of the mesothelioma program at Memorial Sloan Kettering Cancer Center in New York, who was the discussant for Dr. Forde’s presentation.

“I think the improvement in overall survival presented by Dr. Forde is potentially clinically meaningful,” she said, but it was “well within the 95% confidence interval” of the bevacizumab trial. Even so, “I look forward” to the phase 3 results, she said.

Dr. Zauderer also pointed out an April press release from Bristol Myers Squibb that reported improved survival over pemetrexed-cisplatin with two of the company’s immunotherapies, nivolumab and ipilimumab, not as additions but as replacement first-line therapy. However, the randomized trial data haven’t been released yet. “We are all eager to evaluate this option further,” she said.

AstraZeneca, maker of durvalumab, funded the current study. Dr. Forde is an adviser for the company and reported research funding. Dr. Zauderer reported a relationship with Roche, which markets bevacizumab through its subsidiary, Genentech. She also disclosed research funding from Bristol Myers Squibb.

aotto@mdedge.com

SOURCE: Forde PM et al. ASCO 2020, Abstract 9003.

Adding durvalumab to first-line pemetrexed and cisplatin improved survival in patients with unresectable malignant pleural mesothelioma (MPM) in a phase 2 trial, compared with historical controls who received only pemetrexed and cisplatin.

The median overall survival was 20.4 months in patients who received durvalumab plus pemetrexed-cisplatin. This is significantly longer than the median overall survival of 12.1 months (P = .0014) observed with pemetrexed-cisplatin in a prior phase 3 study (J Clin Oncol. 2003 Jul 15;21[14]:2636-44).

The new phase 2 results are “promising,” said lead investigator Patrick Forde, MBBCh, director of the thoracic cancer clinical research program at Johns Hopkins University in Baltimore.

He presented the results as part of the American Society of Clinical Oncology virtual scientific program.

Dr. Forde noted that a phase 3 trial directly comparing pemetrexed-cisplatin plus durvalumab to pemetrexed-cisplatin will begin recruiting this year. The trial is a collaboration between U.S. investigators and Australian researchers who reported their own phase 2 results with durvalumab plus pemetrexed-cisplatin in 2018 (J Thorac Oncol. 2018 Oct;13[10]:S338-339).
 

Study details

Dr. Forde’s phase 2 study enrolled 55 patients with treatment-naive, unresectable MPM. Their median age was 68 years (range, 35-83 years), and 45 (82%) were men. All had an Eastern Cooperative Oncology Group performance status of 0-1.

Epithelioid mesothelioma was the histologic subtype in three-quarters of patients. “It was a fairly typical mesothelioma population,” Dr. Forde said.

The patients received durvalumab at 1,120 mg plus pemetrexed at 500 mg/m² and cisplatin at 75 mg/m² every 3 weeks for up to six cycles. Carboplatin was substituted when cisplatin was contraindicated or patients developed toxicities.

All but one patient had stable or responding disease on radiography and went on to durvalumab maintenance, also given at 1,120 mg every 3 weeks, for up to 1 year from study entry.
 

Results

Dr. Forde said this study had 90% power to detect a 58% improvement in median overall survival, from the 12.1 months seen in historical controls to 19 months, which was the goal of this study.

It was a positive study, he said, as the median overall survival was 20.4 months (P = .0014).

The overall survival rate was 87.2% at 6 months, 70.4% at 12 months, and 44.2% at 24 months. The progression-free survival rate was 69.1% at 6 months, 16.4% at 12 months, and 10.9% at 24 months.

The overall response rate was 56.4%, which comprised 31 partial responses. Forty percent of patients (n = 22) had stable disease. One patient had progressive disease, and one was not evaluable (1.8% each).

To help with future patient selection, the researchers looked for baseline biomarkers that predicted response. Tumor PD-L1 expression, tumor mutation burden, and other potential candidates haven’t worked out so far, but the work continues, Dr. Forde said.

He noted that many of the adverse events in this trial are those typically seen with platinum-based chemotherapy.

Grade 3/4 treatment-emergent adverse events included anemia (n = 14), fatigue (n = 4), decreased appetite (n = 1), and hypomagnesemia (n = 1).

The most common grade 1/2 adverse events of special interest were hypothyroidism (n = 7), rash (n = 5), pruritus (n = 3), AST elevation (n = 3), and hyperthyroidism (n = 3).
 

Putting the results in context

Given the role of inflammation in MPM, durvalumab is among several immunotherapies under investigation for the disease.

A phase 3 French trial showed MPM patients had a median overall survival of 18.8 months with pemetrexed-cisplatin plus bevacizumab versus 16.1 months with pemetrexed-cisplatin only (Lancet. 2016 Apr 2;387[10026]:1405-1414).

The higher overall survival in the French study’s pemetrexed-cisplatin arm, compared with the 2003 trial results, is likely due to the use of modern second-line options, said Marjorie Zauderer, MD, codirector of the mesothelioma program at Memorial Sloan Kettering Cancer Center in New York, who was the discussant for Dr. Forde’s presentation.

“I think the improvement in overall survival presented by Dr. Forde is potentially clinically meaningful,” she said, but it was “well within the 95% confidence interval” of the bevacizumab trial. Even so, “I look forward” to the phase 3 results, she said.

Dr. Zauderer also pointed out an April press release from Bristol Myers Squibb that reported improved survival over pemetrexed-cisplatin with two of the company’s immunotherapies, nivolumab and ipilimumab, not as additions but as replacement first-line therapy. However, the randomized trial data haven’t been released yet. “We are all eager to evaluate this option further,” she said.

AstraZeneca, maker of durvalumab, funded the current study. Dr. Forde is an adviser for the company and reported research funding. Dr. Zauderer reported a relationship with Roche, which markets bevacizumab through its subsidiary, Genentech. She also disclosed research funding from Bristol Myers Squibb.

aotto@mdedge.com

SOURCE: Forde PM et al. ASCO 2020, Abstract 9003.

Adding durvalumab to first-line pemetrexed and cisplatin improved survival in patients with unresectable malignant pleural mesothelioma (MPM) in a phase 2 trial, compared with historical controls who received only pemetrexed and cisplatin.

The median overall survival was 20.4 months in patients who received durvalumab plus pemetrexed-cisplatin. This is significantly longer than the median overall survival of 12.1 months (P = .0014) observed with pemetrexed-cisplatin in a prior phase 3 study (J Clin Oncol. 2003 Jul 15;21[14]:2636-44).

The new phase 2 results are “promising,” said lead investigator Patrick Forde, MBBCh, director of the thoracic cancer clinical research program at Johns Hopkins University in Baltimore.

He presented the results as part of the American Society of Clinical Oncology virtual scientific program.

Dr. Forde noted that a phase 3 trial directly comparing pemetrexed-cisplatin plus durvalumab to pemetrexed-cisplatin will begin recruiting this year. The trial is a collaboration between U.S. investigators and Australian researchers who reported their own phase 2 results with durvalumab plus pemetrexed-cisplatin in 2018 (J Thorac Oncol. 2018 Oct;13[10]:S338-339).
 

Study details

Dr. Forde’s phase 2 study enrolled 55 patients with treatment-naive, unresectable MPM. Their median age was 68 years (range, 35-83 years), and 45 (82%) were men. All had an Eastern Cooperative Oncology Group performance status of 0-1.

Epithelioid mesothelioma was the histologic subtype in three-quarters of patients. “It was a fairly typical mesothelioma population,” Dr. Forde said.

The patients received durvalumab at 1,120 mg plus pemetrexed at 500 mg/m² and cisplatin at 75 mg/m² every 3 weeks for up to six cycles. Carboplatin was substituted when cisplatin was contraindicated or patients developed toxicities.

All but one patient had stable or responding disease on radiography and went on to durvalumab maintenance, also given at 1,120 mg every 3 weeks, for up to 1 year from study entry.
 

Results

Dr. Forde said this study had 90% power to detect a 58% improvement in median overall survival, from the 12.1 months seen in historical controls to 19 months, which was the goal of this study.

It was a positive study, he said, as the median overall survival was 20.4 months (P = .0014).

The overall survival rate was 87.2% at 6 months, 70.4% at 12 months, and 44.2% at 24 months. The progression-free survival rate was 69.1% at 6 months, 16.4% at 12 months, and 10.9% at 24 months.

The overall response rate was 56.4%, which comprised 31 partial responses. Forty percent of patients (n = 22) had stable disease. One patient had progressive disease, and one was not evaluable (1.8% each).

To help with future patient selection, the researchers looked for baseline biomarkers that predicted response. Tumor PD-L1 expression, tumor mutation burden, and other potential candidates haven’t worked out so far, but the work continues, Dr. Forde said.

He noted that many of the adverse events in this trial are those typically seen with platinum-based chemotherapy.

Grade 3/4 treatment-emergent adverse events included anemia (n = 14), fatigue (n = 4), decreased appetite (n = 1), and hypomagnesemia (n = 1).

The most common grade 1/2 adverse events of special interest were hypothyroidism (n = 7), rash (n = 5), pruritus (n = 3), AST elevation (n = 3), and hyperthyroidism (n = 3).
 

Putting the results in context

Given the role of inflammation in MPM, durvalumab is among several immunotherapies under investigation for the disease.

A phase 3 French trial showed MPM patients had a median overall survival of 18.8 months with pemetrexed-cisplatin plus bevacizumab versus 16.1 months with pemetrexed-cisplatin only (Lancet. 2016 Apr 2;387[10026]:1405-1414).

The higher overall survival in the French study’s pemetrexed-cisplatin arm, compared with the 2003 trial results, is likely due to the use of modern second-line options, said Marjorie Zauderer, MD, codirector of the mesothelioma program at Memorial Sloan Kettering Cancer Center in New York, who was the discussant for Dr. Forde’s presentation.

“I think the improvement in overall survival presented by Dr. Forde is potentially clinically meaningful,” she said, but it was “well within the 95% confidence interval” of the bevacizumab trial. Even so, “I look forward” to the phase 3 results, she said.

Dr. Zauderer also pointed out an April press release from Bristol Myers Squibb that reported improved survival over pemetrexed-cisplatin with two of the company’s immunotherapies, nivolumab and ipilimumab, not as additions but as replacement first-line therapy. However, the randomized trial data haven’t been released yet. “We are all eager to evaluate this option further,” she said.

AstraZeneca, maker of durvalumab, funded the current study. Dr. Forde is an adviser for the company and reported research funding. Dr. Zauderer reported a relationship with Roche, which markets bevacizumab through its subsidiary, Genentech. She also disclosed research funding from Bristol Myers Squibb.

aotto@mdedge.com

SOURCE: Forde PM et al. ASCO 2020, Abstract 9003.

Adding celecoxib to standard adjuvant chemotherapy with the FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) regimen did not improve survival for patients with stage III colon cancer, results of the phase 3 CALGB/SWOG 80702 trial showed.

The trial included 2,526 patients randomized to either 6 or 12 cycles of adjuvant FOLFOX with either celecoxib or placebo. The 3-year disease-free survival (DFS) rate was 76.3% for patients on celecoxib and 73.4% for those on placebo. The 5-year overall survival (OS) was 84% and 81.8%, respectively.

“The addition of celecoxib to FOLFOX adjuvant therapy in stage III colon cancer did not significantly improve disease-free or overall survival,” Jeffrey A. Meyerhardt, MD, of the Dana-Farber Cancer Institute in Boston, said while presenting the results as part of the American Society of Clinical Oncology virtual scientific program.

“We did not detect a significant interaction between celecoxib and duration of FOLFOX therapy for disease-free survival. Similarly, we did not detect a significant interaction between celecoxib and duration of FOLFOX therapy for overall survival,” Dr. Meyerhardt said.

“Simply put, celecoxib should not be used for the secondary prevention of colon cancer,” said invited discussant Christopher Lieu, MD, of the University of Colorado Cancer Center, Aurora.
 

Trial details

The 80702 trial was designed to test whether the COX-2 inhibitor celecoxib could help further reduce the risk of recurrence when added to adjuvant chemotherapy with 3 or 6 months of FOLFOX. Data on the FOLFOX portion of the trial were previously reported as part of the International Duration Evaluation of Adjuvant Therapy collaboration (N Engl J Med. 2018;378:1177-88).

The trial enrolled 2,526 patients with resected stage III colon cancer. They were randomized to receive 3 or 6 months (6 or 12 cycles) of FOLFOX with either concurrent celecoxib at 400 mg daily (n = 1,265) or placebo (n = 1,261) for 3 years from the start of the trial.

The primary endpoint of 3-year DFS did not differ between the groups (hazard ratio, 0.90; P = .16). Likewise, 5-year OS rates did not differ significantly (HR, 0.89; P = .22).

As Dr. Meyerhardt said, there were no significant interactions detected among any subgroups for DFS or OS, including by age, N or T stage, risk group, concurrent low-dose aspirin use, sex, race/ethnicity, baseline performance status, FOLFOX duration, body mass index, or tumor location.

Rates of toxicities were similar between the groups, except for a higher incidence of hypertension of any grade with celecoxib during FOLFOX therapy (14.6% vs. 10.9%, P = .01) and a grade 2 or greater creatinine increase with celecoxib after FOLFOX (1.7% vs. 0.5%, P = .01).

About 40% of patients completed all 3 years of celecoxib or placebo. Reasons for discontinuation included recurrent disease, adverse events, patient withdrawal from the study, physician decision, or other complicating disease.
 

Why didn’t it work?

Previous studies have indicated that aspirin and cyclooxygenase (COX)-2 inhibitors are associated with a reduced risk of colorectal polyps and cancer, Dr. Lieu said. So why didn’t celecoxib improve survival in the current trial?

“There are obviously COX-1 and COX-independent targets that aspirin hit that celecoxib does not, and its survival impact of affecting these targets is still largely unclear,” Dr. Lieu said.

He added that ongoing trials – including the Add-Aspirin and ASCOLT studies – should provide more insight.

The current trial was sponsored by the Alliance for Clinical Trials in Oncology in collaboration with the National Cancer Institute. Pfizer provided the celecoxib and placebo. Dr. Meyerhardt disclosed relationships with Cota Healthcare, Taiho Pharmaceutical, and Array BioPharma. Dr. Lieu disclosed relationships with Foundation Medicine, Ipsen, Merck, and Immune Design.

SOURCE: Meyerhardt JA et al. ASCO 2020, Abstract 4003.

Adding celecoxib to standard adjuvant chemotherapy with the FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) regimen did not improve survival for patients with stage III colon cancer, results of the phase 3 CALGB/SWOG 80702 trial showed.

The trial included 2,526 patients randomized to either 6 or 12 cycles of adjuvant FOLFOX with either celecoxib or placebo. The 3-year disease-free survival (DFS) rate was 76.3% for patients on celecoxib and 73.4% for those on placebo. The 5-year overall survival (OS) was 84% and 81.8%, respectively.

“The addition of celecoxib to FOLFOX adjuvant therapy in stage III colon cancer did not significantly improve disease-free or overall survival,” Jeffrey A. Meyerhardt, MD, of the Dana-Farber Cancer Institute in Boston, said while presenting the results as part of the American Society of Clinical Oncology virtual scientific program.

“We did not detect a significant interaction between celecoxib and duration of FOLFOX therapy for disease-free survival. Similarly, we did not detect a significant interaction between celecoxib and duration of FOLFOX therapy for overall survival,” Dr. Meyerhardt said.

“Simply put, celecoxib should not be used for the secondary prevention of colon cancer,” said invited discussant Christopher Lieu, MD, of the University of Colorado Cancer Center, Aurora.
 

Trial details

The 80702 trial was designed to test whether the COX-2 inhibitor celecoxib could help further reduce the risk of recurrence when added to adjuvant chemotherapy with 3 or 6 months of FOLFOX. Data on the FOLFOX portion of the trial were previously reported as part of the International Duration Evaluation of Adjuvant Therapy collaboration (N Engl J Med. 2018;378:1177-88).

The trial enrolled 2,526 patients with resected stage III colon cancer. They were randomized to receive 3 or 6 months (6 or 12 cycles) of FOLFOX with either concurrent celecoxib at 400 mg daily (n = 1,265) or placebo (n = 1,261) for 3 years from the start of the trial.

The primary endpoint of 3-year DFS did not differ between the groups (hazard ratio, 0.90; P = .16). Likewise, 5-year OS rates did not differ significantly (HR, 0.89; P = .22).

As Dr. Meyerhardt said, there were no significant interactions detected among any subgroups for DFS or OS, including by age, N or T stage, risk group, concurrent low-dose aspirin use, sex, race/ethnicity, baseline performance status, FOLFOX duration, body mass index, or tumor location.

Rates of toxicities were similar between the groups, except for a higher incidence of hypertension of any grade with celecoxib during FOLFOX therapy (14.6% vs. 10.9%, P = .01) and a grade 2 or greater creatinine increase with celecoxib after FOLFOX (1.7% vs. 0.5%, P = .01).

About 40% of patients completed all 3 years of celecoxib or placebo. Reasons for discontinuation included recurrent disease, adverse events, patient withdrawal from the study, physician decision, or other complicating disease.
 

Why didn’t it work?

Previous studies have indicated that aspirin and cyclooxygenase (COX)-2 inhibitors are associated with a reduced risk of colorectal polyps and cancer, Dr. Lieu said. So why didn’t celecoxib improve survival in the current trial?

“There are obviously COX-1 and COX-independent targets that aspirin hit that celecoxib does not, and its survival impact of affecting these targets is still largely unclear,” Dr. Lieu said.

He added that ongoing trials – including the Add-Aspirin and ASCOLT studies – should provide more insight.

The current trial was sponsored by the Alliance for Clinical Trials in Oncology in collaboration with the National Cancer Institute. Pfizer provided the celecoxib and placebo. Dr. Meyerhardt disclosed relationships with Cota Healthcare, Taiho Pharmaceutical, and Array BioPharma. Dr. Lieu disclosed relationships with Foundation Medicine, Ipsen, Merck, and Immune Design.

SOURCE: Meyerhardt JA et al. ASCO 2020, Abstract 4003.

Adding celecoxib to standard adjuvant chemotherapy with the FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) regimen did not improve survival for patients with stage III colon cancer, results of the phase 3 CALGB/SWOG 80702 trial showed.

The trial included 2,526 patients randomized to either 6 or 12 cycles of adjuvant FOLFOX with either celecoxib or placebo. The 3-year disease-free survival (DFS) rate was 76.3% for patients on celecoxib and 73.4% for those on placebo. The 5-year overall survival (OS) was 84% and 81.8%, respectively.

“The addition of celecoxib to FOLFOX adjuvant therapy in stage III colon cancer did not significantly improve disease-free or overall survival,” Jeffrey A. Meyerhardt, MD, of the Dana-Farber Cancer Institute in Boston, said while presenting the results as part of the American Society of Clinical Oncology virtual scientific program.

“We did not detect a significant interaction between celecoxib and duration of FOLFOX therapy for disease-free survival. Similarly, we did not detect a significant interaction between celecoxib and duration of FOLFOX therapy for overall survival,” Dr. Meyerhardt said.

“Simply put, celecoxib should not be used for the secondary prevention of colon cancer,” said invited discussant Christopher Lieu, MD, of the University of Colorado Cancer Center, Aurora.
 

Trial details

The 80702 trial was designed to test whether the COX-2 inhibitor celecoxib could help further reduce the risk of recurrence when added to adjuvant chemotherapy with 3 or 6 months of FOLFOX. Data on the FOLFOX portion of the trial were previously reported as part of the International Duration Evaluation of Adjuvant Therapy collaboration (N Engl J Med. 2018;378:1177-88).

The trial enrolled 2,526 patients with resected stage III colon cancer. They were randomized to receive 3 or 6 months (6 or 12 cycles) of FOLFOX with either concurrent celecoxib at 400 mg daily (n = 1,265) or placebo (n = 1,261) for 3 years from the start of the trial.

The primary endpoint of 3-year DFS did not differ between the groups (hazard ratio, 0.90; P = .16). Likewise, 5-year OS rates did not differ significantly (HR, 0.89; P = .22).

As Dr. Meyerhardt said, there were no significant interactions detected among any subgroups for DFS or OS, including by age, N or T stage, risk group, concurrent low-dose aspirin use, sex, race/ethnicity, baseline performance status, FOLFOX duration, body mass index, or tumor location.

Rates of toxicities were similar between the groups, except for a higher incidence of hypertension of any grade with celecoxib during FOLFOX therapy (14.6% vs. 10.9%, P = .01) and a grade 2 or greater creatinine increase with celecoxib after FOLFOX (1.7% vs. 0.5%, P = .01).

About 40% of patients completed all 3 years of celecoxib or placebo. Reasons for discontinuation included recurrent disease, adverse events, patient withdrawal from the study, physician decision, or other complicating disease.
 

Why didn’t it work?

Previous studies have indicated that aspirin and cyclooxygenase (COX)-2 inhibitors are associated with a reduced risk of colorectal polyps and cancer, Dr. Lieu said. So why didn’t celecoxib improve survival in the current trial?

“There are obviously COX-1 and COX-independent targets that aspirin hit that celecoxib does not, and its survival impact of affecting these targets is still largely unclear,” Dr. Lieu said.

He added that ongoing trials – including the Add-Aspirin and ASCOLT studies – should provide more insight.

The current trial was sponsored by the Alliance for Clinical Trials in Oncology in collaboration with the National Cancer Institute. Pfizer provided the celecoxib and placebo. Dr. Meyerhardt disclosed relationships with Cota Healthcare, Taiho Pharmaceutical, and Array BioPharma. Dr. Lieu disclosed relationships with Foundation Medicine, Ipsen, Merck, and Immune Design.

SOURCE: Meyerhardt JA et al. ASCO 2020, Abstract 4003.

For privately insured individuals with type 1 diabetes in the United States, out-of-pocket costs for insulin are typically lower than for other diabetes-related supplies. But overall out-of-pocket expenditure – taking into account everything that is needed to manage diabetes – is still very high.

Indeed, insulin costs have remained relatively stable over time in such private insurance plans, according to another analysis that looked at all types of diabetes.

Those are the findings of two separate research letters published June 1 in JAMA Internal Medicine.

The first research letter examined all costs for privately insured patients with type 1 diabetes, finding a mean out-of-pocket spend of approximately $2,500 a year.

“Insulin is the difference between life and death for patients with type 1 diabetes, and efforts to make it more affordable are critical,” said lead author of the first letter, Kao-Ping Chua, MD, PhD, of the department of pediatrics, University of Michigan, Ann Arbor.

“However, our study shows that even if insulin were free, families would still have substantial out-of-pocket costs for other health care,” he noted in a press release from his institution.

The other research letter examined trends in insulin out-of-pocket costs in 2006-2017 among U.S. patients with any type of diabetes who had different types of private health insurance plans. The study was by Amir Meiri, MD, of Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, and colleagues.

Although the study showed relatively stable costs associated with insulin for many privately insured patients with diabetes over the time period examined, “monthly out-of-pocket payments” may still “be burdensome for low-income individuals,” the authors said.

Writing in an accompanying editorial, Laura M. Nally, MD, and Kasia J. Lipska, MD, both of Yale University, New Haven, Conn., agreed that “insulin is only one component of diabetes management.”

Yet they stressed: “Diabetes does not selectively occur among individuals who can afford insulin and who have health insurance; it affects people regardless of their socioeconomic status.”

“The federal health care system should urgently act to make insulin, diabetes-related supplies, and other health care services affordable and available to everyone who needs them.”

Out-of-pocket costs for supplies higher than for insulin

Dr. Chua and colleagues compared out-of-pocket costs for insulin with those for other diabetes-related items, including insulin pump supplies, and glucose meters/continuous monitors, for privately insured patients with type 1 diabetes during 2018.

They included data for 65,192 patients aged 1-64 years with type 1 diabetes who had employer-sponsored coverage from medium to large firms.

The population included children of employees (12%), and 22.5% of patients had enrolled in high-deductible ($1,350 individual/$2,700 family) private plans. Overall, 56.8% used insulin pumps and/or continuous glucose monitors (CGMs).

Annual out-of-pocket spending was lower for insulin ($435) than other diabetes-related supplies ($490), including insulin pump supplies, continuous and fingerstick glucose monitoring equipment, urine testing strips, pen needles, and syringes.

Mean annual overall out-of-pocket spending was $2,414, but this varied widely.

For 8% of the population spending exceeded $5,000. Insulin accounted for just 18% of overall out-of-pocket spending.

Not surprisingly, out-of-pocket spending increased with the sophistication of the diabetes technology used, ranging from just $79 for those using injections and fingerstick monitoring to $1,037 for those using both insulin pumps and CGMs.

In general, for children, out-of-pocket costs of diabetes-related supplies were considerably higher than for insulin ($823 vs. $497), while for adults the two were similar ($445 vs. $427).

“These technologies can improve quality of life and improve diabetes control for all patients, but can be especially important to the families of children with type 1 diabetes,” Dr. Chua said.

Also not surprisingly, those with high-deductible plans had greater out-of-pocket costs in each category ($3,132 vs. $2,205 overall).

Dr. Chua said the study’s findings are particularly timely given recent efforts by states and insurers to cap out-of-pocket costs for insulin, calling these “important first steps.”

But there is still a long way to go, he said.

“Policymakers should improve the affordability of all care for type 1 diabetes,” Dr. Chua noted.

Dr. Nally and Dr. Lipska agreed.

“Although capping insulin copayments is a step in the right direction, such a state law does not protect many individuals with federally regulated insurance plans, with Medicare, or without any insurance,” they noted.

“In addition, insulin copayment caps do little to ease the financial burden of paying for diabetes-related supplies or other healthcare services,” they pointed out.
 

Private plans shield members from out-of-pocket insulin costs

The other study examined out-of-pocket spending for 10,954,436 insulin claims for 612,071 unique patients with diabetes (either type) in different types of private commercial health plans during 2006-2017:

• High-deductible health plans (HDHP) with a health savings account (HSA), which have high medication costs because they require payment of the full reimbursement price until the annual deductible is reached (7% of claims).
• Plans with health reimbursement arrangement (HRA), which typically have tiered drug copayments and members can use their reimbursement accounts to pay for medical expenses (4% of claims).
• No-account plans (without an HSA) that also typically have tiered drug copayments (80% of claims).

The price of insulin per patient per month rose from $143 in 2006 to $280 in 2012 to $394 in 2017.

However, the share of the insulin price per member per month paid by the patient actually declined from 24% in 2006 to 16% in 2012 to just 10% in 2017.

Because of the increase in insulin price, those corresponding costs still rose from $52 in 2006 to $72 in 2012, but then dropped to $64 in 2017.

By plan type, out-of-pocket costs per member per month were lowest for those no-account plans (from $52 in 2006 to $48 in 2017) and highest for those with HDHP HSA plans ($93 in 2006 to $141 in 2017).

“The data suggest that privately insured patients have been relatively shielded from insulin price increases and that commercial health insurers have accommodated higher insulin prices by increasing premiums or deductibles for all members,” Dr. Meiri and colleagues write.
 

Most vulnerable missing from study: COVID-19 will strike further blow

Although generally agreeing with this conclusion, Dr. Nally and Dr. Lipska nevertheless faulted the data from Dr. Meiri and colleagues on several counts.

First, they reiterated that the population was limited to those with private insurance plans, and therefore “the groups most vulnerable to high insulin costs may be missing from the study.”

Also, the data do not capture all sources of out-of-pocket insulin spending for people with high copayments, such as the federal 340B Drug Pricing Program, GoodRx, or drug manufacturer discounts.

Moreover, the editorialists noted, the study assessed only mean out-of-pocket costs without assessing differences in spending across individuals.

And, Dr. Nally and Dr. Lipska pointed out, the data do not account for rebates and discounts negotiated between pharmacy benefit managers and drug manufacturers. “As a result, these data on health plan spending on insulin may overestimate the net health plan expenditures,” they wrote.

Dr. Chua also warned that the COVID-19 pandemic has had a major adverse impact on the diabetes community.

“Many people with private insurance have lost their jobs and insurance coverage ... This may put health care like insulin and diabetes-related supplies out of reach,” he said.

Dr. Chua has reported receiving support from the National Institute on Drug Abuse. Dr. Meiri has reported receiving grants from the Centers for Disease Control and Prevention and the National Institute of Diabetes and Digestive and Kidney Diseases for the study. Dr. Nally has reported receiving a grant from Novo Nordisk outside the submitted work. Dr. Lipska has reported receiving support from the Centers for Medicare & Medicaid Services and the National Institutes of Health.

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

For privately insured individuals with type 1 diabetes in the United States, out-of-pocket costs for insulin are typically lower than for other diabetes-related supplies. But overall out-of-pocket expenditure – taking into account everything that is needed to manage diabetes – is still very high.

Indeed, insulin costs have remained relatively stable over time in such private insurance plans, according to another analysis that looked at all types of diabetes.

Those are the findings of two separate research letters published June 1 in JAMA Internal Medicine.

The first research letter examined all costs for privately insured patients with type 1 diabetes, finding a mean out-of-pocket spend of approximately $2,500 a year.

“Insulin is the difference between life and death for patients with type 1 diabetes, and efforts to make it more affordable are critical,” said lead author of the first letter, Kao-Ping Chua, MD, PhD, of the department of pediatrics, University of Michigan, Ann Arbor.

“However, our study shows that even if insulin were free, families would still have substantial out-of-pocket costs for other health care,” he noted in a press release from his institution.

The other research letter examined trends in insulin out-of-pocket costs in 2006-2017 among U.S. patients with any type of diabetes who had different types of private health insurance plans. The study was by Amir Meiri, MD, of Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, and colleagues.

Although the study showed relatively stable costs associated with insulin for many privately insured patients with diabetes over the time period examined, “monthly out-of-pocket payments” may still “be burdensome for low-income individuals,” the authors said.

Writing in an accompanying editorial, Laura M. Nally, MD, and Kasia J. Lipska, MD, both of Yale University, New Haven, Conn., agreed that “insulin is only one component of diabetes management.”

Yet they stressed: “Diabetes does not selectively occur among individuals who can afford insulin and who have health insurance; it affects people regardless of their socioeconomic status.”

“The federal health care system should urgently act to make insulin, diabetes-related supplies, and other health care services affordable and available to everyone who needs them.”

Out-of-pocket costs for supplies higher than for insulin

Dr. Chua and colleagues compared out-of-pocket costs for insulin with those for other diabetes-related items, including insulin pump supplies, and glucose meters/continuous monitors, for privately insured patients with type 1 diabetes during 2018.

They included data for 65,192 patients aged 1-64 years with type 1 diabetes who had employer-sponsored coverage from medium to large firms.

The population included children of employees (12%), and 22.5% of patients had enrolled in high-deductible ($1,350 individual/$2,700 family) private plans. Overall, 56.8% used insulin pumps and/or continuous glucose monitors (CGMs).

Annual out-of-pocket spending was lower for insulin ($435) than other diabetes-related supplies ($490), including insulin pump supplies, continuous and fingerstick glucose monitoring equipment, urine testing strips, pen needles, and syringes.

Mean annual overall out-of-pocket spending was $2,414, but this varied widely.

For 8% of the population spending exceeded $5,000. Insulin accounted for just 18% of overall out-of-pocket spending.

Not surprisingly, out-of-pocket spending increased with the sophistication of the diabetes technology used, ranging from just $79 for those using injections and fingerstick monitoring to $1,037 for those using both insulin pumps and CGMs.

In general, for children, out-of-pocket costs of diabetes-related supplies were considerably higher than for insulin ($823 vs. $497), while for adults the two were similar ($445 vs. $427).

“These technologies can improve quality of life and improve diabetes control for all patients, but can be especially important to the families of children with type 1 diabetes,” Dr. Chua said.

Also not surprisingly, those with high-deductible plans had greater out-of-pocket costs in each category ($3,132 vs. $2,205 overall).

Dr. Chua said the study’s findings are particularly timely given recent efforts by states and insurers to cap out-of-pocket costs for insulin, calling these “important first steps.”

But there is still a long way to go, he said.

“Policymakers should improve the affordability of all care for type 1 diabetes,” Dr. Chua noted.

Dr. Nally and Dr. Lipska agreed.

“Although capping insulin copayments is a step in the right direction, such a state law does not protect many individuals with federally regulated insurance plans, with Medicare, or without any insurance,” they noted.

“In addition, insulin copayment caps do little to ease the financial burden of paying for diabetes-related supplies or other healthcare services,” they pointed out.
 

Private plans shield members from out-of-pocket insulin costs

The other study examined out-of-pocket spending for 10,954,436 insulin claims for 612,071 unique patients with diabetes (either type) in different types of private commercial health plans during 2006-2017:

• High-deductible health plans (HDHP) with a health savings account (HSA), which have high medication costs because they require payment of the full reimbursement price until the annual deductible is reached (7% of claims).
• Plans with health reimbursement arrangement (HRA), which typically have tiered drug copayments and members can use their reimbursement accounts to pay for medical expenses (4% of claims).
• No-account plans (without an HSA) that also typically have tiered drug copayments (80% of claims).

The price of insulin per patient per month rose from $143 in 2006 to $280 in 2012 to $394 in 2017.

However, the share of the insulin price per member per month paid by the patient actually declined from 24% in 2006 to 16% in 2012 to just 10% in 2017.

Because of the increase in insulin price, those corresponding costs still rose from $52 in 2006 to $72 in 2012, but then dropped to $64 in 2017.

By plan type, out-of-pocket costs per member per month were lowest for those no-account plans (from $52 in 2006 to $48 in 2017) and highest for those with HDHP HSA plans ($93 in 2006 to $141 in 2017).

“The data suggest that privately insured patients have been relatively shielded from insulin price increases and that commercial health insurers have accommodated higher insulin prices by increasing premiums or deductibles for all members,” Dr. Meiri and colleagues write.
 

Most vulnerable missing from study: COVID-19 will strike further blow

Although generally agreeing with this conclusion, Dr. Nally and Dr. Lipska nevertheless faulted the data from Dr. Meiri and colleagues on several counts.

First, they reiterated that the population was limited to those with private insurance plans, and therefore “the groups most vulnerable to high insulin costs may be missing from the study.”

Also, the data do not capture all sources of out-of-pocket insulin spending for people with high copayments, such as the federal 340B Drug Pricing Program, GoodRx, or drug manufacturer discounts.

Moreover, the editorialists noted, the study assessed only mean out-of-pocket costs without assessing differences in spending across individuals.

And, Dr. Nally and Dr. Lipska pointed out, the data do not account for rebates and discounts negotiated between pharmacy benefit managers and drug manufacturers. “As a result, these data on health plan spending on insulin may overestimate the net health plan expenditures,” they wrote.

Dr. Chua also warned that the COVID-19 pandemic has had a major adverse impact on the diabetes community.

“Many people with private insurance have lost their jobs and insurance coverage ... This may put health care like insulin and diabetes-related supplies out of reach,” he said.

Dr. Chua has reported receiving support from the National Institute on Drug Abuse. Dr. Meiri has reported receiving grants from the Centers for Disease Control and Prevention and the National Institute of Diabetes and Digestive and Kidney Diseases for the study. Dr. Nally has reported receiving a grant from Novo Nordisk outside the submitted work. Dr. Lipska has reported receiving support from the Centers for Medicare & Medicaid Services and the National Institutes of Health.

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

For privately insured individuals with type 1 diabetes in the United States, out-of-pocket costs for insulin are typically lower than for other diabetes-related supplies. But overall out-of-pocket expenditure – taking into account everything that is needed to manage diabetes – is still very high.

Indeed, insulin costs have remained relatively stable over time in such private insurance plans, according to another analysis that looked at all types of diabetes.

Those are the findings of two separate research letters published June 1 in JAMA Internal Medicine.

The first research letter examined all costs for privately insured patients with type 1 diabetes, finding a mean out-of-pocket spend of approximately $2,500 a year.

“Insulin is the difference between life and death for patients with type 1 diabetes, and efforts to make it more affordable are critical,” said lead author of the first letter, Kao-Ping Chua, MD, PhD, of the department of pediatrics, University of Michigan, Ann Arbor.

“However, our study shows that even if insulin were free, families would still have substantial out-of-pocket costs for other health care,” he noted in a press release from his institution.

The other research letter examined trends in insulin out-of-pocket costs in 2006-2017 among U.S. patients with any type of diabetes who had different types of private health insurance plans. The study was by Amir Meiri, MD, of Harvard Pilgrim Health Care Institute, Harvard Medical School, Boston, and colleagues.

Although the study showed relatively stable costs associated with insulin for many privately insured patients with diabetes over the time period examined, “monthly out-of-pocket payments” may still “be burdensome for low-income individuals,” the authors said.

Writing in an accompanying editorial, Laura M. Nally, MD, and Kasia J. Lipska, MD, both of Yale University, New Haven, Conn., agreed that “insulin is only one component of diabetes management.”

Yet they stressed: “Diabetes does not selectively occur among individuals who can afford insulin and who have health insurance; it affects people regardless of their socioeconomic status.”

“The federal health care system should urgently act to make insulin, diabetes-related supplies, and other health care services affordable and available to everyone who needs them.”

Out-of-pocket costs for supplies higher than for insulin

Dr. Chua and colleagues compared out-of-pocket costs for insulin with those for other diabetes-related items, including insulin pump supplies, and glucose meters/continuous monitors, for privately insured patients with type 1 diabetes during 2018.

They included data for 65,192 patients aged 1-64 years with type 1 diabetes who had employer-sponsored coverage from medium to large firms.

The population included children of employees (12%), and 22.5% of patients had enrolled in high-deductible ($1,350 individual/$2,700 family) private plans. Overall, 56.8% used insulin pumps and/or continuous glucose monitors (CGMs).

Annual out-of-pocket spending was lower for insulin ($435) than other diabetes-related supplies ($490), including insulin pump supplies, continuous and fingerstick glucose monitoring equipment, urine testing strips, pen needles, and syringes.

Mean annual overall out-of-pocket spending was $2,414, but this varied widely.

For 8% of the population spending exceeded $5,000. Insulin accounted for just 18% of overall out-of-pocket spending.

Not surprisingly, out-of-pocket spending increased with the sophistication of the diabetes technology used, ranging from just $79 for those using injections and fingerstick monitoring to $1,037 for those using both insulin pumps and CGMs.

In general, for children, out-of-pocket costs of diabetes-related supplies were considerably higher than for insulin ($823 vs. $497), while for adults the two were similar ($445 vs. $427).

“These technologies can improve quality of life and improve diabetes control for all patients, but can be especially important to the families of children with type 1 diabetes,” Dr. Chua said.

Also not surprisingly, those with high-deductible plans had greater out-of-pocket costs in each category ($3,132 vs. $2,205 overall).

Dr. Chua said the study’s findings are particularly timely given recent efforts by states and insurers to cap out-of-pocket costs for insulin, calling these “important first steps.”

But there is still a long way to go, he said.

“Policymakers should improve the affordability of all care for type 1 diabetes,” Dr. Chua noted.

Dr. Nally and Dr. Lipska agreed.

“Although capping insulin copayments is a step in the right direction, such a state law does not protect many individuals with federally regulated insurance plans, with Medicare, or without any insurance,” they noted.

“In addition, insulin copayment caps do little to ease the financial burden of paying for diabetes-related supplies or other healthcare services,” they pointed out.
 

Private plans shield members from out-of-pocket insulin costs

The other study examined out-of-pocket spending for 10,954,436 insulin claims for 612,071 unique patients with diabetes (either type) in different types of private commercial health plans during 2006-2017:

• High-deductible health plans (HDHP) with a health savings account (HSA), which have high medication costs because they require payment of the full reimbursement price until the annual deductible is reached (7% of claims).
• Plans with health reimbursement arrangement (HRA), which typically have tiered drug copayments and members can use their reimbursement accounts to pay for medical expenses (4% of claims).
• No-account plans (without an HSA) that also typically have tiered drug copayments (80% of claims).

The price of insulin per patient per month rose from $143 in 2006 to $280 in 2012 to $394 in 2017.

However, the share of the insulin price per member per month paid by the patient actually declined from 24% in 2006 to 16% in 2012 to just 10% in 2017.

Because of the increase in insulin price, those corresponding costs still rose from $52 in 2006 to $72 in 2012, but then dropped to $64 in 2017.

By plan type, out-of-pocket costs per member per month were lowest for those no-account plans (from $52 in 2006 to $48 in 2017) and highest for those with HDHP HSA plans ($93 in 2006 to $141 in 2017).

“The data suggest that privately insured patients have been relatively shielded from insulin price increases and that commercial health insurers have accommodated higher insulin prices by increasing premiums or deductibles for all members,” Dr. Meiri and colleagues write.
 

Most vulnerable missing from study: COVID-19 will strike further blow

Although generally agreeing with this conclusion, Dr. Nally and Dr. Lipska nevertheless faulted the data from Dr. Meiri and colleagues on several counts.

First, they reiterated that the population was limited to those with private insurance plans, and therefore “the groups most vulnerable to high insulin costs may be missing from the study.”

Also, the data do not capture all sources of out-of-pocket insulin spending for people with high copayments, such as the federal 340B Drug Pricing Program, GoodRx, or drug manufacturer discounts.

Moreover, the editorialists noted, the study assessed only mean out-of-pocket costs without assessing differences in spending across individuals.

And, Dr. Nally and Dr. Lipska pointed out, the data do not account for rebates and discounts negotiated between pharmacy benefit managers and drug manufacturers. “As a result, these data on health plan spending on insulin may overestimate the net health plan expenditures,” they wrote.

Dr. Chua also warned that the COVID-19 pandemic has had a major adverse impact on the diabetes community.

“Many people with private insurance have lost their jobs and insurance coverage ... This may put health care like insulin and diabetes-related supplies out of reach,” he said.

Dr. Chua has reported receiving support from the National Institute on Drug Abuse. Dr. Meiri has reported receiving grants from the Centers for Disease Control and Prevention and the National Institute of Diabetes and Digestive and Kidney Diseases for the study. Dr. Nally has reported receiving a grant from Novo Nordisk outside the submitted work. Dr. Lipska has reported receiving support from the Centers for Medicare & Medicaid Services and the National Institutes of Health.

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