More than half of the 37.9 million persons living with HIV (PLWH) worldwide are women.¹ Between 2010 and 2016, 58% of women living with HIV (WLWH) in the United States were older than 45 years.² As such, an increasing number of WLWH are entering menopause and living well beyond menopause. Despite this, health care providers expressed a lack of confidence in managing menopause in WLWH, and menopausal symptoms often are not recognized by providers.³ Enhancing our knowledge about menopause in WLWH is important, since the physiologic changes associated with menopause impact short- and long-term quality of life and mortality. 

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Amenorrhea

Menstrual irregularities, including amenorrhea and anovulation, are more frequently found in women of low socioeconomic status, presumably due to associated physical and emotional stress.⁴ In addition, women with low body mass index (BMI) have decreased serum estradiol levels, which lead to amenorrhea.^4,5 Furthermore, low parity and many legal and illegal drugs are associated with amenorrhea, including hormonal contraceptives, opiates, stimulants, antipsychotics, and chemotherapeutic agents.^6-8

Because these factors associated with amenorrhea are common in WLWH, it is not surprising that amenorrhea and anovulation are frequently found in this population. However, HIV infection itself also appears to be an independent risk factor for amenorrhea. A recent meta-analysis of 8925 women showed a significant association between HIV status and amenorrhea, even when women with and without HIV had similar rates of substance abuse and smoking and similar socioeconomic status.⁹ The impact of HIV on an increased frequency of amenorrhea was strongest in women with low BMI. Some, but not all, of the studies included in the meta-analysis found a negative association between CD4 cell count and amenorrhea. In addition, a study comparing amenorrhea frequency within subgroups of WLWH also found a higher rate of amenorrhea in women with lower CD4 cell counts.¹⁰

“Prolonged” amenorrhea, defined as amenorrhea lasting 1 year or more, also occurs at a high frequency in WLWH.⁶ This has made determination of age of menopause extremely challenging, since it is likely that many studies defining menopause are misidentifying “prolonged” amenorrhea as menopause. The Women’s Interagency HIV Study (WIHS), a multicenter observational study of women of similar socioeconomic status living with and without HIV, found that more than 50% of WLWH with “prolonged” amenorrhea had serum follicle-stimulating hormone (FSH) levels in the premenopausal range.⁸ In a later study from the same cohort, 37% of 660 WLWH with “prolonged” amenorrhea had documented resumption of menses.⁶

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Age at Menopause

In the United States, the median age of menopause is between 50 and 52 years in middle-class white women.^11,12 Earlier menopause has been observed in women who are African American, are nulliparous, have a lower BMI, smoke tobacco, and have more stress, less education, and higher unemployment rates.^11,13,14 Because 57% of women diagnosed with HIV in 2018 were African American and many WLWH have other risk factors associated with earlier menopause, studies examining the age of menopause in WLWH need to use a comparator group of women without HIV with similar characteristics and control for these factors to determine the influence of HIV on the age of menopause.

It is also necessary to accurately define menopause. The World Health Organization defines natural menopause as the permanent cessation of menstruation for 12 consecutive months without any obvious pathologic or physiologic causes.¹⁵ Most studies have used this definition, and many have found that the age of menopause is earlier in WLWH and is associated with immunosuppression.^14,16,17 The Ms Study found that women with CD4 cell counts < 200 cells/μL had an increased risk of amenorrhea lasting at least 12 months, when compared to women with CD4 cell counts ≥ 200 cells/μL. The median age of menopause was 42.5 years in women with CD4 cell counts < 200 cells/μL, 46.0 years in women with CD4 cell counts between 200 cells/μL and 500 cells/μL, and 46.5 years in women with CD4 cell counts > 500 cells/μL.¹⁴ Similarly, in a cohort of 667 Brazilian WLWH, among whom 160 were postmenopausal, Calvet and colleagues found that 33% of women with CD4 cell counts < 50 cells/μL had premature menopause, as compared to 8% of women with CD4 cell counts ≥ 350 cells/μL.¹⁷ In De Pommerol and colleague’s study of 404 WLWH, among whom 69 were found to be postmenopausal, women with CD4 cell counts < 200 cells/μL were more likely to have premature menopause, as compared to women with CD4 cell counts ≥ 350 cells/μL.¹⁶

Despite these findings, given the data from WIHS showing that many women with amenorrhea for at least 12 consecutive months had FSH levels in the premenopausal range⁸ and that 37% of WLWH have resumption of menses after 12 consecutive months of amenorrhea,⁶ it is probable that the conclusions about the age of menopause in WLWH are invalid, since many of the participants likely had prolonged amenorrhea, not menopause. WIHS found no significant difference in the median age of menopause when WLWH were compared to women without HIV. The median age of menopause was 47.7 years in WLWH and 48.0 years in women without HIV.¹⁸

Menopause-Associated Symptoms

The perimenopausal period, which begins, on average, 4 years prior to the final menstrual period, is characterized by hormonal fluctuations leading to irregular menstrual cycles.^19,20 Symptoms associated with these physiologic changes during the perimenopausal period include vasomotor symptoms (hot flashes), genitourinary symptoms (vaginal dryness and dyspareunia), anxiety, depression, sleep disturbances, and joint aches.^21,22 Such menopausal symptoms can be distressing and negatively impact quality of life.²³ In WLWH, severe menopausal symptoms have been associated with suboptimal adherence to antiretroviral therapy (ART).²⁴ 

It can be difficult to determine which symptoms are caused by the physiologic changes of menopause in WLWH, as these women have multiple potential reasons for these symptoms, such as ART, comorbidities, and HIV infection itself.²⁵ However, several studies show that there are symptoms that occur more commonly in the perimenopausal period and that WLWH experience these symptoms earlier and with greater intensity.^26-30 In addition, the burden of commonly reported HIV symptoms, such as fatigue and muscle aches/joint pains, is higher in women after menopause, suggesting this burden may be exacerbated by menopause.³¹

Vasomotor

In the United States, the most common symptom during perimenopause is hot flashes, which occur in 38% to 80% of women.^32,33 Vasomotor symptoms are most common in women who smoke, use illicit substances, have a high BMI, are of lower socioeconomic status, and are African American.¹¹ As expected, prior studies focusing on hot flash prevalence among premenopausal, perimenopausal, and postmenopausal WLWH found that postmenopausal women experience more hot flashes than premenopausal or perimenopausal women.^27,28 In addition, a comparison of women with and without HIV demonstrated a higher prevalence of hot flashes among WLWH.^26,29 Vasomotor symptoms can be severely distressing, with hot flashes contributing to increased risk of depression.^25,34 In a cross-sectional analysis of 835 WLWH and 335 women without HIV from the WIHS cohort, persistent vasomotor symptoms predicted elevated depressive symptoms in both WLWH and women without HIV.³⁴ In a similar cross-sectional analysis of 536 women, among whom 54% were WLWH and 37% were perimenopausal, psychological symptoms were prevalent in 61% of the women with vasomotor symptoms.²⁹

Genitourinary

Estrogen deficiency, which accompanies the perimenopausal period, leads to vulvovaginal atrophy (VVA), manifesting with symptoms of vaginal dryness, itching, burning, urinary urgency, and dyspareunia (painful intercourse).^33,35,36 Unlike vasomotor symptoms, which diminish with time, genitourinary symptoms generally worsen if left untreated.³⁷ Furthermore, these symptoms are often underreported and underdiagnosed.^38,39 VVA was found in 43% to 84% of postmenopausal women.^36,40,41 In the AGATA study, the prevalence of VVA was associated with years since menopause. ³⁶ Vaginal dryness and dyspareunia were common.

Genitourinary symptoms are most common among women who are African American, have an increased BMI, are of lower socioeconomic status, use tobacco, have a prior history of pelvic inflammatory disease, and have anxiety and depression.^11,42,43 Similar to hot flashes, many of these predisposing factors are more common in WLWH. Fantry and colleagues found that 49.6% of WLWH had vaginal dryness.²⁷ Although 56% of postmenopausal women and 36% of perimenopausal women complained of vaginal dryness, in a multivariate analysis only cocaine use, which can decrease estradiol levels,⁴⁴ was associated with a higher frequency of vaginal dryness.²⁷

Dyspareunia is also common among WLWH. In a cross-sectional study of 178 women without HIV and 128 WLWH between 40 and 60 years of age, Valadares et al found a high prevalence of dyspareunia in WLWH: 41.8%.⁴⁵ However, this was not significantly higher than the prevalence of dyspareunia in women without HIV: 34.8%.⁴⁵ HIV infection itself was not associated with the presence of dyspareunia.

Psychiatric

Anxiety and depression are also common symptoms in perimenopausal women.^46-48 Studies have shown that depression is diagnosed 2.5 times more frequently among perimenopausal women than premenopausal women.⁴⁸ In a study by Miller et al that focused on 536 WLWH, among whom 37% were perimenopausal, 89% reported psychological symptoms.²⁹ Ferreira et al found that perimenopausal WLWH had an increased incidence of psychological symptoms, such as depression and anxiety, compared to women without HIV infection.²⁶ Whether this increased prevalence of psychological symptoms seen in WLWH can be attributed to menopause is unclear, since one third to one half of men and women living with HIV experience symptoms of depression.⁴⁹ However, in the WIHS, which compared findings from 835 WLWH to findings from 335 women without HIV from all menopausal stages, elevated depressive symptoms were seen in the early perimenopausal period.³⁴ There was no increased incidence of such symptoms during the premenopausal or postmenopausal stage, suggesting that factors related to menopause contribute to depressive symptoms during the perimenopausal stage.³⁴

Persistent menopausal symptoms, especially hot flashes, also predicted elevated depressive symptoms in several studies, suggesting the importance of appropriately identifying and treating menopausal symptoms.^29,34 In addition, cognitive decline associated with menopause contributes to depression.^50,51

Other Symptoms

Sleep disturbances are common among perimenopausal women, with an estimated prevalence between 38% and 46%.^52-54 Hot flashes, anxiety, and depression appear to be factors that contribute to sleep difficulty.^52-54 In a cross-sectional study of 273 WLWH and 264 women without HIV between 40 and 60 years of age, insomnia was found in 51% of perimenopausal and 53% of postmenopausal WLWH. The prevalence of insomnia in WLWH and women without HIV was the same.⁵⁵ Joint aches are also commonly reported in the perimenopausal period, with a prevalence as high as 50% to 60% among perimenopausal women in the United States.^22,29 Miller and colleagues found that 63% of menopausal WLWH reported arthralgia.²⁹

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Treatment

Despite the increased severity of menopausal symptoms experienced among WLWH, menopausal replacement therapy (MRT) is used less frequently in WLWH than in  women living without HIV.⁵⁵ Topical treatment is recommended for women who are experiencing vaginal dryness. First-line treatment is topical nonhormonal therapy, such as moisturizers and lubricants.⁵⁶ If symptoms are not relieved, then topical vaginal estrogen therapy is recommended.⁵⁶ Randomized placebo-controlled studies have verified the safety and efficacy of topical estrogen in the general population, and there is no reason to expect different outcomes in WLWH.^57,58 

For women experiencing severe hot flashes and vaginal dryness, short-term oral MRT is indicated.⁵⁶ MRT should be limited to the shortest period of time at the lowest effective dose needed to address these symptoms, as MRT is associated with increased risks of breast cancer, cardiovascular disease, and thromboembolism and increased morbidity.⁵⁶ Drug interactions between MRT and ART are of concern for non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and cobicistat, as these ARTs and MRT are metabolized by the CYP3A4 system.⁵⁹ With any PI, there is potential for an increase or decrease in estradiol or conjugated estrogen levels; an increase in medroxyprogesterone and micronized progesterone levels; and an increase in drospirenone levels. With doravirine and rilpivirine, there is no change in expected hormonal concentrations, but with other NNRTIs (efavirenz, etravirine, and nevirapine) there is a possibility of a decrease in estradiol, conjugated estrogen, medroxyprogesterone, micronized progesterone, and drospirenone levels. None of the integrase strand transfer inhibitors alone leads to changes in hormone level, but elvitegravir is only used when co-formulated with cobicistat, which may lead to increased or decreased estrogen, progesterone, and drospirenone levels.⁶⁰ Since all of these drug interactions are uncertain, and even act in varying directions, clinicians should monitor menopausal symptoms and titrate MRT to the dose that achieves relief of menopausal symptoms. 

Cardiovascular Risk

Estrogen deficiency that occurs during menopause leads to an increased risk of cardiovascular disease, particularly with changes in lipid profiles, insulin resistance, and body composition (eg, increased fat mass and waist circumference).⁶¹ HIV infection also is associated with a higher risk of cardiovascular disease, with studies consistently reporting a 1.5- to 2-fold increase in the rate of cardiovascular events in PLWH compared to persons without HIV.⁶² The inflammatory effects of HIV as well as ART exposure, specifically to PIs and abacavir, increase the risk for cardiovascular disease.⁶² In addition, traditional risk factors, including dyslipidemia, contribute to cardiovascular disease risk in this population.^63,64 

The increased risk for cardiovascular disease seen in HIV infection is likely compounded with the increased risk associated with menopause. Postmenopausal WLWH appear to be at higher risk of cardiovascular disease compared to postmenopausal women without HIV. Modifiable risk factors for cardiovascular disease, such as decreased fitness and smoking, are more commonly seen in WLWH.⁶⁵ Even prior to menopause, WLWH experience lipodystrophy syndrome, with increased truncal visceral adiposity and decreased subcutaneous fat and muscle mass.^65,66 Microbial translocation due to HIV-related damage of the intestinal mucosa can lead to elevated levels of lipopolysaccharides, a component of the cell wall of gram-negative bacteria; this subsequently activates monocytes, macrophages, and
T cells. In a study that compared postmenopausal WLWH to age-matched women without HIV, this HIV-related immune activation was correlated with an increase in biomarkers of cardiovascular disease, suggesting WLWH are at higher risk of developing cardiovascular disease.⁶⁷ Similarly, when comparing sex hormone concentrations in premenopausal WLWH and women without HIV, WLWH had lower estrogen and androgen levels, both of which are linked to carotid artery stiffness.⁶⁸

In addition, postmenopausal WLWH are at higher risk of cardiovascular disease compared to premenopausal WLWH. WLWH with reduced ovarian reserve had increased subclinical coronary atherosclerotic plaque compared to premenopausal WLWH, even when controlling for cardiovascular disease risk factors.⁶⁹

In summary, cardiovascular disease risk is increased in postmenopausal WLWH.⁶⁹ Appropriate measures, such as lipid control, antiplatelet therapy, smoking cessation, aerobic exercise, and other lifestyle changes, should be initiated in WLWH as in any other population. 

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Osteoporosis

Menopause, with its associated estrogen deficiency, is the most important risk factor linked to increased bone turnover and bone loss.⁷⁰ In addition, HIV is associated with bone loss, with low bone mineral density (BMD) described even among men and premenopausal women with HIV infection.⁷¹ Although decreased BMD associated with HIV stabilizes or even improves after initiation of ART in the younger population,^72-74 chronic inflammation caused by HIV stimulates osteoclast differentiation and resorption.⁷¹ Other factors that appear to contribute to decreased BMD among PLWH include ART; vitamin D deficiency; low BMI; poor nutrition; inactivity; use of tobacco, alcohol, and illicit drugs; hepatitis B and C coinfection; and frailty, defined as increased vulnerability to stresses related to aging.^72-80 Among ARTs, tenofovir disoproxil fumarate is associated with an increased risk of osteoporosis, and switching from this agent to tenofovir alafenamide improves bone density.⁸¹ Prolonged amenorrhea is also an added risk factor for osteoporosis in WLWH.⁸²

Once WLWH enter menopause, they have higher rates of osteoporosis and bone loss compared to women without HIV.⁸³ Among postmenopausal WLWH, those taking ritonavir were found to have increased differentiation of osteoclast cells and increased bone loss.⁸⁴ Similarly, methadone use in postmenopausal women has been associated with increased declines in BMD.⁸⁵ African-American postmenopausal WLWH appear to be at the greatest risk for bone loss.⁸⁶

Given the evidence of low BMD and increased fracture risk that occurs during menopause among women living without HIV, and the additional bone loss observed in PLWH, current guidelines recommend screening postmenopausal women ≥ 50 years of age with dual-energy X-ray absorptiometry (DEXA) scan.⁸⁷ Preventive therapy, such as smoking cessation, adequate nutrition, alcohol reduction, and weight-bearing exercises, should be discussed and recommended to all menopausal WLWH.⁸⁸ Adequate calcium and vitamin D intake should be discussed as well, with current evidence indicating that low-dose vitamin D supplementation at 1000 IU is as effective as high-dose vitamin D supplementation at 3000 IU in increasing BMD.⁸⁹ If the DEXA scan shows a T-score < –2.5 at the femoral neck or spine, or between –1 and –2.5 with a 10-year probability of hip fracture ≥ 3% or a 10-year probability of any osteoporosis-related fracture ≥ 20%, bisphosphonates or other medical therapy should be considered. Although the data are limited in WLWH, bisphosphonates have been shown to be effective in improving BMD.⁹⁰

Cognition

Both men and women living with HIV are at higher risk for cognitive impairment, ranging from minor cognitive-motor disorder to HIV-associated dementia.⁹¹ In addition, the menopause transition is characterized by cognitive changes, such as memory loss and difficulty concentrating.^92,93 Studies focusing on the effects of both HIV infection and menopause on cognition have been limited thus far. A cross-sectional study demonstrated that HIV infection, but not menopausal stage, was associated with worse performance on cognitive measures.⁹⁴ While menopausal stage was not associated with cognitive decline, menopausal symptoms like depression, anxiety, and vasomotor symptoms were associated with lower cognitive performance, highlighting the importance of recognition and treatment of menopausal symptoms.⁹⁴

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Cervical Dysplasia

WLWH are at increased risk for low- and high-grade squamous intraepithelial lesions (SILs) and more rapid progression to cervical carcinoma, as compared to women without HIV.⁹⁵ This increased risk of cervical disease is associated with age, human papillomavirus genotype, and degree of immunosuppression.⁹⁶ In addition, menopause appears to affect the risk of cervical disease. Postmenopausal WLWH had a higher risk of progression of SILs and persistence of lower-grade SILs compared to premenopausal women.^97,98 Although studies on progression to cervical cancer in postmenopausal WLWH remain limited, current data suggest that postmenopausal WLWH should continue to be monitored and screened similarly to premenopausal women. 

HIV Acquisition and Transmission

Women aged 50 years and older are primarily exposed to HIV through heterosexual contact.⁹⁹ While the lack of awareness of HIV risk and less frequent use of barrier protection can contribute to new HIV infection in older women, physiologic changes associated with menopause also may be playing a role.¹⁰⁰ Vaginal wall thinning and immunologic changes of the cervix that occur during menopause may serve as a risk factor for HIV acquisition. The cervicovaginal mucosa of postmenopausal women had higher levels of p24 antigen after ex vivo HIV-1 infection, suggesting higher susceptibility to acquire HIV infection.¹⁰¹ Postmenopausal women have been shown to have increased cervical CCR5 expression, which serves as an entry point of HIV into target cells.¹⁰² Finally, anti-HIV-1 activity was significantly decreased in postmenopausal women compared to premenopausal women.¹⁰³ In addition, ex vivo studies demonstrated reduced tenofovir disoproxil fumarate and emtricitabine triphosphate concentrations in cervical tissue of postmenopausal women, suggesting that postmenopausal women may need higher doses of pre-exposure prophylaxis to achieve protective efficacy.¹⁰⁴ 

In contrast, although data are limited, postmenopausal WLWH do not appear to be at increased risk of vaginally transmitting HIV. The intensity of HIV shedding did not differ between premenopausal or postmenopausal women.¹⁰⁵ There was a high prevalence of low-level HIV RNA in genital secretions among perimenopausal WLWH, suggesting WLWH in menopause do not present a major public health risk for HIV transmission.¹⁰⁶

HIV Progression

With prior data suggesting that younger persons experience better immunologic and virologic responses to ART,^107-109 it had previously been hypothesized that virologic and immunologic responses to ART will decline once WLWH reach menopause. However, current studies suggest that menopause does not affect the progression of HIV and that ART-naive women should respond to ART, regardless of their menopausal status. Treatment responses to ART, determined by the median changes in CD4 cell counts and percentages and viral load, in ART-naive individuals did not differ between premenopausal and postmenopausal women.¹¹⁰ In addition, there appear to be no significant changes in CD4 cell counts as WLWH progress through menopause.¹¹¹

Conclusion

As individuals with HIV infection live longer, an increasing number of women will enter menopause and live many years beyond menopause. WLWH experience earlier and more severe menopausal symptoms, but evidence on the appropriate management of these symptoms is still lacking. These conditions require proper surveillance, and can be prevented with an improved understanding of the effects of menopause on WLWH. However, there remain significant gaps in our understanding of menopause in WLWH. As practitioners encounter an increasing number of perimenopausal and postmenopausal WLWH, studies of the effects of HIV on comorbidities and symptoms of menopause and their appropriate management are necessary to improve care of WLWH.

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More than half of the 37.9 million persons living with HIV (PLWH) worldwide are women.¹ Between 2010 and 2016, 58% of women living with HIV (WLWH) in the United States were older than 45 years.² As such, an increasing number of WLWH are entering menopause and living well beyond menopause. Despite this, health care providers expressed a lack of confidence in managing menopause in WLWH, and menopausal symptoms often are not recognized by providers.³ Enhancing our knowledge about menopause in WLWH is important, since the physiologic changes associated with menopause impact short- and long-term quality of life and mortality. 

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Amenorrhea

Menstrual irregularities, including amenorrhea and anovulation, are more frequently found in women of low socioeconomic status, presumably due to associated physical and emotional stress.⁴ In addition, women with low body mass index (BMI) have decreased serum estradiol levels, which lead to amenorrhea.^4,5 Furthermore, low parity and many legal and illegal drugs are associated with amenorrhea, including hormonal contraceptives, opiates, stimulants, antipsychotics, and chemotherapeutic agents.^6-8

Because these factors associated with amenorrhea are common in WLWH, it is not surprising that amenorrhea and anovulation are frequently found in this population. However, HIV infection itself also appears to be an independent risk factor for amenorrhea. A recent meta-analysis of 8925 women showed a significant association between HIV status and amenorrhea, even when women with and without HIV had similar rates of substance abuse and smoking and similar socioeconomic status.⁹ The impact of HIV on an increased frequency of amenorrhea was strongest in women with low BMI. Some, but not all, of the studies included in the meta-analysis found a negative association between CD4 cell count and amenorrhea. In addition, a study comparing amenorrhea frequency within subgroups of WLWH also found a higher rate of amenorrhea in women with lower CD4 cell counts.¹⁰

“Prolonged” amenorrhea, defined as amenorrhea lasting 1 year or more, also occurs at a high frequency in WLWH.⁶ This has made determination of age of menopause extremely challenging, since it is likely that many studies defining menopause are misidentifying “prolonged” amenorrhea as menopause. The Women’s Interagency HIV Study (WIHS), a multicenter observational study of women of similar socioeconomic status living with and without HIV, found that more than 50% of WLWH with “prolonged” amenorrhea had serum follicle-stimulating hormone (FSH) levels in the premenopausal range.⁸ In a later study from the same cohort, 37% of 660 WLWH with “prolonged” amenorrhea had documented resumption of menses.⁶

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Age at Menopause

In the United States, the median age of menopause is between 50 and 52 years in middle-class white women.^11,12 Earlier menopause has been observed in women who are African American, are nulliparous, have a lower BMI, smoke tobacco, and have more stress, less education, and higher unemployment rates.^11,13,14 Because 57% of women diagnosed with HIV in 2018 were African American and many WLWH have other risk factors associated with earlier menopause, studies examining the age of menopause in WLWH need to use a comparator group of women without HIV with similar characteristics and control for these factors to determine the influence of HIV on the age of menopause.

It is also necessary to accurately define menopause. The World Health Organization defines natural menopause as the permanent cessation of menstruation for 12 consecutive months without any obvious pathologic or physiologic causes.¹⁵ Most studies have used this definition, and many have found that the age of menopause is earlier in WLWH and is associated with immunosuppression.^14,16,17 The Ms Study found that women with CD4 cell counts < 200 cells/μL had an increased risk of amenorrhea lasting at least 12 months, when compared to women with CD4 cell counts ≥ 200 cells/μL. The median age of menopause was 42.5 years in women with CD4 cell counts < 200 cells/μL, 46.0 years in women with CD4 cell counts between 200 cells/μL and 500 cells/μL, and 46.5 years in women with CD4 cell counts > 500 cells/μL.¹⁴ Similarly, in a cohort of 667 Brazilian WLWH, among whom 160 were postmenopausal, Calvet and colleagues found that 33% of women with CD4 cell counts < 50 cells/μL had premature menopause, as compared to 8% of women with CD4 cell counts ≥ 350 cells/μL.¹⁷ In De Pommerol and colleague’s study of 404 WLWH, among whom 69 were found to be postmenopausal, women with CD4 cell counts < 200 cells/μL were more likely to have premature menopause, as compared to women with CD4 cell counts ≥ 350 cells/μL.¹⁶

Despite these findings, given the data from WIHS showing that many women with amenorrhea for at least 12 consecutive months had FSH levels in the premenopausal range⁸ and that 37% of WLWH have resumption of menses after 12 consecutive months of amenorrhea,⁶ it is probable that the conclusions about the age of menopause in WLWH are invalid, since many of the participants likely had prolonged amenorrhea, not menopause. WIHS found no significant difference in the median age of menopause when WLWH were compared to women without HIV. The median age of menopause was 47.7 years in WLWH and 48.0 years in women without HIV.¹⁸

Menopause-Associated Symptoms

The perimenopausal period, which begins, on average, 4 years prior to the final menstrual period, is characterized by hormonal fluctuations leading to irregular menstrual cycles.^19,20 Symptoms associated with these physiologic changes during the perimenopausal period include vasomotor symptoms (hot flashes), genitourinary symptoms (vaginal dryness and dyspareunia), anxiety, depression, sleep disturbances, and joint aches.^21,22 Such menopausal symptoms can be distressing and negatively impact quality of life.²³ In WLWH, severe menopausal symptoms have been associated with suboptimal adherence to antiretroviral therapy (ART).²⁴ 

It can be difficult to determine which symptoms are caused by the physiologic changes of menopause in WLWH, as these women have multiple potential reasons for these symptoms, such as ART, comorbidities, and HIV infection itself.²⁵ However, several studies show that there are symptoms that occur more commonly in the perimenopausal period and that WLWH experience these symptoms earlier and with greater intensity.^26-30 In addition, the burden of commonly reported HIV symptoms, such as fatigue and muscle aches/joint pains, is higher in women after menopause, suggesting this burden may be exacerbated by menopause.³¹

Vasomotor

In the United States, the most common symptom during perimenopause is hot flashes, which occur in 38% to 80% of women.^32,33 Vasomotor symptoms are most common in women who smoke, use illicit substances, have a high BMI, are of lower socioeconomic status, and are African American.¹¹ As expected, prior studies focusing on hot flash prevalence among premenopausal, perimenopausal, and postmenopausal WLWH found that postmenopausal women experience more hot flashes than premenopausal or perimenopausal women.^27,28 In addition, a comparison of women with and without HIV demonstrated a higher prevalence of hot flashes among WLWH.^26,29 Vasomotor symptoms can be severely distressing, with hot flashes contributing to increased risk of depression.^25,34 In a cross-sectional analysis of 835 WLWH and 335 women without HIV from the WIHS cohort, persistent vasomotor symptoms predicted elevated depressive symptoms in both WLWH and women without HIV.³⁴ In a similar cross-sectional analysis of 536 women, among whom 54% were WLWH and 37% were perimenopausal, psychological symptoms were prevalent in 61% of the women with vasomotor symptoms.²⁹

Genitourinary

Estrogen deficiency, which accompanies the perimenopausal period, leads to vulvovaginal atrophy (VVA), manifesting with symptoms of vaginal dryness, itching, burning, urinary urgency, and dyspareunia (painful intercourse).^33,35,36 Unlike vasomotor symptoms, which diminish with time, genitourinary symptoms generally worsen if left untreated.³⁷ Furthermore, these symptoms are often underreported and underdiagnosed.^38,39 VVA was found in 43% to 84% of postmenopausal women.^36,40,41 In the AGATA study, the prevalence of VVA was associated with years since menopause. ³⁶ Vaginal dryness and dyspareunia were common.

Genitourinary symptoms are most common among women who are African American, have an increased BMI, are of lower socioeconomic status, use tobacco, have a prior history of pelvic inflammatory disease, and have anxiety and depression.^11,42,43 Similar to hot flashes, many of these predisposing factors are more common in WLWH. Fantry and colleagues found that 49.6% of WLWH had vaginal dryness.²⁷ Although 56% of postmenopausal women and 36% of perimenopausal women complained of vaginal dryness, in a multivariate analysis only cocaine use, which can decrease estradiol levels,⁴⁴ was associated with a higher frequency of vaginal dryness.²⁷

Dyspareunia is also common among WLWH. In a cross-sectional study of 178 women without HIV and 128 WLWH between 40 and 60 years of age, Valadares et al found a high prevalence of dyspareunia in WLWH: 41.8%.⁴⁵ However, this was not significantly higher than the prevalence of dyspareunia in women without HIV: 34.8%.⁴⁵ HIV infection itself was not associated with the presence of dyspareunia.

Psychiatric

Anxiety and depression are also common symptoms in perimenopausal women.^46-48 Studies have shown that depression is diagnosed 2.5 times more frequently among perimenopausal women than premenopausal women.⁴⁸ In a study by Miller et al that focused on 536 WLWH, among whom 37% were perimenopausal, 89% reported psychological symptoms.²⁹ Ferreira et al found that perimenopausal WLWH had an increased incidence of psychological symptoms, such as depression and anxiety, compared to women without HIV infection.²⁶ Whether this increased prevalence of psychological symptoms seen in WLWH can be attributed to menopause is unclear, since one third to one half of men and women living with HIV experience symptoms of depression.⁴⁹ However, in the WIHS, which compared findings from 835 WLWH to findings from 335 women without HIV from all menopausal stages, elevated depressive symptoms were seen in the early perimenopausal period.³⁴ There was no increased incidence of such symptoms during the premenopausal or postmenopausal stage, suggesting that factors related to menopause contribute to depressive symptoms during the perimenopausal stage.³⁴

Persistent menopausal symptoms, especially hot flashes, also predicted elevated depressive symptoms in several studies, suggesting the importance of appropriately identifying and treating menopausal symptoms.^29,34 In addition, cognitive decline associated with menopause contributes to depression.^50,51

Other Symptoms

Sleep disturbances are common among perimenopausal women, with an estimated prevalence between 38% and 46%.^52-54 Hot flashes, anxiety, and depression appear to be factors that contribute to sleep difficulty.^52-54 In a cross-sectional study of 273 WLWH and 264 women without HIV between 40 and 60 years of age, insomnia was found in 51% of perimenopausal and 53% of postmenopausal WLWH. The prevalence of insomnia in WLWH and women without HIV was the same.⁵⁵ Joint aches are also commonly reported in the perimenopausal period, with a prevalence as high as 50% to 60% among perimenopausal women in the United States.^22,29 Miller and colleagues found that 63% of menopausal WLWH reported arthralgia.²⁹

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Treatment

Despite the increased severity of menopausal symptoms experienced among WLWH, menopausal replacement therapy (MRT) is used less frequently in WLWH than in  women living without HIV.⁵⁵ Topical treatment is recommended for women who are experiencing vaginal dryness. First-line treatment is topical nonhormonal therapy, such as moisturizers and lubricants.⁵⁶ If symptoms are not relieved, then topical vaginal estrogen therapy is recommended.⁵⁶ Randomized placebo-controlled studies have verified the safety and efficacy of topical estrogen in the general population, and there is no reason to expect different outcomes in WLWH.^57,58 

For women experiencing severe hot flashes and vaginal dryness, short-term oral MRT is indicated.⁵⁶ MRT should be limited to the shortest period of time at the lowest effective dose needed to address these symptoms, as MRT is associated with increased risks of breast cancer, cardiovascular disease, and thromboembolism and increased morbidity.⁵⁶ Drug interactions between MRT and ART are of concern for non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and cobicistat, as these ARTs and MRT are metabolized by the CYP3A4 system.⁵⁹ With any PI, there is potential for an increase or decrease in estradiol or conjugated estrogen levels; an increase in medroxyprogesterone and micronized progesterone levels; and an increase in drospirenone levels. With doravirine and rilpivirine, there is no change in expected hormonal concentrations, but with other NNRTIs (efavirenz, etravirine, and nevirapine) there is a possibility of a decrease in estradiol, conjugated estrogen, medroxyprogesterone, micronized progesterone, and drospirenone levels. None of the integrase strand transfer inhibitors alone leads to changes in hormone level, but elvitegravir is only used when co-formulated with cobicistat, which may lead to increased or decreased estrogen, progesterone, and drospirenone levels.⁶⁰ Since all of these drug interactions are uncertain, and even act in varying directions, clinicians should monitor menopausal symptoms and titrate MRT to the dose that achieves relief of menopausal symptoms. 

Cardiovascular Risk

Estrogen deficiency that occurs during menopause leads to an increased risk of cardiovascular disease, particularly with changes in lipid profiles, insulin resistance, and body composition (eg, increased fat mass and waist circumference).⁶¹ HIV infection also is associated with a higher risk of cardiovascular disease, with studies consistently reporting a 1.5- to 2-fold increase in the rate of cardiovascular events in PLWH compared to persons without HIV.⁶² The inflammatory effects of HIV as well as ART exposure, specifically to PIs and abacavir, increase the risk for cardiovascular disease.⁶² In addition, traditional risk factors, including dyslipidemia, contribute to cardiovascular disease risk in this population.^63,64 

The increased risk for cardiovascular disease seen in HIV infection is likely compounded with the increased risk associated with menopause. Postmenopausal WLWH appear to be at higher risk of cardiovascular disease compared to postmenopausal women without HIV. Modifiable risk factors for cardiovascular disease, such as decreased fitness and smoking, are more commonly seen in WLWH.⁶⁵ Even prior to menopause, WLWH experience lipodystrophy syndrome, with increased truncal visceral adiposity and decreased subcutaneous fat and muscle mass.^65,66 Microbial translocation due to HIV-related damage of the intestinal mucosa can lead to elevated levels of lipopolysaccharides, a component of the cell wall of gram-negative bacteria; this subsequently activates monocytes, macrophages, and
T cells. In a study that compared postmenopausal WLWH to age-matched women without HIV, this HIV-related immune activation was correlated with an increase in biomarkers of cardiovascular disease, suggesting WLWH are at higher risk of developing cardiovascular disease.⁶⁷ Similarly, when comparing sex hormone concentrations in premenopausal WLWH and women without HIV, WLWH had lower estrogen and androgen levels, both of which are linked to carotid artery stiffness.⁶⁸

In addition, postmenopausal WLWH are at higher risk of cardiovascular disease compared to premenopausal WLWH. WLWH with reduced ovarian reserve had increased subclinical coronary atherosclerotic plaque compared to premenopausal WLWH, even when controlling for cardiovascular disease risk factors.⁶⁹

In summary, cardiovascular disease risk is increased in postmenopausal WLWH.⁶⁹ Appropriate measures, such as lipid control, antiplatelet therapy, smoking cessation, aerobic exercise, and other lifestyle changes, should be initiated in WLWH as in any other population. 

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Osteoporosis

Menopause, with its associated estrogen deficiency, is the most important risk factor linked to increased bone turnover and bone loss.⁷⁰ In addition, HIV is associated with bone loss, with low bone mineral density (BMD) described even among men and premenopausal women with HIV infection.⁷¹ Although decreased BMD associated with HIV stabilizes or even improves after initiation of ART in the younger population,^72-74 chronic inflammation caused by HIV stimulates osteoclast differentiation and resorption.⁷¹ Other factors that appear to contribute to decreased BMD among PLWH include ART; vitamin D deficiency; low BMI; poor nutrition; inactivity; use of tobacco, alcohol, and illicit drugs; hepatitis B and C coinfection; and frailty, defined as increased vulnerability to stresses related to aging.^72-80 Among ARTs, tenofovir disoproxil fumarate is associated with an increased risk of osteoporosis, and switching from this agent to tenofovir alafenamide improves bone density.⁸¹ Prolonged amenorrhea is also an added risk factor for osteoporosis in WLWH.⁸²

Once WLWH enter menopause, they have higher rates of osteoporosis and bone loss compared to women without HIV.⁸³ Among postmenopausal WLWH, those taking ritonavir were found to have increased differentiation of osteoclast cells and increased bone loss.⁸⁴ Similarly, methadone use in postmenopausal women has been associated with increased declines in BMD.⁸⁵ African-American postmenopausal WLWH appear to be at the greatest risk for bone loss.⁸⁶

Given the evidence of low BMD and increased fracture risk that occurs during menopause among women living without HIV, and the additional bone loss observed in PLWH, current guidelines recommend screening postmenopausal women ≥ 50 years of age with dual-energy X-ray absorptiometry (DEXA) scan.⁸⁷ Preventive therapy, such as smoking cessation, adequate nutrition, alcohol reduction, and weight-bearing exercises, should be discussed and recommended to all menopausal WLWH.⁸⁸ Adequate calcium and vitamin D intake should be discussed as well, with current evidence indicating that low-dose vitamin D supplementation at 1000 IU is as effective as high-dose vitamin D supplementation at 3000 IU in increasing BMD.⁸⁹ If the DEXA scan shows a T-score < –2.5 at the femoral neck or spine, or between –1 and –2.5 with a 10-year probability of hip fracture ≥ 3% or a 10-year probability of any osteoporosis-related fracture ≥ 20%, bisphosphonates or other medical therapy should be considered. Although the data are limited in WLWH, bisphosphonates have been shown to be effective in improving BMD.⁹⁰

Cognition

Both men and women living with HIV are at higher risk for cognitive impairment, ranging from minor cognitive-motor disorder to HIV-associated dementia.⁹¹ In addition, the menopause transition is characterized by cognitive changes, such as memory loss and difficulty concentrating.^92,93 Studies focusing on the effects of both HIV infection and menopause on cognition have been limited thus far. A cross-sectional study demonstrated that HIV infection, but not menopausal stage, was associated with worse performance on cognitive measures.⁹⁴ While menopausal stage was not associated with cognitive decline, menopausal symptoms like depression, anxiety, and vasomotor symptoms were associated with lower cognitive performance, highlighting the importance of recognition and treatment of menopausal symptoms.⁹⁴

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Cervical Dysplasia

WLWH are at increased risk for low- and high-grade squamous intraepithelial lesions (SILs) and more rapid progression to cervical carcinoma, as compared to women without HIV.⁹⁵ This increased risk of cervical disease is associated with age, human papillomavirus genotype, and degree of immunosuppression.⁹⁶ In addition, menopause appears to affect the risk of cervical disease. Postmenopausal WLWH had a higher risk of progression of SILs and persistence of lower-grade SILs compared to premenopausal women.^97,98 Although studies on progression to cervical cancer in postmenopausal WLWH remain limited, current data suggest that postmenopausal WLWH should continue to be monitored and screened similarly to premenopausal women. 

HIV Acquisition and Transmission

Women aged 50 years and older are primarily exposed to HIV through heterosexual contact.⁹⁹ While the lack of awareness of HIV risk and less frequent use of barrier protection can contribute to new HIV infection in older women, physiologic changes associated with menopause also may be playing a role.¹⁰⁰ Vaginal wall thinning and immunologic changes of the cervix that occur during menopause may serve as a risk factor for HIV acquisition. The cervicovaginal mucosa of postmenopausal women had higher levels of p24 antigen after ex vivo HIV-1 infection, suggesting higher susceptibility to acquire HIV infection.¹⁰¹ Postmenopausal women have been shown to have increased cervical CCR5 expression, which serves as an entry point of HIV into target cells.¹⁰² Finally, anti-HIV-1 activity was significantly decreased in postmenopausal women compared to premenopausal women.¹⁰³ In addition, ex vivo studies demonstrated reduced tenofovir disoproxil fumarate and emtricitabine triphosphate concentrations in cervical tissue of postmenopausal women, suggesting that postmenopausal women may need higher doses of pre-exposure prophylaxis to achieve protective efficacy.¹⁰⁴ 

In contrast, although data are limited, postmenopausal WLWH do not appear to be at increased risk of vaginally transmitting HIV. The intensity of HIV shedding did not differ between premenopausal or postmenopausal women.¹⁰⁵ There was a high prevalence of low-level HIV RNA in genital secretions among perimenopausal WLWH, suggesting WLWH in menopause do not present a major public health risk for HIV transmission.¹⁰⁶

HIV Progression

With prior data suggesting that younger persons experience better immunologic and virologic responses to ART,^107-109 it had previously been hypothesized that virologic and immunologic responses to ART will decline once WLWH reach menopause. However, current studies suggest that menopause does not affect the progression of HIV and that ART-naive women should respond to ART, regardless of their menopausal status. Treatment responses to ART, determined by the median changes in CD4 cell counts and percentages and viral load, in ART-naive individuals did not differ between premenopausal and postmenopausal women.¹¹⁰ In addition, there appear to be no significant changes in CD4 cell counts as WLWH progress through menopause.¹¹¹

Conclusion

As individuals with HIV infection live longer, an increasing number of women will enter menopause and live many years beyond menopause. WLWH experience earlier and more severe menopausal symptoms, but evidence on the appropriate management of these symptoms is still lacking. These conditions require proper surveillance, and can be prevented with an improved understanding of the effects of menopause on WLWH. However, there remain significant gaps in our understanding of menopause in WLWH. As practitioners encounter an increasing number of perimenopausal and postmenopausal WLWH, studies of the effects of HIV on comorbidities and symptoms of menopause and their appropriate management are necessary to improve care of WLWH.

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More than half of the 37.9 million persons living with HIV (PLWH) worldwide are women.¹ Between 2010 and 2016, 58% of women living with HIV (WLWH) in the United States were older than 45 years.² As such, an increasing number of WLWH are entering menopause and living well beyond menopause. Despite this, health care providers expressed a lack of confidence in managing menopause in WLWH, and menopausal symptoms often are not recognized by providers.³ Enhancing our knowledge about menopause in WLWH is important, since the physiologic changes associated with menopause impact short- and long-term quality of life and mortality. 

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Amenorrhea

Menstrual irregularities, including amenorrhea and anovulation, are more frequently found in women of low socioeconomic status, presumably due to associated physical and emotional stress.⁴ In addition, women with low body mass index (BMI) have decreased serum estradiol levels, which lead to amenorrhea.^4,5 Furthermore, low parity and many legal and illegal drugs are associated with amenorrhea, including hormonal contraceptives, opiates, stimulants, antipsychotics, and chemotherapeutic agents.^6-8

Because these factors associated with amenorrhea are common in WLWH, it is not surprising that amenorrhea and anovulation are frequently found in this population. However, HIV infection itself also appears to be an independent risk factor for amenorrhea. A recent meta-analysis of 8925 women showed a significant association between HIV status and amenorrhea, even when women with and without HIV had similar rates of substance abuse and smoking and similar socioeconomic status.⁹ The impact of HIV on an increased frequency of amenorrhea was strongest in women with low BMI. Some, but not all, of the studies included in the meta-analysis found a negative association between CD4 cell count and amenorrhea. In addition, a study comparing amenorrhea frequency within subgroups of WLWH also found a higher rate of amenorrhea in women with lower CD4 cell counts.¹⁰

“Prolonged” amenorrhea, defined as amenorrhea lasting 1 year or more, also occurs at a high frequency in WLWH.⁶ This has made determination of age of menopause extremely challenging, since it is likely that many studies defining menopause are misidentifying “prolonged” amenorrhea as menopause. The Women’s Interagency HIV Study (WIHS), a multicenter observational study of women of similar socioeconomic status living with and without HIV, found that more than 50% of WLWH with “prolonged” amenorrhea had serum follicle-stimulating hormone (FSH) levels in the premenopausal range.⁸ In a later study from the same cohort, 37% of 660 WLWH with “prolonged” amenorrhea had documented resumption of menses.⁶

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Age at Menopause

In the United States, the median age of menopause is between 50 and 52 years in middle-class white women.^11,12 Earlier menopause has been observed in women who are African American, are nulliparous, have a lower BMI, smoke tobacco, and have more stress, less education, and higher unemployment rates.^11,13,14 Because 57% of women diagnosed with HIV in 2018 were African American and many WLWH have other risk factors associated with earlier menopause, studies examining the age of menopause in WLWH need to use a comparator group of women without HIV with similar characteristics and control for these factors to determine the influence of HIV on the age of menopause.

It is also necessary to accurately define menopause. The World Health Organization defines natural menopause as the permanent cessation of menstruation for 12 consecutive months without any obvious pathologic or physiologic causes.¹⁵ Most studies have used this definition, and many have found that the age of menopause is earlier in WLWH and is associated with immunosuppression.^14,16,17 The Ms Study found that women with CD4 cell counts < 200 cells/μL had an increased risk of amenorrhea lasting at least 12 months, when compared to women with CD4 cell counts ≥ 200 cells/μL. The median age of menopause was 42.5 years in women with CD4 cell counts < 200 cells/μL, 46.0 years in women with CD4 cell counts between 200 cells/μL and 500 cells/μL, and 46.5 years in women with CD4 cell counts > 500 cells/μL.¹⁴ Similarly, in a cohort of 667 Brazilian WLWH, among whom 160 were postmenopausal, Calvet and colleagues found that 33% of women with CD4 cell counts < 50 cells/μL had premature menopause, as compared to 8% of women with CD4 cell counts ≥ 350 cells/μL.¹⁷ In De Pommerol and colleague’s study of 404 WLWH, among whom 69 were found to be postmenopausal, women with CD4 cell counts < 200 cells/μL were more likely to have premature menopause, as compared to women with CD4 cell counts ≥ 350 cells/μL.¹⁶

Despite these findings, given the data from WIHS showing that many women with amenorrhea for at least 12 consecutive months had FSH levels in the premenopausal range⁸ and that 37% of WLWH have resumption of menses after 12 consecutive months of amenorrhea,⁶ it is probable that the conclusions about the age of menopause in WLWH are invalid, since many of the participants likely had prolonged amenorrhea, not menopause. WIHS found no significant difference in the median age of menopause when WLWH were compared to women without HIV. The median age of menopause was 47.7 years in WLWH and 48.0 years in women without HIV.¹⁸

Menopause-Associated Symptoms

The perimenopausal period, which begins, on average, 4 years prior to the final menstrual period, is characterized by hormonal fluctuations leading to irregular menstrual cycles.^19,20 Symptoms associated with these physiologic changes during the perimenopausal period include vasomotor symptoms (hot flashes), genitourinary symptoms (vaginal dryness and dyspareunia), anxiety, depression, sleep disturbances, and joint aches.^21,22 Such menopausal symptoms can be distressing and negatively impact quality of life.²³ In WLWH, severe menopausal symptoms have been associated with suboptimal adherence to antiretroviral therapy (ART).²⁴ 

It can be difficult to determine which symptoms are caused by the physiologic changes of menopause in WLWH, as these women have multiple potential reasons for these symptoms, such as ART, comorbidities, and HIV infection itself.²⁵ However, several studies show that there are symptoms that occur more commonly in the perimenopausal period and that WLWH experience these symptoms earlier and with greater intensity.^26-30 In addition, the burden of commonly reported HIV symptoms, such as fatigue and muscle aches/joint pains, is higher in women after menopause, suggesting this burden may be exacerbated by menopause.³¹

Vasomotor

In the United States, the most common symptom during perimenopause is hot flashes, which occur in 38% to 80% of women.^32,33 Vasomotor symptoms are most common in women who smoke, use illicit substances, have a high BMI, are of lower socioeconomic status, and are African American.¹¹ As expected, prior studies focusing on hot flash prevalence among premenopausal, perimenopausal, and postmenopausal WLWH found that postmenopausal women experience more hot flashes than premenopausal or perimenopausal women.^27,28 In addition, a comparison of women with and without HIV demonstrated a higher prevalence of hot flashes among WLWH.^26,29 Vasomotor symptoms can be severely distressing, with hot flashes contributing to increased risk of depression.^25,34 In a cross-sectional analysis of 835 WLWH and 335 women without HIV from the WIHS cohort, persistent vasomotor symptoms predicted elevated depressive symptoms in both WLWH and women without HIV.³⁴ In a similar cross-sectional analysis of 536 women, among whom 54% were WLWH and 37% were perimenopausal, psychological symptoms were prevalent in 61% of the women with vasomotor symptoms.²⁹

Genitourinary

Estrogen deficiency, which accompanies the perimenopausal period, leads to vulvovaginal atrophy (VVA), manifesting with symptoms of vaginal dryness, itching, burning, urinary urgency, and dyspareunia (painful intercourse).^33,35,36 Unlike vasomotor symptoms, which diminish with time, genitourinary symptoms generally worsen if left untreated.³⁷ Furthermore, these symptoms are often underreported and underdiagnosed.^38,39 VVA was found in 43% to 84% of postmenopausal women.^36,40,41 In the AGATA study, the prevalence of VVA was associated with years since menopause. ³⁶ Vaginal dryness and dyspareunia were common.

Genitourinary symptoms are most common among women who are African American, have an increased BMI, are of lower socioeconomic status, use tobacco, have a prior history of pelvic inflammatory disease, and have anxiety and depression.^11,42,43 Similar to hot flashes, many of these predisposing factors are more common in WLWH. Fantry and colleagues found that 49.6% of WLWH had vaginal dryness.²⁷ Although 56% of postmenopausal women and 36% of perimenopausal women complained of vaginal dryness, in a multivariate analysis only cocaine use, which can decrease estradiol levels,⁴⁴ was associated with a higher frequency of vaginal dryness.²⁷

Dyspareunia is also common among WLWH. In a cross-sectional study of 178 women without HIV and 128 WLWH between 40 and 60 years of age, Valadares et al found a high prevalence of dyspareunia in WLWH: 41.8%.⁴⁵ However, this was not significantly higher than the prevalence of dyspareunia in women without HIV: 34.8%.⁴⁵ HIV infection itself was not associated with the presence of dyspareunia.

Psychiatric

Anxiety and depression are also common symptoms in perimenopausal women.^46-48 Studies have shown that depression is diagnosed 2.5 times more frequently among perimenopausal women than premenopausal women.⁴⁸ In a study by Miller et al that focused on 536 WLWH, among whom 37% were perimenopausal, 89% reported psychological symptoms.²⁹ Ferreira et al found that perimenopausal WLWH had an increased incidence of psychological symptoms, such as depression and anxiety, compared to women without HIV infection.²⁶ Whether this increased prevalence of psychological symptoms seen in WLWH can be attributed to menopause is unclear, since one third to one half of men and women living with HIV experience symptoms of depression.⁴⁹ However, in the WIHS, which compared findings from 835 WLWH to findings from 335 women without HIV from all menopausal stages, elevated depressive symptoms were seen in the early perimenopausal period.³⁴ There was no increased incidence of such symptoms during the premenopausal or postmenopausal stage, suggesting that factors related to menopause contribute to depressive symptoms during the perimenopausal stage.³⁴

Persistent menopausal symptoms, especially hot flashes, also predicted elevated depressive symptoms in several studies, suggesting the importance of appropriately identifying and treating menopausal symptoms.^29,34 In addition, cognitive decline associated with menopause contributes to depression.^50,51

Other Symptoms

Sleep disturbances are common among perimenopausal women, with an estimated prevalence between 38% and 46%.^52-54 Hot flashes, anxiety, and depression appear to be factors that contribute to sleep difficulty.^52-54 In a cross-sectional study of 273 WLWH and 264 women without HIV between 40 and 60 years of age, insomnia was found in 51% of perimenopausal and 53% of postmenopausal WLWH. The prevalence of insomnia in WLWH and women without HIV was the same.⁵⁵ Joint aches are also commonly reported in the perimenopausal period, with a prevalence as high as 50% to 60% among perimenopausal women in the United States.^22,29 Miller and colleagues found that 63% of menopausal WLWH reported arthralgia.²⁹

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Treatment

Despite the increased severity of menopausal symptoms experienced among WLWH, menopausal replacement therapy (MRT) is used less frequently in WLWH than in  women living without HIV.⁵⁵ Topical treatment is recommended for women who are experiencing vaginal dryness. First-line treatment is topical nonhormonal therapy, such as moisturizers and lubricants.⁵⁶ If symptoms are not relieved, then topical vaginal estrogen therapy is recommended.⁵⁶ Randomized placebo-controlled studies have verified the safety and efficacy of topical estrogen in the general population, and there is no reason to expect different outcomes in WLWH.^57,58 

For women experiencing severe hot flashes and vaginal dryness, short-term oral MRT is indicated.⁵⁶ MRT should be limited to the shortest period of time at the lowest effective dose needed to address these symptoms, as MRT is associated with increased risks of breast cancer, cardiovascular disease, and thromboembolism and increased morbidity.⁵⁶ Drug interactions between MRT and ART are of concern for non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and cobicistat, as these ARTs and MRT are metabolized by the CYP3A4 system.⁵⁹ With any PI, there is potential for an increase or decrease in estradiol or conjugated estrogen levels; an increase in medroxyprogesterone and micronized progesterone levels; and an increase in drospirenone levels. With doravirine and rilpivirine, there is no change in expected hormonal concentrations, but with other NNRTIs (efavirenz, etravirine, and nevirapine) there is a possibility of a decrease in estradiol, conjugated estrogen, medroxyprogesterone, micronized progesterone, and drospirenone levels. None of the integrase strand transfer inhibitors alone leads to changes in hormone level, but elvitegravir is only used when co-formulated with cobicistat, which may lead to increased or decreased estrogen, progesterone, and drospirenone levels.⁶⁰ Since all of these drug interactions are uncertain, and even act in varying directions, clinicians should monitor menopausal symptoms and titrate MRT to the dose that achieves relief of menopausal symptoms. 

Cardiovascular Risk

Estrogen deficiency that occurs during menopause leads to an increased risk of cardiovascular disease, particularly with changes in lipid profiles, insulin resistance, and body composition (eg, increased fat mass and waist circumference).⁶¹ HIV infection also is associated with a higher risk of cardiovascular disease, with studies consistently reporting a 1.5- to 2-fold increase in the rate of cardiovascular events in PLWH compared to persons without HIV.⁶² The inflammatory effects of HIV as well as ART exposure, specifically to PIs and abacavir, increase the risk for cardiovascular disease.⁶² In addition, traditional risk factors, including dyslipidemia, contribute to cardiovascular disease risk in this population.^63,64 

The increased risk for cardiovascular disease seen in HIV infection is likely compounded with the increased risk associated with menopause. Postmenopausal WLWH appear to be at higher risk of cardiovascular disease compared to postmenopausal women without HIV. Modifiable risk factors for cardiovascular disease, such as decreased fitness and smoking, are more commonly seen in WLWH.⁶⁵ Even prior to menopause, WLWH experience lipodystrophy syndrome, with increased truncal visceral adiposity and decreased subcutaneous fat and muscle mass.^65,66 Microbial translocation due to HIV-related damage of the intestinal mucosa can lead to elevated levels of lipopolysaccharides, a component of the cell wall of gram-negative bacteria; this subsequently activates monocytes, macrophages, and
T cells. In a study that compared postmenopausal WLWH to age-matched women without HIV, this HIV-related immune activation was correlated with an increase in biomarkers of cardiovascular disease, suggesting WLWH are at higher risk of developing cardiovascular disease.⁶⁷ Similarly, when comparing sex hormone concentrations in premenopausal WLWH and women without HIV, WLWH had lower estrogen and androgen levels, both of which are linked to carotid artery stiffness.⁶⁸

In addition, postmenopausal WLWH are at higher risk of cardiovascular disease compared to premenopausal WLWH. WLWH with reduced ovarian reserve had increased subclinical coronary atherosclerotic plaque compared to premenopausal WLWH, even when controlling for cardiovascular disease risk factors.⁶⁹

In summary, cardiovascular disease risk is increased in postmenopausal WLWH.⁶⁹ Appropriate measures, such as lipid control, antiplatelet therapy, smoking cessation, aerobic exercise, and other lifestyle changes, should be initiated in WLWH as in any other population. 

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Osteoporosis

Menopause, with its associated estrogen deficiency, is the most important risk factor linked to increased bone turnover and bone loss.⁷⁰ In addition, HIV is associated with bone loss, with low bone mineral density (BMD) described even among men and premenopausal women with HIV infection.⁷¹ Although decreased BMD associated with HIV stabilizes or even improves after initiation of ART in the younger population,^72-74 chronic inflammation caused by HIV stimulates osteoclast differentiation and resorption.⁷¹ Other factors that appear to contribute to decreased BMD among PLWH include ART; vitamin D deficiency; low BMI; poor nutrition; inactivity; use of tobacco, alcohol, and illicit drugs; hepatitis B and C coinfection; and frailty, defined as increased vulnerability to stresses related to aging.^72-80 Among ARTs, tenofovir disoproxil fumarate is associated with an increased risk of osteoporosis, and switching from this agent to tenofovir alafenamide improves bone density.⁸¹ Prolonged amenorrhea is also an added risk factor for osteoporosis in WLWH.⁸²

Once WLWH enter menopause, they have higher rates of osteoporosis and bone loss compared to women without HIV.⁸³ Among postmenopausal WLWH, those taking ritonavir were found to have increased differentiation of osteoclast cells and increased bone loss.⁸⁴ Similarly, methadone use in postmenopausal women has been associated with increased declines in BMD.⁸⁵ African-American postmenopausal WLWH appear to be at the greatest risk for bone loss.⁸⁶

Given the evidence of low BMD and increased fracture risk that occurs during menopause among women living without HIV, and the additional bone loss observed in PLWH, current guidelines recommend screening postmenopausal women ≥ 50 years of age with dual-energy X-ray absorptiometry (DEXA) scan.⁸⁷ Preventive therapy, such as smoking cessation, adequate nutrition, alcohol reduction, and weight-bearing exercises, should be discussed and recommended to all menopausal WLWH.⁸⁸ Adequate calcium and vitamin D intake should be discussed as well, with current evidence indicating that low-dose vitamin D supplementation at 1000 IU is as effective as high-dose vitamin D supplementation at 3000 IU in increasing BMD.⁸⁹ If the DEXA scan shows a T-score < –2.5 at the femoral neck or spine, or between –1 and –2.5 with a 10-year probability of hip fracture ≥ 3% or a 10-year probability of any osteoporosis-related fracture ≥ 20%, bisphosphonates or other medical therapy should be considered. Although the data are limited in WLWH, bisphosphonates have been shown to be effective in improving BMD.⁹⁰

Cognition

Both men and women living with HIV are at higher risk for cognitive impairment, ranging from minor cognitive-motor disorder to HIV-associated dementia.⁹¹ In addition, the menopause transition is characterized by cognitive changes, such as memory loss and difficulty concentrating.^92,93 Studies focusing on the effects of both HIV infection and menopause on cognition have been limited thus far. A cross-sectional study demonstrated that HIV infection, but not menopausal stage, was associated with worse performance on cognitive measures.⁹⁴ While menopausal stage was not associated with cognitive decline, menopausal symptoms like depression, anxiety, and vasomotor symptoms were associated with lower cognitive performance, highlighting the importance of recognition and treatment of menopausal symptoms.⁹⁴

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Cervical Dysplasia

WLWH are at increased risk for low- and high-grade squamous intraepithelial lesions (SILs) and more rapid progression to cervical carcinoma, as compared to women without HIV.⁹⁵ This increased risk of cervical disease is associated with age, human papillomavirus genotype, and degree of immunosuppression.⁹⁶ In addition, menopause appears to affect the risk of cervical disease. Postmenopausal WLWH had a higher risk of progression of SILs and persistence of lower-grade SILs compared to premenopausal women.^97,98 Although studies on progression to cervical cancer in postmenopausal WLWH remain limited, current data suggest that postmenopausal WLWH should continue to be monitored and screened similarly to premenopausal women. 

HIV Acquisition and Transmission

Women aged 50 years and older are primarily exposed to HIV through heterosexual contact.⁹⁹ While the lack of awareness of HIV risk and less frequent use of barrier protection can contribute to new HIV infection in older women, physiologic changes associated with menopause also may be playing a role.¹⁰⁰ Vaginal wall thinning and immunologic changes of the cervix that occur during menopause may serve as a risk factor for HIV acquisition. The cervicovaginal mucosa of postmenopausal women had higher levels of p24 antigen after ex vivo HIV-1 infection, suggesting higher susceptibility to acquire HIV infection.¹⁰¹ Postmenopausal women have been shown to have increased cervical CCR5 expression, which serves as an entry point of HIV into target cells.¹⁰² Finally, anti-HIV-1 activity was significantly decreased in postmenopausal women compared to premenopausal women.¹⁰³ In addition, ex vivo studies demonstrated reduced tenofovir disoproxil fumarate and emtricitabine triphosphate concentrations in cervical tissue of postmenopausal women, suggesting that postmenopausal women may need higher doses of pre-exposure prophylaxis to achieve protective efficacy.¹⁰⁴ 

In contrast, although data are limited, postmenopausal WLWH do not appear to be at increased risk of vaginally transmitting HIV. The intensity of HIV shedding did not differ between premenopausal or postmenopausal women.¹⁰⁵ There was a high prevalence of low-level HIV RNA in genital secretions among perimenopausal WLWH, suggesting WLWH in menopause do not present a major public health risk for HIV transmission.¹⁰⁶

HIV Progression

With prior data suggesting that younger persons experience better immunologic and virologic responses to ART,^107-109 it had previously been hypothesized that virologic and immunologic responses to ART will decline once WLWH reach menopause. However, current studies suggest that menopause does not affect the progression of HIV and that ART-naive women should respond to ART, regardless of their menopausal status. Treatment responses to ART, determined by the median changes in CD4 cell counts and percentages and viral load, in ART-naive individuals did not differ between premenopausal and postmenopausal women.¹¹⁰ In addition, there appear to be no significant changes in CD4 cell counts as WLWH progress through menopause.¹¹¹

Conclusion

As individuals with HIV infection live longer, an increasing number of women will enter menopause and live many years beyond menopause. WLWH experience earlier and more severe menopausal symptoms, but evidence on the appropriate management of these symptoms is still lacking. These conditions require proper surveillance, and can be prevented with an improved understanding of the effects of menopause on WLWH. However, there remain significant gaps in our understanding of menopause in WLWH. As practitioners encounter an increasing number of perimenopausal and postmenopausal WLWH, studies of the effects of HIV on comorbidities and symptoms of menopause and their appropriate management are necessary to improve care of WLWH.

Test your knowledge of this topic HERE.

Structural entheseal lesions and reduced bone mineral density detected using high-resolution CT imaging of a pair of knuckle joints in patients with psoriasis strongly linked with subsequent development of psoriatic arthritis (PsA) in a single-center study with 114 patients followed for an average of 2.3 years.

“These findings substantiate the concept of mechano-inflammation in the pathogenesis of psoriatic disease,” and suggest that interventions with high efficacy for controlling entheseal inflammation may be a “particularly valuable strategy in interfering with the onset of PsA in patients with psoriatic disease,” David Simon, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

The study, which is now published in Arthritis & Rheumatology, began with 377 patients with psoriasis who had been referred to the University Hospital in Erlangen, Germany, during 2011-2018, and who tested positive on the German Psoriasis Arthritis Diagnostic questionnaire. The researchers excluded patients with existing signs of PsA, any arthritis or enthesitis or other signs of inflammatory rheumatic disease, and they also excluded patients who had not undergoing a high-resolution peripheral quantitative CT (HR-pQCT) examination of the second and third metacarpal joints of the patient’s nondominant hand, which left 114 patients for their analysis. During a mean follow-up of 28 months, 24 patients (27%) developed PsA. The study patients were an average age of 45 years, and they had been diagnosed with psoriasis for an average of about 16 years.

Dr. Simon and associates used the baseline HR-pQCT scans to make two assessments of each patient: the presence of structural entheseal lesions (SEL) in the two metacarpal joints and the calculated volumetric bone mineral density (vBMD). Their analysis showed that the number and severity of SEL were increased among patients who later developed PsA. In a multivariable model that adjusted for age, sex, body mass index, duration of psoriasis, and arthralgia, patients with any SEL had a fivefold higher rate of developing PsA, compared with patients with no SEL, reported Dr. Simon, a rheumatologist at Erlangen University Hospital.

The analysis of vBMD also showed a strong link between bone density at the entheseal sites of the two studied joints and subsequent PsA development. For every standard deviation increase in vBMD at these sites the subsequent rate of PsA incidence fell by about 67% in an analysis that controlled for the same covariants as well as presence of SEL. The same relationship between higher vBMD and a lower risk for PsA held for both total vBMD measurement and for cortical vBMD, but only at the entheseal site. Levels of vBMD at the intra-articular site of the joints had no statistically significant relationship with subsequent PsA development.

The two metrics also appeared to identify additive risks. Nearly 90% of patients with at least one SEL who also had low vBMD at the entheseal site developed PsA during follow-up, compared with about a 50% rate among patients with at least one SEL but high vBMD.

courtesy EULAR

The imaging method used to run these analyses, HR-pQCT, remains for the time being a “research technique” that “is not generalizable for routine practice,” but further development of this method or of a surrogate measure might make it feasible for future widespread practice, commented Iain McInnes, MD, PhD, president of the European League Against Rheumatism and professor of rheumatology and director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow.

“We’ve thought for many years that psoriasis and psoriatic arthritis are on a spectrum, and this work is consistent with the idea that some patients with psoriasis develop tissue involvement at entheses and joints,” Dr. McInnes said in an interview. The higher incidence of PsA seen in patients with adverse SEL and vBMD markers was in an “interesting range” that warrants further study. A next step is to run an intervention study in which patients with these adverse markers would receive an intervention randomized against placebo to see if it improved their outcomes, he suggested. Good candidate agents to study in psoriasis patients who have these adverse markers include drugs that inhibit the action of interleukin-17, drugs that target the p19 cytokine subunit of IL-23, and possibly Janus kinase inhibitor drugs.

Dr. Simon has been a consultant to AbbVie and Eli Lilly, a speaker on behalf of Eli Lilly, Janssen, and Novartis, and has received research funding from Eli Lilly and Novartis. Dr. McInnes has been a consultant to AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, and he has received research funding from Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB.

mzoler@mdedge.com

SOURCE: Simon D et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:33-4, Abstract OP0051.

Structural entheseal lesions and reduced bone mineral density detected using high-resolution CT imaging of a pair of knuckle joints in patients with psoriasis strongly linked with subsequent development of psoriatic arthritis (PsA) in a single-center study with 114 patients followed for an average of 2.3 years.

“These findings substantiate the concept of mechano-inflammation in the pathogenesis of psoriatic disease,” and suggest that interventions with high efficacy for controlling entheseal inflammation may be a “particularly valuable strategy in interfering with the onset of PsA in patients with psoriatic disease,” David Simon, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

The study, which is now published in Arthritis & Rheumatology, began with 377 patients with psoriasis who had been referred to the University Hospital in Erlangen, Germany, during 2011-2018, and who tested positive on the German Psoriasis Arthritis Diagnostic questionnaire. The researchers excluded patients with existing signs of PsA, any arthritis or enthesitis or other signs of inflammatory rheumatic disease, and they also excluded patients who had not undergoing a high-resolution peripheral quantitative CT (HR-pQCT) examination of the second and third metacarpal joints of the patient’s nondominant hand, which left 114 patients for their analysis. During a mean follow-up of 28 months, 24 patients (27%) developed PsA. The study patients were an average age of 45 years, and they had been diagnosed with psoriasis for an average of about 16 years.

Dr. Simon and associates used the baseline HR-pQCT scans to make two assessments of each patient: the presence of structural entheseal lesions (SEL) in the two metacarpal joints and the calculated volumetric bone mineral density (vBMD). Their analysis showed that the number and severity of SEL were increased among patients who later developed PsA. In a multivariable model that adjusted for age, sex, body mass index, duration of psoriasis, and arthralgia, patients with any SEL had a fivefold higher rate of developing PsA, compared with patients with no SEL, reported Dr. Simon, a rheumatologist at Erlangen University Hospital.

The analysis of vBMD also showed a strong link between bone density at the entheseal sites of the two studied joints and subsequent PsA development. For every standard deviation increase in vBMD at these sites the subsequent rate of PsA incidence fell by about 67% in an analysis that controlled for the same covariants as well as presence of SEL. The same relationship between higher vBMD and a lower risk for PsA held for both total vBMD measurement and for cortical vBMD, but only at the entheseal site. Levels of vBMD at the intra-articular site of the joints had no statistically significant relationship with subsequent PsA development.

The two metrics also appeared to identify additive risks. Nearly 90% of patients with at least one SEL who also had low vBMD at the entheseal site developed PsA during follow-up, compared with about a 50% rate among patients with at least one SEL but high vBMD.

courtesy EULAR

The imaging method used to run these analyses, HR-pQCT, remains for the time being a “research technique” that “is not generalizable for routine practice,” but further development of this method or of a surrogate measure might make it feasible for future widespread practice, commented Iain McInnes, MD, PhD, president of the European League Against Rheumatism and professor of rheumatology and director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow.

“We’ve thought for many years that psoriasis and psoriatic arthritis are on a spectrum, and this work is consistent with the idea that some patients with psoriasis develop tissue involvement at entheses and joints,” Dr. McInnes said in an interview. The higher incidence of PsA seen in patients with adverse SEL and vBMD markers was in an “interesting range” that warrants further study. A next step is to run an intervention study in which patients with these adverse markers would receive an intervention randomized against placebo to see if it improved their outcomes, he suggested. Good candidate agents to study in psoriasis patients who have these adverse markers include drugs that inhibit the action of interleukin-17, drugs that target the p19 cytokine subunit of IL-23, and possibly Janus kinase inhibitor drugs.

Dr. Simon has been a consultant to AbbVie and Eli Lilly, a speaker on behalf of Eli Lilly, Janssen, and Novartis, and has received research funding from Eli Lilly and Novartis. Dr. McInnes has been a consultant to AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, and he has received research funding from Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB.

mzoler@mdedge.com

SOURCE: Simon D et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:33-4, Abstract OP0051.

Structural entheseal lesions and reduced bone mineral density detected using high-resolution CT imaging of a pair of knuckle joints in patients with psoriasis strongly linked with subsequent development of psoriatic arthritis (PsA) in a single-center study with 114 patients followed for an average of 2.3 years.

“These findings substantiate the concept of mechano-inflammation in the pathogenesis of psoriatic disease,” and suggest that interventions with high efficacy for controlling entheseal inflammation may be a “particularly valuable strategy in interfering with the onset of PsA in patients with psoriatic disease,” David Simon, MD, said at the annual European Congress of Rheumatology, held online this year due to COVID-19.

The study, which is now published in Arthritis & Rheumatology, began with 377 patients with psoriasis who had been referred to the University Hospital in Erlangen, Germany, during 2011-2018, and who tested positive on the German Psoriasis Arthritis Diagnostic questionnaire. The researchers excluded patients with existing signs of PsA, any arthritis or enthesitis or other signs of inflammatory rheumatic disease, and they also excluded patients who had not undergoing a high-resolution peripheral quantitative CT (HR-pQCT) examination of the second and third metacarpal joints of the patient’s nondominant hand, which left 114 patients for their analysis. During a mean follow-up of 28 months, 24 patients (27%) developed PsA. The study patients were an average age of 45 years, and they had been diagnosed with psoriasis for an average of about 16 years.

Dr. Simon and associates used the baseline HR-pQCT scans to make two assessments of each patient: the presence of structural entheseal lesions (SEL) in the two metacarpal joints and the calculated volumetric bone mineral density (vBMD). Their analysis showed that the number and severity of SEL were increased among patients who later developed PsA. In a multivariable model that adjusted for age, sex, body mass index, duration of psoriasis, and arthralgia, patients with any SEL had a fivefold higher rate of developing PsA, compared with patients with no SEL, reported Dr. Simon, a rheumatologist at Erlangen University Hospital.

The analysis of vBMD also showed a strong link between bone density at the entheseal sites of the two studied joints and subsequent PsA development. For every standard deviation increase in vBMD at these sites the subsequent rate of PsA incidence fell by about 67% in an analysis that controlled for the same covariants as well as presence of SEL. The same relationship between higher vBMD and a lower risk for PsA held for both total vBMD measurement and for cortical vBMD, but only at the entheseal site. Levels of vBMD at the intra-articular site of the joints had no statistically significant relationship with subsequent PsA development.

The two metrics also appeared to identify additive risks. Nearly 90% of patients with at least one SEL who also had low vBMD at the entheseal site developed PsA during follow-up, compared with about a 50% rate among patients with at least one SEL but high vBMD.

courtesy EULAR

The imaging method used to run these analyses, HR-pQCT, remains for the time being a “research technique” that “is not generalizable for routine practice,” but further development of this method or of a surrogate measure might make it feasible for future widespread practice, commented Iain McInnes, MD, PhD, president of the European League Against Rheumatism and professor of rheumatology and director of the Institute of Infection, Immunity, and Inflammation at the University of Glasgow.

“We’ve thought for many years that psoriasis and psoriatic arthritis are on a spectrum, and this work is consistent with the idea that some patients with psoriasis develop tissue involvement at entheses and joints,” Dr. McInnes said in an interview. The higher incidence of PsA seen in patients with adverse SEL and vBMD markers was in an “interesting range” that warrants further study. A next step is to run an intervention study in which patients with these adverse markers would receive an intervention randomized against placebo to see if it improved their outcomes, he suggested. Good candidate agents to study in psoriasis patients who have these adverse markers include drugs that inhibit the action of interleukin-17, drugs that target the p19 cytokine subunit of IL-23, and possibly Janus kinase inhibitor drugs.

Dr. Simon has been a consultant to AbbVie and Eli Lilly, a speaker on behalf of Eli Lilly, Janssen, and Novartis, and has received research funding from Eli Lilly and Novartis. Dr. McInnes has been a consultant to AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, and he has received research funding from Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB.

mzoler@mdedge.com

SOURCE: Simon D et al. Ann Rheum Dis. 2020 Jun;79[suppl 1]:33-4, Abstract OP0051.

Nearly 80% of US counties have no infectious disease (ID) specialists, and 80% of counties in the top quartile of COVID-19 cases have no ID physicians or a below-average ratio of ID specialists to the population, according to a study published online in Annals of Internal Medicine.

Although the majority of these counties are rural, nearly two-thirds of Americans live in the 80% of counties that have a below-average ID specialist density or no access to ID physicians at all.

There are no data yet on the association between ID physician care and COVID-19 outcomes, the researchers note. “However, for many other infectious diseases, a robust evidence base supports the association between ID physician intervention and improved outcomes, including lower mortality, shorter length of stay, fewer readmissions, and lower total health care spending,” the authors explain.

The national average density of ID specialists was 1.76 ID physicians per 100,000 people in 2017. However, the authors say this distribution “was geographically skewed”: Of the 3142 US counties, 331 (10.5%) had above-average ID physician densities and 312 (9.9%) had below-average ID physician densities. Not a single ID physician practiced in the other 2499 counties.

A US map accompanying the study shows the distribution of ID specialists across the country. The areas with the most ID specialists were in the Northeast and Florida. Below-average densities of ID physicians were shown in the Southwest and on the West Coast. Large swathes of the South, the Midwest, and the Mountain West had no ID specialists.

Among the 785 counties with the highest quartile of COVID-19 burden as of mid-May, 147 (18.7%) and 117 (14.9%) had above- and below-average ID physician densities, respectively. More than two-thirds (521) of these counties had no ID specialist coverage.

Although the literature does not indicate the “right” ratio of ID specialists to a population, the authors conclude, “our current distribution during pandemic times is probably far too sparse. The deficits in our ID physician workforce today have left us poorly prepared for the unprecedented demand ahead.”

The overall shortage of ID specialists is becoming more severe, the researchers note. In 2019 to 2020, ID fellowship programs had fewer than one applicant for every open position, on average. Thirty-eight percent of ID programs were unable to fill their training slots, and 19% could fill no slots at all.

This deficit of interest in the ID field continues a long-term trend. A 2019 Merritt Hawkins report found that between the 2009-2010 and 2016-2017 fellowship matches the number of adult ID programs filling all their positions dropped by 41% and the number of applicants decreased by 31%, according to Medscape Medical News.

The authors tie the decline of interest in the field to the compensation of ID specialists, which is lower than that of procedural specialists. Because their field focuses on cognitive skills, these highly trained physicians are paid about the same as primary care physicians.

Loan Repayment

Young physicians have an average of $200,000 in loans when they graduate from medical school, coauthor Rochelle Walensky, MD, MPH, said in an interview. With the fellowship training required to become an infectious disease specialist, they fall even further in debt. In effect, they earn less than primary care doctors do, she said.

Consequently, any strategy to bolster the ID specialist workforce should include a government loan repayment program, Dr. Walensky explained, adding that perhaps the loan repayment could be tied to practicing in underserved areas where ID specialists are especially needed.

Telehealth is the key to stretching the resources of ID specialists for the duration of the COVID-19 pandemic, she said. “The way to expand [the specialty] in the short run is to reimburse for telehealth.”

Dr. Walensky is also concerned about the rollback of funding for infectious disease research. “I have a whole corps of researchers ... who are really worried about their research future,” she said. “These are Harvard scientists who don’t know if they’ll be funded. If they’re not, we could lose a whole generation of researchers, and where will we be 10-15 years from now?”

Dr. Walensky is Chief of the Infectious Diseases Division at Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston.

Frontline Roles

On the front line of fighting COVID-19 today, ID specialists are also critical to the research required to create a vaccine and find new treatments, Dr. Walensky explained. They are knowledgeable about current drugs such as hydroxychloroquine and can set up protocols for clinical trials.

At Massachusetts General Hospital, she continued, she and her colleagues developed infectious disease control policies to keep patients and health workers safe; they also triage patients to determine which ones should be tested for COVID-19 and give advice to treating doctors when patients who appear to have COVID-19 test negative. In addition, ID specialists are skilled in the management of complex cases, such as COVID patients who have comorbidities.

“We’re not [gastrointestinal] docs or cardiology docs,” Dr. Walensky noted. “We don’t manage a single organ system. We’re trained to worry about the entire patient. Given that this disease manifests itself in so many different ways to so many different patients and affects many different organs that nobody was anticipating — that’s our sweet spot in terms of how we care for patients.”

Dr. Walensky reports grants from Steve and Deborah Gorlin MGH Research Scholar Award, outside the submitted work. The remaining authors have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Nearly 80% of US counties have no infectious disease (ID) specialists, and 80% of counties in the top quartile of COVID-19 cases have no ID physicians or a below-average ratio of ID specialists to the population, according to a study published online in Annals of Internal Medicine.

Although the majority of these counties are rural, nearly two-thirds of Americans live in the 80% of counties that have a below-average ID specialist density or no access to ID physicians at all.

There are no data yet on the association between ID physician care and COVID-19 outcomes, the researchers note. “However, for many other infectious diseases, a robust evidence base supports the association between ID physician intervention and improved outcomes, including lower mortality, shorter length of stay, fewer readmissions, and lower total health care spending,” the authors explain.

The national average density of ID specialists was 1.76 ID physicians per 100,000 people in 2017. However, the authors say this distribution “was geographically skewed”: Of the 3142 US counties, 331 (10.5%) had above-average ID physician densities and 312 (9.9%) had below-average ID physician densities. Not a single ID physician practiced in the other 2499 counties.

A US map accompanying the study shows the distribution of ID specialists across the country. The areas with the most ID specialists were in the Northeast and Florida. Below-average densities of ID physicians were shown in the Southwest and on the West Coast. Large swathes of the South, the Midwest, and the Mountain West had no ID specialists.

Among the 785 counties with the highest quartile of COVID-19 burden as of mid-May, 147 (18.7%) and 117 (14.9%) had above- and below-average ID physician densities, respectively. More than two-thirds (521) of these counties had no ID specialist coverage.

Although the literature does not indicate the “right” ratio of ID specialists to a population, the authors conclude, “our current distribution during pandemic times is probably far too sparse. The deficits in our ID physician workforce today have left us poorly prepared for the unprecedented demand ahead.”

The overall shortage of ID specialists is becoming more severe, the researchers note. In 2019 to 2020, ID fellowship programs had fewer than one applicant for every open position, on average. Thirty-eight percent of ID programs were unable to fill their training slots, and 19% could fill no slots at all.

This deficit of interest in the ID field continues a long-term trend. A 2019 Merritt Hawkins report found that between the 2009-2010 and 2016-2017 fellowship matches the number of adult ID programs filling all their positions dropped by 41% and the number of applicants decreased by 31%, according to Medscape Medical News.

The authors tie the decline of interest in the field to the compensation of ID specialists, which is lower than that of procedural specialists. Because their field focuses on cognitive skills, these highly trained physicians are paid about the same as primary care physicians.

Loan Repayment

Young physicians have an average of $200,000 in loans when they graduate from medical school, coauthor Rochelle Walensky, MD, MPH, said in an interview. With the fellowship training required to become an infectious disease specialist, they fall even further in debt. In effect, they earn less than primary care doctors do, she said.

Consequently, any strategy to bolster the ID specialist workforce should include a government loan repayment program, Dr. Walensky explained, adding that perhaps the loan repayment could be tied to practicing in underserved areas where ID specialists are especially needed.

Telehealth is the key to stretching the resources of ID specialists for the duration of the COVID-19 pandemic, she said. “The way to expand [the specialty] in the short run is to reimburse for telehealth.”

Dr. Walensky is also concerned about the rollback of funding for infectious disease research. “I have a whole corps of researchers ... who are really worried about their research future,” she said. “These are Harvard scientists who don’t know if they’ll be funded. If they’re not, we could lose a whole generation of researchers, and where will we be 10-15 years from now?”

Dr. Walensky is Chief of the Infectious Diseases Division at Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston.

Frontline Roles

On the front line of fighting COVID-19 today, ID specialists are also critical to the research required to create a vaccine and find new treatments, Dr. Walensky explained. They are knowledgeable about current drugs such as hydroxychloroquine and can set up protocols for clinical trials.

At Massachusetts General Hospital, she continued, she and her colleagues developed infectious disease control policies to keep patients and health workers safe; they also triage patients to determine which ones should be tested for COVID-19 and give advice to treating doctors when patients who appear to have COVID-19 test negative. In addition, ID specialists are skilled in the management of complex cases, such as COVID patients who have comorbidities.

“We’re not [gastrointestinal] docs or cardiology docs,” Dr. Walensky noted. “We don’t manage a single organ system. We’re trained to worry about the entire patient. Given that this disease manifests itself in so many different ways to so many different patients and affects many different organs that nobody was anticipating — that’s our sweet spot in terms of how we care for patients.”

Dr. Walensky reports grants from Steve and Deborah Gorlin MGH Research Scholar Award, outside the submitted work. The remaining authors have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

Nearly 80% of US counties have no infectious disease (ID) specialists, and 80% of counties in the top quartile of COVID-19 cases have no ID physicians or a below-average ratio of ID specialists to the population, according to a study published online in Annals of Internal Medicine.

Although the majority of these counties are rural, nearly two-thirds of Americans live in the 80% of counties that have a below-average ID specialist density or no access to ID physicians at all.

There are no data yet on the association between ID physician care and COVID-19 outcomes, the researchers note. “However, for many other infectious diseases, a robust evidence base supports the association between ID physician intervention and improved outcomes, including lower mortality, shorter length of stay, fewer readmissions, and lower total health care spending,” the authors explain.

The national average density of ID specialists was 1.76 ID physicians per 100,000 people in 2017. However, the authors say this distribution “was geographically skewed”: Of the 3142 US counties, 331 (10.5%) had above-average ID physician densities and 312 (9.9%) had below-average ID physician densities. Not a single ID physician practiced in the other 2499 counties.

A US map accompanying the study shows the distribution of ID specialists across the country. The areas with the most ID specialists were in the Northeast and Florida. Below-average densities of ID physicians were shown in the Southwest and on the West Coast. Large swathes of the South, the Midwest, and the Mountain West had no ID specialists.

Among the 785 counties with the highest quartile of COVID-19 burden as of mid-May, 147 (18.7%) and 117 (14.9%) had above- and below-average ID physician densities, respectively. More than two-thirds (521) of these counties had no ID specialist coverage.

Although the literature does not indicate the “right” ratio of ID specialists to a population, the authors conclude, “our current distribution during pandemic times is probably far too sparse. The deficits in our ID physician workforce today have left us poorly prepared for the unprecedented demand ahead.”

The overall shortage of ID specialists is becoming more severe, the researchers note. In 2019 to 2020, ID fellowship programs had fewer than one applicant for every open position, on average. Thirty-eight percent of ID programs were unable to fill their training slots, and 19% could fill no slots at all.

This deficit of interest in the ID field continues a long-term trend. A 2019 Merritt Hawkins report found that between the 2009-2010 and 2016-2017 fellowship matches the number of adult ID programs filling all their positions dropped by 41% and the number of applicants decreased by 31%, according to Medscape Medical News.

The authors tie the decline of interest in the field to the compensation of ID specialists, which is lower than that of procedural specialists. Because their field focuses on cognitive skills, these highly trained physicians are paid about the same as primary care physicians.

Loan Repayment

Young physicians have an average of $200,000 in loans when they graduate from medical school, coauthor Rochelle Walensky, MD, MPH, said in an interview. With the fellowship training required to become an infectious disease specialist, they fall even further in debt. In effect, they earn less than primary care doctors do, she said.

Consequently, any strategy to bolster the ID specialist workforce should include a government loan repayment program, Dr. Walensky explained, adding that perhaps the loan repayment could be tied to practicing in underserved areas where ID specialists are especially needed.

Telehealth is the key to stretching the resources of ID specialists for the duration of the COVID-19 pandemic, she said. “The way to expand [the specialty] in the short run is to reimburse for telehealth.”

Dr. Walensky is also concerned about the rollback of funding for infectious disease research. “I have a whole corps of researchers ... who are really worried about their research future,” she said. “These are Harvard scientists who don’t know if they’ll be funded. If they’re not, we could lose a whole generation of researchers, and where will we be 10-15 years from now?”

Dr. Walensky is Chief of the Infectious Diseases Division at Massachusetts General Hospital and a professor of medicine at Harvard Medical School, both in Boston.

Frontline Roles

On the front line of fighting COVID-19 today, ID specialists are also critical to the research required to create a vaccine and find new treatments, Dr. Walensky explained. They are knowledgeable about current drugs such as hydroxychloroquine and can set up protocols for clinical trials.

At Massachusetts General Hospital, she continued, she and her colleagues developed infectious disease control policies to keep patients and health workers safe; they also triage patients to determine which ones should be tested for COVID-19 and give advice to treating doctors when patients who appear to have COVID-19 test negative. In addition, ID specialists are skilled in the management of complex cases, such as COVID patients who have comorbidities.

“We’re not [gastrointestinal] docs or cardiology docs,” Dr. Walensky noted. “We don’t manage a single organ system. We’re trained to worry about the entire patient. Given that this disease manifests itself in so many different ways to so many different patients and affects many different organs that nobody was anticipating — that’s our sweet spot in terms of how we care for patients.”

Dr. Walensky reports grants from Steve and Deborah Gorlin MGH Research Scholar Award, outside the submitted work. The remaining authors have disclosed no relevant financial relationships.
 

This article first appeared on Medscape.com.

In the midst of the COVID-19 pandemic, health systems, hospitals, and hospitalists – especially in hot spots like New York, Detroit, or Boston – have been challenged to stretch limits, redefine roles, and redeploy critical staff in response to rapidly changing needs on the ground.

Many hospitalists are working above and beyond their normal duties, sometimes beyond their training, specialty, or comfort zone and are rising to the occasion in ways they never imagined. These include doing shifts in ICUs, working with ventilator patients, and reporting to other atypical sites of care like postanesthesia care units and post-acute or step-down units.

Valerie Vaughn, MD, MSc, a hospitalist with Michigan Medicine and assistant professor of medicine at the University of Michigan in Ann Arbor, was doing research on how to reduce overuse of antibiotics in hospitals when the COVID-19 crisis hit and dramatically redefined her job. “We were afraid that we might have 3,000 to 5,000 hospitalized COVID patients by now, based on predictive modeling done while the pandemic was still growing exponentially,” she explained. Although Michigan continues to have high COVID-19 infection rates, centered on nearby Detroit, “things are a lot better today than they were 4 weeks ago.”

Dr. Vaughn helped to mobilize a team of 25 hospitalists, along with other health care providers, who volunteered to manage COVID-19 patients in the ICU and other hospital units. She was asked to help develop an all-COVID unit called the Regional Infectious Containment Unit or RICU, which opened March 16. Then, when the RICU became full, it was supplemented by two COVID-19 Moderate Care Units staffed by hospitalists who had “learned the ropes” in the RICU.

Both of these new models were defined in relation to the ICUs at Michigan Medicine – which were doubling in capacity, up to 200 beds at last count – and to the provision of intensive-level and long-term ventilator care for the sickest patients. The moderate care units are for patients who are not on ventilators but still very sick, for example, those receiving massive high-flow oxygen, often with a medical do-not-resuscitate/do-not-intubate order. “We established these units to do everything (medically) short of vents,” Dr. Vaughn said.

“We are having in-depth conversations about goals of care with patients soon after they arrive at the hospital. We know outcomes from ventilators are worse for COVID-positive patients who have comorbidities, and we’re using that information to inform these conversations. We’ve given scripts to clinicians to help guide them in leading these conversations. We can do other things than `use ventilators to manage their symptoms. But these are still difficult conversations,” Dr. Vaughn said.

“We also engaged palliative care early on and asked them to round with us on every [COVID] patient – until demand got too high.” The bottleneck has been the number of ICU beds available, she explained. “If you want your patient to come in and take that bed, make sure you’ve talked to the family about it.”

The COVID-19 team developed guidelines printed on pocket cards addressing critical care issues such as a refresher on how to treat acute respiratory distress syndrome and how to use vasopressors. (See the COVID-19 Continuing Medical Education Portal for web-accessible educational resources developed by Michigan Health).

It’s amazing how quickly patients can become very sick with COVID-19, Dr. Vaughn said. “One of the good things to happen from the beginning with our RICU is that a group of doctors became COVID care experts very quickly. We joined four to five hospitalists and their teams with each intensivist, so one critical care expert is there to do teaching and answer clinicians’ questions. The hospitalists coordinate the COVID care and talk to the families.”

Working on the front lines of this crisis, Dr. Vaughn said, has generated a powerful sense of purpose and camaraderie, creating bonds like in war time. “All of us on our days off feel a twinge of guilt for not being there in the hospital. The sense of gratitude we get from patients and families has been enormous, even when we were telling them bad news. That just brings us to tears.”

One of the hardest things for the doctors practicing above their typical scope of practice is that, when something bad happens, they can’t know whether it was a mistake on their part or not, she noted. “But I’ve never been so proud of our group or to be a hospitalist. No one has complained or pushed back. Everyone has responded by saying: ‘What can I do to help?’ ”
 

Enough work in hospital medicine

Hospitalists had not been deployed to care for ICU patients at Beth Israel Deaconess Medical Center (BIDMC) in Boston, a major hot spot for COVID-19, said Joseph Ming Wah Li, MD, SFHM, director of the hospital medicine program at BIDMC, when he spoke to The Hospitalist in mid-May. That’s because there were plenty of hospital medicine assignments to keep them busy. Dr. Li leads a service of 120 hospitalists practicing at four hospitals.

“As we speak today, we have 300 patients with COVID, with 70 or 80 of them in our ICU. I’m taking care of 17 patients today, 15 of them COVID-positive, and the other two placed in a former radiology holding suite adapted for COVID-negative patients. Our postanesthesia care unit is now an ICU filled with COVID patients,” he said.

“Half of my day is seeing patients and the other half I’m on Zoom calls. I’m also one of the resource allocation officers for BIDMC,” Dr. Li said. He helped to create a standard of care for the hospital, addressing what to do if there weren’t enough ICU beds or ventilators. “We’ve never actualized it and probably won’t, but it was important to go through this exercise, with a lot of discussion up front.”

Haki Laho, MD, an orthopedic hospitalist at New England Baptist Hospital (NEBH), also in Boston, has been redeployed to care for a different population of patients as his system tries to bunch patients. “All of a sudden – within hours and days – at the beginning of the pandemic and based on the recommendations, our whole system decided to stop all elective procedures and devote the resources to COVID,” he said.

NEBH is Beth Israel Lahey Health’s 141-bed orthopedic and surgical hospital, and the system has tried to keep the specialty facility COVID-19–free as much as possible, with the COVID-19 patients grouped together at BIDMC. Dr. Laho’s orthopedic hospitalist group, just five doctors, has been managing the influx of medical patients with multiple comorbidities – not COVID-19–infected but still a different kind of patient than they are used to.

“So far, so good. We’re dealing with it,” he said. “But if one of us got sick, the others would have to step up and do more shifts. We are physicians, internal medicine trained, but since my residency I hadn’t had to deal with these kinds of issues on a daily basis, such as setting up IV lines. I feel like I am back in residency mode.”
 

Convention Center medicine

Another Boston hospitalist, Amy Baughman, MD, who practices at Massachusetts General Hospital, is using her skills in a new setting, serving as a co-medical director at Boston Hope Medical Center, a 1,000-bed field hospital for patients with COVID-19. Open since April 10 and housed in the Boston Convention and Exhibition Center, it is a four-way collaboration between the Commonwealth of Massachusetts, the City of Boston, Partners HealthCare, and the Boston Health Care for the Homeless Program.

Boston Hope is divided into a post-acute care section for recovering COVID-19 patients and a respite section for undomiciled patients with COVID-19 who need a place to safely quarantine. Built for a maximum of 1,000 beds, it is currently using fewer, with 83 patients on the post-acute side and 73 on the respite side as of May 12. A total of 370 and 315, respectively, had been admitted through May 12.

The team had 5 days to put the field hospital together with the help of the Army National Guard. “During that first week I was installing hand sanitizer dispensers and making [personal protective equipment] signs. Everyone here has had to do things like that,” Dr. Baughman said. “We’ve had to be incredibly creative in our staffing, using doctors from primary care and subspecialties including dermatology, radiology, and orthopedics. We had to fast-track trainings on how to use EPIC and to provide post-acute COVID care. How do you simultaneously build a medical facility and lead teams to provide high quality care?”

Dr. Baughman still works hospitalist shifts half-time at Massachusetts General. Her prior experience providing post-acute care in the VA system was helpful in creating the post-acute level of care at Boston Hope.

“My medical director role involves supervising, staffing, and scheduling. My co-medical director, Dr. Kerri Palamara, and I also supervise the clinical care,” she said. “There are a lot of systems issues, like ordering labs or prescriptions, with couriers going back and forth. And we developed clinical pathways, such as for [deep vein thrombosis] prophylaxis or for COVID retesting to determine when it is safe to end a quarantine. We’re just now rolling out virtual specialist consultations,” she noted.

“It has gone incredibly well. So much of it has been about our ability and willingness to work hard, and take feedback and go forward. We don’t have time to harp on things. We have to be very solution oriented. At the same time, honestly, it’s been fun. Every single day is different,” Dr. Baughman said.

“It’s been an opportunity to use my skills in a totally new setting, and at a level of responsibility I haven’t had before, although that’s probably a common theme with COVID-19. I was put on this team because I am a hospitalist,” she said. “I think hospitalists have been the backbone of the response to COVID in this country. It’s been an opportunity for our specialty to shine. We need to embrace the opportunity.”
 

Balancing expertise and supervision

Mount Sinai Hospital (MSH) in Manhattan is in the New York epicenter of the COVID-19 crisis and has mobilized large numbers of pulmonary critical care and anesthesia physicians to staff up multiple ICUs for COVID-19 patients, said Andrew Dunn, MD, chief of the division of hospital medicine at Mount Sinai School of Medicine.

“My hospitalist group is covering many step-down units, medical wards, and atypical locations, providing advanced oxygen therapies, [bilevel positive airway pressure], high-flow nasal cannulas, and managing some patients on ventilators,” he said.

MSH has teaching services with house staff and nonteaching services. “We combined them into a unified service with house staff dispersed across all of the teams. We drafted a lot of nonhospitalists from different specialties to be attendings, and that has given us a tiered model, with a hospitalist supervising three or four nonhospitalist-led teams. Although the supervising hospitalists carry no patient caseloads of their own, this is primarily a clinical rather than an administrative role.”

At the peak, there were 40 rounding teams at MSH, each with a typical census of 15 patients or more, which meant that 10 supervisory hospitalists were responsible for 300 to 400 patients. “What we learned first was the need to balance the level of expertise. For example, a team may include a postgraduate year 3 resident and a radiology intern,” Dr. Dunn said. As COVID-19 census has started coming down, supervisory hospitalists are returning to direct care attending roles, and some hospitalists have been shared across the Mount Sinai system’s hospitals.

Dr. Dunn’s advice for hospitalists filling a supervisory role like this in a tiered model: Make sure you talk to your team the night before the first day of a scheduling block and try to address as many of their questions as possible. “If you wait until the morning of the shift to connect with them, anxiety will be high. But after going through a couple of scheduling cycles, we find that things are getting better. I think we’ve paid a lot of attention to the risks of burnout by our physicians. We’re using a model of 4 days on/4 off.”

Another variation on these themes is Joshua Shatzkes, MD, assistant professor of medicine and cardiology at Mount Sinai, who practices outpatient cardiology at MSH and in several off-site offices in Brooklyn. He saw early on that COVID-19 would have a huge effect on his practice, so he volunteered to help out with inpatient care. “I made it known to my chief that I was available, and I was deployed in the first week, after a weekend of cramming webinars and lectures on critical care and pulling out critical concepts that I already knew.”

Dr. Shatzkes said his career path led him into outpatient cardiology 11 years ago, where he was quickly too busy to see his patients when they went into the hospital, even though he missed hospital medicine. Working as a temporary hospitalist with the arrival of COVID-19, he has been invigorated and mobilized by the experience and reminded of why he went to medical school in the first place. “Each day’s shift went quickly but felt long. At the end of the day, I was tired but not exhausted. When I walked out of a patient’s room, they could tell, ‘This is a doctor who cared for me,’ ” he said.

After Dr. Shatzkes volunteered, he got the call from his division chief. “I was officially deployed for a 4-day shift at Mount Sinai and then as a backup.” On his first morning as an inpatient doctor, he was still getting oriented when calls started coming from the nurses. “I had five patients struggling to breathe. Their degree of hypoxia was remarkable. I kept them out of the ICU, at least for that day.”

Since then, he has continued to follow some of those patients in the hospital, along with some from his outpatient practice who were hospitalized, and others referred by colleagues, while remaining available to his outpatients through telemedicine. When this is all over, Dr. Shatzkes said, he would love to find a way to incorporate a hospital practice in his job – depending on the realities of New York traffic.

“Joshua is not a hospitalist, but he went on service and felt so fulfilled and rewarded, he asked me if he could stay on service,” Dr. Dunn said. “I also got an email from the nurse manager on the unit. They want him back.”

In the midst of the COVID-19 pandemic, health systems, hospitals, and hospitalists – especially in hot spots like New York, Detroit, or Boston – have been challenged to stretch limits, redefine roles, and redeploy critical staff in response to rapidly changing needs on the ground.

Many hospitalists are working above and beyond their normal duties, sometimes beyond their training, specialty, or comfort zone and are rising to the occasion in ways they never imagined. These include doing shifts in ICUs, working with ventilator patients, and reporting to other atypical sites of care like postanesthesia care units and post-acute or step-down units.

Valerie Vaughn, MD, MSc, a hospitalist with Michigan Medicine and assistant professor of medicine at the University of Michigan in Ann Arbor, was doing research on how to reduce overuse of antibiotics in hospitals when the COVID-19 crisis hit and dramatically redefined her job. “We were afraid that we might have 3,000 to 5,000 hospitalized COVID patients by now, based on predictive modeling done while the pandemic was still growing exponentially,” she explained. Although Michigan continues to have high COVID-19 infection rates, centered on nearby Detroit, “things are a lot better today than they were 4 weeks ago.”

Dr. Vaughn helped to mobilize a team of 25 hospitalists, along with other health care providers, who volunteered to manage COVID-19 patients in the ICU and other hospital units. She was asked to help develop an all-COVID unit called the Regional Infectious Containment Unit or RICU, which opened March 16. Then, when the RICU became full, it was supplemented by two COVID-19 Moderate Care Units staffed by hospitalists who had “learned the ropes” in the RICU.

Both of these new models were defined in relation to the ICUs at Michigan Medicine – which were doubling in capacity, up to 200 beds at last count – and to the provision of intensive-level and long-term ventilator care for the sickest patients. The moderate care units are for patients who are not on ventilators but still very sick, for example, those receiving massive high-flow oxygen, often with a medical do-not-resuscitate/do-not-intubate order. “We established these units to do everything (medically) short of vents,” Dr. Vaughn said.

“We are having in-depth conversations about goals of care with patients soon after they arrive at the hospital. We know outcomes from ventilators are worse for COVID-positive patients who have comorbidities, and we’re using that information to inform these conversations. We’ve given scripts to clinicians to help guide them in leading these conversations. We can do other things than `use ventilators to manage their symptoms. But these are still difficult conversations,” Dr. Vaughn said.

“We also engaged palliative care early on and asked them to round with us on every [COVID] patient – until demand got too high.” The bottleneck has been the number of ICU beds available, she explained. “If you want your patient to come in and take that bed, make sure you’ve talked to the family about it.”

The COVID-19 team developed guidelines printed on pocket cards addressing critical care issues such as a refresher on how to treat acute respiratory distress syndrome and how to use vasopressors. (See the COVID-19 Continuing Medical Education Portal for web-accessible educational resources developed by Michigan Health).

It’s amazing how quickly patients can become very sick with COVID-19, Dr. Vaughn said. “One of the good things to happen from the beginning with our RICU is that a group of doctors became COVID care experts very quickly. We joined four to five hospitalists and their teams with each intensivist, so one critical care expert is there to do teaching and answer clinicians’ questions. The hospitalists coordinate the COVID care and talk to the families.”

Working on the front lines of this crisis, Dr. Vaughn said, has generated a powerful sense of purpose and camaraderie, creating bonds like in war time. “All of us on our days off feel a twinge of guilt for not being there in the hospital. The sense of gratitude we get from patients and families has been enormous, even when we were telling them bad news. That just brings us to tears.”

One of the hardest things for the doctors practicing above their typical scope of practice is that, when something bad happens, they can’t know whether it was a mistake on their part or not, she noted. “But I’ve never been so proud of our group or to be a hospitalist. No one has complained or pushed back. Everyone has responded by saying: ‘What can I do to help?’ ”
 

Enough work in hospital medicine

Hospitalists had not been deployed to care for ICU patients at Beth Israel Deaconess Medical Center (BIDMC) in Boston, a major hot spot for COVID-19, said Joseph Ming Wah Li, MD, SFHM, director of the hospital medicine program at BIDMC, when he spoke to The Hospitalist in mid-May. That’s because there were plenty of hospital medicine assignments to keep them busy. Dr. Li leads a service of 120 hospitalists practicing at four hospitals.

“As we speak today, we have 300 patients with COVID, with 70 or 80 of them in our ICU. I’m taking care of 17 patients today, 15 of them COVID-positive, and the other two placed in a former radiology holding suite adapted for COVID-negative patients. Our postanesthesia care unit is now an ICU filled with COVID patients,” he said.

“Half of my day is seeing patients and the other half I’m on Zoom calls. I’m also one of the resource allocation officers for BIDMC,” Dr. Li said. He helped to create a standard of care for the hospital, addressing what to do if there weren’t enough ICU beds or ventilators. “We’ve never actualized it and probably won’t, but it was important to go through this exercise, with a lot of discussion up front.”

Haki Laho, MD, an orthopedic hospitalist at New England Baptist Hospital (NEBH), also in Boston, has been redeployed to care for a different population of patients as his system tries to bunch patients. “All of a sudden – within hours and days – at the beginning of the pandemic and based on the recommendations, our whole system decided to stop all elective procedures and devote the resources to COVID,” he said.

NEBH is Beth Israel Lahey Health’s 141-bed orthopedic and surgical hospital, and the system has tried to keep the specialty facility COVID-19–free as much as possible, with the COVID-19 patients grouped together at BIDMC. Dr. Laho’s orthopedic hospitalist group, just five doctors, has been managing the influx of medical patients with multiple comorbidities – not COVID-19–infected but still a different kind of patient than they are used to.

“So far, so good. We’re dealing with it,” he said. “But if one of us got sick, the others would have to step up and do more shifts. We are physicians, internal medicine trained, but since my residency I hadn’t had to deal with these kinds of issues on a daily basis, such as setting up IV lines. I feel like I am back in residency mode.”
 

Convention Center medicine

Another Boston hospitalist, Amy Baughman, MD, who practices at Massachusetts General Hospital, is using her skills in a new setting, serving as a co-medical director at Boston Hope Medical Center, a 1,000-bed field hospital for patients with COVID-19. Open since April 10 and housed in the Boston Convention and Exhibition Center, it is a four-way collaboration between the Commonwealth of Massachusetts, the City of Boston, Partners HealthCare, and the Boston Health Care for the Homeless Program.

Boston Hope is divided into a post-acute care section for recovering COVID-19 patients and a respite section for undomiciled patients with COVID-19 who need a place to safely quarantine. Built for a maximum of 1,000 beds, it is currently using fewer, with 83 patients on the post-acute side and 73 on the respite side as of May 12. A total of 370 and 315, respectively, had been admitted through May 12.

The team had 5 days to put the field hospital together with the help of the Army National Guard. “During that first week I was installing hand sanitizer dispensers and making [personal protective equipment] signs. Everyone here has had to do things like that,” Dr. Baughman said. “We’ve had to be incredibly creative in our staffing, using doctors from primary care and subspecialties including dermatology, radiology, and orthopedics. We had to fast-track trainings on how to use EPIC and to provide post-acute COVID care. How do you simultaneously build a medical facility and lead teams to provide high quality care?”

Dr. Baughman still works hospitalist shifts half-time at Massachusetts General. Her prior experience providing post-acute care in the VA system was helpful in creating the post-acute level of care at Boston Hope.

“My medical director role involves supervising, staffing, and scheduling. My co-medical director, Dr. Kerri Palamara, and I also supervise the clinical care,” she said. “There are a lot of systems issues, like ordering labs or prescriptions, with couriers going back and forth. And we developed clinical pathways, such as for [deep vein thrombosis] prophylaxis or for COVID retesting to determine when it is safe to end a quarantine. We’re just now rolling out virtual specialist consultations,” she noted.

“It has gone incredibly well. So much of it has been about our ability and willingness to work hard, and take feedback and go forward. We don’t have time to harp on things. We have to be very solution oriented. At the same time, honestly, it’s been fun. Every single day is different,” Dr. Baughman said.

“It’s been an opportunity to use my skills in a totally new setting, and at a level of responsibility I haven’t had before, although that’s probably a common theme with COVID-19. I was put on this team because I am a hospitalist,” she said. “I think hospitalists have been the backbone of the response to COVID in this country. It’s been an opportunity for our specialty to shine. We need to embrace the opportunity.”
 

Balancing expertise and supervision

Mount Sinai Hospital (MSH) in Manhattan is in the New York epicenter of the COVID-19 crisis and has mobilized large numbers of pulmonary critical care and anesthesia physicians to staff up multiple ICUs for COVID-19 patients, said Andrew Dunn, MD, chief of the division of hospital medicine at Mount Sinai School of Medicine.

“My hospitalist group is covering many step-down units, medical wards, and atypical locations, providing advanced oxygen therapies, [bilevel positive airway pressure], high-flow nasal cannulas, and managing some patients on ventilators,” he said.

MSH has teaching services with house staff and nonteaching services. “We combined them into a unified service with house staff dispersed across all of the teams. We drafted a lot of nonhospitalists from different specialties to be attendings, and that has given us a tiered model, with a hospitalist supervising three or four nonhospitalist-led teams. Although the supervising hospitalists carry no patient caseloads of their own, this is primarily a clinical rather than an administrative role.”

At the peak, there were 40 rounding teams at MSH, each with a typical census of 15 patients or more, which meant that 10 supervisory hospitalists were responsible for 300 to 400 patients. “What we learned first was the need to balance the level of expertise. For example, a team may include a postgraduate year 3 resident and a radiology intern,” Dr. Dunn said. As COVID-19 census has started coming down, supervisory hospitalists are returning to direct care attending roles, and some hospitalists have been shared across the Mount Sinai system’s hospitals.

Dr. Dunn’s advice for hospitalists filling a supervisory role like this in a tiered model: Make sure you talk to your team the night before the first day of a scheduling block and try to address as many of their questions as possible. “If you wait until the morning of the shift to connect with them, anxiety will be high. But after going through a couple of scheduling cycles, we find that things are getting better. I think we’ve paid a lot of attention to the risks of burnout by our physicians. We’re using a model of 4 days on/4 off.”

Another variation on these themes is Joshua Shatzkes, MD, assistant professor of medicine and cardiology at Mount Sinai, who practices outpatient cardiology at MSH and in several off-site offices in Brooklyn. He saw early on that COVID-19 would have a huge effect on his practice, so he volunteered to help out with inpatient care. “I made it known to my chief that I was available, and I was deployed in the first week, after a weekend of cramming webinars and lectures on critical care and pulling out critical concepts that I already knew.”

Dr. Shatzkes said his career path led him into outpatient cardiology 11 years ago, where he was quickly too busy to see his patients when they went into the hospital, even though he missed hospital medicine. Working as a temporary hospitalist with the arrival of COVID-19, he has been invigorated and mobilized by the experience and reminded of why he went to medical school in the first place. “Each day’s shift went quickly but felt long. At the end of the day, I was tired but not exhausted. When I walked out of a patient’s room, they could tell, ‘This is a doctor who cared for me,’ ” he said.

After Dr. Shatzkes volunteered, he got the call from his division chief. “I was officially deployed for a 4-day shift at Mount Sinai and then as a backup.” On his first morning as an inpatient doctor, he was still getting oriented when calls started coming from the nurses. “I had five patients struggling to breathe. Their degree of hypoxia was remarkable. I kept them out of the ICU, at least for that day.”

Since then, he has continued to follow some of those patients in the hospital, along with some from his outpatient practice who were hospitalized, and others referred by colleagues, while remaining available to his outpatients through telemedicine. When this is all over, Dr. Shatzkes said, he would love to find a way to incorporate a hospital practice in his job – depending on the realities of New York traffic.

“Joshua is not a hospitalist, but he went on service and felt so fulfilled and rewarded, he asked me if he could stay on service,” Dr. Dunn said. “I also got an email from the nurse manager on the unit. They want him back.”

In the midst of the COVID-19 pandemic, health systems, hospitals, and hospitalists – especially in hot spots like New York, Detroit, or Boston – have been challenged to stretch limits, redefine roles, and redeploy critical staff in response to rapidly changing needs on the ground.

Many hospitalists are working above and beyond their normal duties, sometimes beyond their training, specialty, or comfort zone and are rising to the occasion in ways they never imagined. These include doing shifts in ICUs, working with ventilator patients, and reporting to other atypical sites of care like postanesthesia care units and post-acute or step-down units.

Valerie Vaughn, MD, MSc, a hospitalist with Michigan Medicine and assistant professor of medicine at the University of Michigan in Ann Arbor, was doing research on how to reduce overuse of antibiotics in hospitals when the COVID-19 crisis hit and dramatically redefined her job. “We were afraid that we might have 3,000 to 5,000 hospitalized COVID patients by now, based on predictive modeling done while the pandemic was still growing exponentially,” she explained. Although Michigan continues to have high COVID-19 infection rates, centered on nearby Detroit, “things are a lot better today than they were 4 weeks ago.”

Dr. Vaughn helped to mobilize a team of 25 hospitalists, along with other health care providers, who volunteered to manage COVID-19 patients in the ICU and other hospital units. She was asked to help develop an all-COVID unit called the Regional Infectious Containment Unit or RICU, which opened March 16. Then, when the RICU became full, it was supplemented by two COVID-19 Moderate Care Units staffed by hospitalists who had “learned the ropes” in the RICU.

Both of these new models were defined in relation to the ICUs at Michigan Medicine – which were doubling in capacity, up to 200 beds at last count – and to the provision of intensive-level and long-term ventilator care for the sickest patients. The moderate care units are for patients who are not on ventilators but still very sick, for example, those receiving massive high-flow oxygen, often with a medical do-not-resuscitate/do-not-intubate order. “We established these units to do everything (medically) short of vents,” Dr. Vaughn said.

“We are having in-depth conversations about goals of care with patients soon after they arrive at the hospital. We know outcomes from ventilators are worse for COVID-positive patients who have comorbidities, and we’re using that information to inform these conversations. We’ve given scripts to clinicians to help guide them in leading these conversations. We can do other things than `use ventilators to manage their symptoms. But these are still difficult conversations,” Dr. Vaughn said.

“We also engaged palliative care early on and asked them to round with us on every [COVID] patient – until demand got too high.” The bottleneck has been the number of ICU beds available, she explained. “If you want your patient to come in and take that bed, make sure you’ve talked to the family about it.”

The COVID-19 team developed guidelines printed on pocket cards addressing critical care issues such as a refresher on how to treat acute respiratory distress syndrome and how to use vasopressors. (See the COVID-19 Continuing Medical Education Portal for web-accessible educational resources developed by Michigan Health).

It’s amazing how quickly patients can become very sick with COVID-19, Dr. Vaughn said. “One of the good things to happen from the beginning with our RICU is that a group of doctors became COVID care experts very quickly. We joined four to five hospitalists and their teams with each intensivist, so one critical care expert is there to do teaching and answer clinicians’ questions. The hospitalists coordinate the COVID care and talk to the families.”

Working on the front lines of this crisis, Dr. Vaughn said, has generated a powerful sense of purpose and camaraderie, creating bonds like in war time. “All of us on our days off feel a twinge of guilt for not being there in the hospital. The sense of gratitude we get from patients and families has been enormous, even when we were telling them bad news. That just brings us to tears.”

One of the hardest things for the doctors practicing above their typical scope of practice is that, when something bad happens, they can’t know whether it was a mistake on their part or not, she noted. “But I’ve never been so proud of our group or to be a hospitalist. No one has complained or pushed back. Everyone has responded by saying: ‘What can I do to help?’ ”
 

Enough work in hospital medicine

Hospitalists had not been deployed to care for ICU patients at Beth Israel Deaconess Medical Center (BIDMC) in Boston, a major hot spot for COVID-19, said Joseph Ming Wah Li, MD, SFHM, director of the hospital medicine program at BIDMC, when he spoke to The Hospitalist in mid-May. That’s because there were plenty of hospital medicine assignments to keep them busy. Dr. Li leads a service of 120 hospitalists practicing at four hospitals.

“As we speak today, we have 300 patients with COVID, with 70 or 80 of them in our ICU. I’m taking care of 17 patients today, 15 of them COVID-positive, and the other two placed in a former radiology holding suite adapted for COVID-negative patients. Our postanesthesia care unit is now an ICU filled with COVID patients,” he said.

“Half of my day is seeing patients and the other half I’m on Zoom calls. I’m also one of the resource allocation officers for BIDMC,” Dr. Li said. He helped to create a standard of care for the hospital, addressing what to do if there weren’t enough ICU beds or ventilators. “We’ve never actualized it and probably won’t, but it was important to go through this exercise, with a lot of discussion up front.”

Haki Laho, MD, an orthopedic hospitalist at New England Baptist Hospital (NEBH), also in Boston, has been redeployed to care for a different population of patients as his system tries to bunch patients. “All of a sudden – within hours and days – at the beginning of the pandemic and based on the recommendations, our whole system decided to stop all elective procedures and devote the resources to COVID,” he said.

NEBH is Beth Israel Lahey Health’s 141-bed orthopedic and surgical hospital, and the system has tried to keep the specialty facility COVID-19–free as much as possible, with the COVID-19 patients grouped together at BIDMC. Dr. Laho’s orthopedic hospitalist group, just five doctors, has been managing the influx of medical patients with multiple comorbidities – not COVID-19–infected but still a different kind of patient than they are used to.

“So far, so good. We’re dealing with it,” he said. “But if one of us got sick, the others would have to step up and do more shifts. We are physicians, internal medicine trained, but since my residency I hadn’t had to deal with these kinds of issues on a daily basis, such as setting up IV lines. I feel like I am back in residency mode.”
 

Convention Center medicine

Another Boston hospitalist, Amy Baughman, MD, who practices at Massachusetts General Hospital, is using her skills in a new setting, serving as a co-medical director at Boston Hope Medical Center, a 1,000-bed field hospital for patients with COVID-19. Open since April 10 and housed in the Boston Convention and Exhibition Center, it is a four-way collaboration between the Commonwealth of Massachusetts, the City of Boston, Partners HealthCare, and the Boston Health Care for the Homeless Program.

Boston Hope is divided into a post-acute care section for recovering COVID-19 patients and a respite section for undomiciled patients with COVID-19 who need a place to safely quarantine. Built for a maximum of 1,000 beds, it is currently using fewer, with 83 patients on the post-acute side and 73 on the respite side as of May 12. A total of 370 and 315, respectively, had been admitted through May 12.

The team had 5 days to put the field hospital together with the help of the Army National Guard. “During that first week I was installing hand sanitizer dispensers and making [personal protective equipment] signs. Everyone here has had to do things like that,” Dr. Baughman said. “We’ve had to be incredibly creative in our staffing, using doctors from primary care and subspecialties including dermatology, radiology, and orthopedics. We had to fast-track trainings on how to use EPIC and to provide post-acute COVID care. How do you simultaneously build a medical facility and lead teams to provide high quality care?”

Dr. Baughman still works hospitalist shifts half-time at Massachusetts General. Her prior experience providing post-acute care in the VA system was helpful in creating the post-acute level of care at Boston Hope.

“My medical director role involves supervising, staffing, and scheduling. My co-medical director, Dr. Kerri Palamara, and I also supervise the clinical care,” she said. “There are a lot of systems issues, like ordering labs or prescriptions, with couriers going back and forth. And we developed clinical pathways, such as for [deep vein thrombosis] prophylaxis or for COVID retesting to determine when it is safe to end a quarantine. We’re just now rolling out virtual specialist consultations,” she noted.

“It has gone incredibly well. So much of it has been about our ability and willingness to work hard, and take feedback and go forward. We don’t have time to harp on things. We have to be very solution oriented. At the same time, honestly, it’s been fun. Every single day is different,” Dr. Baughman said.

“It’s been an opportunity to use my skills in a totally new setting, and at a level of responsibility I haven’t had before, although that’s probably a common theme with COVID-19. I was put on this team because I am a hospitalist,” she said. “I think hospitalists have been the backbone of the response to COVID in this country. It’s been an opportunity for our specialty to shine. We need to embrace the opportunity.”
 

Balancing expertise and supervision

Mount Sinai Hospital (MSH) in Manhattan is in the New York epicenter of the COVID-19 crisis and has mobilized large numbers of pulmonary critical care and anesthesia physicians to staff up multiple ICUs for COVID-19 patients, said Andrew Dunn, MD, chief of the division of hospital medicine at Mount Sinai School of Medicine.

“My hospitalist group is covering many step-down units, medical wards, and atypical locations, providing advanced oxygen therapies, [bilevel positive airway pressure], high-flow nasal cannulas, and managing some patients on ventilators,” he said.

MSH has teaching services with house staff and nonteaching services. “We combined them into a unified service with house staff dispersed across all of the teams. We drafted a lot of nonhospitalists from different specialties to be attendings, and that has given us a tiered model, with a hospitalist supervising three or four nonhospitalist-led teams. Although the supervising hospitalists carry no patient caseloads of their own, this is primarily a clinical rather than an administrative role.”

At the peak, there were 40 rounding teams at MSH, each with a typical census of 15 patients or more, which meant that 10 supervisory hospitalists were responsible for 300 to 400 patients. “What we learned first was the need to balance the level of expertise. For example, a team may include a postgraduate year 3 resident and a radiology intern,” Dr. Dunn said. As COVID-19 census has started coming down, supervisory hospitalists are returning to direct care attending roles, and some hospitalists have been shared across the Mount Sinai system’s hospitals.

Dr. Dunn’s advice for hospitalists filling a supervisory role like this in a tiered model: Make sure you talk to your team the night before the first day of a scheduling block and try to address as many of their questions as possible. “If you wait until the morning of the shift to connect with them, anxiety will be high. But after going through a couple of scheduling cycles, we find that things are getting better. I think we’ve paid a lot of attention to the risks of burnout by our physicians. We’re using a model of 4 days on/4 off.”

Another variation on these themes is Joshua Shatzkes, MD, assistant professor of medicine and cardiology at Mount Sinai, who practices outpatient cardiology at MSH and in several off-site offices in Brooklyn. He saw early on that COVID-19 would have a huge effect on his practice, so he volunteered to help out with inpatient care. “I made it known to my chief that I was available, and I was deployed in the first week, after a weekend of cramming webinars and lectures on critical care and pulling out critical concepts that I already knew.”

Dr. Shatzkes said his career path led him into outpatient cardiology 11 years ago, where he was quickly too busy to see his patients when they went into the hospital, even though he missed hospital medicine. Working as a temporary hospitalist with the arrival of COVID-19, he has been invigorated and mobilized by the experience and reminded of why he went to medical school in the first place. “Each day’s shift went quickly but felt long. At the end of the day, I was tired but not exhausted. When I walked out of a patient’s room, they could tell, ‘This is a doctor who cared for me,’ ” he said.

After Dr. Shatzkes volunteered, he got the call from his division chief. “I was officially deployed for a 4-day shift at Mount Sinai and then as a backup.” On his first morning as an inpatient doctor, he was still getting oriented when calls started coming from the nurses. “I had five patients struggling to breathe. Their degree of hypoxia was remarkable. I kept them out of the ICU, at least for that day.”

Since then, he has continued to follow some of those patients in the hospital, along with some from his outpatient practice who were hospitalized, and others referred by colleagues, while remaining available to his outpatients through telemedicine. When this is all over, Dr. Shatzkes said, he would love to find a way to incorporate a hospital practice in his job – depending on the realities of New York traffic.

“Joshua is not a hospitalist, but he went on service and felt so fulfilled and rewarded, he asked me if he could stay on service,” Dr. Dunn said. “I also got an email from the nurse manager on the unit. They want him back.”

For the first time, weekly cisplatin plus radiotherapy (CDDP+RT) has been shown to be not only less toxic than dosing once every three weeks but to also achieve better outcomes in patients with postoperative squamous cell carcinoma of the head and neck (SCCHN), say Japanese researchers.

These results, from the JCOG1008 trial, suggest the weekly schedule should become the new standard of care in these patients, potentially settling what has been a “contentious” issue.

The research was presented at the 2020 annual meeting of the American Society of Clinical Oncology (abstract 6502), held virtually because of the coronavirus pandemic.

Lead author Naomi Kiyota, MD, PhD, medical oncology and hematology, Cancer Center, Kobe University Hospital, Japan, said the study involving more than 160 high-risk patients with SCCHN demonstrated comparable overall survival in the weekly and three-weekly CDDP+RT groups.

Moreover, it showed that the weekly schedule was associated with better relapse-free and local relapse-free survival, and, in line with previous studies, had a more favorable safety profile.

“This phase II/III study is the first to show that weekly CDDP+RT is noninferior to three-weekly CDDP+RT [and] is a new standard treatment option for these patients,” Dr. Kiyota said.

Study discussant Hisham M. Mehanna, MD, PhD, Warwickshire Head and Neck Clinic, University of Birmingham, UK, described the study as a “significant achievement” that answers “an important question that we’ve been asking for a very long time.”

He said that, despite three-weekly CDDP+RT being the standard treatment in the postoperative setting for SCCHN, there have been “lingering concerns,” as 40% of patients don’t get all three CDDP cycles “and it is toxic.”

Weekly CDDP is, on the other hand, “widely used, although the evidence for it is not as strong,” and has a number of advantages, including that it can be delivered in the outpatient setting and it may be less toxic.

Dr. Mehanna said there was “a surprise” to the current study, in that it was terminated early because it crossed the boundary for non-inferiority because weekly CDDP has better survival than the three-weekly dose; notably, however, superiority was not achieved.

Dr. Mehanna also expressed some reservations over imbalances in the treatment groups that could have meant the three-weekly cohort had an unfavorable prognosis, and said questions remain over longer-term toxicity.
 

‘Contentious issue’

In a highlights session, Nabil F. Saba, MD, director of the head and neck oncology program at Emory University’s Winship Cancer Institute in Atlanta, Georgia, said the dosing of CDDP in these patients has been “a contentious issue.”

One issue has been whether scheduling of CDDP or the cumulative dose achieved is the key determinant of clinical outcome, and he suggested that the superior results seen in the current study can be attributed to the high cumulative dose the investigators achieved in their patients compared with previous investigations.

For Dr. Saba, the take-home message of the trial is that weekly cisplatin “is now, finally, an accepted standard of care in the postoperative high-risk setting, which is a major change at this ASCO meeting.”

Presenting the trial, Dr. Kiyota said, in a recent study (J Clin Oncol. 2017 Dec 8. doi: 10.1200/JCO.2017.74.9457) from the Tata Memorial Hospital, weekly CDDP at 30 mg/m² plus radiotherapy failed to achieve noninferiority to a three-weekly regimen, “albeit with fewer toxicities.”

He suggested that this could be because it was a single-center trial, two different treatment strategies were used, the majority of primary sites were in the oral cavity, and the dose was insufficient.

His team, on the other hand, undertook a randomized trial in which patients with postoperative high-risk SCCHN were recruited from 28 institutions.

The participants, who were aged 20-75 years and had ECOG performance status 0-1, all had pathological stage III/IV disease and a microscopically positive margin and/or extranodal extension.

They were randomly assigned to 100 mg/m² CDDP once every three weeks or weekly 40 mg/m² CDDP, plus radiotherapy at 66 Gy over 33 fractions.

For the intention-to-treat efficacy analysis, 132 patients received three-weekly CDDP+RT and 129 had weekly CDDP+RT, while the per-protocol safety analysis included 129 and 122 patients, respectively.

The median age of the patients was 61-62 years, and 110 patients in both treatment groups were male. Although there was a similar distribution of primary sites and high-risk factors in the two groups, more patients in the weekly group had pathological stage T2 disease (40) than in the three-weekly group (26).

The dose targets were met in both treatment groups. In the three-weekly group, the cumulative dose of CDDP achieved was 280 mg/m^2, and, in the weekly group, it was 239 mg/m².

The second planned interim analysis showed that, over a median follow-up of 2.2 years, 3-year overall survival was estimated at 71.6% in the weekly group versus 59.1% in the three-weekly group (hazard ratio, 0.69).

As this was below the one-sided P value for noninferiority, the data and safety monitoring committee recommended terminating the trial early.

The researchers also found that the 3-year relapse-free survival was higher with weekly CDDP+RT, at 64.5%, vs 53.0% with three-weekly dosing (HR, 0.71).

Local relapse-free survival was also better with weekly dosing, at a 3-year rate of 69.6% versus 59.5% for patients in the three-weekly group (HR, 0.73).

On a planned subgroup analysis, weekly CDDP+RT was nonsignificantly superior to the three-weekly schedule on almost every measure, whether looking at patient age, ECOG performance status, and primary site.

There were also differences in the occurrence of hematologic toxicities between the two groups, with fewer patients given the weekly schedule experiencing grade 3/4 neutropenia than those on the three-weekly dosing. However, there were more cases of any grade thrombocytopenia for patients getting the weekly dosing.

The weekly CDDP+RT regimen demonstrated its lower toxicity when looking at acute nonhematologic adverse events, with fewer occurrences of any grade dysphagia, nausea, hyponatremia, renal impairment, and hearing impairment versus the three-weekly schedule.

The weekly dosing schedule was also associated with lower rates of grade 3/4 dysphagia, nausea, and infection.

The study was funded by the National Cancer Center Research and Development Fund, Japan Agency for Medical Research and Development Fund.

Dr. Kiyota reports honoraria from AstraZeneca, Bayer, Bristol-Myers Squibb Japan, Chugai Pharma, Eisai, Merck Serono, MSD, and Ono Pharmaceutical; speakers bureau fees from AstraZeneca, Bayer, Bristol-Myers Squibb Japan; Eisai, Merck Serono, MSD, and Ono Pharmaceutical; and receiving research funding from AstraZeneca (Inst), Bristol-Myers Squibb (Inst), Ono Pharmaceutical (Inst), Pfizer (Inst), and Roche (Inst). Other study authors report potential conflicts of interest. The full list can be found here.

Dr. Mehanna reports stock and other ownership interests in Warwickshire Head and Neck Clinic; honoraria from AstraZeneca; speakers bureau fess from Merck, MSD, and Sanofi Pasteur; research funding from AstraZeneca, GlaxoSmithKline (Inst), MSD (Inst), Sanofi Pasteur (Inst), and Silence Therapeutics (Inst); and travel, accommodations, and expenses from Merck, MSD, and Sanofi Pasteur.

Dr. Saba reports honoraria from Aduro Biotech, Bristol-Myers Squibb, Cue Biopharma, Genentech/Roche, GSK, Kura, Lilly, Merck, and Pfizer; a consulting or advisory role with Biontech, Bluprint, Bristol-Myers Squibb, Lilly, Merck, and Pfizer; research funding from Bristol-Myers Squibb and Exelixis; travel, accommodations, and expenses from Bluprint, Bristol-Myers Squibb, Genentech/Roche, GSK, Lilly, Merck, and Pfizer.

This article first appeared on Medscape.com.

For the first time, weekly cisplatin plus radiotherapy (CDDP+RT) has been shown to be not only less toxic than dosing once every three weeks but to also achieve better outcomes in patients with postoperative squamous cell carcinoma of the head and neck (SCCHN), say Japanese researchers.

These results, from the JCOG1008 trial, suggest the weekly schedule should become the new standard of care in these patients, potentially settling what has been a “contentious” issue.

The research was presented at the 2020 annual meeting of the American Society of Clinical Oncology (abstract 6502), held virtually because of the coronavirus pandemic.

Lead author Naomi Kiyota, MD, PhD, medical oncology and hematology, Cancer Center, Kobe University Hospital, Japan, said the study involving more than 160 high-risk patients with SCCHN demonstrated comparable overall survival in the weekly and three-weekly CDDP+RT groups.

Moreover, it showed that the weekly schedule was associated with better relapse-free and local relapse-free survival, and, in line with previous studies, had a more favorable safety profile.

“This phase II/III study is the first to show that weekly CDDP+RT is noninferior to three-weekly CDDP+RT [and] is a new standard treatment option for these patients,” Dr. Kiyota said.

Study discussant Hisham M. Mehanna, MD, PhD, Warwickshire Head and Neck Clinic, University of Birmingham, UK, described the study as a “significant achievement” that answers “an important question that we’ve been asking for a very long time.”

He said that, despite three-weekly CDDP+RT being the standard treatment in the postoperative setting for SCCHN, there have been “lingering concerns,” as 40% of patients don’t get all three CDDP cycles “and it is toxic.”

Weekly CDDP is, on the other hand, “widely used, although the evidence for it is not as strong,” and has a number of advantages, including that it can be delivered in the outpatient setting and it may be less toxic.

Dr. Mehanna said there was “a surprise” to the current study, in that it was terminated early because it crossed the boundary for non-inferiority because weekly CDDP has better survival than the three-weekly dose; notably, however, superiority was not achieved.

Dr. Mehanna also expressed some reservations over imbalances in the treatment groups that could have meant the three-weekly cohort had an unfavorable prognosis, and said questions remain over longer-term toxicity.
 

‘Contentious issue’

In a highlights session, Nabil F. Saba, MD, director of the head and neck oncology program at Emory University’s Winship Cancer Institute in Atlanta, Georgia, said the dosing of CDDP in these patients has been “a contentious issue.”

One issue has been whether scheduling of CDDP or the cumulative dose achieved is the key determinant of clinical outcome, and he suggested that the superior results seen in the current study can be attributed to the high cumulative dose the investigators achieved in their patients compared with previous investigations.

For Dr. Saba, the take-home message of the trial is that weekly cisplatin “is now, finally, an accepted standard of care in the postoperative high-risk setting, which is a major change at this ASCO meeting.”

Presenting the trial, Dr. Kiyota said, in a recent study (J Clin Oncol. 2017 Dec 8. doi: 10.1200/JCO.2017.74.9457) from the Tata Memorial Hospital, weekly CDDP at 30 mg/m² plus radiotherapy failed to achieve noninferiority to a three-weekly regimen, “albeit with fewer toxicities.”

He suggested that this could be because it was a single-center trial, two different treatment strategies were used, the majority of primary sites were in the oral cavity, and the dose was insufficient.

His team, on the other hand, undertook a randomized trial in which patients with postoperative high-risk SCCHN were recruited from 28 institutions.

The participants, who were aged 20-75 years and had ECOG performance status 0-1, all had pathological stage III/IV disease and a microscopically positive margin and/or extranodal extension.

They were randomly assigned to 100 mg/m² CDDP once every three weeks or weekly 40 mg/m² CDDP, plus radiotherapy at 66 Gy over 33 fractions.

For the intention-to-treat efficacy analysis, 132 patients received three-weekly CDDP+RT and 129 had weekly CDDP+RT, while the per-protocol safety analysis included 129 and 122 patients, respectively.

The median age of the patients was 61-62 years, and 110 patients in both treatment groups were male. Although there was a similar distribution of primary sites and high-risk factors in the two groups, more patients in the weekly group had pathological stage T2 disease (40) than in the three-weekly group (26).

The dose targets were met in both treatment groups. In the three-weekly group, the cumulative dose of CDDP achieved was 280 mg/m^2, and, in the weekly group, it was 239 mg/m².

The second planned interim analysis showed that, over a median follow-up of 2.2 years, 3-year overall survival was estimated at 71.6% in the weekly group versus 59.1% in the three-weekly group (hazard ratio, 0.69).

As this was below the one-sided P value for noninferiority, the data and safety monitoring committee recommended terminating the trial early.

The researchers also found that the 3-year relapse-free survival was higher with weekly CDDP+RT, at 64.5%, vs 53.0% with three-weekly dosing (HR, 0.71).

Local relapse-free survival was also better with weekly dosing, at a 3-year rate of 69.6% versus 59.5% for patients in the three-weekly group (HR, 0.73).

On a planned subgroup analysis, weekly CDDP+RT was nonsignificantly superior to the three-weekly schedule on almost every measure, whether looking at patient age, ECOG performance status, and primary site.

There were also differences in the occurrence of hematologic toxicities between the two groups, with fewer patients given the weekly schedule experiencing grade 3/4 neutropenia than those on the three-weekly dosing. However, there were more cases of any grade thrombocytopenia for patients getting the weekly dosing.

The weekly CDDP+RT regimen demonstrated its lower toxicity when looking at acute nonhematologic adverse events, with fewer occurrences of any grade dysphagia, nausea, hyponatremia, renal impairment, and hearing impairment versus the three-weekly schedule.

The weekly dosing schedule was also associated with lower rates of grade 3/4 dysphagia, nausea, and infection.

The study was funded by the National Cancer Center Research and Development Fund, Japan Agency for Medical Research and Development Fund.

Dr. Kiyota reports honoraria from AstraZeneca, Bayer, Bristol-Myers Squibb Japan, Chugai Pharma, Eisai, Merck Serono, MSD, and Ono Pharmaceutical; speakers bureau fees from AstraZeneca, Bayer, Bristol-Myers Squibb Japan; Eisai, Merck Serono, MSD, and Ono Pharmaceutical; and receiving research funding from AstraZeneca (Inst), Bristol-Myers Squibb (Inst), Ono Pharmaceutical (Inst), Pfizer (Inst), and Roche (Inst). Other study authors report potential conflicts of interest. The full list can be found here.

Dr. Mehanna reports stock and other ownership interests in Warwickshire Head and Neck Clinic; honoraria from AstraZeneca; speakers bureau fess from Merck, MSD, and Sanofi Pasteur; research funding from AstraZeneca, GlaxoSmithKline (Inst), MSD (Inst), Sanofi Pasteur (Inst), and Silence Therapeutics (Inst); and travel, accommodations, and expenses from Merck, MSD, and Sanofi Pasteur.

Dr. Saba reports honoraria from Aduro Biotech, Bristol-Myers Squibb, Cue Biopharma, Genentech/Roche, GSK, Kura, Lilly, Merck, and Pfizer; a consulting or advisory role with Biontech, Bluprint, Bristol-Myers Squibb, Lilly, Merck, and Pfizer; research funding from Bristol-Myers Squibb and Exelixis; travel, accommodations, and expenses from Bluprint, Bristol-Myers Squibb, Genentech/Roche, GSK, Lilly, Merck, and Pfizer.

This article first appeared on Medscape.com.

For the first time, weekly cisplatin plus radiotherapy (CDDP+RT) has been shown to be not only less toxic than dosing once every three weeks but to also achieve better outcomes in patients with postoperative squamous cell carcinoma of the head and neck (SCCHN), say Japanese researchers.

These results, from the JCOG1008 trial, suggest the weekly schedule should become the new standard of care in these patients, potentially settling what has been a “contentious” issue.

The research was presented at the 2020 annual meeting of the American Society of Clinical Oncology (abstract 6502), held virtually because of the coronavirus pandemic.

Lead author Naomi Kiyota, MD, PhD, medical oncology and hematology, Cancer Center, Kobe University Hospital, Japan, said the study involving more than 160 high-risk patients with SCCHN demonstrated comparable overall survival in the weekly and three-weekly CDDP+RT groups.

Moreover, it showed that the weekly schedule was associated with better relapse-free and local relapse-free survival, and, in line with previous studies, had a more favorable safety profile.

“This phase II/III study is the first to show that weekly CDDP+RT is noninferior to three-weekly CDDP+RT [and] is a new standard treatment option for these patients,” Dr. Kiyota said.

Study discussant Hisham M. Mehanna, MD, PhD, Warwickshire Head and Neck Clinic, University of Birmingham, UK, described the study as a “significant achievement” that answers “an important question that we’ve been asking for a very long time.”

He said that, despite three-weekly CDDP+RT being the standard treatment in the postoperative setting for SCCHN, there have been “lingering concerns,” as 40% of patients don’t get all three CDDP cycles “and it is toxic.”

Weekly CDDP is, on the other hand, “widely used, although the evidence for it is not as strong,” and has a number of advantages, including that it can be delivered in the outpatient setting and it may be less toxic.

Dr. Mehanna said there was “a surprise” to the current study, in that it was terminated early because it crossed the boundary for non-inferiority because weekly CDDP has better survival than the three-weekly dose; notably, however, superiority was not achieved.

Dr. Mehanna also expressed some reservations over imbalances in the treatment groups that could have meant the three-weekly cohort had an unfavorable prognosis, and said questions remain over longer-term toxicity.
 

‘Contentious issue’

In a highlights session, Nabil F. Saba, MD, director of the head and neck oncology program at Emory University’s Winship Cancer Institute in Atlanta, Georgia, said the dosing of CDDP in these patients has been “a contentious issue.”

One issue has been whether scheduling of CDDP or the cumulative dose achieved is the key determinant of clinical outcome, and he suggested that the superior results seen in the current study can be attributed to the high cumulative dose the investigators achieved in their patients compared with previous investigations.

For Dr. Saba, the take-home message of the trial is that weekly cisplatin “is now, finally, an accepted standard of care in the postoperative high-risk setting, which is a major change at this ASCO meeting.”

Presenting the trial, Dr. Kiyota said, in a recent study (J Clin Oncol. 2017 Dec 8. doi: 10.1200/JCO.2017.74.9457) from the Tata Memorial Hospital, weekly CDDP at 30 mg/m² plus radiotherapy failed to achieve noninferiority to a three-weekly regimen, “albeit with fewer toxicities.”

He suggested that this could be because it was a single-center trial, two different treatment strategies were used, the majority of primary sites were in the oral cavity, and the dose was insufficient.

His team, on the other hand, undertook a randomized trial in which patients with postoperative high-risk SCCHN were recruited from 28 institutions.

The participants, who were aged 20-75 years and had ECOG performance status 0-1, all had pathological stage III/IV disease and a microscopically positive margin and/or extranodal extension.

They were randomly assigned to 100 mg/m² CDDP once every three weeks or weekly 40 mg/m² CDDP, plus radiotherapy at 66 Gy over 33 fractions.

For the intention-to-treat efficacy analysis, 132 patients received three-weekly CDDP+RT and 129 had weekly CDDP+RT, while the per-protocol safety analysis included 129 and 122 patients, respectively.

The median age of the patients was 61-62 years, and 110 patients in both treatment groups were male. Although there was a similar distribution of primary sites and high-risk factors in the two groups, more patients in the weekly group had pathological stage T2 disease (40) than in the three-weekly group (26).

The dose targets were met in both treatment groups. In the three-weekly group, the cumulative dose of CDDP achieved was 280 mg/m^2, and, in the weekly group, it was 239 mg/m².

The second planned interim analysis showed that, over a median follow-up of 2.2 years, 3-year overall survival was estimated at 71.6% in the weekly group versus 59.1% in the three-weekly group (hazard ratio, 0.69).

As this was below the one-sided P value for noninferiority, the data and safety monitoring committee recommended terminating the trial early.

The researchers also found that the 3-year relapse-free survival was higher with weekly CDDP+RT, at 64.5%, vs 53.0% with three-weekly dosing (HR, 0.71).

Local relapse-free survival was also better with weekly dosing, at a 3-year rate of 69.6% versus 59.5% for patients in the three-weekly group (HR, 0.73).

On a planned subgroup analysis, weekly CDDP+RT was nonsignificantly superior to the three-weekly schedule on almost every measure, whether looking at patient age, ECOG performance status, and primary site.

There were also differences in the occurrence of hematologic toxicities between the two groups, with fewer patients given the weekly schedule experiencing grade 3/4 neutropenia than those on the three-weekly dosing. However, there were more cases of any grade thrombocytopenia for patients getting the weekly dosing.

The weekly CDDP+RT regimen demonstrated its lower toxicity when looking at acute nonhematologic adverse events, with fewer occurrences of any grade dysphagia, nausea, hyponatremia, renal impairment, and hearing impairment versus the three-weekly schedule.

The weekly dosing schedule was also associated with lower rates of grade 3/4 dysphagia, nausea, and infection.

The study was funded by the National Cancer Center Research and Development Fund, Japan Agency for Medical Research and Development Fund.

Dr. Kiyota reports honoraria from AstraZeneca, Bayer, Bristol-Myers Squibb Japan, Chugai Pharma, Eisai, Merck Serono, MSD, and Ono Pharmaceutical; speakers bureau fees from AstraZeneca, Bayer, Bristol-Myers Squibb Japan; Eisai, Merck Serono, MSD, and Ono Pharmaceutical; and receiving research funding from AstraZeneca (Inst), Bristol-Myers Squibb (Inst), Ono Pharmaceutical (Inst), Pfizer (Inst), and Roche (Inst). Other study authors report potential conflicts of interest. The full list can be found here.

Dr. Mehanna reports stock and other ownership interests in Warwickshire Head and Neck Clinic; honoraria from AstraZeneca; speakers bureau fess from Merck, MSD, and Sanofi Pasteur; research funding from AstraZeneca, GlaxoSmithKline (Inst), MSD (Inst), Sanofi Pasteur (Inst), and Silence Therapeutics (Inst); and travel, accommodations, and expenses from Merck, MSD, and Sanofi Pasteur.

Dr. Saba reports honoraria from Aduro Biotech, Bristol-Myers Squibb, Cue Biopharma, Genentech/Roche, GSK, Kura, Lilly, Merck, and Pfizer; a consulting or advisory role with Biontech, Bluprint, Bristol-Myers Squibb, Lilly, Merck, and Pfizer; research funding from Bristol-Myers Squibb and Exelixis; travel, accommodations, and expenses from Bluprint, Bristol-Myers Squibb, Genentech/Roche, GSK, Lilly, Merck, and Pfizer.

This article first appeared on Medscape.com.

Children with cystic fibrosis have inadequate sleep even during times of normal lung function, according to results from a new study.

Children aged 6-12 years had more sleep issues compared with preschoolers or teenagers, researchers also found, and the quality of sleep among caregivers was seen strongly linked to that of their children with CF.

For research published in the Journal of Cystic Fibrosis, Kelly C. Byars, PsyD, and colleagues at Cincinnati Children’s Medical Center and the University of Cincinnati surveyed parents of 91 medically stable patients with cystic fibrosis aged 18 and younger at a single CF treatment center between 2016 and 2017.

Fifty-four percent of the children in the study were female, the mean age was 9 years, and 90% of the caregivers were mothers. In addition to the sleep questionnaires, the researchers looked at the children’s available lung function data from around the time of the survey. Forced expiratory volume in one second (FEV₁) measures showed the vast majority had no obstructive lung disease (73% of the cohort) or only mild symptoms (18%) at the time their caregivers were surveyed.

Overall, some 40% of caregivers said they had concerns about their own sleep, while 29% said they were concerned for their children’s sleep. Parents reported night waking, daytime sleepiness, and difficulty falling asleep as their main problems, and difficulty falling asleep as the top issue for their children, along with daytime sleepiness, night waking, and mouth breathing.

Sleep issues were most pronounced for children aged 6-12 and their caregivers, a group for which 44% of caregivers said they were concerned for their children’s sleep and 55% for their own sleep. For this same group only 8% of parents reported their children having nocturnal cough, and just 5% reported gastrointestinal problems at night.

Overall, the caregivers in the study reported inadequate sleep, with more than half saying they got less than 7 hours per night. Similarly, more than half of the school-age and adolescent patients with CF were getting less than the nightly minimum recommended by the American Academy of Sleep Medicine.

The researchers noted “large effects for parent and child associations for insomnia symptoms that may be amenable to treatment,” especially trouble returning to sleep and daytime sleepiness.

The study “is the first to examine parent reported sleep disturbances and sleep duration in both parents and their children with CF spanning a broad age range and including patients who were medically stable and predominantly free of lung dysfunction,” Dr. Byars and colleagues wrote in their analysis, adding that sleep health should be integrated into care protocols for CF patients and their families, and families of children with other chronic illnesses.

In a comment on Dr. Byars and colleagues’ study, Hovig Artinian, MD, a pediatric pulmonary and sleep medicine specialist at Helen DeVos Children’s Hospital in Grand Rapids, Mich., said the findings “highlight for all of us that we must regularly assess and address sleep disturbances in our children with CF specifically, but also in all children with chronic conditions.”

Children with CF “carry a heavy burden,” Dr. Artinian said, “balancing living their lives with daily interruptions to their typical day to complete multiple treatments. As a result, sleep can be impacted even when there are no other clinical or objective signs of illness, so that was not an entirely surprising finding.” Difficulties with sleep onset and maintenance can be prevalent in the absence of changes in children’s daytime behavior or any other psychological signs, Dr. Artinian said, noting that in his practice he routinely asks families whether children snore (something recommended by the American Academy of Pediatrics for all well-child checks) and whether they have any other concerns about their sleep.

“Even if the answer is ‘no’ the first time, the act of asking plants a seed in their minds to keep an eye open and to know they can discuss it with us at a future visit if concerns come up,” Dr. Artinian said.

Dr. Byars and colleagues noted several limitations to their study including its cross-sectional, single-center design, potential participant selection bias, reliance on parent reports of child sleep, and use of a novel, nonvalidated survey instrument.

The researchers received funding from the Boomer Esiason Foundation for their study and disclosed no financial conflicts of interest. Dr. Artinian had no relevant disclosures.
 

SOURCE: Byars K et al. J Cyst Fibros. 2020 May. doi: 10.1016/j.jcf.2020.04.003.

Children with cystic fibrosis have inadequate sleep even during times of normal lung function, according to results from a new study.

Children aged 6-12 years had more sleep issues compared with preschoolers or teenagers, researchers also found, and the quality of sleep among caregivers was seen strongly linked to that of their children with CF.

For research published in the Journal of Cystic Fibrosis, Kelly C. Byars, PsyD, and colleagues at Cincinnati Children’s Medical Center and the University of Cincinnati surveyed parents of 91 medically stable patients with cystic fibrosis aged 18 and younger at a single CF treatment center between 2016 and 2017.

Fifty-four percent of the children in the study were female, the mean age was 9 years, and 90% of the caregivers were mothers. In addition to the sleep questionnaires, the researchers looked at the children’s available lung function data from around the time of the survey. Forced expiratory volume in one second (FEV₁) measures showed the vast majority had no obstructive lung disease (73% of the cohort) or only mild symptoms (18%) at the time their caregivers were surveyed.

Overall, some 40% of caregivers said they had concerns about their own sleep, while 29% said they were concerned for their children’s sleep. Parents reported night waking, daytime sleepiness, and difficulty falling asleep as their main problems, and difficulty falling asleep as the top issue for their children, along with daytime sleepiness, night waking, and mouth breathing.

Sleep issues were most pronounced for children aged 6-12 and their caregivers, a group for which 44% of caregivers said they were concerned for their children’s sleep and 55% for their own sleep. For this same group only 8% of parents reported their children having nocturnal cough, and just 5% reported gastrointestinal problems at night.

Overall, the caregivers in the study reported inadequate sleep, with more than half saying they got less than 7 hours per night. Similarly, more than half of the school-age and adolescent patients with CF were getting less than the nightly minimum recommended by the American Academy of Sleep Medicine.

The researchers noted “large effects for parent and child associations for insomnia symptoms that may be amenable to treatment,” especially trouble returning to sleep and daytime sleepiness.

The study “is the first to examine parent reported sleep disturbances and sleep duration in both parents and their children with CF spanning a broad age range and including patients who were medically stable and predominantly free of lung dysfunction,” Dr. Byars and colleagues wrote in their analysis, adding that sleep health should be integrated into care protocols for CF patients and their families, and families of children with other chronic illnesses.

In a comment on Dr. Byars and colleagues’ study, Hovig Artinian, MD, a pediatric pulmonary and sleep medicine specialist at Helen DeVos Children’s Hospital in Grand Rapids, Mich., said the findings “highlight for all of us that we must regularly assess and address sleep disturbances in our children with CF specifically, but also in all children with chronic conditions.”

Children with CF “carry a heavy burden,” Dr. Artinian said, “balancing living their lives with daily interruptions to their typical day to complete multiple treatments. As a result, sleep can be impacted even when there are no other clinical or objective signs of illness, so that was not an entirely surprising finding.” Difficulties with sleep onset and maintenance can be prevalent in the absence of changes in children’s daytime behavior or any other psychological signs, Dr. Artinian said, noting that in his practice he routinely asks families whether children snore (something recommended by the American Academy of Pediatrics for all well-child checks) and whether they have any other concerns about their sleep.

“Even if the answer is ‘no’ the first time, the act of asking plants a seed in their minds to keep an eye open and to know they can discuss it with us at a future visit if concerns come up,” Dr. Artinian said.

Dr. Byars and colleagues noted several limitations to their study including its cross-sectional, single-center design, potential participant selection bias, reliance on parent reports of child sleep, and use of a novel, nonvalidated survey instrument.

The researchers received funding from the Boomer Esiason Foundation for their study and disclosed no financial conflicts of interest. Dr. Artinian had no relevant disclosures.
 

SOURCE: Byars K et al. J Cyst Fibros. 2020 May. doi: 10.1016/j.jcf.2020.04.003.

Children with cystic fibrosis have inadequate sleep even during times of normal lung function, according to results from a new study.

Children aged 6-12 years had more sleep issues compared with preschoolers or teenagers, researchers also found, and the quality of sleep among caregivers was seen strongly linked to that of their children with CF.

For research published in the Journal of Cystic Fibrosis, Kelly C. Byars, PsyD, and colleagues at Cincinnati Children’s Medical Center and the University of Cincinnati surveyed parents of 91 medically stable patients with cystic fibrosis aged 18 and younger at a single CF treatment center between 2016 and 2017.

Fifty-four percent of the children in the study were female, the mean age was 9 years, and 90% of the caregivers were mothers. In addition to the sleep questionnaires, the researchers looked at the children’s available lung function data from around the time of the survey. Forced expiratory volume in one second (FEV₁) measures showed the vast majority had no obstructive lung disease (73% of the cohort) or only mild symptoms (18%) at the time their caregivers were surveyed.

Overall, some 40% of caregivers said they had concerns about their own sleep, while 29% said they were concerned for their children’s sleep. Parents reported night waking, daytime sleepiness, and difficulty falling asleep as their main problems, and difficulty falling asleep as the top issue for their children, along with daytime sleepiness, night waking, and mouth breathing.

Sleep issues were most pronounced for children aged 6-12 and their caregivers, a group for which 44% of caregivers said they were concerned for their children’s sleep and 55% for their own sleep. For this same group only 8% of parents reported their children having nocturnal cough, and just 5% reported gastrointestinal problems at night.

Overall, the caregivers in the study reported inadequate sleep, with more than half saying they got less than 7 hours per night. Similarly, more than half of the school-age and adolescent patients with CF were getting less than the nightly minimum recommended by the American Academy of Sleep Medicine.

The researchers noted “large effects for parent and child associations for insomnia symptoms that may be amenable to treatment,” especially trouble returning to sleep and daytime sleepiness.

The study “is the first to examine parent reported sleep disturbances and sleep duration in both parents and their children with CF spanning a broad age range and including patients who were medically stable and predominantly free of lung dysfunction,” Dr. Byars and colleagues wrote in their analysis, adding that sleep health should be integrated into care protocols for CF patients and their families, and families of children with other chronic illnesses.

In a comment on Dr. Byars and colleagues’ study, Hovig Artinian, MD, a pediatric pulmonary and sleep medicine specialist at Helen DeVos Children’s Hospital in Grand Rapids, Mich., said the findings “highlight for all of us that we must regularly assess and address sleep disturbances in our children with CF specifically, but also in all children with chronic conditions.”

Children with CF “carry a heavy burden,” Dr. Artinian said, “balancing living their lives with daily interruptions to their typical day to complete multiple treatments. As a result, sleep can be impacted even when there are no other clinical or objective signs of illness, so that was not an entirely surprising finding.” Difficulties with sleep onset and maintenance can be prevalent in the absence of changes in children’s daytime behavior or any other psychological signs, Dr. Artinian said, noting that in his practice he routinely asks families whether children snore (something recommended by the American Academy of Pediatrics for all well-child checks) and whether they have any other concerns about their sleep.

“Even if the answer is ‘no’ the first time, the act of asking plants a seed in their minds to keep an eye open and to know they can discuss it with us at a future visit if concerns come up,” Dr. Artinian said.

Dr. Byars and colleagues noted several limitations to their study including its cross-sectional, single-center design, potential participant selection bias, reliance on parent reports of child sleep, and use of a novel, nonvalidated survey instrument.

The researchers received funding from the Boomer Esiason Foundation for their study and disclosed no financial conflicts of interest. Dr. Artinian had no relevant disclosures.
 

SOURCE: Byars K et al. J Cyst Fibros. 2020 May. doi: 10.1016/j.jcf.2020.04.003.

This supplement to Neurology Reviews summarizes summarize findings from English-only, peer-reviewed original articles and meta-analyses of specified cannabinoids’ effect on cognition in preclinical and clinical literature, where known, to guide practitioners with proper evidence and highlighting gaps in knowledge for future research.

Click here to read the supplement. 

Authors

Francesca Filbey, PhD
Bert Moore Chair and Professor
of Cognition and Neuroscience
The University of Texas at Dallas

Chris Hauser, PhD
Medical Science Liaison
Greenwich Biosciences, Inc.

Karthik Rajasekaran, PhD
Sr. Medical Science Liaison
Greenwich Biosciences, Inc.

1. Mead A. Front Plant Sci. 2019;10:697.

This supplement to Neurology Reviews summarizes summarize findings from English-only, peer-reviewed original articles and meta-analyses of specified cannabinoids’ effect on cognition in preclinical and clinical literature, where known, to guide practitioners with proper evidence and highlighting gaps in knowledge for future research.

Click here to read the supplement. 

Authors

Francesca Filbey, PhD
Bert Moore Chair and Professor
of Cognition and Neuroscience
The University of Texas at Dallas

Chris Hauser, PhD
Medical Science Liaison
Greenwich Biosciences, Inc.

Karthik Rajasekaran, PhD
Sr. Medical Science Liaison
Greenwich Biosciences, Inc.

1. Mead A. Front Plant Sci. 2019;10:697.

This supplement to Neurology Reviews summarizes summarize findings from English-only, peer-reviewed original articles and meta-analyses of specified cannabinoids’ effect on cognition in preclinical and clinical literature, where known, to guide practitioners with proper evidence and highlighting gaps in knowledge for future research.

Click here to read the supplement. 

Authors

Francesca Filbey, PhD
Bert Moore Chair and Professor
of Cognition and Neuroscience
The University of Texas at Dallas

Chris Hauser, PhD
Medical Science Liaison
Greenwich Biosciences, Inc.

Karthik Rajasekaran, PhD
Sr. Medical Science Liaison
Greenwich Biosciences, Inc.

1. Mead A. Front Plant Sci. 2019;10:697.

Federal health officials are encouraging clinicians to use the free CURE ID mobile app and web platform as a tool to collect cases on the treatment of patients with COVID-19, in conjunction with ongoing clinical trial efforts.

“By utilizing the CURE ID platform now for COVID-19 case collection – in conjunction with data gathered from other registries, EHR systems, and clinical trials – data collected during an outbreak can be improved and coordinated,” Heather A. Stone, MPH, said during a June 9 webinar sponsored by the Food and Drug Administration. “This may allow us to find possible treatments to help ease this pandemic, and prepare us better to fight the next one.”

During the hour-long webinar, Ms. Stone, a health science policy analyst in the office of medical policy at the FDA’s Center for Drug Evaluation and Research, demonstrated CURE ID, an Internet-based data repository first developed in 2013 as a collaboration between the FDA and the National Center for Advancing Translational Sciences, a part of the National Institutes of Health (NCATS/NIH). It provides licensed clinicians worldwide with an opportunity to report novel uses of existing drugs for patients with difficult-to-treat infectious diseases, including COVID-19, through a website, a smartphone, or other mobile device. The app can be downloaded for free at http://cure.ncats.io. It can also be downloaded from the Apple app store or the Google Play store by searching “CURE ID.”

According to Ms. Stone, the platform’s three main goals are to enhance the understanding of new uses of approved medical products, to facilitate clinical trials and drug development, and to serve as a resource for physicians to share information where no FDA-approved product (which has been proven to be safe and effective) exists for the new use. CURE ID enables users to report their own cases as well as read cases of neglected infectious diseases with no sufficient approved therapies from other clinicians around the world. “It also enables clinicians to engage directly with communities of disease experts around the world, breaking down geographic and specialty silos,” Ms. Stone said. “It also enables them to access information on approved therapies for each disease and as well on active clinical trials.”

To date, CURE-ID contains information on 325 infectious diseases, including 1,580 case reports and 18,907 clinical trials. Initial pilot priority diseases include COVID-19, mycetoma, atypical mycobacteria, drug-resistant gonorrhea, rare and resistant fungal infections, as well as multidrug resistant gram-negative bacteria.

As of June 9, COVID-19-related data on the platform includes 151 case reports that have been extracted from the published literature or entered by clinician users, 80 discussion posts, and links to 694 clinical trials, 303 journal articles, 212 news articles, and 34 events. A total of 65 repurposed drugs have been identified as potential treatments for the virus, including 15 drugs with 10 or more cases.

“This facilitates clinicians reporting their real-world experiences treating COVID-19 patients, when patients are unable to be enrolled in a clinical trial,” Ms. Stone said. “It includes an updated case report form tailored to COVID-19 and data fields that have been harmonized with other real-world data and clinical trial platforms.” She pointed out that voluntary submission of cases to CURE ID is not a substitute for filing information with regulatory and public health authorities, where required. The platform also enables data to be entered and adverse events to be automatically shared with the FDA’s MedWatch Adverse Reporting System.

Ms. Stone concluded the webinar by announcing the formation of a new private-public partnership between the Critical Path Institute and the FDA and NCATS/NIH known as the CURE Drug Repurposing Collaboratory. The effort will begin with a pilot project focused on furthering drug development for COVID-19 through use of the CURE ID platform. “The Collaboratory will demonstrate how data shared from clinicians in real-time can be used to inform ongoing and future clinical trials, and potentially drug labeling,” Ms. Stone said. She reported having no financial disclosures.

dbrunk@mdedge.com

Federal health officials are encouraging clinicians to use the free CURE ID mobile app and web platform as a tool to collect cases on the treatment of patients with COVID-19, in conjunction with ongoing clinical trial efforts.

“By utilizing the CURE ID platform now for COVID-19 case collection – in conjunction with data gathered from other registries, EHR systems, and clinical trials – data collected during an outbreak can be improved and coordinated,” Heather A. Stone, MPH, said during a June 9 webinar sponsored by the Food and Drug Administration. “This may allow us to find possible treatments to help ease this pandemic, and prepare us better to fight the next one.”

During the hour-long webinar, Ms. Stone, a health science policy analyst in the office of medical policy at the FDA’s Center for Drug Evaluation and Research, demonstrated CURE ID, an Internet-based data repository first developed in 2013 as a collaboration between the FDA and the National Center for Advancing Translational Sciences, a part of the National Institutes of Health (NCATS/NIH). It provides licensed clinicians worldwide with an opportunity to report novel uses of existing drugs for patients with difficult-to-treat infectious diseases, including COVID-19, through a website, a smartphone, or other mobile device. The app can be downloaded for free at http://cure.ncats.io. It can also be downloaded from the Apple app store or the Google Play store by searching “CURE ID.”

According to Ms. Stone, the platform’s three main goals are to enhance the understanding of new uses of approved medical products, to facilitate clinical trials and drug development, and to serve as a resource for physicians to share information where no FDA-approved product (which has been proven to be safe and effective) exists for the new use. CURE ID enables users to report their own cases as well as read cases of neglected infectious diseases with no sufficient approved therapies from other clinicians around the world. “It also enables clinicians to engage directly with communities of disease experts around the world, breaking down geographic and specialty silos,” Ms. Stone said. “It also enables them to access information on approved therapies for each disease and as well on active clinical trials.”

To date, CURE-ID contains information on 325 infectious diseases, including 1,580 case reports and 18,907 clinical trials. Initial pilot priority diseases include COVID-19, mycetoma, atypical mycobacteria, drug-resistant gonorrhea, rare and resistant fungal infections, as well as multidrug resistant gram-negative bacteria.

As of June 9, COVID-19-related data on the platform includes 151 case reports that have been extracted from the published literature or entered by clinician users, 80 discussion posts, and links to 694 clinical trials, 303 journal articles, 212 news articles, and 34 events. A total of 65 repurposed drugs have been identified as potential treatments for the virus, including 15 drugs with 10 or more cases.

“This facilitates clinicians reporting their real-world experiences treating COVID-19 patients, when patients are unable to be enrolled in a clinical trial,” Ms. Stone said. “It includes an updated case report form tailored to COVID-19 and data fields that have been harmonized with other real-world data and clinical trial platforms.” She pointed out that voluntary submission of cases to CURE ID is not a substitute for filing information with regulatory and public health authorities, where required. The platform also enables data to be entered and adverse events to be automatically shared with the FDA’s MedWatch Adverse Reporting System.

Ms. Stone concluded the webinar by announcing the formation of a new private-public partnership between the Critical Path Institute and the FDA and NCATS/NIH known as the CURE Drug Repurposing Collaboratory. The effort will begin with a pilot project focused on furthering drug development for COVID-19 through use of the CURE ID platform. “The Collaboratory will demonstrate how data shared from clinicians in real-time can be used to inform ongoing and future clinical trials, and potentially drug labeling,” Ms. Stone said. She reported having no financial disclosures.

dbrunk@mdedge.com

Federal health officials are encouraging clinicians to use the free CURE ID mobile app and web platform as a tool to collect cases on the treatment of patients with COVID-19, in conjunction with ongoing clinical trial efforts.

“By utilizing the CURE ID platform now for COVID-19 case collection – in conjunction with data gathered from other registries, EHR systems, and clinical trials – data collected during an outbreak can be improved and coordinated,” Heather A. Stone, MPH, said during a June 9 webinar sponsored by the Food and Drug Administration. “This may allow us to find possible treatments to help ease this pandemic, and prepare us better to fight the next one.”

During the hour-long webinar, Ms. Stone, a health science policy analyst in the office of medical policy at the FDA’s Center for Drug Evaluation and Research, demonstrated CURE ID, an Internet-based data repository first developed in 2013 as a collaboration between the FDA and the National Center for Advancing Translational Sciences, a part of the National Institutes of Health (NCATS/NIH). It provides licensed clinicians worldwide with an opportunity to report novel uses of existing drugs for patients with difficult-to-treat infectious diseases, including COVID-19, through a website, a smartphone, or other mobile device. The app can be downloaded for free at http://cure.ncats.io. It can also be downloaded from the Apple app store or the Google Play store by searching “CURE ID.”

According to Ms. Stone, the platform’s three main goals are to enhance the understanding of new uses of approved medical products, to facilitate clinical trials and drug development, and to serve as a resource for physicians to share information where no FDA-approved product (which has been proven to be safe and effective) exists for the new use. CURE ID enables users to report their own cases as well as read cases of neglected infectious diseases with no sufficient approved therapies from other clinicians around the world. “It also enables clinicians to engage directly with communities of disease experts around the world, breaking down geographic and specialty silos,” Ms. Stone said. “It also enables them to access information on approved therapies for each disease and as well on active clinical trials.”

To date, CURE-ID contains information on 325 infectious diseases, including 1,580 case reports and 18,907 clinical trials. Initial pilot priority diseases include COVID-19, mycetoma, atypical mycobacteria, drug-resistant gonorrhea, rare and resistant fungal infections, as well as multidrug resistant gram-negative bacteria.

As of June 9, COVID-19-related data on the platform includes 151 case reports that have been extracted from the published literature or entered by clinician users, 80 discussion posts, and links to 694 clinical trials, 303 journal articles, 212 news articles, and 34 events. A total of 65 repurposed drugs have been identified as potential treatments for the virus, including 15 drugs with 10 or more cases.

“This facilitates clinicians reporting their real-world experiences treating COVID-19 patients, when patients are unable to be enrolled in a clinical trial,” Ms. Stone said. “It includes an updated case report form tailored to COVID-19 and data fields that have been harmonized with other real-world data and clinical trial platforms.” She pointed out that voluntary submission of cases to CURE ID is not a substitute for filing information with regulatory and public health authorities, where required. The platform also enables data to be entered and adverse events to be automatically shared with the FDA’s MedWatch Adverse Reporting System.

Ms. Stone concluded the webinar by announcing the formation of a new private-public partnership between the Critical Path Institute and the FDA and NCATS/NIH known as the CURE Drug Repurposing Collaboratory. The effort will begin with a pilot project focused on furthering drug development for COVID-19 through use of the CURE ID platform. “The Collaboratory will demonstrate how data shared from clinicians in real-time can be used to inform ongoing and future clinical trials, and potentially drug labeling,” Ms. Stone said. She reported having no financial disclosures.

dbrunk@mdedge.com

The Food and Drug Administration has approved nivolumab (Opdivo) for use in certain patients with esophageal squamous cell carcinoma (ESCC).

The checkpoint inhibitor is now approved to treat patients with unresectable advanced, recurrent, or metastatic ESCC who previously received fluoropyrimidine- and platinum-based chemotherapy.

Researchers tested nivolumab in this population in the ATTRACTION-3 trial (NCT02569242). The trial enrolled 419 patients.

The patients were randomized to receive nivolumab at 240 mg via intravenous infusion over 30 minutes every 2 weeks (n = 210) or investigator’s choice of taxane chemotherapy (n = 209), which consisted of docetaxel (75 mg/m² intravenously every 3 weeks) or paclitaxel (100 mg/m² intravenously once a week for 6 weeks followed by 1 week off).

Nivolumab significantly improved overall survival but not progression-free survival. The median progression-free survival was 1.7 months in the nivolumab arm and 3.4 months in the chemotherapy arm (hazard ratio, 1.1).

The median overall survival was 10.9 months in the nivolumab arm and 8.4 months in the chemotherapy arm (hazard ratio, 0.77; P = .0189). The overall survival benefit was observed regardless of tumor programmed death–ligand 1 expression.

Response rates were similar between the treatment arms, but responses were more durable with nivolumab. The overall responses rate was 19.3% in the nivolumab arm and 21.5% in the chemotherapy arm. The median duration of response was 6.9 months and 3.9 months, respectively.

Serious adverse events were reported in 38% of patients in the nivolumab arm. Serious adverse events occurring in at least 2% of patients were pneumonia, esophageal fistula, interstitial lung disease, and pyrexia.

Adverse events prompted 13% of patients to discontinue nivolumab and 27% to delay nivolumab treatment.

Fatal adverse events in patients on nivolumab included interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%).

The recommended dose of nivolumab for ESCC is 240 mg every 2 weeks or 480 mg every 4 weeks. For more details, see the full prescribing information.

jensmith@mdedge.com

The Food and Drug Administration has approved nivolumab (Opdivo) for use in certain patients with esophageal squamous cell carcinoma (ESCC).

The checkpoint inhibitor is now approved to treat patients with unresectable advanced, recurrent, or metastatic ESCC who previously received fluoropyrimidine- and platinum-based chemotherapy.

Researchers tested nivolumab in this population in the ATTRACTION-3 trial (NCT02569242). The trial enrolled 419 patients.

The patients were randomized to receive nivolumab at 240 mg via intravenous infusion over 30 minutes every 2 weeks (n = 210) or investigator’s choice of taxane chemotherapy (n = 209), which consisted of docetaxel (75 mg/m² intravenously every 3 weeks) or paclitaxel (100 mg/m² intravenously once a week for 6 weeks followed by 1 week off).

Nivolumab significantly improved overall survival but not progression-free survival. The median progression-free survival was 1.7 months in the nivolumab arm and 3.4 months in the chemotherapy arm (hazard ratio, 1.1).

The median overall survival was 10.9 months in the nivolumab arm and 8.4 months in the chemotherapy arm (hazard ratio, 0.77; P = .0189). The overall survival benefit was observed regardless of tumor programmed death–ligand 1 expression.

Response rates were similar between the treatment arms, but responses were more durable with nivolumab. The overall responses rate was 19.3% in the nivolumab arm and 21.5% in the chemotherapy arm. The median duration of response was 6.9 months and 3.9 months, respectively.

Serious adverse events were reported in 38% of patients in the nivolumab arm. Serious adverse events occurring in at least 2% of patients were pneumonia, esophageal fistula, interstitial lung disease, and pyrexia.

Adverse events prompted 13% of patients to discontinue nivolumab and 27% to delay nivolumab treatment.

Fatal adverse events in patients on nivolumab included interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%).

The recommended dose of nivolumab for ESCC is 240 mg every 2 weeks or 480 mg every 4 weeks. For more details, see the full prescribing information.

jensmith@mdedge.com

The Food and Drug Administration has approved nivolumab (Opdivo) for use in certain patients with esophageal squamous cell carcinoma (ESCC).

The checkpoint inhibitor is now approved to treat patients with unresectable advanced, recurrent, or metastatic ESCC who previously received fluoropyrimidine- and platinum-based chemotherapy.

Researchers tested nivolumab in this population in the ATTRACTION-3 trial (NCT02569242). The trial enrolled 419 patients.

The patients were randomized to receive nivolumab at 240 mg via intravenous infusion over 30 minutes every 2 weeks (n = 210) or investigator’s choice of taxane chemotherapy (n = 209), which consisted of docetaxel (75 mg/m² intravenously every 3 weeks) or paclitaxel (100 mg/m² intravenously once a week for 6 weeks followed by 1 week off).

Nivolumab significantly improved overall survival but not progression-free survival. The median progression-free survival was 1.7 months in the nivolumab arm and 3.4 months in the chemotherapy arm (hazard ratio, 1.1).

The median overall survival was 10.9 months in the nivolumab arm and 8.4 months in the chemotherapy arm (hazard ratio, 0.77; P = .0189). The overall survival benefit was observed regardless of tumor programmed death–ligand 1 expression.

Response rates were similar between the treatment arms, but responses were more durable with nivolumab. The overall responses rate was 19.3% in the nivolumab arm and 21.5% in the chemotherapy arm. The median duration of response was 6.9 months and 3.9 months, respectively.

Serious adverse events were reported in 38% of patients in the nivolumab arm. Serious adverse events occurring in at least 2% of patients were pneumonia, esophageal fistula, interstitial lung disease, and pyrexia.

Adverse events prompted 13% of patients to discontinue nivolumab and 27% to delay nivolumab treatment.

Fatal adverse events in patients on nivolumab included interstitial lung disease or pneumonitis (1.4%), pneumonia (1.0%), septic shock (0.5%), esophageal fistula (0.5%), gastrointestinal hemorrhage (0.5%), pulmonary embolism (0.5%), and sudden death (0.5%).

The recommended dose of nivolumab for ESCC is 240 mg every 2 weeks or 480 mg every 4 weeks. For more details, see the full prescribing information.

jensmith@mdedge.com

Grandma Exie used to tell a story about her grandmother on her father’s side, who lived in northeastern Arkansas. Towards the end of the Civil War, Northern and Southern troops were expected to “live off the land,” and both sides had torn through her poor dirt farm and carried off all the livestock and crops. The only thing they didn’t take was her bull mastiff, who was a pretty fair hunting and guard dog. Starving, she had no other option than to pack up and head east for Tennessee, where her husband was stationed with Joseph Hooker’s army. Many thousands of destitute women and children, most of whom were related to one of the troops, followed the army, where some of the army’s rations could be shared with them.

She headed out on foot and all went well until day 3 or so, when a panther attacked them, but she, armed with a branch, and her loyal dog were able to drive it off. The panther followed them for 3 days while she hid in a tree at night with her dog at the foot of a tree. Eventually, the panther gave up and she made it to Tennessee to safety.

Grandma Exie said her grandmother had “grit” and used this story whenever any of us would complain about how hard times were or how we were mistreated.

It is time for all of us to buck up and show a little grit in the face of a viral pandemic and social unrest. The answers are not easy or clear, but our health care system and our nation have faced much greater challenges. The 1918 flu pandemic was much more devastating, killing millions worldwide, and recall, 620,000 died in the Civil War, more than all other American wars combined. There is a deep seam of grit and resilience in Americans. We don’t always get it right immediately, but we usually do in the end.

The protests are justifiable outrage over police brutality, fueled by a high unemployment rate, both of which are a cause for frustration. The looting and destruction appears to be opportunistic thievery and some organized vandalization in my opinion. Most of the damage caused by riots and looting is not covered by insurance, and this will be a death blow to many small businesses already facing major financial setbacks as customers have stayed home for months and laying off staff has become necessary.

As for the impact on our practices, most physicians have been lucky and not been looted or burned out. Most of us have resumed practice, at least in a limited fashion, wearing masks; keeping the waiting room mostly empty; using social distancing and hand, air, and surface disinfection. In most of the country, the disease incidence has become lower, and the risk of not seeing the doctor is now greater than catching COVID-19.

So show grit, be careful, be vigilant, and practice your profession. Support your local small businesses, particularly if they have been the victims of senseless violence. We will work our way through these times.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. He had no disclosures related to this column. Write to him at dermnews@mdedge.com.

Grandma Exie used to tell a story about her grandmother on her father’s side, who lived in northeastern Arkansas. Towards the end of the Civil War, Northern and Southern troops were expected to “live off the land,” and both sides had torn through her poor dirt farm and carried off all the livestock and crops. The only thing they didn’t take was her bull mastiff, who was a pretty fair hunting and guard dog. Starving, she had no other option than to pack up and head east for Tennessee, where her husband was stationed with Joseph Hooker’s army. Many thousands of destitute women and children, most of whom were related to one of the troops, followed the army, where some of the army’s rations could be shared with them.

She headed out on foot and all went well until day 3 or so, when a panther attacked them, but she, armed with a branch, and her loyal dog were able to drive it off. The panther followed them for 3 days while she hid in a tree at night with her dog at the foot of a tree. Eventually, the panther gave up and she made it to Tennessee to safety.

Grandma Exie said her grandmother had “grit” and used this story whenever any of us would complain about how hard times were or how we were mistreated.

It is time for all of us to buck up and show a little grit in the face of a viral pandemic and social unrest. The answers are not easy or clear, but our health care system and our nation have faced much greater challenges. The 1918 flu pandemic was much more devastating, killing millions worldwide, and recall, 620,000 died in the Civil War, more than all other American wars combined. There is a deep seam of grit and resilience in Americans. We don’t always get it right immediately, but we usually do in the end.

The protests are justifiable outrage over police brutality, fueled by a high unemployment rate, both of which are a cause for frustration. The looting and destruction appears to be opportunistic thievery and some organized vandalization in my opinion. Most of the damage caused by riots and looting is not covered by insurance, and this will be a death blow to many small businesses already facing major financial setbacks as customers have stayed home for months and laying off staff has become necessary.

As for the impact on our practices, most physicians have been lucky and not been looted or burned out. Most of us have resumed practice, at least in a limited fashion, wearing masks; keeping the waiting room mostly empty; using social distancing and hand, air, and surface disinfection. In most of the country, the disease incidence has become lower, and the risk of not seeing the doctor is now greater than catching COVID-19.

So show grit, be careful, be vigilant, and practice your profession. Support your local small businesses, particularly if they have been the victims of senseless violence. We will work our way through these times.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. He had no disclosures related to this column. Write to him at dermnews@mdedge.com.

Grandma Exie used to tell a story about her grandmother on her father’s side, who lived in northeastern Arkansas. Towards the end of the Civil War, Northern and Southern troops were expected to “live off the land,” and both sides had torn through her poor dirt farm and carried off all the livestock and crops. The only thing they didn’t take was her bull mastiff, who was a pretty fair hunting and guard dog. Starving, she had no other option than to pack up and head east for Tennessee, where her husband was stationed with Joseph Hooker’s army. Many thousands of destitute women and children, most of whom were related to one of the troops, followed the army, where some of the army’s rations could be shared with them.

She headed out on foot and all went well until day 3 or so, when a panther attacked them, but she, armed with a branch, and her loyal dog were able to drive it off. The panther followed them for 3 days while she hid in a tree at night with her dog at the foot of a tree. Eventually, the panther gave up and she made it to Tennessee to safety.

Grandma Exie said her grandmother had “grit” and used this story whenever any of us would complain about how hard times were or how we were mistreated.

It is time for all of us to buck up and show a little grit in the face of a viral pandemic and social unrest. The answers are not easy or clear, but our health care system and our nation have faced much greater challenges. The 1918 flu pandemic was much more devastating, killing millions worldwide, and recall, 620,000 died in the Civil War, more than all other American wars combined. There is a deep seam of grit and resilience in Americans. We don’t always get it right immediately, but we usually do in the end.

The protests are justifiable outrage over police brutality, fueled by a high unemployment rate, both of which are a cause for frustration. The looting and destruction appears to be opportunistic thievery and some organized vandalization in my opinion. Most of the damage caused by riots and looting is not covered by insurance, and this will be a death blow to many small businesses already facing major financial setbacks as customers have stayed home for months and laying off staff has become necessary.

As for the impact on our practices, most physicians have been lucky and not been looted or burned out. Most of us have resumed practice, at least in a limited fashion, wearing masks; keeping the waiting room mostly empty; using social distancing and hand, air, and surface disinfection. In most of the country, the disease incidence has become lower, and the risk of not seeing the doctor is now greater than catching COVID-19.

So show grit, be careful, be vigilant, and practice your profession. Support your local small businesses, particularly if they have been the victims of senseless violence. We will work our way through these times.

Dr. Coldiron is in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. He is a past president of the American Academy of Dermatology. He had no disclosures related to this column. Write to him at dermnews@mdedge.com.