Journal of Clinical Outcomes Management

Repeat bone mineral density testing did not improve fracture-risk prediction in a large prospective cohort of postmenopausal women beyond baseline BMD measurement alone, according to new 12-year follow-up data.

Thinkstock

On the basis of the findings, published online in JAMA Internal Medicine, the authors recommend against routine repeat testing in postmenopausal women. Other experts, however, caution that the results may not be so broadly generalizable.

For the investigation, Carolyn J. Crandall, MD, of the division of general internal medicine and health services research at the University of California, Los Angeles, and colleagues analyzed data from 7,419 women enrolled in the prospective Women’s Health Initiative study and who underwent baseline and repeat dual-energy x-ray absorptiometry (DXA) between 1993 and 2010. The researchers excluded patients who reported using bisphosphonates, calcitonin, or selective estrogen-receptor modulators, those with a history of major osteoporotic fracture, or those who lacked follow-up visits. The mean body mass index (BMI) of the study population was 28.7 kg/m², and the mean age was 66.1 years.

The mean follow-up after the repeat BMD test was 9.0 years, during which period 732 (9.9%) of the women experienced a major osteoporotic fracture, and 139 (1.9%) experienced hip fractures.

To determine whether repeat testing improved fracture risk discrimination, the researchers calculated area under the receiver operating characteristic curve (AUROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD.

With respect to any major osteoporotic fracture risk, the AUROC values for total hip BMD at baseline, change in total hip BMD at 3 years, and the combination of the two, respectively, were 0.61 (95% confidence interval, 0.59-0.63), 0.53 (95% CI, 0.51-0.55), and 0.61 (95% CI, 0.59-0.63). For hip fracture risk, the respective AUROC values were 0.71 (95% CI, 0.67-0.75), 0.61 (95% CI, 0.56-0.65), and 0.73 (95% CI, 0.69-0.77), the authors reported.

Similar results were observed for femoral neck and lumbar spine BMD measurements. The associations between BMD changes and fracture risk were consistent across age, race, ethnicity, BMI, and baseline BMD T-score subgroups.

Although baseline BMD and change in BMD were independently associated with incident fracture, the association was stronger for lower baseline BMD than the 3-year absolute change in BMD, the authors stated.

The findings, which are consistent with those of previous investigations that involved older adults, are notable because of the age range of the population, according to the authors. “To our knowledge, this is the first prospective study that addressed this issue in a study cohort that included younger postmenopausal U.S. women,” they wrote. “Forty-four percent of our study population was younger than 65 years.”

The authors wrote that, given the lack of benefit associated with repeat BMD testing, such tests should no longer be routinely performed. “Our findings further suggest that resources should be devoted to increasing the underuse of baseline BMD testing among women aged [between] 65 and 85 years, one-quarter of whom do not receive an initial BMD test.”

Loyola University

However, some experts are not comfortable with the broad recommendation to skip repeat testing in the general population. “This is a great study, and it gives important information. However, we know, even in the real world, that patients can lose BMD in this time frame and not really fracture. This does not mean that they will not fracture further down the road,” said Pauline Camacho, MD, director of Loyola University Medical Center’s Osteoporosis and Metabolic Bone Disease Center in Chicago,. “The value of doing BMD goes beyond predicting fracture risk. It also helps assess patient compliance and detect the presence of uncorrected secondary causes of osteoporosis that are limiting the response to therapy, including failure to absorb oral bisphosphonates, vitamin D deficiency, or hyperparathyroidism.”

In addition, patients for whom treatment is initiated would want to know whether it’s working. “Seeing the BMD response to therapy is helpful to both clinicians and patients,” Dr. Camacho said in an interview.

Another concern is the study population. “The study was designed to assess the clinical utility of repeating a screening BMD test in a population of low-risk women -- older postmenopausal women with remarkably good BMD on initial testing,” according to E. Michael Lewiecki, MD, vice president of the National Osteoporosis Foundation and director of the New Mexico Clinical Research and Osteoporosis Center in Albuquerque. “Not surprisingly, with what we know about the expected age-related rate of bone loss, there was only a modest decrease in BMD and little clinical utility in repeating DXA in 3 years. However, repeat testing is an important component in the care of many patients seen in clinical practice.”

UNM Health Sciences Center

There are numerous situations in clinical practice in which repeat BMD testing can enhance patient care and potentially improve outcomes, Dr. Lewiecki said in an interview. “Repeating BMD 1-2 years after starting osteoporosis therapy is a useful way to assess response and determine whether the patient is on a pathway to achieving an acceptable level of fracture risk with a strategy called treat to target.”

Additionally, patients starting high-dose glucocorticoids who are at high risk for rapid bone loss may benefit from undergoing baseline BMD testing and having a follow-up test 1 year later or even sooner, he said. Further, for early postmenopausal women, the rate of bone loss may be accelerated and may be faster than age-related bone loss later in life. For this reason, “close monitoring of BMD may be used to determine when a treatment threshold has been crossed and pharmacological therapy is indicated.”

The most important message from this study for clinicians and healthcare policymakers is not the relative value of the repeat BMD testing, Dr. Lewiecki stated. Rather, it is the call to action regarding the underuse of BMD testing. “There is a global crisis in the care of osteoporosis that is characterized by underdiagnosis and undertreatment of patients at risk for fracture. Many patients who could benefit from treatment to reduce fracture risk are not receiving it, resulting in disability and deaths from fractures that might have been prevented. We need more bone density testing in appropriately selected patients to identify high-risk patients and intervene to reduce fracture risk,” he said. “DXA is an inexpensive and highly versatile clinical tool with many applications in clinical practice. When used wisely, it can be extraordinarily useful to identify and monitor high-risk patients, with the goal of reducing the burden of osteoporotic fractures.”

The barriers to performing baseline BMD measurement in this population are poorly understood and not well researched, Dr. Crandall said in an interview. “I expect that they relate to the multiple competing demands on primary care physicians, who are, for example, trying to juggle hypertension, a sprained ankle, diabetes, and complex social situations simultaneously with identifying appropriate candidates for osteoporosis screening and considering numerous other screening guidelines.”

The Women’s Health Initiative is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The study authors reported relationships with multiple companies, including Amgen, Pfizer, Bayer, Mithra, Norton Rose Fulbright, TherapeuticsMD, AbbVie, Radius, and Allergan. Dr. Camacho reported relationships with Amgen and Shire. Dr. Lewiecki reported relationships with Amgen, Radius Health, Alexion, Samsung Bioepis, Sandoz, Mereo, and Bindex.

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

Repeat bone mineral density testing did not improve fracture-risk prediction in a large prospective cohort of postmenopausal women beyond baseline BMD measurement alone, according to new 12-year follow-up data.

Thinkstock

On the basis of the findings, published online in JAMA Internal Medicine, the authors recommend against routine repeat testing in postmenopausal women. Other experts, however, caution that the results may not be so broadly generalizable.

For the investigation, Carolyn J. Crandall, MD, of the division of general internal medicine and health services research at the University of California, Los Angeles, and colleagues analyzed data from 7,419 women enrolled in the prospective Women’s Health Initiative study and who underwent baseline and repeat dual-energy x-ray absorptiometry (DXA) between 1993 and 2010. The researchers excluded patients who reported using bisphosphonates, calcitonin, or selective estrogen-receptor modulators, those with a history of major osteoporotic fracture, or those who lacked follow-up visits. The mean body mass index (BMI) of the study population was 28.7 kg/m², and the mean age was 66.1 years.

The mean follow-up after the repeat BMD test was 9.0 years, during which period 732 (9.9%) of the women experienced a major osteoporotic fracture, and 139 (1.9%) experienced hip fractures.

To determine whether repeat testing improved fracture risk discrimination, the researchers calculated area under the receiver operating characteristic curve (AUROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD.

With respect to any major osteoporotic fracture risk, the AUROC values for total hip BMD at baseline, change in total hip BMD at 3 years, and the combination of the two, respectively, were 0.61 (95% confidence interval, 0.59-0.63), 0.53 (95% CI, 0.51-0.55), and 0.61 (95% CI, 0.59-0.63). For hip fracture risk, the respective AUROC values were 0.71 (95% CI, 0.67-0.75), 0.61 (95% CI, 0.56-0.65), and 0.73 (95% CI, 0.69-0.77), the authors reported.

Similar results were observed for femoral neck and lumbar spine BMD measurements. The associations between BMD changes and fracture risk were consistent across age, race, ethnicity, BMI, and baseline BMD T-score subgroups.

Although baseline BMD and change in BMD were independently associated with incident fracture, the association was stronger for lower baseline BMD than the 3-year absolute change in BMD, the authors stated.

The findings, which are consistent with those of previous investigations that involved older adults, are notable because of the age range of the population, according to the authors. “To our knowledge, this is the first prospective study that addressed this issue in a study cohort that included younger postmenopausal U.S. women,” they wrote. “Forty-four percent of our study population was younger than 65 years.”

The authors wrote that, given the lack of benefit associated with repeat BMD testing, such tests should no longer be routinely performed. “Our findings further suggest that resources should be devoted to increasing the underuse of baseline BMD testing among women aged [between] 65 and 85 years, one-quarter of whom do not receive an initial BMD test.”

Loyola University

However, some experts are not comfortable with the broad recommendation to skip repeat testing in the general population. “This is a great study, and it gives important information. However, we know, even in the real world, that patients can lose BMD in this time frame and not really fracture. This does not mean that they will not fracture further down the road,” said Pauline Camacho, MD, director of Loyola University Medical Center’s Osteoporosis and Metabolic Bone Disease Center in Chicago,. “The value of doing BMD goes beyond predicting fracture risk. It also helps assess patient compliance and detect the presence of uncorrected secondary causes of osteoporosis that are limiting the response to therapy, including failure to absorb oral bisphosphonates, vitamin D deficiency, or hyperparathyroidism.”

In addition, patients for whom treatment is initiated would want to know whether it’s working. “Seeing the BMD response to therapy is helpful to both clinicians and patients,” Dr. Camacho said in an interview.

Another concern is the study population. “The study was designed to assess the clinical utility of repeating a screening BMD test in a population of low-risk women -- older postmenopausal women with remarkably good BMD on initial testing,” according to E. Michael Lewiecki, MD, vice president of the National Osteoporosis Foundation and director of the New Mexico Clinical Research and Osteoporosis Center in Albuquerque. “Not surprisingly, with what we know about the expected age-related rate of bone loss, there was only a modest decrease in BMD and little clinical utility in repeating DXA in 3 years. However, repeat testing is an important component in the care of many patients seen in clinical practice.”

UNM Health Sciences Center

There are numerous situations in clinical practice in which repeat BMD testing can enhance patient care and potentially improve outcomes, Dr. Lewiecki said in an interview. “Repeating BMD 1-2 years after starting osteoporosis therapy is a useful way to assess response and determine whether the patient is on a pathway to achieving an acceptable level of fracture risk with a strategy called treat to target.”

Additionally, patients starting high-dose glucocorticoids who are at high risk for rapid bone loss may benefit from undergoing baseline BMD testing and having a follow-up test 1 year later or even sooner, he said. Further, for early postmenopausal women, the rate of bone loss may be accelerated and may be faster than age-related bone loss later in life. For this reason, “close monitoring of BMD may be used to determine when a treatment threshold has been crossed and pharmacological therapy is indicated.”

The most important message from this study for clinicians and healthcare policymakers is not the relative value of the repeat BMD testing, Dr. Lewiecki stated. Rather, it is the call to action regarding the underuse of BMD testing. “There is a global crisis in the care of osteoporosis that is characterized by underdiagnosis and undertreatment of patients at risk for fracture. Many patients who could benefit from treatment to reduce fracture risk are not receiving it, resulting in disability and deaths from fractures that might have been prevented. We need more bone density testing in appropriately selected patients to identify high-risk patients and intervene to reduce fracture risk,” he said. “DXA is an inexpensive and highly versatile clinical tool with many applications in clinical practice. When used wisely, it can be extraordinarily useful to identify and monitor high-risk patients, with the goal of reducing the burden of osteoporotic fractures.”

The barriers to performing baseline BMD measurement in this population are poorly understood and not well researched, Dr. Crandall said in an interview. “I expect that they relate to the multiple competing demands on primary care physicians, who are, for example, trying to juggle hypertension, a sprained ankle, diabetes, and complex social situations simultaneously with identifying appropriate candidates for osteoporosis screening and considering numerous other screening guidelines.”

The Women’s Health Initiative is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The study authors reported relationships with multiple companies, including Amgen, Pfizer, Bayer, Mithra, Norton Rose Fulbright, TherapeuticsMD, AbbVie, Radius, and Allergan. Dr. Camacho reported relationships with Amgen and Shire. Dr. Lewiecki reported relationships with Amgen, Radius Health, Alexion, Samsung Bioepis, Sandoz, Mereo, and Bindex.

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

Repeat bone mineral density testing did not improve fracture-risk prediction in a large prospective cohort of postmenopausal women beyond baseline BMD measurement alone, according to new 12-year follow-up data.

Thinkstock

On the basis of the findings, published online in JAMA Internal Medicine, the authors recommend against routine repeat testing in postmenopausal women. Other experts, however, caution that the results may not be so broadly generalizable.

For the investigation, Carolyn J. Crandall, MD, of the division of general internal medicine and health services research at the University of California, Los Angeles, and colleagues analyzed data from 7,419 women enrolled in the prospective Women’s Health Initiative study and who underwent baseline and repeat dual-energy x-ray absorptiometry (DXA) between 1993 and 2010. The researchers excluded patients who reported using bisphosphonates, calcitonin, or selective estrogen-receptor modulators, those with a history of major osteoporotic fracture, or those who lacked follow-up visits. The mean body mass index (BMI) of the study population was 28.7 kg/m², and the mean age was 66.1 years.

The mean follow-up after the repeat BMD test was 9.0 years, during which period 732 (9.9%) of the women experienced a major osteoporotic fracture, and 139 (1.9%) experienced hip fractures.

To determine whether repeat testing improved fracture risk discrimination, the researchers calculated area under the receiver operating characteristic curve (AUROC) for baseline BMD, absolute change in BMD, and the combination of baseline BMD and change in BMD.

With respect to any major osteoporotic fracture risk, the AUROC values for total hip BMD at baseline, change in total hip BMD at 3 years, and the combination of the two, respectively, were 0.61 (95% confidence interval, 0.59-0.63), 0.53 (95% CI, 0.51-0.55), and 0.61 (95% CI, 0.59-0.63). For hip fracture risk, the respective AUROC values were 0.71 (95% CI, 0.67-0.75), 0.61 (95% CI, 0.56-0.65), and 0.73 (95% CI, 0.69-0.77), the authors reported.

Similar results were observed for femoral neck and lumbar spine BMD measurements. The associations between BMD changes and fracture risk were consistent across age, race, ethnicity, BMI, and baseline BMD T-score subgroups.

Although baseline BMD and change in BMD were independently associated with incident fracture, the association was stronger for lower baseline BMD than the 3-year absolute change in BMD, the authors stated.

The findings, which are consistent with those of previous investigations that involved older adults, are notable because of the age range of the population, according to the authors. “To our knowledge, this is the first prospective study that addressed this issue in a study cohort that included younger postmenopausal U.S. women,” they wrote. “Forty-four percent of our study population was younger than 65 years.”

The authors wrote that, given the lack of benefit associated with repeat BMD testing, such tests should no longer be routinely performed. “Our findings further suggest that resources should be devoted to increasing the underuse of baseline BMD testing among women aged [between] 65 and 85 years, one-quarter of whom do not receive an initial BMD test.”

Loyola University

However, some experts are not comfortable with the broad recommendation to skip repeat testing in the general population. “This is a great study, and it gives important information. However, we know, even in the real world, that patients can lose BMD in this time frame and not really fracture. This does not mean that they will not fracture further down the road,” said Pauline Camacho, MD, director of Loyola University Medical Center’s Osteoporosis and Metabolic Bone Disease Center in Chicago,. “The value of doing BMD goes beyond predicting fracture risk. It also helps assess patient compliance and detect the presence of uncorrected secondary causes of osteoporosis that are limiting the response to therapy, including failure to absorb oral bisphosphonates, vitamin D deficiency, or hyperparathyroidism.”

In addition, patients for whom treatment is initiated would want to know whether it’s working. “Seeing the BMD response to therapy is helpful to both clinicians and patients,” Dr. Camacho said in an interview.

Another concern is the study population. “The study was designed to assess the clinical utility of repeating a screening BMD test in a population of low-risk women -- older postmenopausal women with remarkably good BMD on initial testing,” according to E. Michael Lewiecki, MD, vice president of the National Osteoporosis Foundation and director of the New Mexico Clinical Research and Osteoporosis Center in Albuquerque. “Not surprisingly, with what we know about the expected age-related rate of bone loss, there was only a modest decrease in BMD and little clinical utility in repeating DXA in 3 years. However, repeat testing is an important component in the care of many patients seen in clinical practice.”

UNM Health Sciences Center

There are numerous situations in clinical practice in which repeat BMD testing can enhance patient care and potentially improve outcomes, Dr. Lewiecki said in an interview. “Repeating BMD 1-2 years after starting osteoporosis therapy is a useful way to assess response and determine whether the patient is on a pathway to achieving an acceptable level of fracture risk with a strategy called treat to target.”

Additionally, patients starting high-dose glucocorticoids who are at high risk for rapid bone loss may benefit from undergoing baseline BMD testing and having a follow-up test 1 year later or even sooner, he said. Further, for early postmenopausal women, the rate of bone loss may be accelerated and may be faster than age-related bone loss later in life. For this reason, “close monitoring of BMD may be used to determine when a treatment threshold has been crossed and pharmacological therapy is indicated.”

The most important message from this study for clinicians and healthcare policymakers is not the relative value of the repeat BMD testing, Dr. Lewiecki stated. Rather, it is the call to action regarding the underuse of BMD testing. “There is a global crisis in the care of osteoporosis that is characterized by underdiagnosis and undertreatment of patients at risk for fracture. Many patients who could benefit from treatment to reduce fracture risk are not receiving it, resulting in disability and deaths from fractures that might have been prevented. We need more bone density testing in appropriately selected patients to identify high-risk patients and intervene to reduce fracture risk,” he said. “DXA is an inexpensive and highly versatile clinical tool with many applications in clinical practice. When used wisely, it can be extraordinarily useful to identify and monitor high-risk patients, with the goal of reducing the burden of osteoporotic fractures.”

The barriers to performing baseline BMD measurement in this population are poorly understood and not well researched, Dr. Crandall said in an interview. “I expect that they relate to the multiple competing demands on primary care physicians, who are, for example, trying to juggle hypertension, a sprained ankle, diabetes, and complex social situations simultaneously with identifying appropriate candidates for osteoporosis screening and considering numerous other screening guidelines.”

The Women’s Health Initiative is funded by the National Heart, Lung, and Blood Institute; National Institutes of Health; and the Department of Health & Human Services. The study authors reported relationships with multiple companies, including Amgen, Pfizer, Bayer, Mithra, Norton Rose Fulbright, TherapeuticsMD, AbbVie, Radius, and Allergan. Dr. Camacho reported relationships with Amgen and Shire. Dr. Lewiecki reported relationships with Amgen, Radius Health, Alexion, Samsung Bioepis, Sandoz, Mereo, and Bindex.

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

Topical agents, alternative medicine, and disease severity assessment are the subjects of the latest updated set of guidelines for the management and treatment of psoriasis issued jointly by the American Academy of Dermatology and the National Psoriasis Foundation.

©Rodd100/thinkstockphotos.com

The guidelines, published in the Journal of the American Academy of Dermatology, focus on treatment for adults, and follow the release of other AAD-NPF guidelines on biologics for psoriasis, psoriasis-related comorbidities, pediatric psoriasis, and phototherapy in 2019, and earlier this year, guidelines for systemic nonbiologic treatments. The latest guidelines’ section on topical treatment outlines evidence for the efficacy, effectiveness, and adverse events related to topical steroids, topical tacrolimus and pimecrolimus, vitamin D analogues, tazarotene, moisturizers, salicylic acid, anthralin, coal tar, combinations with biologic agents, and combinations with nonbiologic treatments (methotrexate, cyclosporine, acitretin, and apremilast).

The guidelines noted the “key role” of topical corticosteroids in treating psoriasis “especially for localized disease,” and include a review of the data on low-, moderate-, high-, and ultrahigh-potency topical steroids for psoriasis.

In general, all topical steroids can be used in combination with biologics, according to the guidelines, but the strongest recommendations based on the latest evidence include the addition of an ultra-high potency topical corticosteroid to standard dose etanercept for 12 weeks. Currently, 11 biologics are approved by the Food and Drug Administration for the treatment of psoriasis.

In addition, “while not FDA approved for psoriasis, the topical calcineurin inhibitors tacrolimus and pimecrolimus are often employed in the treatment of psoriasis,” can be helpful for “thinner skin such as facial and intertriginous areas,” and can be steroid sparing when used for more than 4 weeks, according to the guidelines.

Don’t discount the role of patient preferences when choosing topical treatments, the authors noted. “The optimal vehicle choice is the one the patient is mostly likely to use.”

The guidelines also address the evidence for effectiveness, and adverse events in the use of several alternative medicines for psoriasis including traditional Chinese medicine, and the herbal therapies aloe vera and St. John’s wort, as well as the potential role of dietary supplements including fish oil, vitamin D, turmeric, and zinc in managing psoriasis, and the potential role of a gluten-free diet.

In general, research on the efficacy, effectiveness, and potential adverse effects of these strategies are limited, according to the guidelines, although many patients express interest in supplements and herbal products. For example, “Many patients ask about the overall role of vitamin D in skin health. Rather than adding oral vitamin D supplementation, topical therapy with vitamin D agents is effective for the treatment of psoriasis,” the authors noted.

In addition, they noted that mind/body strategies, namely hypnosis and stress reduction or meditation techniques, have been shown to improve symptoms and can be helpful for some patients, but clinical evidence is limited.

The guidelines also addressed methods for assessing disease severity in psoriasis. They recommended using body surface area (BSA) to assess psoriasis severity and patient response to treatment in the clinical setting. However, BSA is a provider assessment tool that “does not take into account location on the body, clinical characteristics of the plaques, symptoms, or quality of life issues,” the authors noted. The Psoriasis Area and Severity Index (PASI) measures erythema, induration, and scaling and is more suited to assessing psoriasis severity and response to treatment in clinical trials rather than in practice, they said.

Prior AAD guidelines on psoriasis were published more than 10 years ago, and major developments including the availability of new biologic drugs and new data on comorbidities have been recognized in the past decade, working group cochair and author of the guidelines Alan Menter, MD, said in an interview.

The key game-changers from previous guidelines include the full section published on comorbidities plus the development of two new important cytokine classes: three IL-17 drugs and three new IL-23 drugs now available for moderate to severe psoriasis, said Dr. Menter, chairman of the division of dermatology at Baylor University Medical Center, Dallas.

Barriers to implementing the guidelines in practice may occur when “third party payers make the decision on which of the 11 biologic drugs now approved for moderate to severe psoriasis should be used,” he noted.

As for next steps in psoriasis studies, “new biomarker research is currently underway,” Dr. Menter said. With 11 biologic agents new formally approved by the FDA for moderate to severe psoriasis, the next steps are to determine which drug is likely to be the most appropriate for each individual patient.

Dr. Menter disclosed relationships with multiple companies that develop and manufacture psoriasis therapies, including Abbott Labs, AbbVie, Amgen, Eli Lilly and Company, Galderma USA, Janssen Pharmaceuticals, LEO Pharma US, Menlo Therapeutics, and Novartis. The updated guidelines were designed by a multidisciplinary work group of psoriasis experts including dermatologists, a rheumatologist, a cardiologist, and representatives from a patient advocacy organization.
 

SOURCE: Elmets CA et al. J Am Acad Dermatol. 2020 Jul 29. doi: 10.1016/j.jaad.2020.07.087.

Topical agents, alternative medicine, and disease severity assessment are the subjects of the latest updated set of guidelines for the management and treatment of psoriasis issued jointly by the American Academy of Dermatology and the National Psoriasis Foundation.

©Rodd100/thinkstockphotos.com

The guidelines, published in the Journal of the American Academy of Dermatology, focus on treatment for adults, and follow the release of other AAD-NPF guidelines on biologics for psoriasis, psoriasis-related comorbidities, pediatric psoriasis, and phototherapy in 2019, and earlier this year, guidelines for systemic nonbiologic treatments. The latest guidelines’ section on topical treatment outlines evidence for the efficacy, effectiveness, and adverse events related to topical steroids, topical tacrolimus and pimecrolimus, vitamin D analogues, tazarotene, moisturizers, salicylic acid, anthralin, coal tar, combinations with biologic agents, and combinations with nonbiologic treatments (methotrexate, cyclosporine, acitretin, and apremilast).

The guidelines noted the “key role” of topical corticosteroids in treating psoriasis “especially for localized disease,” and include a review of the data on low-, moderate-, high-, and ultrahigh-potency topical steroids for psoriasis.

In general, all topical steroids can be used in combination with biologics, according to the guidelines, but the strongest recommendations based on the latest evidence include the addition of an ultra-high potency topical corticosteroid to standard dose etanercept for 12 weeks. Currently, 11 biologics are approved by the Food and Drug Administration for the treatment of psoriasis.

In addition, “while not FDA approved for psoriasis, the topical calcineurin inhibitors tacrolimus and pimecrolimus are often employed in the treatment of psoriasis,” can be helpful for “thinner skin such as facial and intertriginous areas,” and can be steroid sparing when used for more than 4 weeks, according to the guidelines.

Don’t discount the role of patient preferences when choosing topical treatments, the authors noted. “The optimal vehicle choice is the one the patient is mostly likely to use.”

The guidelines also address the evidence for effectiveness, and adverse events in the use of several alternative medicines for psoriasis including traditional Chinese medicine, and the herbal therapies aloe vera and St. John’s wort, as well as the potential role of dietary supplements including fish oil, vitamin D, turmeric, and zinc in managing psoriasis, and the potential role of a gluten-free diet.

In general, research on the efficacy, effectiveness, and potential adverse effects of these strategies are limited, according to the guidelines, although many patients express interest in supplements and herbal products. For example, “Many patients ask about the overall role of vitamin D in skin health. Rather than adding oral vitamin D supplementation, topical therapy with vitamin D agents is effective for the treatment of psoriasis,” the authors noted.

In addition, they noted that mind/body strategies, namely hypnosis and stress reduction or meditation techniques, have been shown to improve symptoms and can be helpful for some patients, but clinical evidence is limited.

The guidelines also addressed methods for assessing disease severity in psoriasis. They recommended using body surface area (BSA) to assess psoriasis severity and patient response to treatment in the clinical setting. However, BSA is a provider assessment tool that “does not take into account location on the body, clinical characteristics of the plaques, symptoms, or quality of life issues,” the authors noted. The Psoriasis Area and Severity Index (PASI) measures erythema, induration, and scaling and is more suited to assessing psoriasis severity and response to treatment in clinical trials rather than in practice, they said.

Prior AAD guidelines on psoriasis were published more than 10 years ago, and major developments including the availability of new biologic drugs and new data on comorbidities have been recognized in the past decade, working group cochair and author of the guidelines Alan Menter, MD, said in an interview.

The key game-changers from previous guidelines include the full section published on comorbidities plus the development of two new important cytokine classes: three IL-17 drugs and three new IL-23 drugs now available for moderate to severe psoriasis, said Dr. Menter, chairman of the division of dermatology at Baylor University Medical Center, Dallas.

Barriers to implementing the guidelines in practice may occur when “third party payers make the decision on which of the 11 biologic drugs now approved for moderate to severe psoriasis should be used,” he noted.

As for next steps in psoriasis studies, “new biomarker research is currently underway,” Dr. Menter said. With 11 biologic agents new formally approved by the FDA for moderate to severe psoriasis, the next steps are to determine which drug is likely to be the most appropriate for each individual patient.

Dr. Menter disclosed relationships with multiple companies that develop and manufacture psoriasis therapies, including Abbott Labs, AbbVie, Amgen, Eli Lilly and Company, Galderma USA, Janssen Pharmaceuticals, LEO Pharma US, Menlo Therapeutics, and Novartis. The updated guidelines were designed by a multidisciplinary work group of psoriasis experts including dermatologists, a rheumatologist, a cardiologist, and representatives from a patient advocacy organization.
 

SOURCE: Elmets CA et al. J Am Acad Dermatol. 2020 Jul 29. doi: 10.1016/j.jaad.2020.07.087.

Topical agents, alternative medicine, and disease severity assessment are the subjects of the latest updated set of guidelines for the management and treatment of psoriasis issued jointly by the American Academy of Dermatology and the National Psoriasis Foundation.

©Rodd100/thinkstockphotos.com

The guidelines, published in the Journal of the American Academy of Dermatology, focus on treatment for adults, and follow the release of other AAD-NPF guidelines on biologics for psoriasis, psoriasis-related comorbidities, pediatric psoriasis, and phototherapy in 2019, and earlier this year, guidelines for systemic nonbiologic treatments. The latest guidelines’ section on topical treatment outlines evidence for the efficacy, effectiveness, and adverse events related to topical steroids, topical tacrolimus and pimecrolimus, vitamin D analogues, tazarotene, moisturizers, salicylic acid, anthralin, coal tar, combinations with biologic agents, and combinations with nonbiologic treatments (methotrexate, cyclosporine, acitretin, and apremilast).

The guidelines noted the “key role” of topical corticosteroids in treating psoriasis “especially for localized disease,” and include a review of the data on low-, moderate-, high-, and ultrahigh-potency topical steroids for psoriasis.

In general, all topical steroids can be used in combination with biologics, according to the guidelines, but the strongest recommendations based on the latest evidence include the addition of an ultra-high potency topical corticosteroid to standard dose etanercept for 12 weeks. Currently, 11 biologics are approved by the Food and Drug Administration for the treatment of psoriasis.

In addition, “while not FDA approved for psoriasis, the topical calcineurin inhibitors tacrolimus and pimecrolimus are often employed in the treatment of psoriasis,” can be helpful for “thinner skin such as facial and intertriginous areas,” and can be steroid sparing when used for more than 4 weeks, according to the guidelines.

Don’t discount the role of patient preferences when choosing topical treatments, the authors noted. “The optimal vehicle choice is the one the patient is mostly likely to use.”

The guidelines also address the evidence for effectiveness, and adverse events in the use of several alternative medicines for psoriasis including traditional Chinese medicine, and the herbal therapies aloe vera and St. John’s wort, as well as the potential role of dietary supplements including fish oil, vitamin D, turmeric, and zinc in managing psoriasis, and the potential role of a gluten-free diet.

In general, research on the efficacy, effectiveness, and potential adverse effects of these strategies are limited, according to the guidelines, although many patients express interest in supplements and herbal products. For example, “Many patients ask about the overall role of vitamin D in skin health. Rather than adding oral vitamin D supplementation, topical therapy with vitamin D agents is effective for the treatment of psoriasis,” the authors noted.

In addition, they noted that mind/body strategies, namely hypnosis and stress reduction or meditation techniques, have been shown to improve symptoms and can be helpful for some patients, but clinical evidence is limited.

The guidelines also addressed methods for assessing disease severity in psoriasis. They recommended using body surface area (BSA) to assess psoriasis severity and patient response to treatment in the clinical setting. However, BSA is a provider assessment tool that “does not take into account location on the body, clinical characteristics of the plaques, symptoms, or quality of life issues,” the authors noted. The Psoriasis Area and Severity Index (PASI) measures erythema, induration, and scaling and is more suited to assessing psoriasis severity and response to treatment in clinical trials rather than in practice, they said.

Prior AAD guidelines on psoriasis were published more than 10 years ago, and major developments including the availability of new biologic drugs and new data on comorbidities have been recognized in the past decade, working group cochair and author of the guidelines Alan Menter, MD, said in an interview.

The key game-changers from previous guidelines include the full section published on comorbidities plus the development of two new important cytokine classes: three IL-17 drugs and three new IL-23 drugs now available for moderate to severe psoriasis, said Dr. Menter, chairman of the division of dermatology at Baylor University Medical Center, Dallas.

Barriers to implementing the guidelines in practice may occur when “third party payers make the decision on which of the 11 biologic drugs now approved for moderate to severe psoriasis should be used,” he noted.

As for next steps in psoriasis studies, “new biomarker research is currently underway,” Dr. Menter said. With 11 biologic agents new formally approved by the FDA for moderate to severe psoriasis, the next steps are to determine which drug is likely to be the most appropriate for each individual patient.

Dr. Menter disclosed relationships with multiple companies that develop and manufacture psoriasis therapies, including Abbott Labs, AbbVie, Amgen, Eli Lilly and Company, Galderma USA, Janssen Pharmaceuticals, LEO Pharma US, Menlo Therapeutics, and Novartis. The updated guidelines were designed by a multidisciplinary work group of psoriasis experts including dermatologists, a rheumatologist, a cardiologist, and representatives from a patient advocacy organization.
 

SOURCE: Elmets CA et al. J Am Acad Dermatol. 2020 Jul 29. doi: 10.1016/j.jaad.2020.07.087.

The cannabidiol (CBD) oral solution Epidiolex has been approved by the Food and Drug Administration for the new indication of treatment of seizures associated with tuberous sclerosis complex in patients 1 year of age and older.

The drug was approved by the FDA in 2018 for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, as reported by Medscape Medical News.

This is the only FDA-approved drug that contains a purified drug substance derived from cannabis. It is also the second FDA approval of a drug for the treatment of seizures associated with tuberous sclerosis complex.

CBD is a chemical component of the cannabis sativa plant, but it does not cause intoxication or euphoria (the “high”) that comes from tetrahydrocannabinol (THC), which is the primary psychoactive component of cannabis.

“The FDA continues to believe the drug approval process represents the best way to make new medicines, including any drugs derived from cannabis, available to patients in need of appropriate medical therapy such as the treatment of seizures associated with these rare conditions,” Douglas Throckmorton, MD, deputy center director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, said in an agency press release.

“This paradigm ensures new therapies are safe, effective, and manufactured to a high quality that provides uniform and reliable dosing for patients,” Dr. Throckmorton said.

He added that the FDA is committed to supporting research on the potential medical uses of cannabis-derived products.
 

Rare genetic disease

Tuberous sclerosis complex is a rare genetic disease that causes benign tumors to grow in the brain and other parts of the body, such as the eyes, heart, kidneys, lungs, and skin.

It usually affects the central nervous system and can result in a combination of symptoms, including seizures, developmental delay, and behavioral problems. The signs and symptoms of the condition, as well as the severity of symptoms, vary widely. The disease affects about 1 in 6,000 individuals.

The effectiveness of Epidiolex in the treatment of seizures associated with tuberous sclerosis complex was established in a randomized, double-blind, placebo-controlled trial in which 148 patients of a total of 224 in the study received the active drug, the FDA noted.

Results showed that for patients treated with CBD, there was a significantly greater reduction in seizure frequency during the treatment period than for patients who received placebo.

This effect was seen within 8 weeks and remained consistent throughout the 16-week treatment period.

The most common side effects that occurred in CBD-treated participants were diarrhea, elevated liver enzyme levels, decreased appetite, sleepiness, fever, and vomiting. Additional side effects that have been reported with the product include liver injury, decreased weight, anemia, and increased creatinine level.

As is true for all drugs that currently treat epilepsy, including Epidiolex, the most serious risks may include an increase in suicidal thoughts and behavior or thoughts of self-harm, the FDA reports.

Patients, their caregivers, and their families should be advised to monitor for any unusual changes in mood or behavior, such as worsening depression or suicidal thoughts or behavior. They should report behaviors of concern immediately to health care providers, the agency notes.

It also points out that Epidiolex can cause liver injury, of which most cases are generally mild. However, there is a risk for rare but more severe liver injury. More severe liver injury can cause nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice, and/or dark urine.

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

The cannabidiol (CBD) oral solution Epidiolex has been approved by the Food and Drug Administration for the new indication of treatment of seizures associated with tuberous sclerosis complex in patients 1 year of age and older.

The drug was approved by the FDA in 2018 for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, as reported by Medscape Medical News.

This is the only FDA-approved drug that contains a purified drug substance derived from cannabis. It is also the second FDA approval of a drug for the treatment of seizures associated with tuberous sclerosis complex.

CBD is a chemical component of the cannabis sativa plant, but it does not cause intoxication or euphoria (the “high”) that comes from tetrahydrocannabinol (THC), which is the primary psychoactive component of cannabis.

“The FDA continues to believe the drug approval process represents the best way to make new medicines, including any drugs derived from cannabis, available to patients in need of appropriate medical therapy such as the treatment of seizures associated with these rare conditions,” Douglas Throckmorton, MD, deputy center director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, said in an agency press release.

“This paradigm ensures new therapies are safe, effective, and manufactured to a high quality that provides uniform and reliable dosing for patients,” Dr. Throckmorton said.

He added that the FDA is committed to supporting research on the potential medical uses of cannabis-derived products.
 

Rare genetic disease

Tuberous sclerosis complex is a rare genetic disease that causes benign tumors to grow in the brain and other parts of the body, such as the eyes, heart, kidneys, lungs, and skin.

It usually affects the central nervous system and can result in a combination of symptoms, including seizures, developmental delay, and behavioral problems. The signs and symptoms of the condition, as well as the severity of symptoms, vary widely. The disease affects about 1 in 6,000 individuals.

The effectiveness of Epidiolex in the treatment of seizures associated with tuberous sclerosis complex was established in a randomized, double-blind, placebo-controlled trial in which 148 patients of a total of 224 in the study received the active drug, the FDA noted.

Results showed that for patients treated with CBD, there was a significantly greater reduction in seizure frequency during the treatment period than for patients who received placebo.

This effect was seen within 8 weeks and remained consistent throughout the 16-week treatment period.

The most common side effects that occurred in CBD-treated participants were diarrhea, elevated liver enzyme levels, decreased appetite, sleepiness, fever, and vomiting. Additional side effects that have been reported with the product include liver injury, decreased weight, anemia, and increased creatinine level.

As is true for all drugs that currently treat epilepsy, including Epidiolex, the most serious risks may include an increase in suicidal thoughts and behavior or thoughts of self-harm, the FDA reports.

Patients, their caregivers, and their families should be advised to monitor for any unusual changes in mood or behavior, such as worsening depression or suicidal thoughts or behavior. They should report behaviors of concern immediately to health care providers, the agency notes.

It also points out that Epidiolex can cause liver injury, of which most cases are generally mild. However, there is a risk for rare but more severe liver injury. More severe liver injury can cause nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice, and/or dark urine.

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

The cannabidiol (CBD) oral solution Epidiolex has been approved by the Food and Drug Administration for the new indication of treatment of seizures associated with tuberous sclerosis complex in patients 1 year of age and older.

The drug was approved by the FDA in 2018 for the treatment of seizures associated with two rare and severe forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, as reported by Medscape Medical News.

This is the only FDA-approved drug that contains a purified drug substance derived from cannabis. It is also the second FDA approval of a drug for the treatment of seizures associated with tuberous sclerosis complex.

CBD is a chemical component of the cannabis sativa plant, but it does not cause intoxication or euphoria (the “high”) that comes from tetrahydrocannabinol (THC), which is the primary psychoactive component of cannabis.

“The FDA continues to believe the drug approval process represents the best way to make new medicines, including any drugs derived from cannabis, available to patients in need of appropriate medical therapy such as the treatment of seizures associated with these rare conditions,” Douglas Throckmorton, MD, deputy center director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, said in an agency press release.

“This paradigm ensures new therapies are safe, effective, and manufactured to a high quality that provides uniform and reliable dosing for patients,” Dr. Throckmorton said.

He added that the FDA is committed to supporting research on the potential medical uses of cannabis-derived products.
 

Rare genetic disease

Tuberous sclerosis complex is a rare genetic disease that causes benign tumors to grow in the brain and other parts of the body, such as the eyes, heart, kidneys, lungs, and skin.

It usually affects the central nervous system and can result in a combination of symptoms, including seizures, developmental delay, and behavioral problems. The signs and symptoms of the condition, as well as the severity of symptoms, vary widely. The disease affects about 1 in 6,000 individuals.

The effectiveness of Epidiolex in the treatment of seizures associated with tuberous sclerosis complex was established in a randomized, double-blind, placebo-controlled trial in which 148 patients of a total of 224 in the study received the active drug, the FDA noted.

Results showed that for patients treated with CBD, there was a significantly greater reduction in seizure frequency during the treatment period than for patients who received placebo.

This effect was seen within 8 weeks and remained consistent throughout the 16-week treatment period.

The most common side effects that occurred in CBD-treated participants were diarrhea, elevated liver enzyme levels, decreased appetite, sleepiness, fever, and vomiting. Additional side effects that have been reported with the product include liver injury, decreased weight, anemia, and increased creatinine level.

As is true for all drugs that currently treat epilepsy, including Epidiolex, the most serious risks may include an increase in suicidal thoughts and behavior or thoughts of self-harm, the FDA reports.

Patients, their caregivers, and their families should be advised to monitor for any unusual changes in mood or behavior, such as worsening depression or suicidal thoughts or behavior. They should report behaviors of concern immediately to health care providers, the agency notes.

It also points out that Epidiolex can cause liver injury, of which most cases are generally mild. However, there is a risk for rare but more severe liver injury. More severe liver injury can cause nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice, and/or dark urine.

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

A novel drug, tafasitamab-cxix (Monjuvi, MorphoSys US), has been approved by the Food and Drug Administration for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The product is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. It mediates B-cell lysis through apoptosis and immune effector mechanism, including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

It is indicated for use in combination with lenalidomide for adult patients with relapsed/refractory DLBCL that is not otherwise specified, including DLBCL arising from low-grade lymphoma, and in patients who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab-cxix in combination with lenalidomide is the first treatment that approved by the FDA for second-line use for patients with relapsed or refractory DLBCL, notes the manufacturer.

The approval “brings a new treatment option to patients in dire need across the United States,” said Gilles Salles, MD, chair of the clinical hematology department at the University of Lyon (France), and lead investigator of the L-MIND study.

The FDA granted an accelerated approval on the basis of overall response rate from an open-label, single-arm, phase 2 trial in 81 patients (known as L-MIND). Further trials are underway to confirm clinical benefit.

The L-MIND trial was conducted in patients with relapsed or refractory DLBCL who had received at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who were not eligible for high-dose chemotherapy or who refused subsequent ASCT.

All patients received tafasitamab-cxix 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) for a maximum of 12 cycles, followed by tafasitamab-cxix as monotherapy.

The best ORR (defined as complete and partial responders) in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55%, with complete responses in 37% and partial responses in 18% of patients. The median response duration was 21.7 months (range, 0-24).

The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, fever, peripheral edema, respiratory tract infection, and decreased appetite.

Precautions and warnings include infusion-related reactions (6%), serious or severe myelosuppression (including neutropenia [50%], thrombocytopenia [18%], and anemia [7%]), infections (73%), and embryo-fetal toxicity.

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter, notes the manufacturer. In the United States each year approximately 10,000 patients who are not eligible for ASCT are diagnosed with relapsed or refractory DLBCL.

This article first appeared on Medscape.com.

A novel drug, tafasitamab-cxix (Monjuvi, MorphoSys US), has been approved by the Food and Drug Administration for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The product is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. It mediates B-cell lysis through apoptosis and immune effector mechanism, including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

It is indicated for use in combination with lenalidomide for adult patients with relapsed/refractory DLBCL that is not otherwise specified, including DLBCL arising from low-grade lymphoma, and in patients who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab-cxix in combination with lenalidomide is the first treatment that approved by the FDA for second-line use for patients with relapsed or refractory DLBCL, notes the manufacturer.

The approval “brings a new treatment option to patients in dire need across the United States,” said Gilles Salles, MD, chair of the clinical hematology department at the University of Lyon (France), and lead investigator of the L-MIND study.

The FDA granted an accelerated approval on the basis of overall response rate from an open-label, single-arm, phase 2 trial in 81 patients (known as L-MIND). Further trials are underway to confirm clinical benefit.

The L-MIND trial was conducted in patients with relapsed or refractory DLBCL who had received at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who were not eligible for high-dose chemotherapy or who refused subsequent ASCT.

All patients received tafasitamab-cxix 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) for a maximum of 12 cycles, followed by tafasitamab-cxix as monotherapy.

The best ORR (defined as complete and partial responders) in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55%, with complete responses in 37% and partial responses in 18% of patients. The median response duration was 21.7 months (range, 0-24).

The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, fever, peripheral edema, respiratory tract infection, and decreased appetite.

Precautions and warnings include infusion-related reactions (6%), serious or severe myelosuppression (including neutropenia [50%], thrombocytopenia [18%], and anemia [7%]), infections (73%), and embryo-fetal toxicity.

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter, notes the manufacturer. In the United States each year approximately 10,000 patients who are not eligible for ASCT are diagnosed with relapsed or refractory DLBCL.

This article first appeared on Medscape.com.

A novel drug, tafasitamab-cxix (Monjuvi, MorphoSys US), has been approved by the Food and Drug Administration for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The product is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. It mediates B-cell lysis through apoptosis and immune effector mechanism, including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

It is indicated for use in combination with lenalidomide for adult patients with relapsed/refractory DLBCL that is not otherwise specified, including DLBCL arising from low-grade lymphoma, and in patients who are not eligible for autologous stem cell transplant (ASCT).

Tafasitamab-cxix in combination with lenalidomide is the first treatment that approved by the FDA for second-line use for patients with relapsed or refractory DLBCL, notes the manufacturer.

The approval “brings a new treatment option to patients in dire need across the United States,” said Gilles Salles, MD, chair of the clinical hematology department at the University of Lyon (France), and lead investigator of the L-MIND study.

The FDA granted an accelerated approval on the basis of overall response rate from an open-label, single-arm, phase 2 trial in 81 patients (known as L-MIND). Further trials are underway to confirm clinical benefit.

The L-MIND trial was conducted in patients with relapsed or refractory DLBCL who had received at least one, but no more than three, prior lines of therapy, including an anti-CD20 targeting therapy (e.g., rituximab), who were not eligible for high-dose chemotherapy or who refused subsequent ASCT.

All patients received tafasitamab-cxix 12 mg/kg intravenously with lenalidomide (25 mg orally on days 1-21 of each 28-day cycle) for a maximum of 12 cycles, followed by tafasitamab-cxix as monotherapy.

The best ORR (defined as complete and partial responders) in 71 patients with a diagnosis of DLBCL confirmed by central pathology was 55%, with complete responses in 37% and partial responses in 18% of patients. The median response duration was 21.7 months (range, 0-24).

The most common adverse reactions (≥20%) were neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, fever, peripheral edema, respiratory tract infection, and decreased appetite.

Precautions and warnings include infusion-related reactions (6%), serious or severe myelosuppression (including neutropenia [50%], thrombocytopenia [18%], and anemia [7%]), infections (73%), and embryo-fetal toxicity.

DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter, notes the manufacturer. In the United States each year approximately 10,000 patients who are not eligible for ASCT are diagnosed with relapsed or refractory DLBCL.

This article first appeared on Medscape.com.

Older adults are being “overscreened” for cancer, say researchers who discovered that many patients reported undergoing screening for cancer even though they were older than the upper age limit recommended.

The U.S. Preventive Services Task Force recommends an upper age limit on cancer screening that varies by cancer type – 75 years old for colorectal cancer, 74 for breast cancer, and 65 for cervical cancer.

The study found that 59.3% of men and 56.2% of women being screening for colorectal cancer were above that cut-off age, as were 45.8% of women being screened for cervical cancer and 74.1% of women being screened for breast cancer.    

Overscreening was particularly high for women living in metropolitan areas.

The finding is of concern, say the researchers, because “continuing to screen patients who are older and/or who have limited life expectancy may cause more harms than benefits.”

“The development of successful interventions to address this problem are thus essential,” they write.

The study was published online July 27 in JAMA Network Open.

Clinicians, patients, and health care systems can be changed – and should be changed – to minimize overscreening,” said lead author Jennifer L. Moss, PhD, assistant professor of family and community medicine and public health sciences at Penn State University, Hershey.

“It will probably take many changes to meaningfully decrease overscreening,” she told Medscape Medical News.

One change that would help is if health insurance companies stopped reimbursing providers for screening after the recommended upper age limit, she continued. “Another change is if providers had evidence-based tools to guide conversations about stopping screening, given an individual patient’s demographics, health status, and risks and benefits of the screening test.”

Approached for comment on the study, Nancy Schoenborn, MD, MHS, an associate professor of medicine in the Division of Geriatric Medicine and Gerontology at Johns Hopkins University, Baltimore, noted that the finding of high overscreening is not surprising and is consistent with prior works that found similar results.

“One value of this paper is that the timing of the study is more recent and confirms that the issue of overscreening is one that is still ongoing,” she told Medscape Medical News. Schoenborn was not associated with the study.

As for what physicians should do about the findings in this study, Schoenborn suggested the first step is to simply recognize that overscreening is likely a problem and “to reflect if there are instances in one’s own practice where overscreening may occur.”

In her own work, Schoenborn continued, “I was recently surprised that a substantial minority of clinicians actually do not believe overscreening to be a problem in older adults, and they have a number of concerns about how overscreening is defined and about unintended consequences that can occur from efforts to reduce overscreening.”

She added that there are a number of reasons why overscreening occurs. These include guideline inconsistencies, inertia, patient request, clinician knowledge gaps, and discomfort with discussing stopping. “A lot of work is ongoing to address each of these issues, but I think the first step would be the clinician recognizing and agreeing that this is a problem that needs to be addressed,” she said.

Unnecessary screening

The authors note that the prevalence estimates for overscreening have not been reported on a national level, and it is also unclear how overscreening may vary among subgroups.

“The reason I focused on colorectal, cervical, and breast cancers is because USPSTF has very clear, age-based recommendations for these cancers in terms of who should and should not get screened routinely,” explained Moss. “This was important because it allowed me and my coauthors to clearly say, based on age alone, this person probably was screened unnecessarily, and this person was not.”

She noted that the age-based recommendations for routine screening are based on very large clinical trials to examine the effectiveness of the screening tool. “The recommendations for lung and prostate cancer screening are not so clear cut, and we would not be able to tell, based only on the available survey data, if someone was overscreened,” she said.

For their study, the team used data from the 2018 Behavioral Risk Factor Surveillance System, administered by the Centers for Disease Control and Prevention.

Overscreening was assessed in a cohort of 20,937 men and 34,244 women for colorectal cancer, 82,811 women for cervical cancer, and 38,356 women for breast cancer. Most the participants lived in a metropolitan area (about 80%) and were white (about 80%).

Being overscreened was also more common in metropolitan vs. nonmetropolitan areas for colorectal cancer in women (adjusted odds ratio, 1.23), cervical cancer (aOR, 1.20), and breast cancer (aOR, 1.36).

Overscreening for cervical and breast cancers was also associated with having a usual source of care, good/very good/excellent self-reported health, education beyond a high school diploma, and being married or living as married.

The study was carried out in 2018, and the situation is likely to have changed over recent months during the COVID-19 pandemic.

“We have already seen dramatic reductions in routine cancer screening among age-eligible adults, so part of this problem of overscreening among older adults will likely diminish,” said Moss. “State and national cancer surveillance systems will continue to monitor trends in cancer screening, including overscreening, cancer incidence, and cancer mortality.”

Johns Hopkins’ Schoenborn said one finding of particular interest was that the colorectal cancer overscreening rate was higher in those older than 80 and in those with higher mortality risk.

“It makes me wonder if this is due to the increasing use of noninvasive colorectal cancer screening modalities, such as the fecal immunochemical test FIT or Cologuard,” Schoenborn commented. “It would be important for clinicians to consider downstream effects even when the initial test is low risk, such as if the stool test screens positive, would the patient still need a colonoscopy, and is that something the patient can undergo and wants to undergo?”

The study was funded by the National Cancer Institute and American Cancer Society. Moss, study coauthors, and Schoenborn have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Older adults are being “overscreened” for cancer, say researchers who discovered that many patients reported undergoing screening for cancer even though they were older than the upper age limit recommended.

The U.S. Preventive Services Task Force recommends an upper age limit on cancer screening that varies by cancer type – 75 years old for colorectal cancer, 74 for breast cancer, and 65 for cervical cancer.

The study found that 59.3% of men and 56.2% of women being screening for colorectal cancer were above that cut-off age, as were 45.8% of women being screened for cervical cancer and 74.1% of women being screened for breast cancer.    

Overscreening was particularly high for women living in metropolitan areas.

The finding is of concern, say the researchers, because “continuing to screen patients who are older and/or who have limited life expectancy may cause more harms than benefits.”

“The development of successful interventions to address this problem are thus essential,” they write.

The study was published online July 27 in JAMA Network Open.

Clinicians, patients, and health care systems can be changed – and should be changed – to minimize overscreening,” said lead author Jennifer L. Moss, PhD, assistant professor of family and community medicine and public health sciences at Penn State University, Hershey.

“It will probably take many changes to meaningfully decrease overscreening,” she told Medscape Medical News.

One change that would help is if health insurance companies stopped reimbursing providers for screening after the recommended upper age limit, she continued. “Another change is if providers had evidence-based tools to guide conversations about stopping screening, given an individual patient’s demographics, health status, and risks and benefits of the screening test.”

Approached for comment on the study, Nancy Schoenborn, MD, MHS, an associate professor of medicine in the Division of Geriatric Medicine and Gerontology at Johns Hopkins University, Baltimore, noted that the finding of high overscreening is not surprising and is consistent with prior works that found similar results.

“One value of this paper is that the timing of the study is more recent and confirms that the issue of overscreening is one that is still ongoing,” she told Medscape Medical News. Schoenborn was not associated with the study.

As for what physicians should do about the findings in this study, Schoenborn suggested the first step is to simply recognize that overscreening is likely a problem and “to reflect if there are instances in one’s own practice where overscreening may occur.”

In her own work, Schoenborn continued, “I was recently surprised that a substantial minority of clinicians actually do not believe overscreening to be a problem in older adults, and they have a number of concerns about how overscreening is defined and about unintended consequences that can occur from efforts to reduce overscreening.”

She added that there are a number of reasons why overscreening occurs. These include guideline inconsistencies, inertia, patient request, clinician knowledge gaps, and discomfort with discussing stopping. “A lot of work is ongoing to address each of these issues, but I think the first step would be the clinician recognizing and agreeing that this is a problem that needs to be addressed,” she said.

Unnecessary screening

The authors note that the prevalence estimates for overscreening have not been reported on a national level, and it is also unclear how overscreening may vary among subgroups.

“The reason I focused on colorectal, cervical, and breast cancers is because USPSTF has very clear, age-based recommendations for these cancers in terms of who should and should not get screened routinely,” explained Moss. “This was important because it allowed me and my coauthors to clearly say, based on age alone, this person probably was screened unnecessarily, and this person was not.”

She noted that the age-based recommendations for routine screening are based on very large clinical trials to examine the effectiveness of the screening tool. “The recommendations for lung and prostate cancer screening are not so clear cut, and we would not be able to tell, based only on the available survey data, if someone was overscreened,” she said.

For their study, the team used data from the 2018 Behavioral Risk Factor Surveillance System, administered by the Centers for Disease Control and Prevention.

Overscreening was assessed in a cohort of 20,937 men and 34,244 women for colorectal cancer, 82,811 women for cervical cancer, and 38,356 women for breast cancer. Most the participants lived in a metropolitan area (about 80%) and were white (about 80%).

Being overscreened was also more common in metropolitan vs. nonmetropolitan areas for colorectal cancer in women (adjusted odds ratio, 1.23), cervical cancer (aOR, 1.20), and breast cancer (aOR, 1.36).

Overscreening for cervical and breast cancers was also associated with having a usual source of care, good/very good/excellent self-reported health, education beyond a high school diploma, and being married or living as married.

The study was carried out in 2018, and the situation is likely to have changed over recent months during the COVID-19 pandemic.

“We have already seen dramatic reductions in routine cancer screening among age-eligible adults, so part of this problem of overscreening among older adults will likely diminish,” said Moss. “State and national cancer surveillance systems will continue to monitor trends in cancer screening, including overscreening, cancer incidence, and cancer mortality.”

Johns Hopkins’ Schoenborn said one finding of particular interest was that the colorectal cancer overscreening rate was higher in those older than 80 and in those with higher mortality risk.

“It makes me wonder if this is due to the increasing use of noninvasive colorectal cancer screening modalities, such as the fecal immunochemical test FIT or Cologuard,” Schoenborn commented. “It would be important for clinicians to consider downstream effects even when the initial test is low risk, such as if the stool test screens positive, would the patient still need a colonoscopy, and is that something the patient can undergo and wants to undergo?”

The study was funded by the National Cancer Institute and American Cancer Society. Moss, study coauthors, and Schoenborn have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Older adults are being “overscreened” for cancer, say researchers who discovered that many patients reported undergoing screening for cancer even though they were older than the upper age limit recommended.

The U.S. Preventive Services Task Force recommends an upper age limit on cancer screening that varies by cancer type – 75 years old for colorectal cancer, 74 for breast cancer, and 65 for cervical cancer.

The study found that 59.3% of men and 56.2% of women being screening for colorectal cancer were above that cut-off age, as were 45.8% of women being screened for cervical cancer and 74.1% of women being screened for breast cancer.    

Overscreening was particularly high for women living in metropolitan areas.

The finding is of concern, say the researchers, because “continuing to screen patients who are older and/or who have limited life expectancy may cause more harms than benefits.”

“The development of successful interventions to address this problem are thus essential,” they write.

The study was published online July 27 in JAMA Network Open.

Clinicians, patients, and health care systems can be changed – and should be changed – to minimize overscreening,” said lead author Jennifer L. Moss, PhD, assistant professor of family and community medicine and public health sciences at Penn State University, Hershey.

“It will probably take many changes to meaningfully decrease overscreening,” she told Medscape Medical News.

One change that would help is if health insurance companies stopped reimbursing providers for screening after the recommended upper age limit, she continued. “Another change is if providers had evidence-based tools to guide conversations about stopping screening, given an individual patient’s demographics, health status, and risks and benefits of the screening test.”

Approached for comment on the study, Nancy Schoenborn, MD, MHS, an associate professor of medicine in the Division of Geriatric Medicine and Gerontology at Johns Hopkins University, Baltimore, noted that the finding of high overscreening is not surprising and is consistent with prior works that found similar results.

“One value of this paper is that the timing of the study is more recent and confirms that the issue of overscreening is one that is still ongoing,” she told Medscape Medical News. Schoenborn was not associated with the study.

As for what physicians should do about the findings in this study, Schoenborn suggested the first step is to simply recognize that overscreening is likely a problem and “to reflect if there are instances in one’s own practice where overscreening may occur.”

In her own work, Schoenborn continued, “I was recently surprised that a substantial minority of clinicians actually do not believe overscreening to be a problem in older adults, and they have a number of concerns about how overscreening is defined and about unintended consequences that can occur from efforts to reduce overscreening.”

She added that there are a number of reasons why overscreening occurs. These include guideline inconsistencies, inertia, patient request, clinician knowledge gaps, and discomfort with discussing stopping. “A lot of work is ongoing to address each of these issues, but I think the first step would be the clinician recognizing and agreeing that this is a problem that needs to be addressed,” she said.

Unnecessary screening

The authors note that the prevalence estimates for overscreening have not been reported on a national level, and it is also unclear how overscreening may vary among subgroups.

“The reason I focused on colorectal, cervical, and breast cancers is because USPSTF has very clear, age-based recommendations for these cancers in terms of who should and should not get screened routinely,” explained Moss. “This was important because it allowed me and my coauthors to clearly say, based on age alone, this person probably was screened unnecessarily, and this person was not.”

She noted that the age-based recommendations for routine screening are based on very large clinical trials to examine the effectiveness of the screening tool. “The recommendations for lung and prostate cancer screening are not so clear cut, and we would not be able to tell, based only on the available survey data, if someone was overscreened,” she said.

For their study, the team used data from the 2018 Behavioral Risk Factor Surveillance System, administered by the Centers for Disease Control and Prevention.

Overscreening was assessed in a cohort of 20,937 men and 34,244 women for colorectal cancer, 82,811 women for cervical cancer, and 38,356 women for breast cancer. Most the participants lived in a metropolitan area (about 80%) and were white (about 80%).

Being overscreened was also more common in metropolitan vs. nonmetropolitan areas for colorectal cancer in women (adjusted odds ratio, 1.23), cervical cancer (aOR, 1.20), and breast cancer (aOR, 1.36).

Overscreening for cervical and breast cancers was also associated with having a usual source of care, good/very good/excellent self-reported health, education beyond a high school diploma, and being married or living as married.

The study was carried out in 2018, and the situation is likely to have changed over recent months during the COVID-19 pandemic.

“We have already seen dramatic reductions in routine cancer screening among age-eligible adults, so part of this problem of overscreening among older adults will likely diminish,” said Moss. “State and national cancer surveillance systems will continue to monitor trends in cancer screening, including overscreening, cancer incidence, and cancer mortality.”

Johns Hopkins’ Schoenborn said one finding of particular interest was that the colorectal cancer overscreening rate was higher in those older than 80 and in those with higher mortality risk.

“It makes me wonder if this is due to the increasing use of noninvasive colorectal cancer screening modalities, such as the fecal immunochemical test FIT or Cologuard,” Schoenborn commented. “It would be important for clinicians to consider downstream effects even when the initial test is low risk, such as if the stool test screens positive, would the patient still need a colonoscopy, and is that something the patient can undergo and wants to undergo?”

The study was funded by the National Cancer Institute and American Cancer Society. Moss, study coauthors, and Schoenborn have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The Food and Drug Administration has approved the supplemental new drug application for esketamine nasal spray (Spravato, Janssen Pharmaceuticals) to treat depressive symptoms in adults with major depressive disorder (MDD) and acute suicidal ideation or behavior.

The FDA approved esketamine nasal spray for treatment-resistant depression in March 2019, as reported by Medscape Medical News.

The new indication is based on data from two identical phase 3 trials – ASPIRE I and ASPIRE II – which evaluated the efficacy and safety of the nasal spray in addition to a comprehensive standard of care in adults with MDD who had active suicidal ideation with intent.

The standard of care included initial hospitalization, a newly initiated or optimized oral antidepressant, and twice-weekly treatment visits for 4 weeks. During that time, patients received esketamine nasal spray 84 mg or placebo nasal spray.

Results from the trials showed that the active treatment significantly reduced depressive symptoms within 24 hours, with some patients starting to respond as early as 4 hours after the first dose.

“Traditional oral antidepressants need weeks or more to take effect, so the availability of a medicine that can begin providing relief within a day is potentially life changing,” Theresa Nguyen, chief program officer at Mental Health America, said in a company news release.

“The clinical trials supporting this new indication provide compelling evidence that esketamine may offer clinicians a new way to provide support to patients quickly in the midst of an urgent depressive episode and help set them on the path to remission,” Gerard Sanacora, MD, PhD, director of the Yale Depression Research Program, New Haven, Conn., and esketamine clinical trial investigator, said in the same release.

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

The Food and Drug Administration has approved the supplemental new drug application for esketamine nasal spray (Spravato, Janssen Pharmaceuticals) to treat depressive symptoms in adults with major depressive disorder (MDD) and acute suicidal ideation or behavior.

The FDA approved esketamine nasal spray for treatment-resistant depression in March 2019, as reported by Medscape Medical News.

The new indication is based on data from two identical phase 3 trials – ASPIRE I and ASPIRE II – which evaluated the efficacy and safety of the nasal spray in addition to a comprehensive standard of care in adults with MDD who had active suicidal ideation with intent.

The standard of care included initial hospitalization, a newly initiated or optimized oral antidepressant, and twice-weekly treatment visits for 4 weeks. During that time, patients received esketamine nasal spray 84 mg or placebo nasal spray.

Results from the trials showed that the active treatment significantly reduced depressive symptoms within 24 hours, with some patients starting to respond as early as 4 hours after the first dose.

“Traditional oral antidepressants need weeks or more to take effect, so the availability of a medicine that can begin providing relief within a day is potentially life changing,” Theresa Nguyen, chief program officer at Mental Health America, said in a company news release.

“The clinical trials supporting this new indication provide compelling evidence that esketamine may offer clinicians a new way to provide support to patients quickly in the midst of an urgent depressive episode and help set them on the path to remission,” Gerard Sanacora, MD, PhD, director of the Yale Depression Research Program, New Haven, Conn., and esketamine clinical trial investigator, said in the same release.

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

The Food and Drug Administration has approved the supplemental new drug application for esketamine nasal spray (Spravato, Janssen Pharmaceuticals) to treat depressive symptoms in adults with major depressive disorder (MDD) and acute suicidal ideation or behavior.

The FDA approved esketamine nasal spray for treatment-resistant depression in March 2019, as reported by Medscape Medical News.

The new indication is based on data from two identical phase 3 trials – ASPIRE I and ASPIRE II – which evaluated the efficacy and safety of the nasal spray in addition to a comprehensive standard of care in adults with MDD who had active suicidal ideation with intent.

The standard of care included initial hospitalization, a newly initiated or optimized oral antidepressant, and twice-weekly treatment visits for 4 weeks. During that time, patients received esketamine nasal spray 84 mg or placebo nasal spray.

Results from the trials showed that the active treatment significantly reduced depressive symptoms within 24 hours, with some patients starting to respond as early as 4 hours after the first dose.

“Traditional oral antidepressants need weeks or more to take effect, so the availability of a medicine that can begin providing relief within a day is potentially life changing,” Theresa Nguyen, chief program officer at Mental Health America, said in a company news release.

“The clinical trials supporting this new indication provide compelling evidence that esketamine may offer clinicians a new way to provide support to patients quickly in the midst of an urgent depressive episode and help set them on the path to remission,” Gerard Sanacora, MD, PhD, director of the Yale Depression Research Program, New Haven, Conn., and esketamine clinical trial investigator, said in the same release.

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

At its annual meeting, the Alzheimer’s Association announced the launch of a global study to examine the impact of COVID-19 on the brain, as well as policy recommendations to better address the COVID-19 crisis in long-term care facilities. The study will be led by researchers at the Alzheimer’s Association and the University of Texas Health, San Antonio, with participation from more than 30 countries and technical guidance from the World Health Organization.

The research will track and evaluate the short- and long-term impact of the novel coronavirus on the brain, including cognition, behavior, and function. The target sample size is 20,000-40,000 total participants.

Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, announced the study’s launch during a COVID-19–focused panel discussion at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.

“To build a strong foundation for this research, we will align with existing studies, such as the Framingham Heart Study, and clinicians from around the world on how the data are going to be collected, obtained, and shared. We are going to have cross-study collaborations to understand the impact of the virus on the brain directly,” said Dr. Carrillo. “We will have some very good data to present next year at AAIC.”
 

‘Frightening’ headlines

As previously reported, mounting evidence suggests that SARS-CoV-2 invades the central nervous system, causing a wide range of neurologic and neuropsychiatric complications, including stroke, psychosis, altered mental state, and dementia-like syndrome. It’s likely that “dementia does not increase the risk for COVID-19, just like dementia does not increase risk for the flu. But increased age, being in a long-term care setting, and common health conditions that often accompany dementia may increase the risk,” Dr. Carrillo said.

Panel member Beth Kallmyer, MSW, vice president of care and support at the Alzheimer’s Association, spoke about the ongoing challenges long-term care facilities are facing during the pandemic. “You’ve all seen the headlines, and they’re frightening, frankly,” she said. An estimated 59,000 residents and employees of long-term care have died as a result of COVID-19, which is 42% of all U.S. deaths.

The long-term care community is being impacted at “significantly greater rates than the rest of society and yet we don’t have things in place to protect them. We also know that individuals living with dementia make up a large percentage of those that are living in long-term care,” Ms. Kallmyer said.

She noted that infection control is always a challenge in long-term care settings, but infection control during a pandemic “takes it to a whole other level.” Quarantining is hard for anyone, “but when you layer dementia on top of that we have a real challenge.” One long-term care provider told Ms. Kallmyer that “we might be saving them from COVID, but we’re losing them to social isolation and cognitive decline.”
 

New recommendations

Ms. Kallmyer outlined new policy recommendations from the Alzheimer’s Association to address the COVID-19 crisis in long-term and community-based care settings. They include:

• Testing every resident, employee, and visitor each time they leave and come back, so residents would not need to be confined to their own rooms
• Having a single portal that is easy and efficient for reporting cases
• Developing “surge activation” protocols to respond to hot spots, including the possibility of “strike teams” that go in and help during an outbreak
• Making sure all long-term care providers have full access to all needed personal protective equipment (PPE)

“Five months in and long-term care providers still don’t have adequate PPE. This is unacceptable,” said Ms. Kallmyer. “We have to be able to provide them with PPE.”

Panel member Gregory A. Jicha, MD, PhD, Sanders-Brown Center on Aging, University of Kentucky, Lexington, spoke about the critical need to continue Alzheimer’s disease research during the pandemic, noting that the number of promising targets for Alzheimer’s disease and related dementias has “never been higher or more comprehensive.”

Measures to ensure safety of researchers and participants include screening for symptoms (50% effective), social distancing (93% effective), minimizing exposure time (50% effective), limiting staff to 50% (50% effective), cloth/paper masks (80% effective), and testing (99.25% effective), Dr. Jicha noted.

With no safety measures in place, the risk of getting COVID-19 from a research visit is 1 in 20; when all these safety measures are combined, the risk is 1 in over 1.5 million, so “we can essentially eradicate or minimize the risks for COVID to less that of a lightning strike,” he said.

Dr. Carrillo, Ms. Kallmyer, and Dr. Jicha disclosed no relevant financial relationships.

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

At its annual meeting, the Alzheimer’s Association announced the launch of a global study to examine the impact of COVID-19 on the brain, as well as policy recommendations to better address the COVID-19 crisis in long-term care facilities. The study will be led by researchers at the Alzheimer’s Association and the University of Texas Health, San Antonio, with participation from more than 30 countries and technical guidance from the World Health Organization.

The research will track and evaluate the short- and long-term impact of the novel coronavirus on the brain, including cognition, behavior, and function. The target sample size is 20,000-40,000 total participants.

Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, announced the study’s launch during a COVID-19–focused panel discussion at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.

“To build a strong foundation for this research, we will align with existing studies, such as the Framingham Heart Study, and clinicians from around the world on how the data are going to be collected, obtained, and shared. We are going to have cross-study collaborations to understand the impact of the virus on the brain directly,” said Dr. Carrillo. “We will have some very good data to present next year at AAIC.”
 

‘Frightening’ headlines

As previously reported, mounting evidence suggests that SARS-CoV-2 invades the central nervous system, causing a wide range of neurologic and neuropsychiatric complications, including stroke, psychosis, altered mental state, and dementia-like syndrome. It’s likely that “dementia does not increase the risk for COVID-19, just like dementia does not increase risk for the flu. But increased age, being in a long-term care setting, and common health conditions that often accompany dementia may increase the risk,” Dr. Carrillo said.

Panel member Beth Kallmyer, MSW, vice president of care and support at the Alzheimer’s Association, spoke about the ongoing challenges long-term care facilities are facing during the pandemic. “You’ve all seen the headlines, and they’re frightening, frankly,” she said. An estimated 59,000 residents and employees of long-term care have died as a result of COVID-19, which is 42% of all U.S. deaths.

The long-term care community is being impacted at “significantly greater rates than the rest of society and yet we don’t have things in place to protect them. We also know that individuals living with dementia make up a large percentage of those that are living in long-term care,” Ms. Kallmyer said.

She noted that infection control is always a challenge in long-term care settings, but infection control during a pandemic “takes it to a whole other level.” Quarantining is hard for anyone, “but when you layer dementia on top of that we have a real challenge.” One long-term care provider told Ms. Kallmyer that “we might be saving them from COVID, but we’re losing them to social isolation and cognitive decline.”
 

New recommendations

Ms. Kallmyer outlined new policy recommendations from the Alzheimer’s Association to address the COVID-19 crisis in long-term and community-based care settings. They include:

• Testing every resident, employee, and visitor each time they leave and come back, so residents would not need to be confined to their own rooms
• Having a single portal that is easy and efficient for reporting cases
• Developing “surge activation” protocols to respond to hot spots, including the possibility of “strike teams” that go in and help during an outbreak
• Making sure all long-term care providers have full access to all needed personal protective equipment (PPE)

“Five months in and long-term care providers still don’t have adequate PPE. This is unacceptable,” said Ms. Kallmyer. “We have to be able to provide them with PPE.”

Panel member Gregory A. Jicha, MD, PhD, Sanders-Brown Center on Aging, University of Kentucky, Lexington, spoke about the critical need to continue Alzheimer’s disease research during the pandemic, noting that the number of promising targets for Alzheimer’s disease and related dementias has “never been higher or more comprehensive.”

Measures to ensure safety of researchers and participants include screening for symptoms (50% effective), social distancing (93% effective), minimizing exposure time (50% effective), limiting staff to 50% (50% effective), cloth/paper masks (80% effective), and testing (99.25% effective), Dr. Jicha noted.

With no safety measures in place, the risk of getting COVID-19 from a research visit is 1 in 20; when all these safety measures are combined, the risk is 1 in over 1.5 million, so “we can essentially eradicate or minimize the risks for COVID to less that of a lightning strike,” he said.

Dr. Carrillo, Ms. Kallmyer, and Dr. Jicha disclosed no relevant financial relationships.

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

At its annual meeting, the Alzheimer’s Association announced the launch of a global study to examine the impact of COVID-19 on the brain, as well as policy recommendations to better address the COVID-19 crisis in long-term care facilities. The study will be led by researchers at the Alzheimer’s Association and the University of Texas Health, San Antonio, with participation from more than 30 countries and technical guidance from the World Health Organization.

The research will track and evaluate the short- and long-term impact of the novel coronavirus on the brain, including cognition, behavior, and function. The target sample size is 20,000-40,000 total participants.

Maria C. Carrillo, PhD, chief science officer for the Alzheimer’s Association, announced the study’s launch during a COVID-19–focused panel discussion at the virtual annual meeting of the Alzheimer’s Association International Conference 2020.

“To build a strong foundation for this research, we will align with existing studies, such as the Framingham Heart Study, and clinicians from around the world on how the data are going to be collected, obtained, and shared. We are going to have cross-study collaborations to understand the impact of the virus on the brain directly,” said Dr. Carrillo. “We will have some very good data to present next year at AAIC.”
 

‘Frightening’ headlines

As previously reported, mounting evidence suggests that SARS-CoV-2 invades the central nervous system, causing a wide range of neurologic and neuropsychiatric complications, including stroke, psychosis, altered mental state, and dementia-like syndrome. It’s likely that “dementia does not increase the risk for COVID-19, just like dementia does not increase risk for the flu. But increased age, being in a long-term care setting, and common health conditions that often accompany dementia may increase the risk,” Dr. Carrillo said.

Panel member Beth Kallmyer, MSW, vice president of care and support at the Alzheimer’s Association, spoke about the ongoing challenges long-term care facilities are facing during the pandemic. “You’ve all seen the headlines, and they’re frightening, frankly,” she said. An estimated 59,000 residents and employees of long-term care have died as a result of COVID-19, which is 42% of all U.S. deaths.

The long-term care community is being impacted at “significantly greater rates than the rest of society and yet we don’t have things in place to protect them. We also know that individuals living with dementia make up a large percentage of those that are living in long-term care,” Ms. Kallmyer said.

She noted that infection control is always a challenge in long-term care settings, but infection control during a pandemic “takes it to a whole other level.” Quarantining is hard for anyone, “but when you layer dementia on top of that we have a real challenge.” One long-term care provider told Ms. Kallmyer that “we might be saving them from COVID, but we’re losing them to social isolation and cognitive decline.”
 

New recommendations

Ms. Kallmyer outlined new policy recommendations from the Alzheimer’s Association to address the COVID-19 crisis in long-term and community-based care settings. They include:

• Testing every resident, employee, and visitor each time they leave and come back, so residents would not need to be confined to their own rooms
• Having a single portal that is easy and efficient for reporting cases
• Developing “surge activation” protocols to respond to hot spots, including the possibility of “strike teams” that go in and help during an outbreak
• Making sure all long-term care providers have full access to all needed personal protective equipment (PPE)

“Five months in and long-term care providers still don’t have adequate PPE. This is unacceptable,” said Ms. Kallmyer. “We have to be able to provide them with PPE.”

Panel member Gregory A. Jicha, MD, PhD, Sanders-Brown Center on Aging, University of Kentucky, Lexington, spoke about the critical need to continue Alzheimer’s disease research during the pandemic, noting that the number of promising targets for Alzheimer’s disease and related dementias has “never been higher or more comprehensive.”

Measures to ensure safety of researchers and participants include screening for symptoms (50% effective), social distancing (93% effective), minimizing exposure time (50% effective), limiting staff to 50% (50% effective), cloth/paper masks (80% effective), and testing (99.25% effective), Dr. Jicha noted.

With no safety measures in place, the risk of getting COVID-19 from a research visit is 1 in 20; when all these safety measures are combined, the risk is 1 in over 1.5 million, so “we can essentially eradicate or minimize the risks for COVID to less that of a lightning strike,” he said.

Dr. Carrillo, Ms. Kallmyer, and Dr. Jicha disclosed no relevant financial relationships.

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

The COVID-19 pandemic is taking a particularly severe financial toll on people with diabetes, new research from the United States suggests.

Results from a national online survey of 5,000 people with diabetes conducted between June 26 and July 1, 2020, were posted July 29 on the American Diabetes Association website.

The survey, conducted by the diabetes research company dQ&A in association with the ADA, revealed that Americans with diabetes are experiencing extreme financial pressures, leading to medication and supply rationing.

A high proportion of respondents had either lost income or are working in jobs that place them at risk for catching the novel coronavirus.

“These new numbers show the urgency needed to adopt measures to protect and assist the millions of people with diabetes who are suffering through this pandemic,” Tracey D. Brown, CEO of the ADA, said in a statement.

She called for states to extend health care coverage to people who have lost their jobs, for the eradication of insulin copays during the pandemic, and for increased COVID-19 testing capacity in high-risk communities.

“If these actions aren’t taken immediately, we will continue to see devastating impacts and outcomes for millions of vulnerable Americans,” Ms. Brown stressed.
 

COVID-19 has worsened financial pressures for people with diabetes

In the survey, 24% of respondents reported having used savings, loans, or stimulus check money to pay for diabetes care in the past 3 months. Among those who have lost income, half are using savings or stimulus money.

A quarter of respondents said they have been self-rationing supplies to cut costs.

Extrapolating to the entire U.S. population with diabetes, dQ&A estimated that roughly 650,000 are skipping insulin doses or taking less than prescribed, and 3 million are skipping blood glucose tests.

In June, the unemployment rate for people with diabetes was 18%, higher than the national rate of 12%.

Also higher is the proportion of those working prior to the pandemic who have since lost income: 33%, compared with 29% for the general population.

Among those who are self-employed, 7 in 10 of those with diabetes have lost some or all of their income.
 

Many with diabetes who are employed are vulnerable to exposure

Of those who remain employed, half said they can’t work from home.

Of those, 60% work in essential industries, with 22% in health care. A large majority, 90%, reported lack of social distancing at work and nearly a third work in places that don’t require masks.

“People with diabetes are helping to provide the services we all depend on during this pandemic, even as it puts their own well-being at risk,” the report said.

It concluded that “these numbers represent a conservative estimate of the pandemic’s impact. They are generated from an ongoing online study of the diabetes population amongst people who have opted in to participate.”

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

The COVID-19 pandemic is taking a particularly severe financial toll on people with diabetes, new research from the United States suggests.

Results from a national online survey of 5,000 people with diabetes conducted between June 26 and July 1, 2020, were posted July 29 on the American Diabetes Association website.

The survey, conducted by the diabetes research company dQ&A in association with the ADA, revealed that Americans with diabetes are experiencing extreme financial pressures, leading to medication and supply rationing.

A high proportion of respondents had either lost income or are working in jobs that place them at risk for catching the novel coronavirus.

“These new numbers show the urgency needed to adopt measures to protect and assist the millions of people with diabetes who are suffering through this pandemic,” Tracey D. Brown, CEO of the ADA, said in a statement.

She called for states to extend health care coverage to people who have lost their jobs, for the eradication of insulin copays during the pandemic, and for increased COVID-19 testing capacity in high-risk communities.

“If these actions aren’t taken immediately, we will continue to see devastating impacts and outcomes for millions of vulnerable Americans,” Ms. Brown stressed.
 

COVID-19 has worsened financial pressures for people with diabetes

In the survey, 24% of respondents reported having used savings, loans, or stimulus check money to pay for diabetes care in the past 3 months. Among those who have lost income, half are using savings or stimulus money.

A quarter of respondents said they have been self-rationing supplies to cut costs.

Extrapolating to the entire U.S. population with diabetes, dQ&A estimated that roughly 650,000 are skipping insulin doses or taking less than prescribed, and 3 million are skipping blood glucose tests.

In June, the unemployment rate for people with diabetes was 18%, higher than the national rate of 12%.

Also higher is the proportion of those working prior to the pandemic who have since lost income: 33%, compared with 29% for the general population.

Among those who are self-employed, 7 in 10 of those with diabetes have lost some or all of their income.
 

Many with diabetes who are employed are vulnerable to exposure

Of those who remain employed, half said they can’t work from home.

Of those, 60% work in essential industries, with 22% in health care. A large majority, 90%, reported lack of social distancing at work and nearly a third work in places that don’t require masks.

“People with diabetes are helping to provide the services we all depend on during this pandemic, even as it puts their own well-being at risk,” the report said.

It concluded that “these numbers represent a conservative estimate of the pandemic’s impact. They are generated from an ongoing online study of the diabetes population amongst people who have opted in to participate.”

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

The COVID-19 pandemic is taking a particularly severe financial toll on people with diabetes, new research from the United States suggests.

Results from a national online survey of 5,000 people with diabetes conducted between June 26 and July 1, 2020, were posted July 29 on the American Diabetes Association website.

The survey, conducted by the diabetes research company dQ&A in association with the ADA, revealed that Americans with diabetes are experiencing extreme financial pressures, leading to medication and supply rationing.

A high proportion of respondents had either lost income or are working in jobs that place them at risk for catching the novel coronavirus.

“These new numbers show the urgency needed to adopt measures to protect and assist the millions of people with diabetes who are suffering through this pandemic,” Tracey D. Brown, CEO of the ADA, said in a statement.

She called for states to extend health care coverage to people who have lost their jobs, for the eradication of insulin copays during the pandemic, and for increased COVID-19 testing capacity in high-risk communities.

“If these actions aren’t taken immediately, we will continue to see devastating impacts and outcomes for millions of vulnerable Americans,” Ms. Brown stressed.
 

COVID-19 has worsened financial pressures for people with diabetes

In the survey, 24% of respondents reported having used savings, loans, or stimulus check money to pay for diabetes care in the past 3 months. Among those who have lost income, half are using savings or stimulus money.

A quarter of respondents said they have been self-rationing supplies to cut costs.

Extrapolating to the entire U.S. population with diabetes, dQ&A estimated that roughly 650,000 are skipping insulin doses or taking less than prescribed, and 3 million are skipping blood glucose tests.

In June, the unemployment rate for people with diabetes was 18%, higher than the national rate of 12%.

Also higher is the proportion of those working prior to the pandemic who have since lost income: 33%, compared with 29% for the general population.

Among those who are self-employed, 7 in 10 of those with diabetes have lost some or all of their income.
 

Many with diabetes who are employed are vulnerable to exposure

Of those who remain employed, half said they can’t work from home.

Of those, 60% work in essential industries, with 22% in health care. A large majority, 90%, reported lack of social distancing at work and nearly a third work in places that don’t require masks.

“People with diabetes are helping to provide the services we all depend on during this pandemic, even as it puts their own well-being at risk,” the report said.

It concluded that “these numbers represent a conservative estimate of the pandemic’s impact. They are generated from an ongoing online study of the diabetes population amongst people who have opted in to participate.”

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

A new palliative care intervention for U.S. patients with advanced heart failure did not improve quality of life or mood after 16 weeks of participation in a randomized trial.

“Future analyses and studies will examine both the patient factors and intervention components to find the right palliative care dose, for the right patient, at the right time,” wrote Marie A. Bakitas, DNSc, of the University of Alabama at Birmingham, and coauthors. The study was published in JAMA Internal Medicine.

“My first reaction is disappointment,” Larry Allen, MD, of the University of Colorado in Denver, said in an interview. “We had hoped to see the ENABLE program, which had been successful in cancer, translate to the heart failure setting.”
 

Improvement of palliative care in heart failure patients might rest on who needs it most

“One thing to note,” Dr. Allen added in an interview, “is that, in this population of patients, some of the measures they were trying to improve were already relatively mild to start with. It may not be that the intervention didn’t help but that they picked a patient population that wasn’t particularly in need. If you treat someone who doesn’t have a problem, it’s hard to make them better.”

In a separate interview, Dr. Bakitas acknowledged a similar sentiment. “We were a little surprised until we looked at our sample,” she said. “We realized that we had recruited all these very high-functioning, good quality-of-life patients. What we then did was look at a subsample of patients who had low quality of life at baseline. Low and behold, the intervention had an effect. The patients who started with a poor quality of life had a statistically and clinically significant benefit. Their KCCQ score increased by over 5 points.”

As for next steps. Dr. Bakitas noted that they’re twofold: “One is refining the patient population who can benefit, and the second is working on the intervention and figuring out which pieces are the ones that provide the most benefit.

“Because of logistics and practical issues, not everyone in the study got all the intervention that they should have. Think of it like a drug trial; if someone misses a pill, they don’t get the full dose that we thought would work. We need to make sure our interventions have the right pieces in place. We don’t want to develop a great intervention that’s not practical for patients.”

Study design and outcomes

To determine the benefits of early palliative care for patients with heart failure, the researchers developed the ENABLE CHF-PC (Educate, Nurture, Advise, Before Life Ends Comprehensive Heartcare for Patients and Caregivers) intervention. This nurse-led program includes an in-person consultant followed by six telehealth nurse coaching sessions lasting 30-40 minutes and then monthly follow-up calls through either 48 weeks or the patient’s death.

To test the effectiveness of their intervention after 16 weeks, the researchers launched a two-site, single-blind randomized clinical trial made up of 415 patients who were 50 years or older with advanced heart failure. Among the patients, 53% were men and the mean age was 64 years; 55% were African American, 26% lived in a rural area, and 46% had a high school education or less. The average length of time since heart failure diagnosis was 5.1 years.

Patients were randomized evenly to receive either the ENABLE CHF-PC intervention (208) or usual care. The primary outcomes were quality of life (QOL), which was measured by the heart failure–specific 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) and the 14-item Functional Assessment of Chronic Illness Therapy–Palliative-14 (FACIT Pal-14), and mood, which was measured by the 14-item Hospital Anxiety and Depression Scale (HADS). Pain was measured via 3-item pain intensity and 2-item pain interference scales.

Effect size was measured as Cohen d or d-equivalent, where a small effect is 0.2, medium is 0.5, and large is about 0.854.

At baseline, the mean KCCQ score of 52.6 at baseline indicated a “fairly good” QOL across all patients. After 16 weeks, the mean KCCQ score improved 3.9 points in the intervention group, compared with 2.3 points in the usual care group (d = 0.07; [95% confidence interval, –0.09-0.24]). In addition, the mean FACIT-Pal-14 score improved 1.4 points in the intervention group compared to 0.2 points in the usual care group (d = 0.12 [95% CI, –0.03-0.28]). Only small differences were observed between groups regarding anxiety and depression, but pain intensity (difference, –2.8; SE, 0.9; d = –0.26 [95% CI, –0.43-0.09]) and pain interference (difference, –2.3; SE, 1; d = –0.21 [95% CI, –0.40 to –0.02]) demonstrated a statistically significant and clinically important decrease.
 

As heart failure care evolves, so must palliative care

Though the study and intervention developed by Dr. Bakitas and colleagues is commendable, it is only somewhat surprising that it did not drastically improve patients’ quality of life, Nathan E. Goldstein, MD, of the Icahn School of Medicine at Mount Sinai in New York, wrote in an accompanying editorial.

He noted several reasons for the lack of improvement, including a large proportion of patients still being in the early stages of the disease. Ultimately, however, he wonders if innovation in heart failure care ultimately impacted the study while it was occurring. Medications and technological advancements evolve rapidly in this field, he said, especially over the course of a 3-year study period.

To continue this work and produce real benefits in patients with advanced heart failure, Dr. Goldstein emphasized the need for “dynamic palliative care interventions that can adapt to the constantly changing landscape of the patient’s needs caused by the underlying nature of the disease, as well as the innovations in the field of cardiology.”

The authors acknowledged their study’s limitations, including data attrition at 16 weeks that was higher than expected – a turn of events they attributed to “unique socioeconomic factors … and lack of regular health care appointments” among some participants. In addition, a minority of patients were unable to stick to the study protocol, which has led the researchers to begin investigating video alternatives to in-person consultation.

The study was supported by the National Institutes of Health/National Institutes of Nursing Research. Four of the authors reported received grants from the National Institutes of Nursing Research outside the submitted work or during the study. Dr. Goldstein reported no conflicts of interest.

SOURCE: Bakitas MA et al. JAMA Intern Med. 2020 July 27. doi: 10.1001/jamainternmed.2020.2861.

A new palliative care intervention for U.S. patients with advanced heart failure did not improve quality of life or mood after 16 weeks of participation in a randomized trial.

“Future analyses and studies will examine both the patient factors and intervention components to find the right palliative care dose, for the right patient, at the right time,” wrote Marie A. Bakitas, DNSc, of the University of Alabama at Birmingham, and coauthors. The study was published in JAMA Internal Medicine.

“My first reaction is disappointment,” Larry Allen, MD, of the University of Colorado in Denver, said in an interview. “We had hoped to see the ENABLE program, which had been successful in cancer, translate to the heart failure setting.”
 

Improvement of palliative care in heart failure patients might rest on who needs it most

“One thing to note,” Dr. Allen added in an interview, “is that, in this population of patients, some of the measures they were trying to improve were already relatively mild to start with. It may not be that the intervention didn’t help but that they picked a patient population that wasn’t particularly in need. If you treat someone who doesn’t have a problem, it’s hard to make them better.”

In a separate interview, Dr. Bakitas acknowledged a similar sentiment. “We were a little surprised until we looked at our sample,” she said. “We realized that we had recruited all these very high-functioning, good quality-of-life patients. What we then did was look at a subsample of patients who had low quality of life at baseline. Low and behold, the intervention had an effect. The patients who started with a poor quality of life had a statistically and clinically significant benefit. Their KCCQ score increased by over 5 points.”

As for next steps. Dr. Bakitas noted that they’re twofold: “One is refining the patient population who can benefit, and the second is working on the intervention and figuring out which pieces are the ones that provide the most benefit.

“Because of logistics and practical issues, not everyone in the study got all the intervention that they should have. Think of it like a drug trial; if someone misses a pill, they don’t get the full dose that we thought would work. We need to make sure our interventions have the right pieces in place. We don’t want to develop a great intervention that’s not practical for patients.”

Study design and outcomes

To determine the benefits of early palliative care for patients with heart failure, the researchers developed the ENABLE CHF-PC (Educate, Nurture, Advise, Before Life Ends Comprehensive Heartcare for Patients and Caregivers) intervention. This nurse-led program includes an in-person consultant followed by six telehealth nurse coaching sessions lasting 30-40 minutes and then monthly follow-up calls through either 48 weeks or the patient’s death.

To test the effectiveness of their intervention after 16 weeks, the researchers launched a two-site, single-blind randomized clinical trial made up of 415 patients who were 50 years or older with advanced heart failure. Among the patients, 53% were men and the mean age was 64 years; 55% were African American, 26% lived in a rural area, and 46% had a high school education or less. The average length of time since heart failure diagnosis was 5.1 years.

Patients were randomized evenly to receive either the ENABLE CHF-PC intervention (208) or usual care. The primary outcomes were quality of life (QOL), which was measured by the heart failure–specific 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) and the 14-item Functional Assessment of Chronic Illness Therapy–Palliative-14 (FACIT Pal-14), and mood, which was measured by the 14-item Hospital Anxiety and Depression Scale (HADS). Pain was measured via 3-item pain intensity and 2-item pain interference scales.

Effect size was measured as Cohen d or d-equivalent, where a small effect is 0.2, medium is 0.5, and large is about 0.854.

At baseline, the mean KCCQ score of 52.6 at baseline indicated a “fairly good” QOL across all patients. After 16 weeks, the mean KCCQ score improved 3.9 points in the intervention group, compared with 2.3 points in the usual care group (d = 0.07; [95% confidence interval, –0.09-0.24]). In addition, the mean FACIT-Pal-14 score improved 1.4 points in the intervention group compared to 0.2 points in the usual care group (d = 0.12 [95% CI, –0.03-0.28]). Only small differences were observed between groups regarding anxiety and depression, but pain intensity (difference, –2.8; SE, 0.9; d = –0.26 [95% CI, –0.43-0.09]) and pain interference (difference, –2.3; SE, 1; d = –0.21 [95% CI, –0.40 to –0.02]) demonstrated a statistically significant and clinically important decrease.
 

As heart failure care evolves, so must palliative care

Though the study and intervention developed by Dr. Bakitas and colleagues is commendable, it is only somewhat surprising that it did not drastically improve patients’ quality of life, Nathan E. Goldstein, MD, of the Icahn School of Medicine at Mount Sinai in New York, wrote in an accompanying editorial.

He noted several reasons for the lack of improvement, including a large proportion of patients still being in the early stages of the disease. Ultimately, however, he wonders if innovation in heart failure care ultimately impacted the study while it was occurring. Medications and technological advancements evolve rapidly in this field, he said, especially over the course of a 3-year study period.

To continue this work and produce real benefits in patients with advanced heart failure, Dr. Goldstein emphasized the need for “dynamic palliative care interventions that can adapt to the constantly changing landscape of the patient’s needs caused by the underlying nature of the disease, as well as the innovations in the field of cardiology.”

The authors acknowledged their study’s limitations, including data attrition at 16 weeks that was higher than expected – a turn of events they attributed to “unique socioeconomic factors … and lack of regular health care appointments” among some participants. In addition, a minority of patients were unable to stick to the study protocol, which has led the researchers to begin investigating video alternatives to in-person consultation.

The study was supported by the National Institutes of Health/National Institutes of Nursing Research. Four of the authors reported received grants from the National Institutes of Nursing Research outside the submitted work or during the study. Dr. Goldstein reported no conflicts of interest.

SOURCE: Bakitas MA et al. JAMA Intern Med. 2020 July 27. doi: 10.1001/jamainternmed.2020.2861.

A new palliative care intervention for U.S. patients with advanced heart failure did not improve quality of life or mood after 16 weeks of participation in a randomized trial.

“Future analyses and studies will examine both the patient factors and intervention components to find the right palliative care dose, for the right patient, at the right time,” wrote Marie A. Bakitas, DNSc, of the University of Alabama at Birmingham, and coauthors. The study was published in JAMA Internal Medicine.

“My first reaction is disappointment,” Larry Allen, MD, of the University of Colorado in Denver, said in an interview. “We had hoped to see the ENABLE program, which had been successful in cancer, translate to the heart failure setting.”
 

Improvement of palliative care in heart failure patients might rest on who needs it most

“One thing to note,” Dr. Allen added in an interview, “is that, in this population of patients, some of the measures they were trying to improve were already relatively mild to start with. It may not be that the intervention didn’t help but that they picked a patient population that wasn’t particularly in need. If you treat someone who doesn’t have a problem, it’s hard to make them better.”

In a separate interview, Dr. Bakitas acknowledged a similar sentiment. “We were a little surprised until we looked at our sample,” she said. “We realized that we had recruited all these very high-functioning, good quality-of-life patients. What we then did was look at a subsample of patients who had low quality of life at baseline. Low and behold, the intervention had an effect. The patients who started with a poor quality of life had a statistically and clinically significant benefit. Their KCCQ score increased by over 5 points.”

As for next steps. Dr. Bakitas noted that they’re twofold: “One is refining the patient population who can benefit, and the second is working on the intervention and figuring out which pieces are the ones that provide the most benefit.

“Because of logistics and practical issues, not everyone in the study got all the intervention that they should have. Think of it like a drug trial; if someone misses a pill, they don’t get the full dose that we thought would work. We need to make sure our interventions have the right pieces in place. We don’t want to develop a great intervention that’s not practical for patients.”

Study design and outcomes

To determine the benefits of early palliative care for patients with heart failure, the researchers developed the ENABLE CHF-PC (Educate, Nurture, Advise, Before Life Ends Comprehensive Heartcare for Patients and Caregivers) intervention. This nurse-led program includes an in-person consultant followed by six telehealth nurse coaching sessions lasting 30-40 minutes and then monthly follow-up calls through either 48 weeks or the patient’s death.

To test the effectiveness of their intervention after 16 weeks, the researchers launched a two-site, single-blind randomized clinical trial made up of 415 patients who were 50 years or older with advanced heart failure. Among the patients, 53% were men and the mean age was 64 years; 55% were African American, 26% lived in a rural area, and 46% had a high school education or less. The average length of time since heart failure diagnosis was 5.1 years.

Patients were randomized evenly to receive either the ENABLE CHF-PC intervention (208) or usual care. The primary outcomes were quality of life (QOL), which was measured by the heart failure–specific 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ) and the 14-item Functional Assessment of Chronic Illness Therapy–Palliative-14 (FACIT Pal-14), and mood, which was measured by the 14-item Hospital Anxiety and Depression Scale (HADS). Pain was measured via 3-item pain intensity and 2-item pain interference scales.

Effect size was measured as Cohen d or d-equivalent, where a small effect is 0.2, medium is 0.5, and large is about 0.854.

At baseline, the mean KCCQ score of 52.6 at baseline indicated a “fairly good” QOL across all patients. After 16 weeks, the mean KCCQ score improved 3.9 points in the intervention group, compared with 2.3 points in the usual care group (d = 0.07; [95% confidence interval, –0.09-0.24]). In addition, the mean FACIT-Pal-14 score improved 1.4 points in the intervention group compared to 0.2 points in the usual care group (d = 0.12 [95% CI, –0.03-0.28]). Only small differences were observed between groups regarding anxiety and depression, but pain intensity (difference, –2.8; SE, 0.9; d = –0.26 [95% CI, –0.43-0.09]) and pain interference (difference, –2.3; SE, 1; d = –0.21 [95% CI, –0.40 to –0.02]) demonstrated a statistically significant and clinically important decrease.
 

As heart failure care evolves, so must palliative care

Though the study and intervention developed by Dr. Bakitas and colleagues is commendable, it is only somewhat surprising that it did not drastically improve patients’ quality of life, Nathan E. Goldstein, MD, of the Icahn School of Medicine at Mount Sinai in New York, wrote in an accompanying editorial.

He noted several reasons for the lack of improvement, including a large proportion of patients still being in the early stages of the disease. Ultimately, however, he wonders if innovation in heart failure care ultimately impacted the study while it was occurring. Medications and technological advancements evolve rapidly in this field, he said, especially over the course of a 3-year study period.

To continue this work and produce real benefits in patients with advanced heart failure, Dr. Goldstein emphasized the need for “dynamic palliative care interventions that can adapt to the constantly changing landscape of the patient’s needs caused by the underlying nature of the disease, as well as the innovations in the field of cardiology.”

The authors acknowledged their study’s limitations, including data attrition at 16 weeks that was higher than expected – a turn of events they attributed to “unique socioeconomic factors … and lack of regular health care appointments” among some participants. In addition, a minority of patients were unable to stick to the study protocol, which has led the researchers to begin investigating video alternatives to in-person consultation.

The study was supported by the National Institutes of Health/National Institutes of Nursing Research. Four of the authors reported received grants from the National Institutes of Nursing Research outside the submitted work or during the study. Dr. Goldstein reported no conflicts of interest.

SOURCE: Bakitas MA et al. JAMA Intern Med. 2020 July 27. doi: 10.1001/jamainternmed.2020.2861.

A strategy that includes a urine steroid test along with imaging characteristics and tumor size criteria can significantly improve the challenging diagnosis of adrenocortical cancer, helping to avoid unnecessary, and often unsuccessful, further imaging and even surgery, new research shows.

“A triple-test strategy of tumor diameter, imaging characteristics, and urine steroid metabolomics improves detection of adrenocortical carcinoma, which could shorten time to surgery for patients with ... carcinoma and help to avoid unnecessary surgery in patients with benign tumors,” the authors say in research published online July 23 in The Lancet Diabetes & Endocrinology.

The triple-test strategy can be expected to make its way into international guidelines, notes joint lead author Irina Bancos, MD, an associate professor of endocrinology at the Mayo Clinic, Rochester, Minn., in a press statement issued by the University of Birmingham (England), which also had a number of researchers involved in the study.

“The findings of this study will feed into the next international guidelines on the management of adrenal tumors and the implementation of the new test will hopefully improve the overall outlook for patients diagnosed with adrenal tumors,” Dr. Bancos emphasized.

More imaging has led to detection of more adrenal tumors

Advances in CT and MRI imaging have increased the ability to detect adrenal incidentalomas, which are now picked up on about 5% of scans, and the widespread use of imaging has compounded the prevalence of such findings, particularly in older people.

Adrenocortical carcinomas represent only about 2%-12% of adrenal incidentalomas, but the prognosis is very poor, and early detection and surgery can improve outcomes, so findings of any adrenal tumor typically trigger additional multimodal imaging to rule out malignancy.

Evidence is lacking on the accuracy of imaging in determining whether such masses are truly cancerous, or benign, and such procedures add costs, as well as expose patients to radiation that may ultimately have no benefit. However, a previous proof-of-concept study from the same authors did show that the presence of excess adrenal steroid hormones in the urine is a key indicator of adrenal tumors, and other research has supported the findings.

All three tests together give best predictive value: EURINE-ACT

To further validate this work, the authors conducted the EURINE-ACT trial, a prospective 14-center study that is the first of its kind to evaluate the efficacy of a screening strategy for adrenocortical carcinoma that combines urine steroid profiling with tumor size and imaging characteristics.

The study of 2,017 participants with newly diagnosed adrenal masses, recruited from January 2011 to July 2016 from specialist centers in 11 different countries, assessed the diagnostic accuracy of three components: maximum tumor diameter (≥4 cm vs. <4 cm), imaging characteristics (positive vs. negative), and urine steroid metabolomics (low, medium, or high risk of adrenocortical carcinoma), separately and in combination.

Of the patients, 98 (4.9%) had adrenocortical carcinoma confirmed clinically, histopathologically, or biochemically.

Tumors with diameters of 4 cm or larger were identified in 488 patients (24.2%) and were observed in the vast majority of patients with adrenocortical carcinoma (96 of 98), for a positive predictive value (PPV) of 19.7%.

Likewise, the PPV for imaging characteristics was 19.7%. However, increasing the unenhanced CT tumor attenuation threshold to 20 Hounsfield units (HU) from the recommended 10 HU increased specificity for adrenocortical carcinoma (80.0% vs. 64.0%) while maintaining sensitivity (99.0% vs. 100.0%).

Comparatively, a urine steroid metabolomics result suggesting a high risk of adrenocortical carcinoma had a PPV of 34.6%.

A total of 106 patients (5.3%) met the criteria for all three measures, and the PPV for all three was 76.4%.

Using the criteria, 70 patients (3.5%) were classified as being at moderate risk of adrenocortical carcinoma and 1,841 (91.3%) at low risk, for a negative predictive value (NPV) of 99.7%.

“Use of radiation-free, noninvasive urine steroid metabolomics has a higher PPV than two standard imaging tests, and best performance was seen with the combination of all three tests,” the authors state.

Limit urine test to patients with larger tumors

They note that the use of the combined diagnostic strategy would have led to additional imaging in only 488 (24.2%) of the study’s 2,017 patients, compared with the 2,737 scans that were actually conducted before reaching a diagnostic decision.

“Implementation of urine steroid metabolomics in the routine diagnostic assessment of newly discovered adrenal masses could reduce the number of imaging procedures required to diagnose adrenocortical carcinoma and avoid unnecessary surgery of benign adrenal tumors, potentially yielding beneficial effects with respect to patient burden and health care costs,” they stress.

And regarding imaging parameters, “we also showed that using a cutoff of 20 HU for unenhanced CT tumor attenuation increases the accuracy of imaging characteristic assessment for exclusion of adrenocortical carcinoma, compared with the currently recommended cutoff of 10 HU, which has immediate implications for clinical practice,” they emphasize.

In an accompanying editorial, Adina F. Turcu, MD, of the division of metabolism, endocrinology, and diabetes, University of Michigan, Ann Arbor, and Axel K. Walch, MD, of the Helmholtz Zentrum München–German Research Centre for Environmental Health, agree. “The introduction of urine steroid metabolomics into routine clinical practice would provide major advantages,” they state.

However, they point out that, although the overall negative predictive value of the test was excellent, the specificity was weak.

“Thus, urine steroid metabolomics should be limited to patients who have adrenal nodules larger than 4 cm and have qualitative imaging characteristics suggestive of malignancy,” say Dr. Turcu and Dr. Walch.

The EURINE-ACT study results suggest this subgroup would represent roughly only 12% of all patients with adrenal incidentalomas, they add.

Issues that remain to be addressed with regard to the implementation of the screening strategy include how to best respond to patients who are classified as having intermediate or moderate risk of malignancy, and whether the diagnostic value of steroid metabolomics could be refined by adding analytes or parameters, the editorialists conclude.

The study was funded by the European Commission, U.K. Medical Research Council, Wellcome Trust, U.K. National Institute for Health Research, U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.
 

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

A strategy that includes a urine steroid test along with imaging characteristics and tumor size criteria can significantly improve the challenging diagnosis of adrenocortical cancer, helping to avoid unnecessary, and often unsuccessful, further imaging and even surgery, new research shows.

“A triple-test strategy of tumor diameter, imaging characteristics, and urine steroid metabolomics improves detection of adrenocortical carcinoma, which could shorten time to surgery for patients with ... carcinoma and help to avoid unnecessary surgery in patients with benign tumors,” the authors say in research published online July 23 in The Lancet Diabetes & Endocrinology.

The triple-test strategy can be expected to make its way into international guidelines, notes joint lead author Irina Bancos, MD, an associate professor of endocrinology at the Mayo Clinic, Rochester, Minn., in a press statement issued by the University of Birmingham (England), which also had a number of researchers involved in the study.

“The findings of this study will feed into the next international guidelines on the management of adrenal tumors and the implementation of the new test will hopefully improve the overall outlook for patients diagnosed with adrenal tumors,” Dr. Bancos emphasized.

More imaging has led to detection of more adrenal tumors

Advances in CT and MRI imaging have increased the ability to detect adrenal incidentalomas, which are now picked up on about 5% of scans, and the widespread use of imaging has compounded the prevalence of such findings, particularly in older people.

Adrenocortical carcinomas represent only about 2%-12% of adrenal incidentalomas, but the prognosis is very poor, and early detection and surgery can improve outcomes, so findings of any adrenal tumor typically trigger additional multimodal imaging to rule out malignancy.

Evidence is lacking on the accuracy of imaging in determining whether such masses are truly cancerous, or benign, and such procedures add costs, as well as expose patients to radiation that may ultimately have no benefit. However, a previous proof-of-concept study from the same authors did show that the presence of excess adrenal steroid hormones in the urine is a key indicator of adrenal tumors, and other research has supported the findings.

All three tests together give best predictive value: EURINE-ACT

To further validate this work, the authors conducted the EURINE-ACT trial, a prospective 14-center study that is the first of its kind to evaluate the efficacy of a screening strategy for adrenocortical carcinoma that combines urine steroid profiling with tumor size and imaging characteristics.

The study of 2,017 participants with newly diagnosed adrenal masses, recruited from January 2011 to July 2016 from specialist centers in 11 different countries, assessed the diagnostic accuracy of three components: maximum tumor diameter (≥4 cm vs. <4 cm), imaging characteristics (positive vs. negative), and urine steroid metabolomics (low, medium, or high risk of adrenocortical carcinoma), separately and in combination.

Of the patients, 98 (4.9%) had adrenocortical carcinoma confirmed clinically, histopathologically, or biochemically.

Tumors with diameters of 4 cm or larger were identified in 488 patients (24.2%) and were observed in the vast majority of patients with adrenocortical carcinoma (96 of 98), for a positive predictive value (PPV) of 19.7%.

Likewise, the PPV for imaging characteristics was 19.7%. However, increasing the unenhanced CT tumor attenuation threshold to 20 Hounsfield units (HU) from the recommended 10 HU increased specificity for adrenocortical carcinoma (80.0% vs. 64.0%) while maintaining sensitivity (99.0% vs. 100.0%).

Comparatively, a urine steroid metabolomics result suggesting a high risk of adrenocortical carcinoma had a PPV of 34.6%.

A total of 106 patients (5.3%) met the criteria for all three measures, and the PPV for all three was 76.4%.

Using the criteria, 70 patients (3.5%) were classified as being at moderate risk of adrenocortical carcinoma and 1,841 (91.3%) at low risk, for a negative predictive value (NPV) of 99.7%.

“Use of radiation-free, noninvasive urine steroid metabolomics has a higher PPV than two standard imaging tests, and best performance was seen with the combination of all three tests,” the authors state.

Limit urine test to patients with larger tumors

They note that the use of the combined diagnostic strategy would have led to additional imaging in only 488 (24.2%) of the study’s 2,017 patients, compared with the 2,737 scans that were actually conducted before reaching a diagnostic decision.

“Implementation of urine steroid metabolomics in the routine diagnostic assessment of newly discovered adrenal masses could reduce the number of imaging procedures required to diagnose adrenocortical carcinoma and avoid unnecessary surgery of benign adrenal tumors, potentially yielding beneficial effects with respect to patient burden and health care costs,” they stress.

And regarding imaging parameters, “we also showed that using a cutoff of 20 HU for unenhanced CT tumor attenuation increases the accuracy of imaging characteristic assessment for exclusion of adrenocortical carcinoma, compared with the currently recommended cutoff of 10 HU, which has immediate implications for clinical practice,” they emphasize.

In an accompanying editorial, Adina F. Turcu, MD, of the division of metabolism, endocrinology, and diabetes, University of Michigan, Ann Arbor, and Axel K. Walch, MD, of the Helmholtz Zentrum München–German Research Centre for Environmental Health, agree. “The introduction of urine steroid metabolomics into routine clinical practice would provide major advantages,” they state.

However, they point out that, although the overall negative predictive value of the test was excellent, the specificity was weak.

“Thus, urine steroid metabolomics should be limited to patients who have adrenal nodules larger than 4 cm and have qualitative imaging characteristics suggestive of malignancy,” say Dr. Turcu and Dr. Walch.

The EURINE-ACT study results suggest this subgroup would represent roughly only 12% of all patients with adrenal incidentalomas, they add.

Issues that remain to be addressed with regard to the implementation of the screening strategy include how to best respond to patients who are classified as having intermediate or moderate risk of malignancy, and whether the diagnostic value of steroid metabolomics could be refined by adding analytes or parameters, the editorialists conclude.

The study was funded by the European Commission, U.K. Medical Research Council, Wellcome Trust, U.K. National Institute for Health Research, U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.
 

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

A strategy that includes a urine steroid test along with imaging characteristics and tumor size criteria can significantly improve the challenging diagnosis of adrenocortical cancer, helping to avoid unnecessary, and often unsuccessful, further imaging and even surgery, new research shows.

“A triple-test strategy of tumor diameter, imaging characteristics, and urine steroid metabolomics improves detection of adrenocortical carcinoma, which could shorten time to surgery for patients with ... carcinoma and help to avoid unnecessary surgery in patients with benign tumors,” the authors say in research published online July 23 in The Lancet Diabetes & Endocrinology.

The triple-test strategy can be expected to make its way into international guidelines, notes joint lead author Irina Bancos, MD, an associate professor of endocrinology at the Mayo Clinic, Rochester, Minn., in a press statement issued by the University of Birmingham (England), which also had a number of researchers involved in the study.

“The findings of this study will feed into the next international guidelines on the management of adrenal tumors and the implementation of the new test will hopefully improve the overall outlook for patients diagnosed with adrenal tumors,” Dr. Bancos emphasized.

More imaging has led to detection of more adrenal tumors

Advances in CT and MRI imaging have increased the ability to detect adrenal incidentalomas, which are now picked up on about 5% of scans, and the widespread use of imaging has compounded the prevalence of such findings, particularly in older people.

Adrenocortical carcinomas represent only about 2%-12% of adrenal incidentalomas, but the prognosis is very poor, and early detection and surgery can improve outcomes, so findings of any adrenal tumor typically trigger additional multimodal imaging to rule out malignancy.

Evidence is lacking on the accuracy of imaging in determining whether such masses are truly cancerous, or benign, and such procedures add costs, as well as expose patients to radiation that may ultimately have no benefit. However, a previous proof-of-concept study from the same authors did show that the presence of excess adrenal steroid hormones in the urine is a key indicator of adrenal tumors, and other research has supported the findings.

All three tests together give best predictive value: EURINE-ACT

To further validate this work, the authors conducted the EURINE-ACT trial, a prospective 14-center study that is the first of its kind to evaluate the efficacy of a screening strategy for adrenocortical carcinoma that combines urine steroid profiling with tumor size and imaging characteristics.

The study of 2,017 participants with newly diagnosed adrenal masses, recruited from January 2011 to July 2016 from specialist centers in 11 different countries, assessed the diagnostic accuracy of three components: maximum tumor diameter (≥4 cm vs. <4 cm), imaging characteristics (positive vs. negative), and urine steroid metabolomics (low, medium, or high risk of adrenocortical carcinoma), separately and in combination.

Of the patients, 98 (4.9%) had adrenocortical carcinoma confirmed clinically, histopathologically, or biochemically.

Tumors with diameters of 4 cm or larger were identified in 488 patients (24.2%) and were observed in the vast majority of patients with adrenocortical carcinoma (96 of 98), for a positive predictive value (PPV) of 19.7%.

Likewise, the PPV for imaging characteristics was 19.7%. However, increasing the unenhanced CT tumor attenuation threshold to 20 Hounsfield units (HU) from the recommended 10 HU increased specificity for adrenocortical carcinoma (80.0% vs. 64.0%) while maintaining sensitivity (99.0% vs. 100.0%).

Comparatively, a urine steroid metabolomics result suggesting a high risk of adrenocortical carcinoma had a PPV of 34.6%.

A total of 106 patients (5.3%) met the criteria for all three measures, and the PPV for all three was 76.4%.

Using the criteria, 70 patients (3.5%) were classified as being at moderate risk of adrenocortical carcinoma and 1,841 (91.3%) at low risk, for a negative predictive value (NPV) of 99.7%.

“Use of radiation-free, noninvasive urine steroid metabolomics has a higher PPV than two standard imaging tests, and best performance was seen with the combination of all three tests,” the authors state.

Limit urine test to patients with larger tumors

They note that the use of the combined diagnostic strategy would have led to additional imaging in only 488 (24.2%) of the study’s 2,017 patients, compared with the 2,737 scans that were actually conducted before reaching a diagnostic decision.

“Implementation of urine steroid metabolomics in the routine diagnostic assessment of newly discovered adrenal masses could reduce the number of imaging procedures required to diagnose adrenocortical carcinoma and avoid unnecessary surgery of benign adrenal tumors, potentially yielding beneficial effects with respect to patient burden and health care costs,” they stress.

And regarding imaging parameters, “we also showed that using a cutoff of 20 HU for unenhanced CT tumor attenuation increases the accuracy of imaging characteristic assessment for exclusion of adrenocortical carcinoma, compared with the currently recommended cutoff of 10 HU, which has immediate implications for clinical practice,” they emphasize.

In an accompanying editorial, Adina F. Turcu, MD, of the division of metabolism, endocrinology, and diabetes, University of Michigan, Ann Arbor, and Axel K. Walch, MD, of the Helmholtz Zentrum München–German Research Centre for Environmental Health, agree. “The introduction of urine steroid metabolomics into routine clinical practice would provide major advantages,” they state.

However, they point out that, although the overall negative predictive value of the test was excellent, the specificity was weak.

“Thus, urine steroid metabolomics should be limited to patients who have adrenal nodules larger than 4 cm and have qualitative imaging characteristics suggestive of malignancy,” say Dr. Turcu and Dr. Walch.

The EURINE-ACT study results suggest this subgroup would represent roughly only 12% of all patients with adrenal incidentalomas, they add.

Issues that remain to be addressed with regard to the implementation of the screening strategy include how to best respond to patients who are classified as having intermediate or moderate risk of malignancy, and whether the diagnostic value of steroid metabolomics could be refined by adding analytes or parameters, the editorialists conclude.

The study was funded by the European Commission, U.K. Medical Research Council, Wellcome Trust, U.K. National Institute for Health Research, U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.
 

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