Bianca Nogrady

The interleukin-17A antagonist ixekizumab has shown sustained efficacy over 4 years of treatment in patients with moderate to severe plaque psoriasis, according to a study published in the Journal of the European Academy of Dermatology and Venereology.

The UNCOVER-3 trial was a double-blind, multicenter, phase 3 study in 1,346 individuals with moderate to severe psoriasis who were randomized to placebo, 80 mg of ixekizumab every 2 or 4 weeks, or 50 mg of etanercept twice weekly. At week 12, all patients were transferred to 80 mg of ixekizumab every 4 weeks for the long-term extension period, and after 60 weeks, some were dose adjusted to 80 mg every 2 weeks.

At week 204, 48.3% of the 385 patients who were receiving treatment either every 2 or 4 weeks achieved Psoriasis Area and Severity Index (PASI) 100 according to the modified nonresponder imputation method to summarize efficacy – in which patients who drop out of the study are counted as nonresponders – 66.4% achieved PASI 90 and 82.8% achieved PASI 75.

Using the as-observed method for assessing efficacy, 67.1% of patients achieved PASI 100, 87.8% achieved PASI 90, and 98.2% achieved PASI 75. Using the multiple-imputation method, those same figures were 52.7%, 73.3%, and 94.8% respectively.

They also saw consistently high response rates according to the static Physician’s Global Assessment (sPGA) score, which goes from 0 (clear) to 5 (severe disease). Using the as-observed, multiple imputation and modified nonresponder imputation methods, 68.9%, 54.6%, and 49.7% of patients respectively achieved a score of 0.

The study also saw complete resolution in 95.8% of patients with baseline palmoplantar involvement, 75.9% of those with baseline nail involvement, and 87.1% of those with scalp involvement, using the as-observed method.

“These results corroborate the results that were reported previously in patients with moderate to severe psoriasis,” wrote Mark G. Lebwohl, MD, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. “Sustained high response was observed with all the efficacy parameters such as PASI 75, 90, 100, and sPGA (0) or (0, 1), regardless of the statistical analyses ... performed.”

The majority of adverse events were mild or moderate, but serious adverse events were seen in 18.1% of patients in the long-term extension and 9.4% of patients stopped taking the study drug because of adverse events.

The most frequently reported adverse events of special interest were infections, such as nasopharyngitis (28.5% of patients), upper respiratory tract infections (10.8%), and Candida infection (5.2%). However, clinically significant neutropenia only occurred in 0.7% of patients, and malignancies occurred in 2.2% of patients.

“These safety findings support the consistency in the safety profile of [ixekizumab] treatment with no new signals occurring even after the longer exposure,” the authors wrote.

The study was funded by Eli Lilly, which manufactures ixekizumab. Two authors were employees of Eli Lilly and own company stocks. The remaining three authors reported receiving research funding and consultancies from different pharmaceutical companies, including Eli Lilly.

SOURCE: Lebwohl MG et al. J Eur Acad Dermatol Venereol. 2019 Sep 3. doi: 10.1111/jdv.15921.

The interleukin-17A antagonist ixekizumab has shown sustained efficacy over 4 years of treatment in patients with moderate to severe plaque psoriasis, according to a study published in the Journal of the European Academy of Dermatology and Venereology.

The UNCOVER-3 trial was a double-blind, multicenter, phase 3 study in 1,346 individuals with moderate to severe psoriasis who were randomized to placebo, 80 mg of ixekizumab every 2 or 4 weeks, or 50 mg of etanercept twice weekly. At week 12, all patients were transferred to 80 mg of ixekizumab every 4 weeks for the long-term extension period, and after 60 weeks, some were dose adjusted to 80 mg every 2 weeks.

At week 204, 48.3% of the 385 patients who were receiving treatment either every 2 or 4 weeks achieved Psoriasis Area and Severity Index (PASI) 100 according to the modified nonresponder imputation method to summarize efficacy – in which patients who drop out of the study are counted as nonresponders – 66.4% achieved PASI 90 and 82.8% achieved PASI 75.

Using the as-observed method for assessing efficacy, 67.1% of patients achieved PASI 100, 87.8% achieved PASI 90, and 98.2% achieved PASI 75. Using the multiple-imputation method, those same figures were 52.7%, 73.3%, and 94.8% respectively.

They also saw consistently high response rates according to the static Physician’s Global Assessment (sPGA) score, which goes from 0 (clear) to 5 (severe disease). Using the as-observed, multiple imputation and modified nonresponder imputation methods, 68.9%, 54.6%, and 49.7% of patients respectively achieved a score of 0.

The study also saw complete resolution in 95.8% of patients with baseline palmoplantar involvement, 75.9% of those with baseline nail involvement, and 87.1% of those with scalp involvement, using the as-observed method.

“These results corroborate the results that were reported previously in patients with moderate to severe psoriasis,” wrote Mark G. Lebwohl, MD, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. “Sustained high response was observed with all the efficacy parameters such as PASI 75, 90, 100, and sPGA (0) or (0, 1), regardless of the statistical analyses ... performed.”

The majority of adverse events were mild or moderate, but serious adverse events were seen in 18.1% of patients in the long-term extension and 9.4% of patients stopped taking the study drug because of adverse events.

The most frequently reported adverse events of special interest were infections, such as nasopharyngitis (28.5% of patients), upper respiratory tract infections (10.8%), and Candida infection (5.2%). However, clinically significant neutropenia only occurred in 0.7% of patients, and malignancies occurred in 2.2% of patients.

“These safety findings support the consistency in the safety profile of [ixekizumab] treatment with no new signals occurring even after the longer exposure,” the authors wrote.

The study was funded by Eli Lilly, which manufactures ixekizumab. Two authors were employees of Eli Lilly and own company stocks. The remaining three authors reported receiving research funding and consultancies from different pharmaceutical companies, including Eli Lilly.

SOURCE: Lebwohl MG et al. J Eur Acad Dermatol Venereol. 2019 Sep 3. doi: 10.1111/jdv.15921.

The interleukin-17A antagonist ixekizumab has shown sustained efficacy over 4 years of treatment in patients with moderate to severe plaque psoriasis, according to a study published in the Journal of the European Academy of Dermatology and Venereology.

The UNCOVER-3 trial was a double-blind, multicenter, phase 3 study in 1,346 individuals with moderate to severe psoriasis who were randomized to placebo, 80 mg of ixekizumab every 2 or 4 weeks, or 50 mg of etanercept twice weekly. At week 12, all patients were transferred to 80 mg of ixekizumab every 4 weeks for the long-term extension period, and after 60 weeks, some were dose adjusted to 80 mg every 2 weeks.

At week 204, 48.3% of the 385 patients who were receiving treatment either every 2 or 4 weeks achieved Psoriasis Area and Severity Index (PASI) 100 according to the modified nonresponder imputation method to summarize efficacy – in which patients who drop out of the study are counted as nonresponders – 66.4% achieved PASI 90 and 82.8% achieved PASI 75.

Using the as-observed method for assessing efficacy, 67.1% of patients achieved PASI 100, 87.8% achieved PASI 90, and 98.2% achieved PASI 75. Using the multiple-imputation method, those same figures were 52.7%, 73.3%, and 94.8% respectively.

They also saw consistently high response rates according to the static Physician’s Global Assessment (sPGA) score, which goes from 0 (clear) to 5 (severe disease). Using the as-observed, multiple imputation and modified nonresponder imputation methods, 68.9%, 54.6%, and 49.7% of patients respectively achieved a score of 0.

The study also saw complete resolution in 95.8% of patients with baseline palmoplantar involvement, 75.9% of those with baseline nail involvement, and 87.1% of those with scalp involvement, using the as-observed method.

“These results corroborate the results that were reported previously in patients with moderate to severe psoriasis,” wrote Mark G. Lebwohl, MD, professor and chair of the department of dermatology at the Icahn School of Medicine at Mount Sinai, New York, and coauthors. “Sustained high response was observed with all the efficacy parameters such as PASI 75, 90, 100, and sPGA (0) or (0, 1), regardless of the statistical analyses ... performed.”

The majority of adverse events were mild or moderate, but serious adverse events were seen in 18.1% of patients in the long-term extension and 9.4% of patients stopped taking the study drug because of adverse events.

The most frequently reported adverse events of special interest were infections, such as nasopharyngitis (28.5% of patients), upper respiratory tract infections (10.8%), and Candida infection (5.2%). However, clinically significant neutropenia only occurred in 0.7% of patients, and malignancies occurred in 2.2% of patients.

“These safety findings support the consistency in the safety profile of [ixekizumab] treatment with no new signals occurring even after the longer exposure,” the authors wrote.

The study was funded by Eli Lilly, which manufactures ixekizumab. Two authors were employees of Eli Lilly and own company stocks. The remaining three authors reported receiving research funding and consultancies from different pharmaceutical companies, including Eli Lilly.

SOURCE: Lebwohl MG et al. J Eur Acad Dermatol Venereol. 2019 Sep 3. doi: 10.1111/jdv.15921.

Adolescence is a critical period of development that brings with it unique health challenges, which has prompted the American Academy of Pediatrics to publish a policy statement addressing those issues.

“The importance of addressing the physical and mental health of adolescents has become more evident, with investigators in recent studies pointing to the fact that unmet health needs during adolescence and in the transition to adulthood predict not only poor health outcomes as adults but also lower quality of life in adulthood,” wrote lead authors Elizabeth M. Alderman, MD, and Cora Collette Breuner, MD, MPH, of the AAP’s Committee on Adolescence.

Lisa Quarfoth/Thinkstock

The first key health risk the authors highlighted was risky and risk-taking behaviors, pointing out that nearly three-quarters of adolescent deaths result from vehicle crashes, injuries from firearms, alcohol and illicit substances, homicide, or suicide. They also cited increased concern about the use of e-cigarettes among adolescents.

Recommendations exist on screening for and counseling on high-risk behaviors, but evidence showing that relatively few adolescents actually receive any kind of preventive counseling or discuss these health risks with pediatricians or primary care physicians suggests that improvement is needed.

“New screening codes for depression, substance use, and alcohol and tobacco use as well as brief intervention services may provide opportunities to receive payment for the services pediatricians are providing to adolescents,” wrote Dr. Alderman of the division of adolescent medicine in the department of pediatrics at Albert Einstein College of Medicine and the Children’s Hospital at Montefiore, New York, and Dr. Breuner of the division of adolescent medicine at the University of Washington and Seattle Children’s Hospital.

Thanks to technological advances in pediatric medical care, more adolescents are being identified with chronic medical conditions and developmental challenges. One survey suggested that as many as 31% of adolescents have one moderate to severe chronic health condition, such as asthma, cardiac disease, HIV, and developmental disabilities. Many, however, have unmet health needs that could affect their physical growth and development during adolescence.

The paper also raised the importance of providing culturally competent health care approaches and support for minority youth, with evidence suggesting this group of adolescents is at risk of depression because of the isolation and discrimination they experience.

Similarly, the statement acknowledged the growing diversity of adolescent populations – for example, adolescents who identify as lesbian, gay, bisexual, or transgender – and the importance of delivering appropriate care to those populations.

“Sexual orientation and behaviors should be assessed by the pediatrician without making assumptions,” the authors wrote. “Adolescents should be allowed to apply and explain the labels they choose to use for sexuality and gender using open-ended questions.”

The authors drew attention to the greater mental health risks of adolescents, pointing out that about one in five adolescents have a diagnosable mental health disorder and one-quarter of adults with mood disorders had their first major depressive episode during adolescence. They also cited the Centers for Disease Control and Prevention’s 2017 Youth Risk Behavior Survey of high school students, which showed that adolescents with a parent serving in the military are at increased risk of suicidal ideation.

In addition, Dr. Alderman and Dr. Breuner said, mental health problems experienced by adolescents often are comorbid with eating disorders. Formerly obese adolescents, male teenagers, and young people from lower socioeconomic groups are increasingly developing anorexia nervosa, bulimia nervosa, and other disordered eating.

The paper called for more financial, educational, and training support for pediatricians and other health care professionals to enable them to better meet the health and developmental needs of adolescents.

Dr. Alderman and Dr. Breuner declared having no conflicts of interest.

SOURCE: Alderman EM and Breuner CC. Pediatrics. 2019 Nov 18. doi: 10.1542/peds.2019-3150 .

Adolescence is a critical period of development that brings with it unique health challenges, which has prompted the American Academy of Pediatrics to publish a policy statement addressing those issues.

“The importance of addressing the physical and mental health of adolescents has become more evident, with investigators in recent studies pointing to the fact that unmet health needs during adolescence and in the transition to adulthood predict not only poor health outcomes as adults but also lower quality of life in adulthood,” wrote lead authors Elizabeth M. Alderman, MD, and Cora Collette Breuner, MD, MPH, of the AAP’s Committee on Adolescence.

Lisa Quarfoth/Thinkstock

The first key health risk the authors highlighted was risky and risk-taking behaviors, pointing out that nearly three-quarters of adolescent deaths result from vehicle crashes, injuries from firearms, alcohol and illicit substances, homicide, or suicide. They also cited increased concern about the use of e-cigarettes among adolescents.

Recommendations exist on screening for and counseling on high-risk behaviors, but evidence showing that relatively few adolescents actually receive any kind of preventive counseling or discuss these health risks with pediatricians or primary care physicians suggests that improvement is needed.

“New screening codes for depression, substance use, and alcohol and tobacco use as well as brief intervention services may provide opportunities to receive payment for the services pediatricians are providing to adolescents,” wrote Dr. Alderman of the division of adolescent medicine in the department of pediatrics at Albert Einstein College of Medicine and the Children’s Hospital at Montefiore, New York, and Dr. Breuner of the division of adolescent medicine at the University of Washington and Seattle Children’s Hospital.

Thanks to technological advances in pediatric medical care, more adolescents are being identified with chronic medical conditions and developmental challenges. One survey suggested that as many as 31% of adolescents have one moderate to severe chronic health condition, such as asthma, cardiac disease, HIV, and developmental disabilities. Many, however, have unmet health needs that could affect their physical growth and development during adolescence.

The paper also raised the importance of providing culturally competent health care approaches and support for minority youth, with evidence suggesting this group of adolescents is at risk of depression because of the isolation and discrimination they experience.

Similarly, the statement acknowledged the growing diversity of adolescent populations – for example, adolescents who identify as lesbian, gay, bisexual, or transgender – and the importance of delivering appropriate care to those populations.

“Sexual orientation and behaviors should be assessed by the pediatrician without making assumptions,” the authors wrote. “Adolescents should be allowed to apply and explain the labels they choose to use for sexuality and gender using open-ended questions.”

The authors drew attention to the greater mental health risks of adolescents, pointing out that about one in five adolescents have a diagnosable mental health disorder and one-quarter of adults with mood disorders had their first major depressive episode during adolescence. They also cited the Centers for Disease Control and Prevention’s 2017 Youth Risk Behavior Survey of high school students, which showed that adolescents with a parent serving in the military are at increased risk of suicidal ideation.

In addition, Dr. Alderman and Dr. Breuner said, mental health problems experienced by adolescents often are comorbid with eating disorders. Formerly obese adolescents, male teenagers, and young people from lower socioeconomic groups are increasingly developing anorexia nervosa, bulimia nervosa, and other disordered eating.

The paper called for more financial, educational, and training support for pediatricians and other health care professionals to enable them to better meet the health and developmental needs of adolescents.

Dr. Alderman and Dr. Breuner declared having no conflicts of interest.

SOURCE: Alderman EM and Breuner CC. Pediatrics. 2019 Nov 18. doi: 10.1542/peds.2019-3150 .

Adolescence is a critical period of development that brings with it unique health challenges, which has prompted the American Academy of Pediatrics to publish a policy statement addressing those issues.

“The importance of addressing the physical and mental health of adolescents has become more evident, with investigators in recent studies pointing to the fact that unmet health needs during adolescence and in the transition to adulthood predict not only poor health outcomes as adults but also lower quality of life in adulthood,” wrote lead authors Elizabeth M. Alderman, MD, and Cora Collette Breuner, MD, MPH, of the AAP’s Committee on Adolescence.

Lisa Quarfoth/Thinkstock

The first key health risk the authors highlighted was risky and risk-taking behaviors, pointing out that nearly three-quarters of adolescent deaths result from vehicle crashes, injuries from firearms, alcohol and illicit substances, homicide, or suicide. They also cited increased concern about the use of e-cigarettes among adolescents.

Recommendations exist on screening for and counseling on high-risk behaviors, but evidence showing that relatively few adolescents actually receive any kind of preventive counseling or discuss these health risks with pediatricians or primary care physicians suggests that improvement is needed.

“New screening codes for depression, substance use, and alcohol and tobacco use as well as brief intervention services may provide opportunities to receive payment for the services pediatricians are providing to adolescents,” wrote Dr. Alderman of the division of adolescent medicine in the department of pediatrics at Albert Einstein College of Medicine and the Children’s Hospital at Montefiore, New York, and Dr. Breuner of the division of adolescent medicine at the University of Washington and Seattle Children’s Hospital.

Thanks to technological advances in pediatric medical care, more adolescents are being identified with chronic medical conditions and developmental challenges. One survey suggested that as many as 31% of adolescents have one moderate to severe chronic health condition, such as asthma, cardiac disease, HIV, and developmental disabilities. Many, however, have unmet health needs that could affect their physical growth and development during adolescence.

The paper also raised the importance of providing culturally competent health care approaches and support for minority youth, with evidence suggesting this group of adolescents is at risk of depression because of the isolation and discrimination they experience.

Similarly, the statement acknowledged the growing diversity of adolescent populations – for example, adolescents who identify as lesbian, gay, bisexual, or transgender – and the importance of delivering appropriate care to those populations.

“Sexual orientation and behaviors should be assessed by the pediatrician without making assumptions,” the authors wrote. “Adolescents should be allowed to apply and explain the labels they choose to use for sexuality and gender using open-ended questions.”

The authors drew attention to the greater mental health risks of adolescents, pointing out that about one in five adolescents have a diagnosable mental health disorder and one-quarter of adults with mood disorders had their first major depressive episode during adolescence. They also cited the Centers for Disease Control and Prevention’s 2017 Youth Risk Behavior Survey of high school students, which showed that adolescents with a parent serving in the military are at increased risk of suicidal ideation.

In addition, Dr. Alderman and Dr. Breuner said, mental health problems experienced by adolescents often are comorbid with eating disorders. Formerly obese adolescents, male teenagers, and young people from lower socioeconomic groups are increasingly developing anorexia nervosa, bulimia nervosa, and other disordered eating.

The paper called for more financial, educational, and training support for pediatricians and other health care professionals to enable them to better meet the health and developmental needs of adolescents.

Dr. Alderman and Dr. Breuner declared having no conflicts of interest.

SOURCE: Alderman EM and Breuner CC. Pediatrics. 2019 Nov 18. doi: 10.1542/peds.2019-3150 .

Dobutamine stress echocardiography could be used to predict which patients with single-vessel stable coronary artery disease are most likely to benefit from percutaneous coronary intervention, according to secondary analysis of data from the ORBITA trial.

In a study to be presented at the American Heart Association scientific sessions on Nov. 16, researchers outline the results of a stress-echo stratification of patients who participated in the Objective Randomized Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina (ORBITA) trial.

©Thinkstock

Patients with a prerandomization stress echo score at or above 1 were three times more likely to have a lower angina frequency score with PCI than with placebo (odds ratio, 3.18; 95% confidence interval, 1.38, 7.34; P = .007). They were also more than four times more likely to be free from angina with PCI compared to placebo (OR, 4.62; 95% CI, 1.70, 12.60; P = .003).

“We have previously found that there is a clear relationship between invasive physiology and stress echo score but no relationship between invasive physiology and placebo-controlled symptom improvement,” the authors wrote. “The present analysis shows that there is clear evidence of a relationship between ischemia on stress echo and the placebo-controlled efficacy of PCI on frequency of angina.”

The analysis, however, found no detectable interaction between prerandomization stress echo score and the effect of PCI on physical limitation score, quality of life, Canadian Cardiovascular Society angina class score, or treadmill time.

The mean prerandomization stress echo score was 1.56 in the PCI arm and 1.61 in the placebo arm.

The study also looked at the relationship between prerandomization stress echo score and fractional flow reserve. This revealed that, as the stress echo score increased with a greater number of ischemia myocardial segments, the fractional flow reserve value decreased, pointing to a greater degree of ischemia. Researchers also noted that as the stress echo score became larger, the instantaneous wave-free ratio also decreased significantly.

“This stress echo-stratified analysis shows the link between stress-induced myocardial wall motion abnormalities and patient-reported angina frequency,” the authors wrote. “The greater the ischemia on [dobutamine stress echocardiography], the greater the placebo-controlled angina relief from PCI.”

The study was funded by grants from the National Institute for Health Research Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, and in-kind support from Philips Volcano. Two authors declared patents relating to technology used in the study and three declared consultancies, speakers’ fees, and research grants from Philips Volcano. No other conflicts of interest were declared.

SOURCE: Al-Lamee R et al. Circulation. 2019 Nov 11. doi: doi.org/10.1161/CIRCULATIONAHA.119.042918.

Dobutamine stress echocardiography could be used to predict which patients with single-vessel stable coronary artery disease are most likely to benefit from percutaneous coronary intervention, according to secondary analysis of data from the ORBITA trial.

In a study to be presented at the American Heart Association scientific sessions on Nov. 16, researchers outline the results of a stress-echo stratification of patients who participated in the Objective Randomized Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina (ORBITA) trial.

©Thinkstock

Patients with a prerandomization stress echo score at or above 1 were three times more likely to have a lower angina frequency score with PCI than with placebo (odds ratio, 3.18; 95% confidence interval, 1.38, 7.34; P = .007). They were also more than four times more likely to be free from angina with PCI compared to placebo (OR, 4.62; 95% CI, 1.70, 12.60; P = .003).

“We have previously found that there is a clear relationship between invasive physiology and stress echo score but no relationship between invasive physiology and placebo-controlled symptom improvement,” the authors wrote. “The present analysis shows that there is clear evidence of a relationship between ischemia on stress echo and the placebo-controlled efficacy of PCI on frequency of angina.”

The analysis, however, found no detectable interaction between prerandomization stress echo score and the effect of PCI on physical limitation score, quality of life, Canadian Cardiovascular Society angina class score, or treadmill time.

The mean prerandomization stress echo score was 1.56 in the PCI arm and 1.61 in the placebo arm.

The study also looked at the relationship between prerandomization stress echo score and fractional flow reserve. This revealed that, as the stress echo score increased with a greater number of ischemia myocardial segments, the fractional flow reserve value decreased, pointing to a greater degree of ischemia. Researchers also noted that as the stress echo score became larger, the instantaneous wave-free ratio also decreased significantly.

“This stress echo-stratified analysis shows the link between stress-induced myocardial wall motion abnormalities and patient-reported angina frequency,” the authors wrote. “The greater the ischemia on [dobutamine stress echocardiography], the greater the placebo-controlled angina relief from PCI.”

The study was funded by grants from the National Institute for Health Research Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, and in-kind support from Philips Volcano. Two authors declared patents relating to technology used in the study and three declared consultancies, speakers’ fees, and research grants from Philips Volcano. No other conflicts of interest were declared.

SOURCE: Al-Lamee R et al. Circulation. 2019 Nov 11. doi: doi.org/10.1161/CIRCULATIONAHA.119.042918.

Dobutamine stress echocardiography could be used to predict which patients with single-vessel stable coronary artery disease are most likely to benefit from percutaneous coronary intervention, according to secondary analysis of data from the ORBITA trial.

In a study to be presented at the American Heart Association scientific sessions on Nov. 16, researchers outline the results of a stress-echo stratification of patients who participated in the Objective Randomized Blinded Investigation with Optimal Medical Therapy of Angioplasty in Stable Angina (ORBITA) trial.

©Thinkstock

Patients with a prerandomization stress echo score at or above 1 were three times more likely to have a lower angina frequency score with PCI than with placebo (odds ratio, 3.18; 95% confidence interval, 1.38, 7.34; P = .007). They were also more than four times more likely to be free from angina with PCI compared to placebo (OR, 4.62; 95% CI, 1.70, 12.60; P = .003).

“We have previously found that there is a clear relationship between invasive physiology and stress echo score but no relationship between invasive physiology and placebo-controlled symptom improvement,” the authors wrote. “The present analysis shows that there is clear evidence of a relationship between ischemia on stress echo and the placebo-controlled efficacy of PCI on frequency of angina.”

The analysis, however, found no detectable interaction between prerandomization stress echo score and the effect of PCI on physical limitation score, quality of life, Canadian Cardiovascular Society angina class score, or treadmill time.

The mean prerandomization stress echo score was 1.56 in the PCI arm and 1.61 in the placebo arm.

The study also looked at the relationship between prerandomization stress echo score and fractional flow reserve. This revealed that, as the stress echo score increased with a greater number of ischemia myocardial segments, the fractional flow reserve value decreased, pointing to a greater degree of ischemia. Researchers also noted that as the stress echo score became larger, the instantaneous wave-free ratio also decreased significantly.

“This stress echo-stratified analysis shows the link between stress-induced myocardial wall motion abnormalities and patient-reported angina frequency,” the authors wrote. “The greater the ischemia on [dobutamine stress echocardiography], the greater the placebo-controlled angina relief from PCI.”

The study was funded by grants from the National Institute for Health Research Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, and in-kind support from Philips Volcano. Two authors declared patents relating to technology used in the study and three declared consultancies, speakers’ fees, and research grants from Philips Volcano. No other conflicts of interest were declared.

SOURCE: Al-Lamee R et al. Circulation. 2019 Nov 11. doi: doi.org/10.1161/CIRCULATIONAHA.119.042918.

The rising cost of prescription drugs in the United States has prompted new recommendations by the American College of Physicians such as promoting the use of lower-cost generics and introducing annual out-of-pocket spending caps.

Darwin Brandis/Getty Images

Two position papers, published in Annals of Internal Medicine, outlined the College’s concerns about the increasing price of prescription drugs for Medicare and Medicaid, pointing out that the United States has an average annual per capita spend of $1,443 on pharmaceutical drugs and $1,026 on retail prescription drugs.

“The primary differences between health care expenditures in the United States versus other high-income nations are pricing of medical goods and services and the lack of direct price controls or negotiating power by centralized government health care systems,” wrote Hilary Daniel and Sue S. Bornstein, MD, of the Health Public Policy Committee of the American College of Physicians, in one of the papers.

They cited the example of new drugs for hepatitis C which, at more than $80,000 for a treatment course, accounted for 40% of the net growth in prescription drug spending in 2014.

Their first recommendation was to modify the Medicare Part D low-income subsidy (LIS) program, which currently supports approximately 12 million beneficiaries, to encourage the use of lower-cost generic or biosimilar drugs.

The rate of generic drug dispensing among LIS enrollees has been consistently 4%-5% lower than among non-LIS enrollees, they wrote. The Centers for Medicare & Medicaid Services estimated that Medicare could have saved nearly $9 billion, and passed on $3 billion in savings to the Part D program and its beneficiaries, if available equivalent generics were prescribed instead of brand-name drugs.

The authors wrote that zero-copay generics have had the strongest effect on generic drug use, both for LIS and non-LIS enrollees.

“Reducing or eliminating cost sharing for LIS enrollees would not require legislative action, because it would not increase cost sharing, would reduce overall out-of pocket costs for LIS enrollees, and would encourage use of generics among them,” they wrote. They authors of the paper also argued that this move could reduce Medicare spending on reinsurance payments, because most enrollees who reach the ‘catastrophic’ phase of coverage were in the LIS program.

The second recommendation was for annual out-of-pocket spending caps for Medicare Part D beneficiaries who reach the catastrophic phase of coverage. During 2007-2015, the number of seniors in Medicare Part D who reached this catastrophic limit of coverage doubled to more than 1 million, with those enrollees paying an average of more than $3,000 out of pocket in 2015 alone, the authors noted.

“Caps have been proposed in other areas of Medicare; a 2016 resolution from the House Committee on the Budget included a Medicare proposal with a catastrophic coverage cap on annual out-of-pocket expenses, which it called, ‘an important aspect of the private insurance market currently absent from Medicare that would safeguard the sickest and poorest beneficiaries,’ ” they wrote.

In an accompanying editorial, Shelley A. Jazowski of the University of North Carolina at Chapel Hill and coauthor Stacie B. Dusetzina, PhD, of Vanderbilt University, in Nashville, Tenn., said that, while a cap would improve financial protection for beneficiaries, it could result in trade-offs such as increased premiums to accommodate lower spending by some beneficiaries.

The American College of Physicians (ACP) supports a full repeal of the noninterference clause in the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, wrote the position paper’s authors. This Act prohibits Medicare from negotiating directly with pharmaceutical manufacturers over the price of drugs.

The position paper also advocated for interim approaches, such as allowing the Secretary of Health and Human Services to negotiate on the price of a limited set of high-cost or sole-source drugs.

“Although negotiation alone may not be enough to rein in drug prices, this approach would allow the government to leverage its purchasing power to reduce Medicare program costs while also allowing plan sponsors to maintain the power to negotiate for the vast majority of drugs covered in the program,” they wrote.

The editorial’s authors pointed out that the success of these negotiations would rely on the ability of Medicare to walk away from a bad deal, which could delay or limit the availability of some drugs with limited competitors.

The ACP also called for efforts to minimize the financial impact of misclassifications of prescription drugs in the Medicaid Drug Rebate Program on the federal government. One study found that these misclassifications occurred in 885 of the 30,000 drugs in the program. The EpiPen and EpiPen Jr autoinjectors, for example, were improperly classified as generic drugs, the paper states.

The authors’ final recommendation in the position paper was for further study of payment models that could reduce incentives to prescribe higher-priced drugs instead of lower-cost and similarly effective options.

In the second position paper, Ms. Daniel and Dr. Bornstein made policy recommendations targeted at pharmacy benefit managers. The first was to improve transparency for pharmacy benefit managers, such as by banning gag clauses that might prevent pharmacies from sharing pricing information with consumers.

“The continued lack of transparency from [pharmacy benefit managers] and insurers can hinder how patients, physicians, and others view the drug supply chain and can make it difficult to identify whether a particular entity is inappropriately driving up drug prices,” the authors wrote in the second position paper.

This was accompanied by a recommendation that accurate, understandable and actionable information on the price of prescription medication should be made available to physicians and patients at the point of prescription. They also called for health plans, pharmacy benefit managers and pharmaceutical manufacturers to share information on the amount paid for prescription drugs, aggregate amount of rebates, and pricing decisions to the Department of Health & Human Services and make that information publicly available, with exceptions for confidential data.

The editorial’s authors commented that many of the policy recommendations raised in the position paper were currently being debated in Congress, and there was clear support from physician groups to address drug pricing, out-of-pocket spending, and access.

“Although trade-offs will need to be considered before selection or implementation of policy solutions, policymakers must act to ensure that patients have access to the prescription drugs they need at a price that reflects the benefits to patients and society,” they wrote.

One author declared book royalties but no other conflicts of interest were declared.

SOURCES: Daniel H et al. Ann Intern Med. 2019 Nov 12. doi. 10.7326/M19-0013; doi. 10.7326/M19-0035.

The rising cost of prescription drugs in the United States has prompted new recommendations by the American College of Physicians such as promoting the use of lower-cost generics and introducing annual out-of-pocket spending caps.

Darwin Brandis/Getty Images

Two position papers, published in Annals of Internal Medicine, outlined the College’s concerns about the increasing price of prescription drugs for Medicare and Medicaid, pointing out that the United States has an average annual per capita spend of $1,443 on pharmaceutical drugs and $1,026 on retail prescription drugs.

“The primary differences between health care expenditures in the United States versus other high-income nations are pricing of medical goods and services and the lack of direct price controls or negotiating power by centralized government health care systems,” wrote Hilary Daniel and Sue S. Bornstein, MD, of the Health Public Policy Committee of the American College of Physicians, in one of the papers.

They cited the example of new drugs for hepatitis C which, at more than $80,000 for a treatment course, accounted for 40% of the net growth in prescription drug spending in 2014.

Their first recommendation was to modify the Medicare Part D low-income subsidy (LIS) program, which currently supports approximately 12 million beneficiaries, to encourage the use of lower-cost generic or biosimilar drugs.

The rate of generic drug dispensing among LIS enrollees has been consistently 4%-5% lower than among non-LIS enrollees, they wrote. The Centers for Medicare & Medicaid Services estimated that Medicare could have saved nearly $9 billion, and passed on $3 billion in savings to the Part D program and its beneficiaries, if available equivalent generics were prescribed instead of brand-name drugs.

The authors wrote that zero-copay generics have had the strongest effect on generic drug use, both for LIS and non-LIS enrollees.

“Reducing or eliminating cost sharing for LIS enrollees would not require legislative action, because it would not increase cost sharing, would reduce overall out-of pocket costs for LIS enrollees, and would encourage use of generics among them,” they wrote. They authors of the paper also argued that this move could reduce Medicare spending on reinsurance payments, because most enrollees who reach the ‘catastrophic’ phase of coverage were in the LIS program.

The second recommendation was for annual out-of-pocket spending caps for Medicare Part D beneficiaries who reach the catastrophic phase of coverage. During 2007-2015, the number of seniors in Medicare Part D who reached this catastrophic limit of coverage doubled to more than 1 million, with those enrollees paying an average of more than $3,000 out of pocket in 2015 alone, the authors noted.

“Caps have been proposed in other areas of Medicare; a 2016 resolution from the House Committee on the Budget included a Medicare proposal with a catastrophic coverage cap on annual out-of-pocket expenses, which it called, ‘an important aspect of the private insurance market currently absent from Medicare that would safeguard the sickest and poorest beneficiaries,’ ” they wrote.

In an accompanying editorial, Shelley A. Jazowski of the University of North Carolina at Chapel Hill and coauthor Stacie B. Dusetzina, PhD, of Vanderbilt University, in Nashville, Tenn., said that, while a cap would improve financial protection for beneficiaries, it could result in trade-offs such as increased premiums to accommodate lower spending by some beneficiaries.

The American College of Physicians (ACP) supports a full repeal of the noninterference clause in the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, wrote the position paper’s authors. This Act prohibits Medicare from negotiating directly with pharmaceutical manufacturers over the price of drugs.

The position paper also advocated for interim approaches, such as allowing the Secretary of Health and Human Services to negotiate on the price of a limited set of high-cost or sole-source drugs.

“Although negotiation alone may not be enough to rein in drug prices, this approach would allow the government to leverage its purchasing power to reduce Medicare program costs while also allowing plan sponsors to maintain the power to negotiate for the vast majority of drugs covered in the program,” they wrote.

The editorial’s authors pointed out that the success of these negotiations would rely on the ability of Medicare to walk away from a bad deal, which could delay or limit the availability of some drugs with limited competitors.

The ACP also called for efforts to minimize the financial impact of misclassifications of prescription drugs in the Medicaid Drug Rebate Program on the federal government. One study found that these misclassifications occurred in 885 of the 30,000 drugs in the program. The EpiPen and EpiPen Jr autoinjectors, for example, were improperly classified as generic drugs, the paper states.

The authors’ final recommendation in the position paper was for further study of payment models that could reduce incentives to prescribe higher-priced drugs instead of lower-cost and similarly effective options.

In the second position paper, Ms. Daniel and Dr. Bornstein made policy recommendations targeted at pharmacy benefit managers. The first was to improve transparency for pharmacy benefit managers, such as by banning gag clauses that might prevent pharmacies from sharing pricing information with consumers.

“The continued lack of transparency from [pharmacy benefit managers] and insurers can hinder how patients, physicians, and others view the drug supply chain and can make it difficult to identify whether a particular entity is inappropriately driving up drug prices,” the authors wrote in the second position paper.

This was accompanied by a recommendation that accurate, understandable and actionable information on the price of prescription medication should be made available to physicians and patients at the point of prescription. They also called for health plans, pharmacy benefit managers and pharmaceutical manufacturers to share information on the amount paid for prescription drugs, aggregate amount of rebates, and pricing decisions to the Department of Health & Human Services and make that information publicly available, with exceptions for confidential data.

The editorial’s authors commented that many of the policy recommendations raised in the position paper were currently being debated in Congress, and there was clear support from physician groups to address drug pricing, out-of-pocket spending, and access.

“Although trade-offs will need to be considered before selection or implementation of policy solutions, policymakers must act to ensure that patients have access to the prescription drugs they need at a price that reflects the benefits to patients and society,” they wrote.

One author declared book royalties but no other conflicts of interest were declared.

SOURCES: Daniel H et al. Ann Intern Med. 2019 Nov 12. doi. 10.7326/M19-0013; doi. 10.7326/M19-0035.

The rising cost of prescription drugs in the United States has prompted new recommendations by the American College of Physicians such as promoting the use of lower-cost generics and introducing annual out-of-pocket spending caps.

Darwin Brandis/Getty Images

Two position papers, published in Annals of Internal Medicine, outlined the College’s concerns about the increasing price of prescription drugs for Medicare and Medicaid, pointing out that the United States has an average annual per capita spend of $1,443 on pharmaceutical drugs and $1,026 on retail prescription drugs.

“The primary differences between health care expenditures in the United States versus other high-income nations are pricing of medical goods and services and the lack of direct price controls or negotiating power by centralized government health care systems,” wrote Hilary Daniel and Sue S. Bornstein, MD, of the Health Public Policy Committee of the American College of Physicians, in one of the papers.

They cited the example of new drugs for hepatitis C which, at more than $80,000 for a treatment course, accounted for 40% of the net growth in prescription drug spending in 2014.

Their first recommendation was to modify the Medicare Part D low-income subsidy (LIS) program, which currently supports approximately 12 million beneficiaries, to encourage the use of lower-cost generic or biosimilar drugs.

The rate of generic drug dispensing among LIS enrollees has been consistently 4%-5% lower than among non-LIS enrollees, they wrote. The Centers for Medicare & Medicaid Services estimated that Medicare could have saved nearly $9 billion, and passed on $3 billion in savings to the Part D program and its beneficiaries, if available equivalent generics were prescribed instead of brand-name drugs.

The authors wrote that zero-copay generics have had the strongest effect on generic drug use, both for LIS and non-LIS enrollees.

“Reducing or eliminating cost sharing for LIS enrollees would not require legislative action, because it would not increase cost sharing, would reduce overall out-of pocket costs for LIS enrollees, and would encourage use of generics among them,” they wrote. They authors of the paper also argued that this move could reduce Medicare spending on reinsurance payments, because most enrollees who reach the ‘catastrophic’ phase of coverage were in the LIS program.

The second recommendation was for annual out-of-pocket spending caps for Medicare Part D beneficiaries who reach the catastrophic phase of coverage. During 2007-2015, the number of seniors in Medicare Part D who reached this catastrophic limit of coverage doubled to more than 1 million, with those enrollees paying an average of more than $3,000 out of pocket in 2015 alone, the authors noted.

“Caps have been proposed in other areas of Medicare; a 2016 resolution from the House Committee on the Budget included a Medicare proposal with a catastrophic coverage cap on annual out-of-pocket expenses, which it called, ‘an important aspect of the private insurance market currently absent from Medicare that would safeguard the sickest and poorest beneficiaries,’ ” they wrote.

In an accompanying editorial, Shelley A. Jazowski of the University of North Carolina at Chapel Hill and coauthor Stacie B. Dusetzina, PhD, of Vanderbilt University, in Nashville, Tenn., said that, while a cap would improve financial protection for beneficiaries, it could result in trade-offs such as increased premiums to accommodate lower spending by some beneficiaries.

The American College of Physicians (ACP) supports a full repeal of the noninterference clause in the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, wrote the position paper’s authors. This Act prohibits Medicare from negotiating directly with pharmaceutical manufacturers over the price of drugs.

The position paper also advocated for interim approaches, such as allowing the Secretary of Health and Human Services to negotiate on the price of a limited set of high-cost or sole-source drugs.

“Although negotiation alone may not be enough to rein in drug prices, this approach would allow the government to leverage its purchasing power to reduce Medicare program costs while also allowing plan sponsors to maintain the power to negotiate for the vast majority of drugs covered in the program,” they wrote.

The editorial’s authors pointed out that the success of these negotiations would rely on the ability of Medicare to walk away from a bad deal, which could delay or limit the availability of some drugs with limited competitors.

The ACP also called for efforts to minimize the financial impact of misclassifications of prescription drugs in the Medicaid Drug Rebate Program on the federal government. One study found that these misclassifications occurred in 885 of the 30,000 drugs in the program. The EpiPen and EpiPen Jr autoinjectors, for example, were improperly classified as generic drugs, the paper states.

The authors’ final recommendation in the position paper was for further study of payment models that could reduce incentives to prescribe higher-priced drugs instead of lower-cost and similarly effective options.

In the second position paper, Ms. Daniel and Dr. Bornstein made policy recommendations targeted at pharmacy benefit managers. The first was to improve transparency for pharmacy benefit managers, such as by banning gag clauses that might prevent pharmacies from sharing pricing information with consumers.

“The continued lack of transparency from [pharmacy benefit managers] and insurers can hinder how patients, physicians, and others view the drug supply chain and can make it difficult to identify whether a particular entity is inappropriately driving up drug prices,” the authors wrote in the second position paper.

This was accompanied by a recommendation that accurate, understandable and actionable information on the price of prescription medication should be made available to physicians and patients at the point of prescription. They also called for health plans, pharmacy benefit managers and pharmaceutical manufacturers to share information on the amount paid for prescription drugs, aggregate amount of rebates, and pricing decisions to the Department of Health & Human Services and make that information publicly available, with exceptions for confidential data.

The editorial’s authors commented that many of the policy recommendations raised in the position paper were currently being debated in Congress, and there was clear support from physician groups to address drug pricing, out-of-pocket spending, and access.

“Although trade-offs will need to be considered before selection or implementation of policy solutions, policymakers must act to ensure that patients have access to the prescription drugs they need at a price that reflects the benefits to patients and society,” they wrote.

One author declared book royalties but no other conflicts of interest were declared.

SOURCES: Daniel H et al. Ann Intern Med. 2019 Nov 12. doi. 10.7326/M19-0013; doi. 10.7326/M19-0035.

Women with vulval cancer who have a negative sentinel node biopsy have a low risk of recurrence and good disease-specific survival outcomes, investigators report.

One of two current standard treatment approaches for early-stage vulval cancer is radical excision of the tumor and inguinofemoral lymph node dissection, wrote Ligita P. Froeding, MD, of Copenhagen University Hospital Rigshospitalet, and coauthors. Their report is in Gynecologic Oncology. However, this procedure is associated with the disabling complication of leg lymphedema, which can significantly affect a woman’s quality of life.

Radical excision with sentinel biopsy is also an option, but the authors said large, population-based studies on the safety of this procedure when performed outside multicenter clinical trials were lacking.

In a prospective, nationwide cohort study, researchers analyzed data from 190 patients with vulval cancer who underwent the sentinel node procedure and had a negative biopsy. Of these, 73 patients had a unilateral procedure and 117 had a bilateral biopsy.

Over a median follow-up of 30 months’ follow-up, 32 patients (16.8%) died – 12 (37.5%) of vulval cancer and 20 (62.5%) from other causes. The 3-year overall survival rate was 84% and disease-specific survival was 93%.

The overall rate of recurrence in these sentinel node–negative women was 12.1% during the follow-up period. Fourteen patients (7.4%) experienced an isolated local vulval recurrence at a median time of 16 months after their primary treatment, and eight of these patients subsequently underwent inguinofemoral lymph node dissection following treatment of the recurrence. Three patients in this group died from vulval cancer, so the 3-year overall survival rate for patients with recurrent disease was 58%.

Four patients developed an isolated groin recurrence at a median of 12 months, and were treated with a combination of inguinofemoral lymph node dissection and chemoradiation. Two then developed a second recurrence.

Histopathological revision of original sentinel node specimens from the four women who experienced groin recurrences revealed that two patients actually had metastases at the time of the sentinel node procedure. In one case there were scattered tumor cells measuring less than 0.1 mm, while in the other there was a metastasis measuring 0.9 mm that was seen in six consecutive slides.

The authors noted that the failure to detect these metastases occurred despite strict adherence to histopathological procedure protocols. They suggested the first misdiagnosis may have been the result of the pathologist’s reluctance to make a histological diagnosis with so few tumor cells present. The second slide was originally screened microscopically by a specially trained medical laboratory technician, before being signed out by a pathologist, which “potentially decreases the pathologist’s diagnostic awareness,” they suggested.

“In conclusion, our study showed that the SN procedure is safe in selected VC patients when the current guidelines are strictly followed, and the procedure is performed in specialized gynecological oncology centers with a high volume of patients.”

No conflicts of interest were declared.

SOURCE: Froeding L et al. Gynecol Oncol 2019 Nov 8. doi: 10.1016/j.ygyno.2019.10.024.

Women with vulval cancer who have a negative sentinel node biopsy have a low risk of recurrence and good disease-specific survival outcomes, investigators report.

One of two current standard treatment approaches for early-stage vulval cancer is radical excision of the tumor and inguinofemoral lymph node dissection, wrote Ligita P. Froeding, MD, of Copenhagen University Hospital Rigshospitalet, and coauthors. Their report is in Gynecologic Oncology. However, this procedure is associated with the disabling complication of leg lymphedema, which can significantly affect a woman’s quality of life.

Radical excision with sentinel biopsy is also an option, but the authors said large, population-based studies on the safety of this procedure when performed outside multicenter clinical trials were lacking.

In a prospective, nationwide cohort study, researchers analyzed data from 190 patients with vulval cancer who underwent the sentinel node procedure and had a negative biopsy. Of these, 73 patients had a unilateral procedure and 117 had a bilateral biopsy.

Over a median follow-up of 30 months’ follow-up, 32 patients (16.8%) died – 12 (37.5%) of vulval cancer and 20 (62.5%) from other causes. The 3-year overall survival rate was 84% and disease-specific survival was 93%.

The overall rate of recurrence in these sentinel node–negative women was 12.1% during the follow-up period. Fourteen patients (7.4%) experienced an isolated local vulval recurrence at a median time of 16 months after their primary treatment, and eight of these patients subsequently underwent inguinofemoral lymph node dissection following treatment of the recurrence. Three patients in this group died from vulval cancer, so the 3-year overall survival rate for patients with recurrent disease was 58%.

Four patients developed an isolated groin recurrence at a median of 12 months, and were treated with a combination of inguinofemoral lymph node dissection and chemoradiation. Two then developed a second recurrence.

Histopathological revision of original sentinel node specimens from the four women who experienced groin recurrences revealed that two patients actually had metastases at the time of the sentinel node procedure. In one case there were scattered tumor cells measuring less than 0.1 mm, while in the other there was a metastasis measuring 0.9 mm that was seen in six consecutive slides.

The authors noted that the failure to detect these metastases occurred despite strict adherence to histopathological procedure protocols. They suggested the first misdiagnosis may have been the result of the pathologist’s reluctance to make a histological diagnosis with so few tumor cells present. The second slide was originally screened microscopically by a specially trained medical laboratory technician, before being signed out by a pathologist, which “potentially decreases the pathologist’s diagnostic awareness,” they suggested.

“In conclusion, our study showed that the SN procedure is safe in selected VC patients when the current guidelines are strictly followed, and the procedure is performed in specialized gynecological oncology centers with a high volume of patients.”

No conflicts of interest were declared.

SOURCE: Froeding L et al. Gynecol Oncol 2019 Nov 8. doi: 10.1016/j.ygyno.2019.10.024.

Women with vulval cancer who have a negative sentinel node biopsy have a low risk of recurrence and good disease-specific survival outcomes, investigators report.

One of two current standard treatment approaches for early-stage vulval cancer is radical excision of the tumor and inguinofemoral lymph node dissection, wrote Ligita P. Froeding, MD, of Copenhagen University Hospital Rigshospitalet, and coauthors. Their report is in Gynecologic Oncology. However, this procedure is associated with the disabling complication of leg lymphedema, which can significantly affect a woman’s quality of life.

Radical excision with sentinel biopsy is also an option, but the authors said large, population-based studies on the safety of this procedure when performed outside multicenter clinical trials were lacking.

In a prospective, nationwide cohort study, researchers analyzed data from 190 patients with vulval cancer who underwent the sentinel node procedure and had a negative biopsy. Of these, 73 patients had a unilateral procedure and 117 had a bilateral biopsy.

Over a median follow-up of 30 months’ follow-up, 32 patients (16.8%) died – 12 (37.5%) of vulval cancer and 20 (62.5%) from other causes. The 3-year overall survival rate was 84% and disease-specific survival was 93%.

The overall rate of recurrence in these sentinel node–negative women was 12.1% during the follow-up period. Fourteen patients (7.4%) experienced an isolated local vulval recurrence at a median time of 16 months after their primary treatment, and eight of these patients subsequently underwent inguinofemoral lymph node dissection following treatment of the recurrence. Three patients in this group died from vulval cancer, so the 3-year overall survival rate for patients with recurrent disease was 58%.

Four patients developed an isolated groin recurrence at a median of 12 months, and were treated with a combination of inguinofemoral lymph node dissection and chemoradiation. Two then developed a second recurrence.

Histopathological revision of original sentinel node specimens from the four women who experienced groin recurrences revealed that two patients actually had metastases at the time of the sentinel node procedure. In one case there were scattered tumor cells measuring less than 0.1 mm, while in the other there was a metastasis measuring 0.9 mm that was seen in six consecutive slides.

The authors noted that the failure to detect these metastases occurred despite strict adherence to histopathological procedure protocols. They suggested the first misdiagnosis may have been the result of the pathologist’s reluctance to make a histological diagnosis with so few tumor cells present. The second slide was originally screened microscopically by a specially trained medical laboratory technician, before being signed out by a pathologist, which “potentially decreases the pathologist’s diagnostic awareness,” they suggested.

“In conclusion, our study showed that the SN procedure is safe in selected VC patients when the current guidelines are strictly followed, and the procedure is performed in specialized gynecological oncology centers with a high volume of patients.”

No conflicts of interest were declared.

SOURCE: Froeding L et al. Gynecol Oncol 2019 Nov 8. doi: 10.1016/j.ygyno.2019.10.024.

Veterans may be at higher risk of idiopathic rapid eye movement sleep behavior disorders, particularly if they have traumatic brain injury (TBI) or posttraumatic stress disorder (PTSD) according to a paper published in Sleep.

©marcociannarel/Thinkstock

In a prospective, cross-sectional study, researchers recruited 394 veterans – 94% of whom were male – who underwent in-lab video-polysomnography and questionnaires about REM sleep behavior disorder (RBD), as well as assessment of their trauma status and medical history.

Overall, 9% of subjects had RBD, a figure considerably higher than has been estimated in the general population (prevalence of 0.38%-1.0%). Seven percent had REM sleep without atonia, 31% had other parasomnias such as a history of dream enactment behavior, and 53% were classified as normal.

The majority of subjects determined to have RBD (n = 34) had either PTSD or comorbid TBI+PTSD (n = 19, 56%). The combined overall crude prevalence of RBD in subjects with either PTSD alone or TBI+PTSD was 16.8% (n = 19 out of 113).

The individuals with PTSD had a 2.81-fold greater odds of RBD and 3.13-fold greater odds of other parasomnias compared with those without PTSD.

Those with both traumatic brain injury and PTSD had 3.43-fold greater odds of RBD and 3.22-fold greater odds of other parasomnias compared with individuals without.

“Interestingly, the neuropathology underpinning PTSD shares common features with RBD, raising the question as to whether or not PTSD has a causal role in the development of RBD, or if a single pathophysiologic process generates two clinical entities,” wrote Jonathan E. Elliott, PhD, of the VA Portland Health Care System, and coauthors.

The researchers also looked for evidence of trauma-associated sleep disorder (TASD), a recently proposed phenomenological sleep disorder whose diagnostic criteria overlaps with REM sleep behavior disorder but includes subjects reporting having an inciting traumatic experience and a history of dreaming related to this experience as well as evidence of autonomic hyperarousal.

The researchers found 22 of the subjects with REM behavior disorder had a traumatic brain injury and/or PTSD, and 9 of these subjects reported evidence of altered dream mentation related to that prior traumatic experience. However, none showed evidence of autonomic nervous system hyperarousal that coincided with abnormal REM sleep activity.

The investigators noted that although the sample of 394 subjects with in-lab video-polysomnography is large, the study is underpowered to draw broader conclusions about prevalence of RBD among veterans. In addition, the study did not establish whether or not trauma exposure preceded, and contributed to, the development of parasomnias and this question should be pursued in further studies.

“Given the purported relationships between TBI, PTSD, RBD, and neurodegeneration, we sought to determine the crude prevalence and related associations of RBD following TBI and PTSD among veterans. Our data show that the prevalence of RBD and related parasomnias is significantly higher in veterans with PTSD and TBI+PTSD compared to veterans without a history of neuropsychiatric trauma,” the authors wrote.

No funding or conflicts of interest were declared.

SOURCE: Elliott JE et al. Sleep 2019 Oct 7. doi: 10.1093/sleep/zsz237.

Veterans may be at higher risk of idiopathic rapid eye movement sleep behavior disorders, particularly if they have traumatic brain injury (TBI) or posttraumatic stress disorder (PTSD) according to a paper published in Sleep.

©marcociannarel/Thinkstock

In a prospective, cross-sectional study, researchers recruited 394 veterans – 94% of whom were male – who underwent in-lab video-polysomnography and questionnaires about REM sleep behavior disorder (RBD), as well as assessment of their trauma status and medical history.

Overall, 9% of subjects had RBD, a figure considerably higher than has been estimated in the general population (prevalence of 0.38%-1.0%). Seven percent had REM sleep without atonia, 31% had other parasomnias such as a history of dream enactment behavior, and 53% were classified as normal.

The majority of subjects determined to have RBD (n = 34) had either PTSD or comorbid TBI+PTSD (n = 19, 56%). The combined overall crude prevalence of RBD in subjects with either PTSD alone or TBI+PTSD was 16.8% (n = 19 out of 113).

The individuals with PTSD had a 2.81-fold greater odds of RBD and 3.13-fold greater odds of other parasomnias compared with those without PTSD.

Those with both traumatic brain injury and PTSD had 3.43-fold greater odds of RBD and 3.22-fold greater odds of other parasomnias compared with individuals without.

“Interestingly, the neuropathology underpinning PTSD shares common features with RBD, raising the question as to whether or not PTSD has a causal role in the development of RBD, or if a single pathophysiologic process generates two clinical entities,” wrote Jonathan E. Elliott, PhD, of the VA Portland Health Care System, and coauthors.

The researchers also looked for evidence of trauma-associated sleep disorder (TASD), a recently proposed phenomenological sleep disorder whose diagnostic criteria overlaps with REM sleep behavior disorder but includes subjects reporting having an inciting traumatic experience and a history of dreaming related to this experience as well as evidence of autonomic hyperarousal.

The researchers found 22 of the subjects with REM behavior disorder had a traumatic brain injury and/or PTSD, and 9 of these subjects reported evidence of altered dream mentation related to that prior traumatic experience. However, none showed evidence of autonomic nervous system hyperarousal that coincided with abnormal REM sleep activity.

The investigators noted that although the sample of 394 subjects with in-lab video-polysomnography is large, the study is underpowered to draw broader conclusions about prevalence of RBD among veterans. In addition, the study did not establish whether or not trauma exposure preceded, and contributed to, the development of parasomnias and this question should be pursued in further studies.

“Given the purported relationships between TBI, PTSD, RBD, and neurodegeneration, we sought to determine the crude prevalence and related associations of RBD following TBI and PTSD among veterans. Our data show that the prevalence of RBD and related parasomnias is significantly higher in veterans with PTSD and TBI+PTSD compared to veterans without a history of neuropsychiatric trauma,” the authors wrote.

No funding or conflicts of interest were declared.

SOURCE: Elliott JE et al. Sleep 2019 Oct 7. doi: 10.1093/sleep/zsz237.

Veterans may be at higher risk of idiopathic rapid eye movement sleep behavior disorders, particularly if they have traumatic brain injury (TBI) or posttraumatic stress disorder (PTSD) according to a paper published in Sleep.

©marcociannarel/Thinkstock

In a prospective, cross-sectional study, researchers recruited 394 veterans – 94% of whom were male – who underwent in-lab video-polysomnography and questionnaires about REM sleep behavior disorder (RBD), as well as assessment of their trauma status and medical history.

Overall, 9% of subjects had RBD, a figure considerably higher than has been estimated in the general population (prevalence of 0.38%-1.0%). Seven percent had REM sleep without atonia, 31% had other parasomnias such as a history of dream enactment behavior, and 53% were classified as normal.

The majority of subjects determined to have RBD (n = 34) had either PTSD or comorbid TBI+PTSD (n = 19, 56%). The combined overall crude prevalence of RBD in subjects with either PTSD alone or TBI+PTSD was 16.8% (n = 19 out of 113).

The individuals with PTSD had a 2.81-fold greater odds of RBD and 3.13-fold greater odds of other parasomnias compared with those without PTSD.

Those with both traumatic brain injury and PTSD had 3.43-fold greater odds of RBD and 3.22-fold greater odds of other parasomnias compared with individuals without.

“Interestingly, the neuropathology underpinning PTSD shares common features with RBD, raising the question as to whether or not PTSD has a causal role in the development of RBD, or if a single pathophysiologic process generates two clinical entities,” wrote Jonathan E. Elliott, PhD, of the VA Portland Health Care System, and coauthors.

The researchers also looked for evidence of trauma-associated sleep disorder (TASD), a recently proposed phenomenological sleep disorder whose diagnostic criteria overlaps with REM sleep behavior disorder but includes subjects reporting having an inciting traumatic experience and a history of dreaming related to this experience as well as evidence of autonomic hyperarousal.

The researchers found 22 of the subjects with REM behavior disorder had a traumatic brain injury and/or PTSD, and 9 of these subjects reported evidence of altered dream mentation related to that prior traumatic experience. However, none showed evidence of autonomic nervous system hyperarousal that coincided with abnormal REM sleep activity.

The investigators noted that although the sample of 394 subjects with in-lab video-polysomnography is large, the study is underpowered to draw broader conclusions about prevalence of RBD among veterans. In addition, the study did not establish whether or not trauma exposure preceded, and contributed to, the development of parasomnias and this question should be pursued in further studies.

“Given the purported relationships between TBI, PTSD, RBD, and neurodegeneration, we sought to determine the crude prevalence and related associations of RBD following TBI and PTSD among veterans. Our data show that the prevalence of RBD and related parasomnias is significantly higher in veterans with PTSD and TBI+PTSD compared to veterans without a history of neuropsychiatric trauma,” the authors wrote.

No funding or conflicts of interest were declared.

SOURCE: Elliott JE et al. Sleep 2019 Oct 7. doi: 10.1093/sleep/zsz237.

Data from more than 5 million individuals has been used to develop an equation for predicting the risk of incident chronic kidney disease (CKD) in people with or without diabetes, according to a presentation at Kidney Week 2019, sponsored by the American Society of Nephrology.

In a paper published simultaneously online in JAMA, researchers reported the outcome of an individual-level data analysis of 34 multinational cohorts involving 5,222,711 individuals – including 781,627 with diabetes – from 28 countries as part of the Chronic Kidney Disease Prognosis Consortium.

“An equation for kidney failure risk may help improve care for patients with established CKD, but relatively little work has been performed to develop predictive tools to identify those at increased risk of developing CKD – defined by reduced eGFR [estimated glomerular filtration rate], despite the high lifetime risk of CKD – which is estimated to be 59.1% in the United States,” wrote Robert G. Nelson, MD, PhD, from the National Institute of Diabetes and Digestive and Kidney Diseases in Phoenix and colleagues.

Over a mean follow-up of 4 years, 15% of individuals without diabetes and 40% of individuals with diabetes developed incident chronic kidney disease, defined as an eGFR below 60 mL/min per 1.73m².

The key risk factors were older age, female sex, black race, hypertension, history of cardiovascular disease, lower eGFR values, and higher urine albumin to creatinine ratio. Smoking was also significantly associated with reduced eGFR but only in cohorts without diabetes. In cohorts with diabetes, elevated hemoglobin A_1c and the presence and type of diabetes medication were also significantly associated with reduced eGFR.

Using this information, the researchers developed a prediction model built from weighted-average hazard ratios and validated it in nine external validation cohorts of 18 study populations involving a total of 2,253,540 individuals. They found that in 16 of the 18 study populations, the slope of observed to predicted risk ranged from 0.80 to 1.25.

Moreover, in the cohorts without diabetes, the risk equations had a median C-statistic for the 5-year predicted probability of 0.845 (interquartile range, 0.789-0.890) and of 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes, the investigators reported.

“Several models have been developed for estimating the risk of prevalent and incident CKD and end-stage kidney disease, but even those with good discriminative performance have not always performed well for cohorts of people outside the original derivation cohort,” the authors wrote. They argued that their model “demonstrated high discrimination and variable calibration in diverse populations.”

However, they stressed that further study was needed to determine if use of the equations would actually lead to improvements in clinical care and patient outcomes. In an accompanying editorial, Sri Lekha Tummalapalli, MD, and Michelle M. Estrella, MD, of the Kidney Health Research Collaborative at the University of California, San Francisco, said the study and its focus on primary, rather than secondary, prevention of kidney disease is a critical step toward reducing the burden of that disease, especially given that an estimated 37 million people in the United States have chronic kidney disease.

It is also important, they added, that primary prevention of kidney disease is tailored to the individual patient’s risk because risk prediction and screening strategies are unlikely to improve outcomes if they are not paired with effective individualized interventions, such as lifestyle modification or management of blood pressure.

These risk equations could be more holistic by integrating the prediction of both elevated albuminuria and reduced eGFR because more than 40% of individuals with chronic kidney disease have increased albuminuria without reduced eGFR, they noted (JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17378).

The study and CKD Prognosis Consortium were supported by the U.S. National Kidney Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases. One author was supported by a grant from the German Research Foundation. Nine authors declared grants, consultancies, and other support from the private sector and research organizations. No other conflicts of interest were declared. Dr. Tummalapalli and Dr. Estrella reported no conflicts of interest.

SOURCE: Nelson R et al. JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17379.

Data from more than 5 million individuals has been used to develop an equation for predicting the risk of incident chronic kidney disease (CKD) in people with or without diabetes, according to a presentation at Kidney Week 2019, sponsored by the American Society of Nephrology.

In a paper published simultaneously online in JAMA, researchers reported the outcome of an individual-level data analysis of 34 multinational cohorts involving 5,222,711 individuals – including 781,627 with diabetes – from 28 countries as part of the Chronic Kidney Disease Prognosis Consortium.

“An equation for kidney failure risk may help improve care for patients with established CKD, but relatively little work has been performed to develop predictive tools to identify those at increased risk of developing CKD – defined by reduced eGFR [estimated glomerular filtration rate], despite the high lifetime risk of CKD – which is estimated to be 59.1% in the United States,” wrote Robert G. Nelson, MD, PhD, from the National Institute of Diabetes and Digestive and Kidney Diseases in Phoenix and colleagues.

Over a mean follow-up of 4 years, 15% of individuals without diabetes and 40% of individuals with diabetes developed incident chronic kidney disease, defined as an eGFR below 60 mL/min per 1.73m².

The key risk factors were older age, female sex, black race, hypertension, history of cardiovascular disease, lower eGFR values, and higher urine albumin to creatinine ratio. Smoking was also significantly associated with reduced eGFR but only in cohorts without diabetes. In cohorts with diabetes, elevated hemoglobin A_1c and the presence and type of diabetes medication were also significantly associated with reduced eGFR.

Using this information, the researchers developed a prediction model built from weighted-average hazard ratios and validated it in nine external validation cohorts of 18 study populations involving a total of 2,253,540 individuals. They found that in 16 of the 18 study populations, the slope of observed to predicted risk ranged from 0.80 to 1.25.

Moreover, in the cohorts without diabetes, the risk equations had a median C-statistic for the 5-year predicted probability of 0.845 (interquartile range, 0.789-0.890) and of 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes, the investigators reported.

“Several models have been developed for estimating the risk of prevalent and incident CKD and end-stage kidney disease, but even those with good discriminative performance have not always performed well for cohorts of people outside the original derivation cohort,” the authors wrote. They argued that their model “demonstrated high discrimination and variable calibration in diverse populations.”

However, they stressed that further study was needed to determine if use of the equations would actually lead to improvements in clinical care and patient outcomes. In an accompanying editorial, Sri Lekha Tummalapalli, MD, and Michelle M. Estrella, MD, of the Kidney Health Research Collaborative at the University of California, San Francisco, said the study and its focus on primary, rather than secondary, prevention of kidney disease is a critical step toward reducing the burden of that disease, especially given that an estimated 37 million people in the United States have chronic kidney disease.

It is also important, they added, that primary prevention of kidney disease is tailored to the individual patient’s risk because risk prediction and screening strategies are unlikely to improve outcomes if they are not paired with effective individualized interventions, such as lifestyle modification or management of blood pressure.

These risk equations could be more holistic by integrating the prediction of both elevated albuminuria and reduced eGFR because more than 40% of individuals with chronic kidney disease have increased albuminuria without reduced eGFR, they noted (JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17378).

The study and CKD Prognosis Consortium were supported by the U.S. National Kidney Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases. One author was supported by a grant from the German Research Foundation. Nine authors declared grants, consultancies, and other support from the private sector and research organizations. No other conflicts of interest were declared. Dr. Tummalapalli and Dr. Estrella reported no conflicts of interest.

SOURCE: Nelson R et al. JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17379.

Data from more than 5 million individuals has been used to develop an equation for predicting the risk of incident chronic kidney disease (CKD) in people with or without diabetes, according to a presentation at Kidney Week 2019, sponsored by the American Society of Nephrology.

In a paper published simultaneously online in JAMA, researchers reported the outcome of an individual-level data analysis of 34 multinational cohorts involving 5,222,711 individuals – including 781,627 with diabetes – from 28 countries as part of the Chronic Kidney Disease Prognosis Consortium.

“An equation for kidney failure risk may help improve care for patients with established CKD, but relatively little work has been performed to develop predictive tools to identify those at increased risk of developing CKD – defined by reduced eGFR [estimated glomerular filtration rate], despite the high lifetime risk of CKD – which is estimated to be 59.1% in the United States,” wrote Robert G. Nelson, MD, PhD, from the National Institute of Diabetes and Digestive and Kidney Diseases in Phoenix and colleagues.

Over a mean follow-up of 4 years, 15% of individuals without diabetes and 40% of individuals with diabetes developed incident chronic kidney disease, defined as an eGFR below 60 mL/min per 1.73m².

The key risk factors were older age, female sex, black race, hypertension, history of cardiovascular disease, lower eGFR values, and higher urine albumin to creatinine ratio. Smoking was also significantly associated with reduced eGFR but only in cohorts without diabetes. In cohorts with diabetes, elevated hemoglobin A_1c and the presence and type of diabetes medication were also significantly associated with reduced eGFR.

Using this information, the researchers developed a prediction model built from weighted-average hazard ratios and validated it in nine external validation cohorts of 18 study populations involving a total of 2,253,540 individuals. They found that in 16 of the 18 study populations, the slope of observed to predicted risk ranged from 0.80 to 1.25.

Moreover, in the cohorts without diabetes, the risk equations had a median C-statistic for the 5-year predicted probability of 0.845 (interquartile range, 0.789-0.890) and of 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes, the investigators reported.

“Several models have been developed for estimating the risk of prevalent and incident CKD and end-stage kidney disease, but even those with good discriminative performance have not always performed well for cohorts of people outside the original derivation cohort,” the authors wrote. They argued that their model “demonstrated high discrimination and variable calibration in diverse populations.”

However, they stressed that further study was needed to determine if use of the equations would actually lead to improvements in clinical care and patient outcomes. In an accompanying editorial, Sri Lekha Tummalapalli, MD, and Michelle M. Estrella, MD, of the Kidney Health Research Collaborative at the University of California, San Francisco, said the study and its focus on primary, rather than secondary, prevention of kidney disease is a critical step toward reducing the burden of that disease, especially given that an estimated 37 million people in the United States have chronic kidney disease.

It is also important, they added, that primary prevention of kidney disease is tailored to the individual patient’s risk because risk prediction and screening strategies are unlikely to improve outcomes if they are not paired with effective individualized interventions, such as lifestyle modification or management of blood pressure.

These risk equations could be more holistic by integrating the prediction of both elevated albuminuria and reduced eGFR because more than 40% of individuals with chronic kidney disease have increased albuminuria without reduced eGFR, they noted (JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17378).

The study and CKD Prognosis Consortium were supported by the U.S. National Kidney Foundation and the National Institute of Diabetes and Digestive and Kidney Diseases. One author was supported by a grant from the German Research Foundation. Nine authors declared grants, consultancies, and other support from the private sector and research organizations. No other conflicts of interest were declared. Dr. Tummalapalli and Dr. Estrella reported no conflicts of interest.

SOURCE: Nelson R et al. JAMA. 2019 Nov 8. doi: 10.1001/jama.2019.17379.

Integrating geriatric assessments into oncology consultations for older patients with cancer could help address aging-related concerns about their disease and treatment, a study has found.

In a study published in JAMA Oncology, researchers reported the outcomes of a cluster-randomized clinical trial involving 541 cancer patients aged 70 years and older, from 31 community oncology practices.

The trial examined the effects of an intervention in which the patient’s oncologist was provided with a geriatric assessment summary of that patient’s age-related impairments, and guided recommendations on how to manage these.

“As an example, the summary would include information that a patient recently fell, that falls increase the risk of chemotherapy toxic effects, and a recommendation for physical therapy to prevent falls,” wrote Supriya G. Mohile, MD, of the University of Rochester (N.Y.), and coauthors. The usual care control arm provided oncologists with alerts only if their patients had scored abnormally on depression and cognitive tests.

The study found that over 6 months, patients in the intervention group reported significantly greater satisfaction with communication about aging-related concerns and greater satisfaction with their overall care.

The intervention group had an adjusted mean of 8.02 conversations about aging-related concerns compared with 4.43 conversations in the usual care group, and an adjusted mean of 4.6 high-quality conversations compared with 2.59 in the usual care group. There were also significantly more conversations about the assessment recommendations in the intervention group compared with the usual care group.

There were no significant differences between the two groups in health-related quality of life for patients or their caregivers. However, caregivers in the intervention group did report significantly greater satisfaction with communication about aging-related concerns and the patient’s condition. They also reported significantly greater satisfaction with their own communications with oncologists about overall care.

“Evidence increasingly supports the use of GA for evaluation and management of older patients with cancer to guide shared decision-making between older patients, caregivers, and oncologists,” the authors wrote. “Despite patient and caregiver concerns and preferences for maintaining function and cognition, oncologists often do not discuss implications of aging-related conditions or inform older patients and caregivers of heightened risk of adverse events from treatment.”

Overall, 90% of patients had at least three geriatric assessment domain impairments; 93.7% had impairments in physical performance, 25.1% reported impairments in psychological status, and 33.3% had possible cognitive impairments.

“These patients represent less-fit individuals for whom there is limited evidence for the risks and benefits of cancer treatment, yet these patients are commonly seen in real-world community practices,” the authors wrote.

The study was supported by funding and individual research grants from the Patient-Centered Outcomes Research Institute, the University of Rochester, the National Institute of Aging, and the National Cancer Institute. Two authors also declared funding from the pharmaceutical sector outside the study.

SOURCE: Mohile S et al. JAMA Oncol. 2019 Nov 7. doi: 10.1001/jamaoncol.2019.4728.

Integrating geriatric assessments into oncology consultations for older patients with cancer could help address aging-related concerns about their disease and treatment, a study has found.

In a study published in JAMA Oncology, researchers reported the outcomes of a cluster-randomized clinical trial involving 541 cancer patients aged 70 years and older, from 31 community oncology practices.

The trial examined the effects of an intervention in which the patient’s oncologist was provided with a geriatric assessment summary of that patient’s age-related impairments, and guided recommendations on how to manage these.

“As an example, the summary would include information that a patient recently fell, that falls increase the risk of chemotherapy toxic effects, and a recommendation for physical therapy to prevent falls,” wrote Supriya G. Mohile, MD, of the University of Rochester (N.Y.), and coauthors. The usual care control arm provided oncologists with alerts only if their patients had scored abnormally on depression and cognitive tests.

The study found that over 6 months, patients in the intervention group reported significantly greater satisfaction with communication about aging-related concerns and greater satisfaction with their overall care.

The intervention group had an adjusted mean of 8.02 conversations about aging-related concerns compared with 4.43 conversations in the usual care group, and an adjusted mean of 4.6 high-quality conversations compared with 2.59 in the usual care group. There were also significantly more conversations about the assessment recommendations in the intervention group compared with the usual care group.

There were no significant differences between the two groups in health-related quality of life for patients or their caregivers. However, caregivers in the intervention group did report significantly greater satisfaction with communication about aging-related concerns and the patient’s condition. They also reported significantly greater satisfaction with their own communications with oncologists about overall care.

“Evidence increasingly supports the use of GA for evaluation and management of older patients with cancer to guide shared decision-making between older patients, caregivers, and oncologists,” the authors wrote. “Despite patient and caregiver concerns and preferences for maintaining function and cognition, oncologists often do not discuss implications of aging-related conditions or inform older patients and caregivers of heightened risk of adverse events from treatment.”

Overall, 90% of patients had at least three geriatric assessment domain impairments; 93.7% had impairments in physical performance, 25.1% reported impairments in psychological status, and 33.3% had possible cognitive impairments.

“These patients represent less-fit individuals for whom there is limited evidence for the risks and benefits of cancer treatment, yet these patients are commonly seen in real-world community practices,” the authors wrote.

The study was supported by funding and individual research grants from the Patient-Centered Outcomes Research Institute, the University of Rochester, the National Institute of Aging, and the National Cancer Institute. Two authors also declared funding from the pharmaceutical sector outside the study.

SOURCE: Mohile S et al. JAMA Oncol. 2019 Nov 7. doi: 10.1001/jamaoncol.2019.4728.

Integrating geriatric assessments into oncology consultations for older patients with cancer could help address aging-related concerns about their disease and treatment, a study has found.

In a study published in JAMA Oncology, researchers reported the outcomes of a cluster-randomized clinical trial involving 541 cancer patients aged 70 years and older, from 31 community oncology practices.

The trial examined the effects of an intervention in which the patient’s oncologist was provided with a geriatric assessment summary of that patient’s age-related impairments, and guided recommendations on how to manage these.

“As an example, the summary would include information that a patient recently fell, that falls increase the risk of chemotherapy toxic effects, and a recommendation for physical therapy to prevent falls,” wrote Supriya G. Mohile, MD, of the University of Rochester (N.Y.), and coauthors. The usual care control arm provided oncologists with alerts only if their patients had scored abnormally on depression and cognitive tests.

The study found that over 6 months, patients in the intervention group reported significantly greater satisfaction with communication about aging-related concerns and greater satisfaction with their overall care.

The intervention group had an adjusted mean of 8.02 conversations about aging-related concerns compared with 4.43 conversations in the usual care group, and an adjusted mean of 4.6 high-quality conversations compared with 2.59 in the usual care group. There were also significantly more conversations about the assessment recommendations in the intervention group compared with the usual care group.

There were no significant differences between the two groups in health-related quality of life for patients or their caregivers. However, caregivers in the intervention group did report significantly greater satisfaction with communication about aging-related concerns and the patient’s condition. They also reported significantly greater satisfaction with their own communications with oncologists about overall care.

“Evidence increasingly supports the use of GA for evaluation and management of older patients with cancer to guide shared decision-making between older patients, caregivers, and oncologists,” the authors wrote. “Despite patient and caregiver concerns and preferences for maintaining function and cognition, oncologists often do not discuss implications of aging-related conditions or inform older patients and caregivers of heightened risk of adverse events from treatment.”

Overall, 90% of patients had at least three geriatric assessment domain impairments; 93.7% had impairments in physical performance, 25.1% reported impairments in psychological status, and 33.3% had possible cognitive impairments.

“These patients represent less-fit individuals for whom there is limited evidence for the risks and benefits of cancer treatment, yet these patients are commonly seen in real-world community practices,” the authors wrote.

The study was supported by funding and individual research grants from the Patient-Centered Outcomes Research Institute, the University of Rochester, the National Institute of Aging, and the National Cancer Institute. Two authors also declared funding from the pharmaceutical sector outside the study.

SOURCE: Mohile S et al. JAMA Oncol. 2019 Nov 7. doi: 10.1001/jamaoncol.2019.4728.

Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.

CDC/Molly Kurnit, M.P.H.

The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.

“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.

“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”

In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 the children experienced mild measles, and 43 had severe measles.

They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.

This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.

The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.

“These results suggest that, rather than a simple loss of total IgG, there is a restructuring of the antibody repertoire after measles,” Dr. Mina and associates wrote.

They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.

In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.

The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
 

SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.

Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.

CDC/Molly Kurnit, M.P.H.

The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.

“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.

“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”

In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 the children experienced mild measles, and 43 had severe measles.

They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.

This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.

The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.

“These results suggest that, rather than a simple loss of total IgG, there is a restructuring of the antibody repertoire after measles,” Dr. Mina and associates wrote.

They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.

In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.

The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
 

SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.

Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.

CDC/Molly Kurnit, M.P.H.

The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.

“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.

“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”

In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 the children experienced mild measles, and 43 had severe measles.

They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.

This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.

The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.

“These results suggest that, rather than a simple loss of total IgG, there is a restructuring of the antibody repertoire after measles,” Dr. Mina and associates wrote.

They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.

In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.

Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).

In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.

The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
 

SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.

Patients with ankylosing spondylitis who are male, have evidence of spinal damage, or have higher levels of inflammatory markers may be at higher risk of disease progression, a study has found.

“Assessment of AS-related structural changes longitudinally is essential for understanding the natural course of progression and its underlying factors,” Ismail Sari, MD, of the University of Toronto and coauthors wrote in Arthritis Care & Research. “This could help identify the mechanisms responsible for progression and thereby personalizing treatment.”

The researchers found that nearly one-quarter (24.3%) of 350 individuals with ankylosing spondylitis in a longitudinal cohort study showed radiographic evidence of progression, defined as a change of 2 units on the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in 2 years. Overall, 76% of the group were males, and the group had a mean age of about 38 years with a mean symptom duration of nearly 15 years.

Over the 6-year follow-up, the mean mSASSS increased from 9.3 units at baseline to 17.7 units, with more progression seen in the cervical spine than the lumbar segments. During the first 2 years, the total mSASSS increased by a mean of 1.23 units; in years 2-4, it increased by a mean of 1.47 units, and from 4 to 6 years, it increased by a mean of 1.52 units.

Male sex was associated with more than double the risk of radiographic progression (hazard ratio, 2.46; 95% confidence interval, 1.05-5.76), while individuals with radiographic evidence of spinal damage at baseline had a nearly eightfold higher risk of progression (HR, 7.98; 95% CI, 3.98-16). The risk for disease progression also increased with higher levels of C-reactive protein.

The investigators also found that patients who had used tumor necrosis factor inhibitor therapy for at least 1 year had an 18% reduction in the rate of spinal progression.

However, other factors including symptom duration, presence of HLA-B27, smoking status, presence of radiographic hip disease, or use of disease-modifying antirheumatic drugs or NSAIDs did not appear to influence the risk of disease progression.

No funding or conflicts of interest were declared.

SOURCE: Sari I et al. Arthritis Care Res. 2019 Nov 1. doi: 10.1002/acr.24104.

Patients with ankylosing spondylitis who are male, have evidence of spinal damage, or have higher levels of inflammatory markers may be at higher risk of disease progression, a study has found.

“Assessment of AS-related structural changes longitudinally is essential for understanding the natural course of progression and its underlying factors,” Ismail Sari, MD, of the University of Toronto and coauthors wrote in Arthritis Care & Research. “This could help identify the mechanisms responsible for progression and thereby personalizing treatment.”

The researchers found that nearly one-quarter (24.3%) of 350 individuals with ankylosing spondylitis in a longitudinal cohort study showed radiographic evidence of progression, defined as a change of 2 units on the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in 2 years. Overall, 76% of the group were males, and the group had a mean age of about 38 years with a mean symptom duration of nearly 15 years.

Over the 6-year follow-up, the mean mSASSS increased from 9.3 units at baseline to 17.7 units, with more progression seen in the cervical spine than the lumbar segments. During the first 2 years, the total mSASSS increased by a mean of 1.23 units; in years 2-4, it increased by a mean of 1.47 units, and from 4 to 6 years, it increased by a mean of 1.52 units.

Male sex was associated with more than double the risk of radiographic progression (hazard ratio, 2.46; 95% confidence interval, 1.05-5.76), while individuals with radiographic evidence of spinal damage at baseline had a nearly eightfold higher risk of progression (HR, 7.98; 95% CI, 3.98-16). The risk for disease progression also increased with higher levels of C-reactive protein.

The investigators also found that patients who had used tumor necrosis factor inhibitor therapy for at least 1 year had an 18% reduction in the rate of spinal progression.

However, other factors including symptom duration, presence of HLA-B27, smoking status, presence of radiographic hip disease, or use of disease-modifying antirheumatic drugs or NSAIDs did not appear to influence the risk of disease progression.

No funding or conflicts of interest were declared.

SOURCE: Sari I et al. Arthritis Care Res. 2019 Nov 1. doi: 10.1002/acr.24104.

Patients with ankylosing spondylitis who are male, have evidence of spinal damage, or have higher levels of inflammatory markers may be at higher risk of disease progression, a study has found.

“Assessment of AS-related structural changes longitudinally is essential for understanding the natural course of progression and its underlying factors,” Ismail Sari, MD, of the University of Toronto and coauthors wrote in Arthritis Care & Research. “This could help identify the mechanisms responsible for progression and thereby personalizing treatment.”

The researchers found that nearly one-quarter (24.3%) of 350 individuals with ankylosing spondylitis in a longitudinal cohort study showed radiographic evidence of progression, defined as a change of 2 units on the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) in 2 years. Overall, 76% of the group were males, and the group had a mean age of about 38 years with a mean symptom duration of nearly 15 years.

Over the 6-year follow-up, the mean mSASSS increased from 9.3 units at baseline to 17.7 units, with more progression seen in the cervical spine than the lumbar segments. During the first 2 years, the total mSASSS increased by a mean of 1.23 units; in years 2-4, it increased by a mean of 1.47 units, and from 4 to 6 years, it increased by a mean of 1.52 units.

Male sex was associated with more than double the risk of radiographic progression (hazard ratio, 2.46; 95% confidence interval, 1.05-5.76), while individuals with radiographic evidence of spinal damage at baseline had a nearly eightfold higher risk of progression (HR, 7.98; 95% CI, 3.98-16). The risk for disease progression also increased with higher levels of C-reactive protein.

The investigators also found that patients who had used tumor necrosis factor inhibitor therapy for at least 1 year had an 18% reduction in the rate of spinal progression.

However, other factors including symptom duration, presence of HLA-B27, smoking status, presence of radiographic hip disease, or use of disease-modifying antirheumatic drugs or NSAIDs did not appear to influence the risk of disease progression.

No funding or conflicts of interest were declared.

SOURCE: Sari I et al. Arthritis Care Res. 2019 Nov 1. doi: 10.1002/acr.24104.