Journal of Clinical Outcomes Management

Parents who did not vaccinate their children against influenza last year were significantly less likely to do so this year than parents whose children were vaccinated last year, based on survey data from more than 2,000 parents with babies and young children.

Choreograph/Thinkstock

“Pediatric vaccination will be an important component to mitigating a dual influenza/COVID-19 epidemic,” Rebeccah L. Sokol, PhD, of Wayne State University, Detroit, and Anna H. Grummon, PhD, of Harvard School of Public Health, Boston, reported in Pediatrics.

Although the pandemic has increased acceptance of some healthy behaviors including handwashing and social distancing, the impact on influenza vaccination rates remains unknown, they said.

To assess parents’ current intentions for flu vaccination of young children this season, the researchers conducted an online survey of 2,164 parents or guardians of children aged between 6 months and 5 years in the United States. The 15-minute online survey was conducted in May 2020 and participants received gift cards. The primary outcome was the impact of the COVID-19 pandemic on parental intentions for having their child vaccinated against seasonal flu this year.

“We measured change categorically, with response options ranging from 1 (I became much less likely to get my child the flu shot next year) to 5 (I became much more likely to get my child the flu shot next year),” the researchers said.
 

Pandemic changes some parents’ plans

Overall, 60% of parents said that the ongoing pandemic had altered their flu vaccination intentions for their children. About 34% percent of parents whose children did not receive flu vaccine last year said they would not seek the vaccine this year because of the pandemic, compared with 25% of parents whose children received last year’s flu vaccine, a statistically significant difference (P < .001).

Approximately 21% of parents whose children received no flu vaccine last year said the pandemic made them more likely to seek vaccination for the 2020-2021 season, compared with 38% of parents whose children received last year’s flu vaccine.

“These results suggest that overall seasonal influenza vaccination rates may not increase simply because of an ongoing infectious disease pandemic. Instead, a significant predictor of future behavior remains past behavior,” Dr. Sokol and Dr. Grummon said.

The study findings were limited by several factors including the use of a convenience sample and the timing of the survey in May 2020, meaning that survey results might not be generalizable this fall as the pandemic persists, they noted. “Additionally, we assessed intentions to vaccinate; future research will clarify the COVID-19 pandemic’s influence on actual vaccination behaviors.”

The challenge of how to increase uptake of the influenza vaccine during the era of COVID-19 remains, and targeted efforts could include social norms messaging through social media, mass media, or health care providers to increase parents’ intentions to vaccinate, as well as vaccination reminders and presumptive announcements from health care providers that present vaccination as the default option, the researchers added.
 

Potential for ‘twindemic’ is real

The uptake of flu vaccination is especially important this year, Christopher J. Harrison, MD, director of the vaccine and treatment evaluation unit and professor of pediatrics at the University of Missouri–Kansas City, said in an interview.

“This year we are entering a flu season where the certainty of the timing as well as the potential severity of the season are not known. That said, social distancing and wearing masks – to the extent that enough people conform to COVID-19 precautions – could delay or even blunt the usual influenza season,” he noted.

Unfortunately, the Centers for Disease Control and Prevention and the Food and Drug Administration have had their credibility damaged by the challenges of creating a successful response on the fly to a uniquely multifaceted virus to which previous rules do not apply, Dr. Harrison said. In addition, public confidence was eroded when information about testing and reopening policies were released by non-CDC nonscientists and labeled “CDC recommended,” with no opportunity for the scientific community to correct inaccuracies.

“The current study reveals that public trust in influenza vaccine and indirectly in health authorities has been affected by the pandemic,” said Dr. Harrison. “Vaccine hesitancy has increased somewhat even among previous vaccine accepters. One wonders if promises of a quick COVID-19 vaccine increased mistrust of the FDA because of safety concerns, even among the most ardent provaccine population, and whether these concerns are bleeding over into influenza vaccine concerns.

“This only adds to the anxiety that families feel about visiting any medical facility for routine vaccines while the pandemic rages, and we now are in a fall SARS-CoV-2 resurgence,” he added.

Although the current study data are concerning, “there could still be a net gain of pediatric influenza vaccine uptake this season because the 34% less likely to immunize among previously nonimmunizing families would be counterbalanced by 21% of the same group being more likely to immunize their children [theoretical net loss of 13%],” Dr. Harrison explained. “But the pandemic seems to have motivated previously influenza-immunizing families, i.e. while 24% were less likely, 39% are more likely to immunize [theoretical net gain of 15%]. That said, we would still be way short of the number needed to get to herd immunity.”

Dr. Harrison said he found the findings somewhat surprising, but perhaps he should not have. “I had hoped for more acceptance rather than most people staying in their prior vaccine ‘opinion lanes,’ ending up with likely little overall net change in plans to immunize despite increased health awareness caused by a pandemic.”

However, “the U.S. population has been polarized on vaccines and particularly influenza vaccines for more than 50 years, so why would a pandemic make us less polarized, particularly when the pandemic itself has been a polarizing event?” he questioned.

The greatest barriers to flu vaccination for children this year include a lack of motivation among families to visit immunization sites, given the ongoing need for social distancing and masks, Dr. Harrison said.

“Another barrier is the waning public confidence in our medical/scientific national leaders and organizations,” he emphasized. “This makes it crucial that primary care providers step up and be extra strong vaccine advocates, despite the fact that pandemic economics and necessary safety processes have stressed providers and devastated practices. Indeed, in times of medical stress, no one gets more trust from families than their own personal provider.”

Ultimately, avenues for future research include asking diverse groups of families what they feel they need to hear to be more engaged in immunizing children against influenza. But for now, the current study findings identify that “the public is not uniformly responding to the pandemic’s influence on their likelihood of immunizing their children against influenza,” Dr. Harrison said.

“We now know the size of the problem and hopefully governments, public health organizations, pediatric advocates and clinical care givers can find ways to magnify the message that a pandemic year is not a year to avoid seasonal influenza vaccine unless one has a true contraindication,” Dr. Harrison said.

In addition, “one wonders if the poll were taken today – post the president’s COVID-19 illness – would the answers be different?” he noted.

Dr. Sokol’s work was supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development but otherwise had no financial conflicts to disclose. Dr. Harrison disclosed that his institution receives grant funding from Merck, Pfizer, and GlaxoSmithKline for pediatric noninfluenza vaccine studies on which he is a subinvestigator, and support from the CDC for pediatric respiratory and gastrointestinal virus surveillance studies on which he is an investigator.

SOURCE: Sokol RL, Grummon AH. Pediatrics. 2020 Sep 30. doi: 10.1542/peds.2020-022871.

Parents who did not vaccinate their children against influenza last year were significantly less likely to do so this year than parents whose children were vaccinated last year, based on survey data from more than 2,000 parents with babies and young children.

Choreograph/Thinkstock

“Pediatric vaccination will be an important component to mitigating a dual influenza/COVID-19 epidemic,” Rebeccah L. Sokol, PhD, of Wayne State University, Detroit, and Anna H. Grummon, PhD, of Harvard School of Public Health, Boston, reported in Pediatrics.

Although the pandemic has increased acceptance of some healthy behaviors including handwashing and social distancing, the impact on influenza vaccination rates remains unknown, they said.

To assess parents’ current intentions for flu vaccination of young children this season, the researchers conducted an online survey of 2,164 parents or guardians of children aged between 6 months and 5 years in the United States. The 15-minute online survey was conducted in May 2020 and participants received gift cards. The primary outcome was the impact of the COVID-19 pandemic on parental intentions for having their child vaccinated against seasonal flu this year.

“We measured change categorically, with response options ranging from 1 (I became much less likely to get my child the flu shot next year) to 5 (I became much more likely to get my child the flu shot next year),” the researchers said.
 

Pandemic changes some parents’ plans

Overall, 60% of parents said that the ongoing pandemic had altered their flu vaccination intentions for their children. About 34% percent of parents whose children did not receive flu vaccine last year said they would not seek the vaccine this year because of the pandemic, compared with 25% of parents whose children received last year’s flu vaccine, a statistically significant difference (P < .001).

Approximately 21% of parents whose children received no flu vaccine last year said the pandemic made them more likely to seek vaccination for the 2020-2021 season, compared with 38% of parents whose children received last year’s flu vaccine.

“These results suggest that overall seasonal influenza vaccination rates may not increase simply because of an ongoing infectious disease pandemic. Instead, a significant predictor of future behavior remains past behavior,” Dr. Sokol and Dr. Grummon said.

The study findings were limited by several factors including the use of a convenience sample and the timing of the survey in May 2020, meaning that survey results might not be generalizable this fall as the pandemic persists, they noted. “Additionally, we assessed intentions to vaccinate; future research will clarify the COVID-19 pandemic’s influence on actual vaccination behaviors.”

The challenge of how to increase uptake of the influenza vaccine during the era of COVID-19 remains, and targeted efforts could include social norms messaging through social media, mass media, or health care providers to increase parents’ intentions to vaccinate, as well as vaccination reminders and presumptive announcements from health care providers that present vaccination as the default option, the researchers added.
 

Potential for ‘twindemic’ is real

The uptake of flu vaccination is especially important this year, Christopher J. Harrison, MD, director of the vaccine and treatment evaluation unit and professor of pediatrics at the University of Missouri–Kansas City, said in an interview.

“This year we are entering a flu season where the certainty of the timing as well as the potential severity of the season are not known. That said, social distancing and wearing masks – to the extent that enough people conform to COVID-19 precautions – could delay or even blunt the usual influenza season,” he noted.

Unfortunately, the Centers for Disease Control and Prevention and the Food and Drug Administration have had their credibility damaged by the challenges of creating a successful response on the fly to a uniquely multifaceted virus to which previous rules do not apply, Dr. Harrison said. In addition, public confidence was eroded when information about testing and reopening policies were released by non-CDC nonscientists and labeled “CDC recommended,” with no opportunity for the scientific community to correct inaccuracies.

“The current study reveals that public trust in influenza vaccine and indirectly in health authorities has been affected by the pandemic,” said Dr. Harrison. “Vaccine hesitancy has increased somewhat even among previous vaccine accepters. One wonders if promises of a quick COVID-19 vaccine increased mistrust of the FDA because of safety concerns, even among the most ardent provaccine population, and whether these concerns are bleeding over into influenza vaccine concerns.

“This only adds to the anxiety that families feel about visiting any medical facility for routine vaccines while the pandemic rages, and we now are in a fall SARS-CoV-2 resurgence,” he added.

Although the current study data are concerning, “there could still be a net gain of pediatric influenza vaccine uptake this season because the 34% less likely to immunize among previously nonimmunizing families would be counterbalanced by 21% of the same group being more likely to immunize their children [theoretical net loss of 13%],” Dr. Harrison explained. “But the pandemic seems to have motivated previously influenza-immunizing families, i.e. while 24% were less likely, 39% are more likely to immunize [theoretical net gain of 15%]. That said, we would still be way short of the number needed to get to herd immunity.”

Dr. Harrison said he found the findings somewhat surprising, but perhaps he should not have. “I had hoped for more acceptance rather than most people staying in their prior vaccine ‘opinion lanes,’ ending up with likely little overall net change in plans to immunize despite increased health awareness caused by a pandemic.”

However, “the U.S. population has been polarized on vaccines and particularly influenza vaccines for more than 50 years, so why would a pandemic make us less polarized, particularly when the pandemic itself has been a polarizing event?” he questioned.

The greatest barriers to flu vaccination for children this year include a lack of motivation among families to visit immunization sites, given the ongoing need for social distancing and masks, Dr. Harrison said.

“Another barrier is the waning public confidence in our medical/scientific national leaders and organizations,” he emphasized. “This makes it crucial that primary care providers step up and be extra strong vaccine advocates, despite the fact that pandemic economics and necessary safety processes have stressed providers and devastated practices. Indeed, in times of medical stress, no one gets more trust from families than their own personal provider.”

Ultimately, avenues for future research include asking diverse groups of families what they feel they need to hear to be more engaged in immunizing children against influenza. But for now, the current study findings identify that “the public is not uniformly responding to the pandemic’s influence on their likelihood of immunizing their children against influenza,” Dr. Harrison said.

“We now know the size of the problem and hopefully governments, public health organizations, pediatric advocates and clinical care givers can find ways to magnify the message that a pandemic year is not a year to avoid seasonal influenza vaccine unless one has a true contraindication,” Dr. Harrison said.

In addition, “one wonders if the poll were taken today – post the president’s COVID-19 illness – would the answers be different?” he noted.

Dr. Sokol’s work was supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development but otherwise had no financial conflicts to disclose. Dr. Harrison disclosed that his institution receives grant funding from Merck, Pfizer, and GlaxoSmithKline for pediatric noninfluenza vaccine studies on which he is a subinvestigator, and support from the CDC for pediatric respiratory and gastrointestinal virus surveillance studies on which he is an investigator.

SOURCE: Sokol RL, Grummon AH. Pediatrics. 2020 Sep 30. doi: 10.1542/peds.2020-022871.

Parents who did not vaccinate their children against influenza last year were significantly less likely to do so this year than parents whose children were vaccinated last year, based on survey data from more than 2,000 parents with babies and young children.

Choreograph/Thinkstock

“Pediatric vaccination will be an important component to mitigating a dual influenza/COVID-19 epidemic,” Rebeccah L. Sokol, PhD, of Wayne State University, Detroit, and Anna H. Grummon, PhD, of Harvard School of Public Health, Boston, reported in Pediatrics.

Although the pandemic has increased acceptance of some healthy behaviors including handwashing and social distancing, the impact on influenza vaccination rates remains unknown, they said.

To assess parents’ current intentions for flu vaccination of young children this season, the researchers conducted an online survey of 2,164 parents or guardians of children aged between 6 months and 5 years in the United States. The 15-minute online survey was conducted in May 2020 and participants received gift cards. The primary outcome was the impact of the COVID-19 pandemic on parental intentions for having their child vaccinated against seasonal flu this year.

“We measured change categorically, with response options ranging from 1 (I became much less likely to get my child the flu shot next year) to 5 (I became much more likely to get my child the flu shot next year),” the researchers said.
 

Pandemic changes some parents’ plans

Overall, 60% of parents said that the ongoing pandemic had altered their flu vaccination intentions for their children. About 34% percent of parents whose children did not receive flu vaccine last year said they would not seek the vaccine this year because of the pandemic, compared with 25% of parents whose children received last year’s flu vaccine, a statistically significant difference (P < .001).

Approximately 21% of parents whose children received no flu vaccine last year said the pandemic made them more likely to seek vaccination for the 2020-2021 season, compared with 38% of parents whose children received last year’s flu vaccine.

“These results suggest that overall seasonal influenza vaccination rates may not increase simply because of an ongoing infectious disease pandemic. Instead, a significant predictor of future behavior remains past behavior,” Dr. Sokol and Dr. Grummon said.

The study findings were limited by several factors including the use of a convenience sample and the timing of the survey in May 2020, meaning that survey results might not be generalizable this fall as the pandemic persists, they noted. “Additionally, we assessed intentions to vaccinate; future research will clarify the COVID-19 pandemic’s influence on actual vaccination behaviors.”

The challenge of how to increase uptake of the influenza vaccine during the era of COVID-19 remains, and targeted efforts could include social norms messaging through social media, mass media, or health care providers to increase parents’ intentions to vaccinate, as well as vaccination reminders and presumptive announcements from health care providers that present vaccination as the default option, the researchers added.
 

Potential for ‘twindemic’ is real

The uptake of flu vaccination is especially important this year, Christopher J. Harrison, MD, director of the vaccine and treatment evaluation unit and professor of pediatrics at the University of Missouri–Kansas City, said in an interview.

“This year we are entering a flu season where the certainty of the timing as well as the potential severity of the season are not known. That said, social distancing and wearing masks – to the extent that enough people conform to COVID-19 precautions – could delay or even blunt the usual influenza season,” he noted.

Unfortunately, the Centers for Disease Control and Prevention and the Food and Drug Administration have had their credibility damaged by the challenges of creating a successful response on the fly to a uniquely multifaceted virus to which previous rules do not apply, Dr. Harrison said. In addition, public confidence was eroded when information about testing and reopening policies were released by non-CDC nonscientists and labeled “CDC recommended,” with no opportunity for the scientific community to correct inaccuracies.

“The current study reveals that public trust in influenza vaccine and indirectly in health authorities has been affected by the pandemic,” said Dr. Harrison. “Vaccine hesitancy has increased somewhat even among previous vaccine accepters. One wonders if promises of a quick COVID-19 vaccine increased mistrust of the FDA because of safety concerns, even among the most ardent provaccine population, and whether these concerns are bleeding over into influenza vaccine concerns.

“This only adds to the anxiety that families feel about visiting any medical facility for routine vaccines while the pandemic rages, and we now are in a fall SARS-CoV-2 resurgence,” he added.

Although the current study data are concerning, “there could still be a net gain of pediatric influenza vaccine uptake this season because the 34% less likely to immunize among previously nonimmunizing families would be counterbalanced by 21% of the same group being more likely to immunize their children [theoretical net loss of 13%],” Dr. Harrison explained. “But the pandemic seems to have motivated previously influenza-immunizing families, i.e. while 24% were less likely, 39% are more likely to immunize [theoretical net gain of 15%]. That said, we would still be way short of the number needed to get to herd immunity.”

Dr. Harrison said he found the findings somewhat surprising, but perhaps he should not have. “I had hoped for more acceptance rather than most people staying in their prior vaccine ‘opinion lanes,’ ending up with likely little overall net change in plans to immunize despite increased health awareness caused by a pandemic.”

However, “the U.S. population has been polarized on vaccines and particularly influenza vaccines for more than 50 years, so why would a pandemic make us less polarized, particularly when the pandemic itself has been a polarizing event?” he questioned.

The greatest barriers to flu vaccination for children this year include a lack of motivation among families to visit immunization sites, given the ongoing need for social distancing and masks, Dr. Harrison said.

“Another barrier is the waning public confidence in our medical/scientific national leaders and organizations,” he emphasized. “This makes it crucial that primary care providers step up and be extra strong vaccine advocates, despite the fact that pandemic economics and necessary safety processes have stressed providers and devastated practices. Indeed, in times of medical stress, no one gets more trust from families than their own personal provider.”

Ultimately, avenues for future research include asking diverse groups of families what they feel they need to hear to be more engaged in immunizing children against influenza. But for now, the current study findings identify that “the public is not uniformly responding to the pandemic’s influence on their likelihood of immunizing their children against influenza,” Dr. Harrison said.

“We now know the size of the problem and hopefully governments, public health organizations, pediatric advocates and clinical care givers can find ways to magnify the message that a pandemic year is not a year to avoid seasonal influenza vaccine unless one has a true contraindication,” Dr. Harrison said.

In addition, “one wonders if the poll were taken today – post the president’s COVID-19 illness – would the answers be different?” he noted.

Dr. Sokol’s work was supported in part by the Eunice Kennedy Shriver National Institute of Child Health and Human Development but otherwise had no financial conflicts to disclose. Dr. Harrison disclosed that his institution receives grant funding from Merck, Pfizer, and GlaxoSmithKline for pediatric noninfluenza vaccine studies on which he is a subinvestigator, and support from the CDC for pediatric respiratory and gastrointestinal virus surveillance studies on which he is an investigator.

SOURCE: Sokol RL, Grummon AH. Pediatrics. 2020 Sep 30. doi: 10.1542/peds.2020-022871.

Cardiac stress testing before hip and knee replacements has dropped steadily since 2006, according to results from a new study that also showed major cardiac complications to be low in the absence of stress testing – even among people with established risk factors.

Routine stress testing before noncardiac surgeries has come under fire in recent decades as an overuse of resources and a burden on patients. Practice guidelines issued in 2007 and 2014 by the American College of Cardiology and the American Heart Association sought to limit the use of preoperative testing to patients with specific cardiovascular risk factors who might have their management changed by the test results.

For their study, published online in JAMA Cardiology, Daniel S. Rubin, MD, of the University of Chicago and colleagues looked at employee-based insurance data, which included Medicare Advantage claims, for more than 800,000 total hip or knee arthroplasties (28% hip and 72% knee replacements) conducted between 2004 and 2017.

While some 10% of the cohort (mean age 62, 58% women) received a stress test in the 2 months before surgery, the investigators found that the frequency of preoperative stress testing dropped annually starting in late 2006, when it peaked at about 14%, to about 7% in 2017. Older age, male sex and a Revised Cardiac Risk Index score of 1 or greater were all associated with a higher likelihood of being tested.

The overall frequency of myocardial infarction or cardiac arrest was 0.24%, occurring in 1,677 of 686,067 patients. While the rate was higher in patients with at least one RCRI condition, this did not differ significantly between those who received a preoperative stress test and those who did not (0.60%; 221 of 36,554 vs. 0.57%; 694 of 122,466 patients.

The 2007 and 2014 ACC/AHA guidelines make clear that patients with zero RCRI conditions – which comprise a history of ischemic heart disease, heart failure, insulin therapy for diabetes, cerebrovascular disease, or chronic kidney disease – should not receive a stress test before an intermediate-risk surgery such as a hip or knee replacement. But in this study, Dr. Rubin and his colleagues found that almost half of patients who had no RCRI risk factors were stress tested anyway. This means, Dr. Rubin said in an interview, that “there’s still room for improvement” in reducing testing.

“I never want to question how a physician chooses to practice, but I have to applaud physicians for reining in the use of this test. We’re using less of this test and yet the incidence of myocardial infarction and cardiac arrest is also going down, which also calls into question whether we’re getting better at choosing the right patients for the test; or the test doesn’t impact outcomes; or overall health of these patients is improving,” he said.

One surprise finding in the study, Dr. Rubin noted, was a higher rate of complications among people without RCRI conditions who were stress tested, compared with those who were not, with a mean complication rate of 0.27%, compared with 0.14% among those who did not receive a test (P < .001). “The RCRI doesn’t capture certain things,” Dr. Rubin said. “And we know that no risk stratification tool is going to capture everything.”

The RCRI, he noted, is based on a clinical history. “If you haven’t been diagnosed yet, it won’t appear as a risk factor, even if you’re clearly at risk. The question then becomes for a physician, do you do the test or not? On a day-to-day basis it’s hard to make that decision because you want what’s best for the individual patient – and it’s hard to generalize from a study of 800,000 people what’s right for that one patient. That said, it doesn’t appear that stress testing improves outcomes and a decrease in testing appears appropriate.”

Dr. Rubin and his colleagues described as a weakness of their study that it did not capture the full scope of preoperative stress testing among Medicare patients, who are older and therefore more likely to be tested.

That the 2007 and 2014 practice guidelines bore on the drop in testing was not demonstrated by Dr. Rubin and colleagues’ study, which saw declines begin even before the guidelines were published. Nonetheless, the results appear to validate the approach advocated in the guidelines, said guideline coauthor Joshua Beckman, MD, of Vanderbilt University, whose recent research has focused on identifying risk factors for MI after noncardiac surgery.

“I hope that the guidelines have helped in changing the culture for the use of preoperative stress testing as a regular thing,” Dr. Beckman said in an interview. “In fact, the guidelines say you shouldn’t do anything before an operation that you wouldn’t do anyway. So these findings are certainly in agreement with what we’re suggesting and support the idea that unless you have something that is unstable or active, stress testing isn’t likely to help.”

Annemarie Thompson, MD, of Duke University in Durham, N.C., another coauthor on the 2014 guidelines, commented in an interview that Dr. Rubin and colleagues’ findings of a doubled rate of complications among people without RCRI conditions who were stress tested, compared with those who were not might mean something “other than just sheer overuse or overordering of tests inappropriately.”

Rather, she said, physicians might be seeing something in the clinic that cannot be captured by a screening tool reliant on existing diagnoses. “Maybe when they’re sitting in front of you in a clinic, they’re so immobile that you’re left wondering. Or maybe they haven’t been seen by a doctor in a long time,” Dr. Thompson said. “So they don’t have diagnoses if they haven’t been followed. I think what [this finding] shows is that clinicians are detecting something. They may not know what it is. But we have to give a little wiggle room to the clinician who is sitting there looking at a patient who looks like they may not make it through surgery.”

Dr. Thompson said it would be helpful, after a big-data study like this one, to go through the clinical histories of those patients – in this study fewer than 100 – who had no RCRI risk factors and yet were stress tested and ended up having complications. “Until then we’re not going to solve the mystery,” she said. “But it’s a very, very interesting study.”

Dr. Rubin is the president of DRDR Mobile Health, a company that creates mobile applications for health care and from which he has not received compensation. One of his coauthors on the study, Dr. Peter Nagele, reported fee income from Roche Diagnostics. Dr. Beckman disclosed personal fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and other pharmaceutical manufacturers. Dr. Thompson has no disclosures.

SOURCE: Rubin et al. JAMA Cardiol. 2020 Sep 30. doi: 10.1001/jamacardio.2020.4311.

Cardiac stress testing before hip and knee replacements has dropped steadily since 2006, according to results from a new study that also showed major cardiac complications to be low in the absence of stress testing – even among people with established risk factors.

Routine stress testing before noncardiac surgeries has come under fire in recent decades as an overuse of resources and a burden on patients. Practice guidelines issued in 2007 and 2014 by the American College of Cardiology and the American Heart Association sought to limit the use of preoperative testing to patients with specific cardiovascular risk factors who might have their management changed by the test results.

For their study, published online in JAMA Cardiology, Daniel S. Rubin, MD, of the University of Chicago and colleagues looked at employee-based insurance data, which included Medicare Advantage claims, for more than 800,000 total hip or knee arthroplasties (28% hip and 72% knee replacements) conducted between 2004 and 2017.

While some 10% of the cohort (mean age 62, 58% women) received a stress test in the 2 months before surgery, the investigators found that the frequency of preoperative stress testing dropped annually starting in late 2006, when it peaked at about 14%, to about 7% in 2017. Older age, male sex and a Revised Cardiac Risk Index score of 1 or greater were all associated with a higher likelihood of being tested.

The overall frequency of myocardial infarction or cardiac arrest was 0.24%, occurring in 1,677 of 686,067 patients. While the rate was higher in patients with at least one RCRI condition, this did not differ significantly between those who received a preoperative stress test and those who did not (0.60%; 221 of 36,554 vs. 0.57%; 694 of 122,466 patients.

The 2007 and 2014 ACC/AHA guidelines make clear that patients with zero RCRI conditions – which comprise a history of ischemic heart disease, heart failure, insulin therapy for diabetes, cerebrovascular disease, or chronic kidney disease – should not receive a stress test before an intermediate-risk surgery such as a hip or knee replacement. But in this study, Dr. Rubin and his colleagues found that almost half of patients who had no RCRI risk factors were stress tested anyway. This means, Dr. Rubin said in an interview, that “there’s still room for improvement” in reducing testing.

“I never want to question how a physician chooses to practice, but I have to applaud physicians for reining in the use of this test. We’re using less of this test and yet the incidence of myocardial infarction and cardiac arrest is also going down, which also calls into question whether we’re getting better at choosing the right patients for the test; or the test doesn’t impact outcomes; or overall health of these patients is improving,” he said.

One surprise finding in the study, Dr. Rubin noted, was a higher rate of complications among people without RCRI conditions who were stress tested, compared with those who were not, with a mean complication rate of 0.27%, compared with 0.14% among those who did not receive a test (P < .001). “The RCRI doesn’t capture certain things,” Dr. Rubin said. “And we know that no risk stratification tool is going to capture everything.”

The RCRI, he noted, is based on a clinical history. “If you haven’t been diagnosed yet, it won’t appear as a risk factor, even if you’re clearly at risk. The question then becomes for a physician, do you do the test or not? On a day-to-day basis it’s hard to make that decision because you want what’s best for the individual patient – and it’s hard to generalize from a study of 800,000 people what’s right for that one patient. That said, it doesn’t appear that stress testing improves outcomes and a decrease in testing appears appropriate.”

Dr. Rubin and his colleagues described as a weakness of their study that it did not capture the full scope of preoperative stress testing among Medicare patients, who are older and therefore more likely to be tested.

That the 2007 and 2014 practice guidelines bore on the drop in testing was not demonstrated by Dr. Rubin and colleagues’ study, which saw declines begin even before the guidelines were published. Nonetheless, the results appear to validate the approach advocated in the guidelines, said guideline coauthor Joshua Beckman, MD, of Vanderbilt University, whose recent research has focused on identifying risk factors for MI after noncardiac surgery.

“I hope that the guidelines have helped in changing the culture for the use of preoperative stress testing as a regular thing,” Dr. Beckman said in an interview. “In fact, the guidelines say you shouldn’t do anything before an operation that you wouldn’t do anyway. So these findings are certainly in agreement with what we’re suggesting and support the idea that unless you have something that is unstable or active, stress testing isn’t likely to help.”

Annemarie Thompson, MD, of Duke University in Durham, N.C., another coauthor on the 2014 guidelines, commented in an interview that Dr. Rubin and colleagues’ findings of a doubled rate of complications among people without RCRI conditions who were stress tested, compared with those who were not might mean something “other than just sheer overuse or overordering of tests inappropriately.”

Rather, she said, physicians might be seeing something in the clinic that cannot be captured by a screening tool reliant on existing diagnoses. “Maybe when they’re sitting in front of you in a clinic, they’re so immobile that you’re left wondering. Or maybe they haven’t been seen by a doctor in a long time,” Dr. Thompson said. “So they don’t have diagnoses if they haven’t been followed. I think what [this finding] shows is that clinicians are detecting something. They may not know what it is. But we have to give a little wiggle room to the clinician who is sitting there looking at a patient who looks like they may not make it through surgery.”

Dr. Thompson said it would be helpful, after a big-data study like this one, to go through the clinical histories of those patients – in this study fewer than 100 – who had no RCRI risk factors and yet were stress tested and ended up having complications. “Until then we’re not going to solve the mystery,” she said. “But it’s a very, very interesting study.”

Dr. Rubin is the president of DRDR Mobile Health, a company that creates mobile applications for health care and from which he has not received compensation. One of his coauthors on the study, Dr. Peter Nagele, reported fee income from Roche Diagnostics. Dr. Beckman disclosed personal fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and other pharmaceutical manufacturers. Dr. Thompson has no disclosures.

SOURCE: Rubin et al. JAMA Cardiol. 2020 Sep 30. doi: 10.1001/jamacardio.2020.4311.

Cardiac stress testing before hip and knee replacements has dropped steadily since 2006, according to results from a new study that also showed major cardiac complications to be low in the absence of stress testing – even among people with established risk factors.

Routine stress testing before noncardiac surgeries has come under fire in recent decades as an overuse of resources and a burden on patients. Practice guidelines issued in 2007 and 2014 by the American College of Cardiology and the American Heart Association sought to limit the use of preoperative testing to patients with specific cardiovascular risk factors who might have their management changed by the test results.

For their study, published online in JAMA Cardiology, Daniel S. Rubin, MD, of the University of Chicago and colleagues looked at employee-based insurance data, which included Medicare Advantage claims, for more than 800,000 total hip or knee arthroplasties (28% hip and 72% knee replacements) conducted between 2004 and 2017.

While some 10% of the cohort (mean age 62, 58% women) received a stress test in the 2 months before surgery, the investigators found that the frequency of preoperative stress testing dropped annually starting in late 2006, when it peaked at about 14%, to about 7% in 2017. Older age, male sex and a Revised Cardiac Risk Index score of 1 or greater were all associated with a higher likelihood of being tested.

The overall frequency of myocardial infarction or cardiac arrest was 0.24%, occurring in 1,677 of 686,067 patients. While the rate was higher in patients with at least one RCRI condition, this did not differ significantly between those who received a preoperative stress test and those who did not (0.60%; 221 of 36,554 vs. 0.57%; 694 of 122,466 patients.

The 2007 and 2014 ACC/AHA guidelines make clear that patients with zero RCRI conditions – which comprise a history of ischemic heart disease, heart failure, insulin therapy for diabetes, cerebrovascular disease, or chronic kidney disease – should not receive a stress test before an intermediate-risk surgery such as a hip or knee replacement. But in this study, Dr. Rubin and his colleagues found that almost half of patients who had no RCRI risk factors were stress tested anyway. This means, Dr. Rubin said in an interview, that “there’s still room for improvement” in reducing testing.

“I never want to question how a physician chooses to practice, but I have to applaud physicians for reining in the use of this test. We’re using less of this test and yet the incidence of myocardial infarction and cardiac arrest is also going down, which also calls into question whether we’re getting better at choosing the right patients for the test; or the test doesn’t impact outcomes; or overall health of these patients is improving,” he said.

One surprise finding in the study, Dr. Rubin noted, was a higher rate of complications among people without RCRI conditions who were stress tested, compared with those who were not, with a mean complication rate of 0.27%, compared with 0.14% among those who did not receive a test (P < .001). “The RCRI doesn’t capture certain things,” Dr. Rubin said. “And we know that no risk stratification tool is going to capture everything.”

The RCRI, he noted, is based on a clinical history. “If you haven’t been diagnosed yet, it won’t appear as a risk factor, even if you’re clearly at risk. The question then becomes for a physician, do you do the test or not? On a day-to-day basis it’s hard to make that decision because you want what’s best for the individual patient – and it’s hard to generalize from a study of 800,000 people what’s right for that one patient. That said, it doesn’t appear that stress testing improves outcomes and a decrease in testing appears appropriate.”

Dr. Rubin and his colleagues described as a weakness of their study that it did not capture the full scope of preoperative stress testing among Medicare patients, who are older and therefore more likely to be tested.

That the 2007 and 2014 practice guidelines bore on the drop in testing was not demonstrated by Dr. Rubin and colleagues’ study, which saw declines begin even before the guidelines were published. Nonetheless, the results appear to validate the approach advocated in the guidelines, said guideline coauthor Joshua Beckman, MD, of Vanderbilt University, whose recent research has focused on identifying risk factors for MI after noncardiac surgery.

“I hope that the guidelines have helped in changing the culture for the use of preoperative stress testing as a regular thing,” Dr. Beckman said in an interview. “In fact, the guidelines say you shouldn’t do anything before an operation that you wouldn’t do anyway. So these findings are certainly in agreement with what we’re suggesting and support the idea that unless you have something that is unstable or active, stress testing isn’t likely to help.”

Annemarie Thompson, MD, of Duke University in Durham, N.C., another coauthor on the 2014 guidelines, commented in an interview that Dr. Rubin and colleagues’ findings of a doubled rate of complications among people without RCRI conditions who were stress tested, compared with those who were not might mean something “other than just sheer overuse or overordering of tests inappropriately.”

Rather, she said, physicians might be seeing something in the clinic that cannot be captured by a screening tool reliant on existing diagnoses. “Maybe when they’re sitting in front of you in a clinic, they’re so immobile that you’re left wondering. Or maybe they haven’t been seen by a doctor in a long time,” Dr. Thompson said. “So they don’t have diagnoses if they haven’t been followed. I think what [this finding] shows is that clinicians are detecting something. They may not know what it is. But we have to give a little wiggle room to the clinician who is sitting there looking at a patient who looks like they may not make it through surgery.”

Dr. Thompson said it would be helpful, after a big-data study like this one, to go through the clinical histories of those patients – in this study fewer than 100 – who had no RCRI risk factors and yet were stress tested and ended up having complications. “Until then we’re not going to solve the mystery,” she said. “But it’s a very, very interesting study.”

Dr. Rubin is the president of DRDR Mobile Health, a company that creates mobile applications for health care and from which he has not received compensation. One of his coauthors on the study, Dr. Peter Nagele, reported fee income from Roche Diagnostics. Dr. Beckman disclosed personal fees from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, and other pharmaceutical manufacturers. Dr. Thompson has no disclosures.

SOURCE: Rubin et al. JAMA Cardiol. 2020 Sep 30. doi: 10.1001/jamacardio.2020.4311.

Black children and children living in urban areas are less likely to have opioid-related poisoning or withdrawal but more likely to experience abuse or dependence, compared with their White or rural/suburban counterparts, according to a study of 3.2 million Medicaid-enrolled children in North Carolina.

Analysis of the almost 138,000 prescription fills also showed that Black and urban children in North Carolina were less likely to fill a opioid prescription, suggesting a need “for future studies to explore racial and geographic opioid-related inequities in children,” Kelby W. Brown, MA, and associates at Duke University, Durham, N.C., said Oct. 5 in Health Affairs.

In 2016-2018, the prevalence of opioid-related adverse events, such as poisoning or withdrawal, was 24.0 per 100,000 children among Blacks aged 1-17 years, compared with 27.5 per 100,000 for whites. For other opioid-related harms such as abuse or dependence, the order was reversed: 60.2 for Blacks and 51.7 for Whites, the investigators reported. Children of all other races were lowest in both measures.

Geography also appears to play a part. The children in urban areas had the lowest rate of adverse events – 23.2 per 100,000 vs. 26.2 (suburban) and 26.7 (rural) – and the highest rate of other opioid-related harms – 58.1 vs. 49.0 (suburban) and 38.7 (rural), the Medicaid claims data showed.

Analysis of prescription fills revealed that black children aged 1-17 years had a significantly lower rate (2.7%) than Whites (3.1%) or those of other races (3.0%) and that urban children were significantly less likely to fill a prescription (2.7%) for opioids than the other two groups (suburban, 3.1%; rural, 3.4%), Mr. Brown and associates said.

The prescription data also showed that 48.4% of children aged 6-17 years who had an adverse event had filled a prescription for an opioid in the previous 6 months, compared with just 9.4% of those with other opioid-related harms. The median length of time since the last fill? Three days for children with an adverse event and 67 days for those with other harms, they said.

And those prescriptions, it turns out, were not coming just from the physicians of North Carolina. Physicians, with 35.5% of the prescription load, were the main source, but 33.3% of opioid fills in 2016-2018 came from dentists, and another 17.7% were written by advanced practice providers. Among physicians, the leading opioid-prescribing specialists were surgeons, with 17.3% of the total, the investigators reported.

“The distinct and separate groups of clinicians who prescribe opioids to children suggest the need for pediatric opioid prescribing guidelines, particularly for postprocedural pain,” Mr. Brown and associates wrote.

[email protected]

SOURCE: Brown KW et al. Health Aff. 2020;39(10):1737-42.

Black children and children living in urban areas are less likely to have opioid-related poisoning or withdrawal but more likely to experience abuse or dependence, compared with their White or rural/suburban counterparts, according to a study of 3.2 million Medicaid-enrolled children in North Carolina.

Analysis of the almost 138,000 prescription fills also showed that Black and urban children in North Carolina were less likely to fill a opioid prescription, suggesting a need “for future studies to explore racial and geographic opioid-related inequities in children,” Kelby W. Brown, MA, and associates at Duke University, Durham, N.C., said Oct. 5 in Health Affairs.

In 2016-2018, the prevalence of opioid-related adverse events, such as poisoning or withdrawal, was 24.0 per 100,000 children among Blacks aged 1-17 years, compared with 27.5 per 100,000 for whites. For other opioid-related harms such as abuse or dependence, the order was reversed: 60.2 for Blacks and 51.7 for Whites, the investigators reported. Children of all other races were lowest in both measures.

Geography also appears to play a part. The children in urban areas had the lowest rate of adverse events – 23.2 per 100,000 vs. 26.2 (suburban) and 26.7 (rural) – and the highest rate of other opioid-related harms – 58.1 vs. 49.0 (suburban) and 38.7 (rural), the Medicaid claims data showed.

Analysis of prescription fills revealed that black children aged 1-17 years had a significantly lower rate (2.7%) than Whites (3.1%) or those of other races (3.0%) and that urban children were significantly less likely to fill a prescription (2.7%) for opioids than the other two groups (suburban, 3.1%; rural, 3.4%), Mr. Brown and associates said.

The prescription data also showed that 48.4% of children aged 6-17 years who had an adverse event had filled a prescription for an opioid in the previous 6 months, compared with just 9.4% of those with other opioid-related harms. The median length of time since the last fill? Three days for children with an adverse event and 67 days for those with other harms, they said.

And those prescriptions, it turns out, were not coming just from the physicians of North Carolina. Physicians, with 35.5% of the prescription load, were the main source, but 33.3% of opioid fills in 2016-2018 came from dentists, and another 17.7% were written by advanced practice providers. Among physicians, the leading opioid-prescribing specialists were surgeons, with 17.3% of the total, the investigators reported.

“The distinct and separate groups of clinicians who prescribe opioids to children suggest the need for pediatric opioid prescribing guidelines, particularly for postprocedural pain,” Mr. Brown and associates wrote.

[email protected]

SOURCE: Brown KW et al. Health Aff. 2020;39(10):1737-42.

Black children and children living in urban areas are less likely to have opioid-related poisoning or withdrawal but more likely to experience abuse or dependence, compared with their White or rural/suburban counterparts, according to a study of 3.2 million Medicaid-enrolled children in North Carolina.

Analysis of the almost 138,000 prescription fills also showed that Black and urban children in North Carolina were less likely to fill a opioid prescription, suggesting a need “for future studies to explore racial and geographic opioid-related inequities in children,” Kelby W. Brown, MA, and associates at Duke University, Durham, N.C., said Oct. 5 in Health Affairs.

In 2016-2018, the prevalence of opioid-related adverse events, such as poisoning or withdrawal, was 24.0 per 100,000 children among Blacks aged 1-17 years, compared with 27.5 per 100,000 for whites. For other opioid-related harms such as abuse or dependence, the order was reversed: 60.2 for Blacks and 51.7 for Whites, the investigators reported. Children of all other races were lowest in both measures.

Geography also appears to play a part. The children in urban areas had the lowest rate of adverse events – 23.2 per 100,000 vs. 26.2 (suburban) and 26.7 (rural) – and the highest rate of other opioid-related harms – 58.1 vs. 49.0 (suburban) and 38.7 (rural), the Medicaid claims data showed.

Analysis of prescription fills revealed that black children aged 1-17 years had a significantly lower rate (2.7%) than Whites (3.1%) or those of other races (3.0%) and that urban children were significantly less likely to fill a prescription (2.7%) for opioids than the other two groups (suburban, 3.1%; rural, 3.4%), Mr. Brown and associates said.

The prescription data also showed that 48.4% of children aged 6-17 years who had an adverse event had filled a prescription for an opioid in the previous 6 months, compared with just 9.4% of those with other opioid-related harms. The median length of time since the last fill? Three days for children with an adverse event and 67 days for those with other harms, they said.

And those prescriptions, it turns out, were not coming just from the physicians of North Carolina. Physicians, with 35.5% of the prescription load, were the main source, but 33.3% of opioid fills in 2016-2018 came from dentists, and another 17.7% were written by advanced practice providers. Among physicians, the leading opioid-prescribing specialists were surgeons, with 17.3% of the total, the investigators reported.

“The distinct and separate groups of clinicians who prescribe opioids to children suggest the need for pediatric opioid prescribing guidelines, particularly for postprocedural pain,” Mr. Brown and associates wrote.

[email protected]

SOURCE: Brown KW et al. Health Aff. 2020;39(10):1737-42.

Spain and China used very different public health responses to the COVID-19 crisis, and that has had significant consequences in terms of the mental health as well as physical health of the two countries’ citizens, Roger Ho, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.
 

Dr. Ho, a psychiatrist at the National University of Singapore, presented a first-of-its-kind cross-cultural comparative study of the impact of the COVID-19 pandemic in two epicenters on opposite sides of the world. A total of 1,539 participants drawn from the general populations in the two countries completed the online National University of Singapore COVID-19 Questionnaire. The survey was conducted in late February/early March in China and in mid-April in Spain, times of intense disease activity in the countries.

The questionnaire assesses knowledge and concerns about COVID, precautionary measures taken in the last 14 days, contact history, and physical symptoms related to COVID in the last 14 days. The pandemic’s psychological impact was evaluated using the Impact of Event Scale–Revised (IES-R). Participants also completed the Depression, Anxiety, and Stress-21 Scale (DASS-21).

Of note, the pandemic has taken a vastly greater physical toll in Spain than China. As of May 5, there were 83,000 confirmed cases of COVID-19 in China, with a population of 1.39 billion, compared with 248,000 in Spain, with a population of 46.9 million. The Spanish case rate of 5,500 per 1 million population was 100 times greater than China’s; the Spanish mortality rate of 585 per million was 185-fold greater.
 

Mental health findings

Spaniards experienced significantly higher levels of stress and depression as reflected in DASS-21 subscale scores of 14.22 and 8.65, respectively, compared with 7.86 and 6.38, in Chinese respondents. Spanish subjects also reported greater anxiety levels than the Chinese on the DASS-21 anxiety subscale, although not to a statistically significant extent. Yet, counterintuitively, given the DASS-21 results, the pandemic had a greater adverse psychological impact on the Chinese subjects as reflected in their significantly higher average IES-D score of 30.76 versus 27.64 in Spain. Dr. Ho offered a hypothesis as to why: The survey documented that many Chinese respondents felt socially stigmatized, and that their nation had been discriminated against by the rest of the world because the pandemic started in China.

Satisfaction with the public health response

Spanish respondents reported less confidence in their COVID-related medical services.

“This could be due to the rising number of infected health care workers in Spain. In contrast, the Chinese had more confidence in their medical services, probably because the government quickly deployed medical personnel and treated COVID-19 patients at rapidly built hospitals,” according to Dr. Ho.

Spain and other European countries shared four shortcomings in their pandemic response, he continued: lack of personal protective equipment for health care workers, delay in developing response strategies, a shortage of hospital beds, and inability to protect vulnerable elderly individuals from infection in nursing homes.

Experiencing cough, shortness of breath, myalgia, or other physical symptoms potentially associated with COVID-19 within the past 14 days was associated with worse depression, anxiety, and stress scores in both China and Spain. This underscores from a mental health standpoint the importance of rapid and accurate testing for the infection, Dr. Ho said.

Significantly more Spanish respondents felt there was too much unnecessary worry about COVID-19, suggesting a need for better health education regarding the pandemic.
 

Use of face masks

Consistent use of face masks regardless of the presence or absence of symptoms was far more common in the Chinese epicenter, where, unlike in Spain, this precautionary measure was associated with significantly lower IES-R and DASS-21 scores.

“One of the important findings in our study is that wearing a face mask seems to protect the mental health in China, but for the Spanish, wearing a face mask was associated with higher IES-R scores,” Dr. Ho said. “We understand that it is difficult for Europeans to accept the need to use masks for healthy people because mask-wearing suggests vulnerability to sickness and concealment of identity. The Chinese have a collective culture. They believe they should wear a face mask to protect their health and that of other people.”

Dr. Ho reported no financial conflicts regarding his study, conducted with coinvestigators at Huaibei (China) Normal University and Complutense University of Madrid.
 

[email protected]

SOURCE: Ho R. ECNP 2020, Session ISE01.

Spain and China used very different public health responses to the COVID-19 crisis, and that has had significant consequences in terms of the mental health as well as physical health of the two countries’ citizens, Roger Ho, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.
 

Dr. Ho, a psychiatrist at the National University of Singapore, presented a first-of-its-kind cross-cultural comparative study of the impact of the COVID-19 pandemic in two epicenters on opposite sides of the world. A total of 1,539 participants drawn from the general populations in the two countries completed the online National University of Singapore COVID-19 Questionnaire. The survey was conducted in late February/early March in China and in mid-April in Spain, times of intense disease activity in the countries.

The questionnaire assesses knowledge and concerns about COVID, precautionary measures taken in the last 14 days, contact history, and physical symptoms related to COVID in the last 14 days. The pandemic’s psychological impact was evaluated using the Impact of Event Scale–Revised (IES-R). Participants also completed the Depression, Anxiety, and Stress-21 Scale (DASS-21).

Of note, the pandemic has taken a vastly greater physical toll in Spain than China. As of May 5, there were 83,000 confirmed cases of COVID-19 in China, with a population of 1.39 billion, compared with 248,000 in Spain, with a population of 46.9 million. The Spanish case rate of 5,500 per 1 million population was 100 times greater than China’s; the Spanish mortality rate of 585 per million was 185-fold greater.
 

Mental health findings

Spaniards experienced significantly higher levels of stress and depression as reflected in DASS-21 subscale scores of 14.22 and 8.65, respectively, compared with 7.86 and 6.38, in Chinese respondents. Spanish subjects also reported greater anxiety levels than the Chinese on the DASS-21 anxiety subscale, although not to a statistically significant extent. Yet, counterintuitively, given the DASS-21 results, the pandemic had a greater adverse psychological impact on the Chinese subjects as reflected in their significantly higher average IES-D score of 30.76 versus 27.64 in Spain. Dr. Ho offered a hypothesis as to why: The survey documented that many Chinese respondents felt socially stigmatized, and that their nation had been discriminated against by the rest of the world because the pandemic started in China.

Satisfaction with the public health response

Spanish respondents reported less confidence in their COVID-related medical services.

“This could be due to the rising number of infected health care workers in Spain. In contrast, the Chinese had more confidence in their medical services, probably because the government quickly deployed medical personnel and treated COVID-19 patients at rapidly built hospitals,” according to Dr. Ho.

Spain and other European countries shared four shortcomings in their pandemic response, he continued: lack of personal protective equipment for health care workers, delay in developing response strategies, a shortage of hospital beds, and inability to protect vulnerable elderly individuals from infection in nursing homes.

Experiencing cough, shortness of breath, myalgia, or other physical symptoms potentially associated with COVID-19 within the past 14 days was associated with worse depression, anxiety, and stress scores in both China and Spain. This underscores from a mental health standpoint the importance of rapid and accurate testing for the infection, Dr. Ho said.

Significantly more Spanish respondents felt there was too much unnecessary worry about COVID-19, suggesting a need for better health education regarding the pandemic.
 

Use of face masks

Consistent use of face masks regardless of the presence or absence of symptoms was far more common in the Chinese epicenter, where, unlike in Spain, this precautionary measure was associated with significantly lower IES-R and DASS-21 scores.

“One of the important findings in our study is that wearing a face mask seems to protect the mental health in China, but for the Spanish, wearing a face mask was associated with higher IES-R scores,” Dr. Ho said. “We understand that it is difficult for Europeans to accept the need to use masks for healthy people because mask-wearing suggests vulnerability to sickness and concealment of identity. The Chinese have a collective culture. They believe they should wear a face mask to protect their health and that of other people.”

Dr. Ho reported no financial conflicts regarding his study, conducted with coinvestigators at Huaibei (China) Normal University and Complutense University of Madrid.
 

[email protected]

SOURCE: Ho R. ECNP 2020, Session ISE01.

Spain and China used very different public health responses to the COVID-19 crisis, and that has had significant consequences in terms of the mental health as well as physical health of the two countries’ citizens, Roger Ho, MD, reported at the virtual congress of the European College of Neuropsychopharmacology.
 

Dr. Ho, a psychiatrist at the National University of Singapore, presented a first-of-its-kind cross-cultural comparative study of the impact of the COVID-19 pandemic in two epicenters on opposite sides of the world. A total of 1,539 participants drawn from the general populations in the two countries completed the online National University of Singapore COVID-19 Questionnaire. The survey was conducted in late February/early March in China and in mid-April in Spain, times of intense disease activity in the countries.

The questionnaire assesses knowledge and concerns about COVID, precautionary measures taken in the last 14 days, contact history, and physical symptoms related to COVID in the last 14 days. The pandemic’s psychological impact was evaluated using the Impact of Event Scale–Revised (IES-R). Participants also completed the Depression, Anxiety, and Stress-21 Scale (DASS-21).

Of note, the pandemic has taken a vastly greater physical toll in Spain than China. As of May 5, there were 83,000 confirmed cases of COVID-19 in China, with a population of 1.39 billion, compared with 248,000 in Spain, with a population of 46.9 million. The Spanish case rate of 5,500 per 1 million population was 100 times greater than China’s; the Spanish mortality rate of 585 per million was 185-fold greater.
 

Mental health findings

Spaniards experienced significantly higher levels of stress and depression as reflected in DASS-21 subscale scores of 14.22 and 8.65, respectively, compared with 7.86 and 6.38, in Chinese respondents. Spanish subjects also reported greater anxiety levels than the Chinese on the DASS-21 anxiety subscale, although not to a statistically significant extent. Yet, counterintuitively, given the DASS-21 results, the pandemic had a greater adverse psychological impact on the Chinese subjects as reflected in their significantly higher average IES-D score of 30.76 versus 27.64 in Spain. Dr. Ho offered a hypothesis as to why: The survey documented that many Chinese respondents felt socially stigmatized, and that their nation had been discriminated against by the rest of the world because the pandemic started in China.

Satisfaction with the public health response

Spanish respondents reported less confidence in their COVID-related medical services.

“This could be due to the rising number of infected health care workers in Spain. In contrast, the Chinese had more confidence in their medical services, probably because the government quickly deployed medical personnel and treated COVID-19 patients at rapidly built hospitals,” according to Dr. Ho.

Spain and other European countries shared four shortcomings in their pandemic response, he continued: lack of personal protective equipment for health care workers, delay in developing response strategies, a shortage of hospital beds, and inability to protect vulnerable elderly individuals from infection in nursing homes.

Experiencing cough, shortness of breath, myalgia, or other physical symptoms potentially associated with COVID-19 within the past 14 days was associated with worse depression, anxiety, and stress scores in both China and Spain. This underscores from a mental health standpoint the importance of rapid and accurate testing for the infection, Dr. Ho said.

Significantly more Spanish respondents felt there was too much unnecessary worry about COVID-19, suggesting a need for better health education regarding the pandemic.
 

Use of face masks

Consistent use of face masks regardless of the presence or absence of symptoms was far more common in the Chinese epicenter, where, unlike in Spain, this precautionary measure was associated with significantly lower IES-R and DASS-21 scores.

“One of the important findings in our study is that wearing a face mask seems to protect the mental health in China, but for the Spanish, wearing a face mask was associated with higher IES-R scores,” Dr. Ho said. “We understand that it is difficult for Europeans to accept the need to use masks for healthy people because mask-wearing suggests vulnerability to sickness and concealment of identity. The Chinese have a collective culture. They believe they should wear a face mask to protect their health and that of other people.”

Dr. Ho reported no financial conflicts regarding his study, conducted with coinvestigators at Huaibei (China) Normal University and Complutense University of Madrid.
 

[email protected]

SOURCE: Ho R. ECNP 2020, Session ISE01.

President Donald Trump’s COVID-19 diagnosis is raising fresh questions about the White House’s strategy for testing and containing the virus for a president whose cavalier attitude about the coronavirus has persisted since it landed on American shores.

The president has said others are tested before getting close to him, appearing to hold it as an iron shield of safety. He has largely eschewed mask-wearing and social distancing in meetings, travel and public events, while holding rallies for thousands of often maskless supporters.

The Trump administration has increasingly pinned its coronavirus testing strategy for the nation on antigen tests, which do not need a traditional lab for processing and quickly return results to patients. But the results are less accurate than those of the slower PCR tests. 

An early antigen test used by the White House was woefully inaccurate. But the new antigen test the White House is using has not been independently evaluated for accuracy and reliability. Moreover, this is the kit the Trump administration is pushing out to thousands of nursing homes to test residents and staff.

Testing “isn’t a ‘get out of jail free card,’” said Dr. Alan Wells, medical director of clinical labs at the University of Pittsburgh Medical Center and creator of its test for the novel coronavirus. In general, antigen tests can miss up to half the cases that are detected by polymerase chain reaction tests, depending on the population of patients tested, he said.

The White House said the president’s diagnosis was confirmed with a PCR test but declined to say which test delivered his initial result. The White House has been using a new antigen test from Abbott Laboratories to screen its staff for COVID-19, according to two administration officials. 

The test, known as BinaxNOW, received an emergency use authorization from the Food and Drug Administration in August. It produces results in 15 minutes. Yet little is independently known about how effective it is. According to the company, the test is 97% accurate in detecting positives and 98.5% accurate in identifying those without disease. Abbott’s stated performance of its antigen test was based on examining people within 7 days of COVID symptoms appearing.

The president and first lady have both had symptoms, according to White House chief of staff Mark Meadows and the first lady’s Twitter account. The president was admitted to Walter Reed National Military Medical Center on Friday evening “out of an abundance of caution,” White House press secretary Kayleigh McEnany said in a statement.

Vice President Mike Pence is also tested daily for the virus and tested negative, spokesperson Devin O’Malley said Friday, but he did not respond to a follow-up question about which test was used.

Trump heavily promoted another Abbott rapid testing device, the ID NOW, earlier this year. But that test relies on different technology than the newer Abbott antigen test.

“I have not seen any independent evaluation of the Binax assay in the literature or in the blogs,” Wells said. “It is an unknown.”

The Department of Health and Human Services announced in August that it had signed a $760 million contract with Abbott for 150 million BinaxNOW antigen tests, which are now being distributed to nursing homes and historically black colleges and universities, as well as to governors to help inform decisions about opening and closing schools. The Big Ten football conference has also pinned playing hopes on the deployment of antigen tests following Trump’s political pressure.

However, even senior federal officials concede that a test alone isn’t likely to stop the spread of a virus that has sickened more than 7 million Americans.

“Testing does not substitute for avoiding crowded indoor spaces, washing hands, or wearing a mask when you can’t physically distance; further, a negative test today does not mean that you won’t be positive tomorrow,” Adm. Brett Giroir, the senior HHS official helming the administration’s testing effort, said in a statement at the time.

Trump could be part of a “super-spreading event,” said Dr. Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

Given the timing of Trump’s positive test — which he announced on Twitter early Friday – his infection “likely happened 5 or more days ago,” Osterholm said. “If so, then he was widely infectious as early as Tuesday,” the day of the first presidential debate in Cleveland.

At least seven people who attended a Rose Garden announcement last Saturday, when Trump announced his nomination of Judge Amy Coney Barrett to the Supreme Court, have since tested positive for the coronavirus. They include Trump’s former adviser Kellyanne Conway, Republican Sens. Mike Lee and Thom Tillis, and the president of the University of Notre Dame, the Rev. John Jenkins.

“Having that many infected people there all at one time, we’re still going to see transmission coming off that event for a couple days,” Osterholm said.

Osterholm notes that about 20% of infected people lead to 80% of COVID-19 cases, because “super spreaders” can infect so many people at once.

He notes that participants and audience members at Tuesday’s debate were separated by at least 6 feet. But 6 feet isn’t always enough to prevent infection, he said.

While many COVID-19 infections appear to be spread by respiratory droplets, which usually fall to the ground within 6 feet, people who are singing or speaking loudly can project virus much further. Evidence also suggests that the novel coronavirus can spread through aerosols, floating in the air like a speck of dust.

“I wonder how much virus was floating in that room that night,” Osterholm said.

Other experts say it’s too soon to say whether Trump was infected in a super-spreader event. “The president and his wife have had many exposures to many people in enclosed venues without protection,” so they could have been infected at any number of places, said Dr. William Schaffner, an infectious disease specialist at the Vanderbilt University School of Medicine. 

Although Democratic presidential candidate and former Vice President Joe Biden tested negative for the virus with a PCR test Friday, experts note that false-negative results are common in the first few days after infection. Test results over the next several days will yield more useful information.

It can take more than a week for the virus to reproduce enough to be detected, Wells said: “You are probably not detectable for 3, 5, 7, even 10 days after you’re exposed.”

In Minnesota, where Trump held an outdoor campaign rally in Duluth with hundreds of attendees Wednesday, health officials warned that a 14-day quarantine is necessary, regardless of test results.

“Anyone who was a direct contact of President Trump or known COVID-19 cases needs to quarantine and should get tested,” the Minnesota Department of Health said.

Ongoing lapses in test result reporting could hamper efforts to track and isolate sick people. As of Sept. 10, 21 states and the District of Columbia were not reporting all antigen test results, according to a KHN investigation, a lapse in reporting that officials say leaves them blind to disease spread. Since then, public health departments in Arizona, North Carolina and South Dakota all have announced plans to add antigen testing to their case reporting.

Requests for comment to the D.C. Department of Health were referred to Mayor Muriel Bowser’s office, which did not respond. District health officials told KHN in early September that the White House does not report antigen test results to them – a potential violation of federal law under the CARES Act, which says any institution performing tests to diagnose COVID-19 must report all results to local or state public health departments.

Dr. Amesh Adalja, a senior scholar at the Johns Hopkins University Center for Health Security, said it’s not surprising that Trump tested positive, given that so many of his close associates – including his national security adviser and Secret Service officers – have also been infected by the virus.

“When you look at the number of social contacts and travel schedules, it’s not surprising,” Adalja said.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

President Donald Trump’s COVID-19 diagnosis is raising fresh questions about the White House’s strategy for testing and containing the virus for a president whose cavalier attitude about the coronavirus has persisted since it landed on American shores.

The president has said others are tested before getting close to him, appearing to hold it as an iron shield of safety. He has largely eschewed mask-wearing and social distancing in meetings, travel and public events, while holding rallies for thousands of often maskless supporters.

The Trump administration has increasingly pinned its coronavirus testing strategy for the nation on antigen tests, which do not need a traditional lab for processing and quickly return results to patients. But the results are less accurate than those of the slower PCR tests. 

An early antigen test used by the White House was woefully inaccurate. But the new antigen test the White House is using has not been independently evaluated for accuracy and reliability. Moreover, this is the kit the Trump administration is pushing out to thousands of nursing homes to test residents and staff.

Testing “isn’t a ‘get out of jail free card,’” said Dr. Alan Wells, medical director of clinical labs at the University of Pittsburgh Medical Center and creator of its test for the novel coronavirus. In general, antigen tests can miss up to half the cases that are detected by polymerase chain reaction tests, depending on the population of patients tested, he said.

The White House said the president’s diagnosis was confirmed with a PCR test but declined to say which test delivered his initial result. The White House has been using a new antigen test from Abbott Laboratories to screen its staff for COVID-19, according to two administration officials. 

The test, known as BinaxNOW, received an emergency use authorization from the Food and Drug Administration in August. It produces results in 15 minutes. Yet little is independently known about how effective it is. According to the company, the test is 97% accurate in detecting positives and 98.5% accurate in identifying those without disease. Abbott’s stated performance of its antigen test was based on examining people within 7 days of COVID symptoms appearing.

The president and first lady have both had symptoms, according to White House chief of staff Mark Meadows and the first lady’s Twitter account. The president was admitted to Walter Reed National Military Medical Center on Friday evening “out of an abundance of caution,” White House press secretary Kayleigh McEnany said in a statement.

Vice President Mike Pence is also tested daily for the virus and tested negative, spokesperson Devin O’Malley said Friday, but he did not respond to a follow-up question about which test was used.

Trump heavily promoted another Abbott rapid testing device, the ID NOW, earlier this year. But that test relies on different technology than the newer Abbott antigen test.

“I have not seen any independent evaluation of the Binax assay in the literature or in the blogs,” Wells said. “It is an unknown.”

The Department of Health and Human Services announced in August that it had signed a $760 million contract with Abbott for 150 million BinaxNOW antigen tests, which are now being distributed to nursing homes and historically black colleges and universities, as well as to governors to help inform decisions about opening and closing schools. The Big Ten football conference has also pinned playing hopes on the deployment of antigen tests following Trump’s political pressure.

However, even senior federal officials concede that a test alone isn’t likely to stop the spread of a virus that has sickened more than 7 million Americans.

“Testing does not substitute for avoiding crowded indoor spaces, washing hands, or wearing a mask when you can’t physically distance; further, a negative test today does not mean that you won’t be positive tomorrow,” Adm. Brett Giroir, the senior HHS official helming the administration’s testing effort, said in a statement at the time.

Trump could be part of a “super-spreading event,” said Dr. Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

Given the timing of Trump’s positive test — which he announced on Twitter early Friday – his infection “likely happened 5 or more days ago,” Osterholm said. “If so, then he was widely infectious as early as Tuesday,” the day of the first presidential debate in Cleveland.

At least seven people who attended a Rose Garden announcement last Saturday, when Trump announced his nomination of Judge Amy Coney Barrett to the Supreme Court, have since tested positive for the coronavirus. They include Trump’s former adviser Kellyanne Conway, Republican Sens. Mike Lee and Thom Tillis, and the president of the University of Notre Dame, the Rev. John Jenkins.

“Having that many infected people there all at one time, we’re still going to see transmission coming off that event for a couple days,” Osterholm said.

Osterholm notes that about 20% of infected people lead to 80% of COVID-19 cases, because “super spreaders” can infect so many people at once.

He notes that participants and audience members at Tuesday’s debate were separated by at least 6 feet. But 6 feet isn’t always enough to prevent infection, he said.

While many COVID-19 infections appear to be spread by respiratory droplets, which usually fall to the ground within 6 feet, people who are singing or speaking loudly can project virus much further. Evidence also suggests that the novel coronavirus can spread through aerosols, floating in the air like a speck of dust.

“I wonder how much virus was floating in that room that night,” Osterholm said.

Other experts say it’s too soon to say whether Trump was infected in a super-spreader event. “The president and his wife have had many exposures to many people in enclosed venues without protection,” so they could have been infected at any number of places, said Dr. William Schaffner, an infectious disease specialist at the Vanderbilt University School of Medicine. 

Although Democratic presidential candidate and former Vice President Joe Biden tested negative for the virus with a PCR test Friday, experts note that false-negative results are common in the first few days after infection. Test results over the next several days will yield more useful information.

It can take more than a week for the virus to reproduce enough to be detected, Wells said: “You are probably not detectable for 3, 5, 7, even 10 days after you’re exposed.”

In Minnesota, where Trump held an outdoor campaign rally in Duluth with hundreds of attendees Wednesday, health officials warned that a 14-day quarantine is necessary, regardless of test results.

“Anyone who was a direct contact of President Trump or known COVID-19 cases needs to quarantine and should get tested,” the Minnesota Department of Health said.

Ongoing lapses in test result reporting could hamper efforts to track and isolate sick people. As of Sept. 10, 21 states and the District of Columbia were not reporting all antigen test results, according to a KHN investigation, a lapse in reporting that officials say leaves them blind to disease spread. Since then, public health departments in Arizona, North Carolina and South Dakota all have announced plans to add antigen testing to their case reporting.

Requests for comment to the D.C. Department of Health were referred to Mayor Muriel Bowser’s office, which did not respond. District health officials told KHN in early September that the White House does not report antigen test results to them – a potential violation of federal law under the CARES Act, which says any institution performing tests to diagnose COVID-19 must report all results to local or state public health departments.

Dr. Amesh Adalja, a senior scholar at the Johns Hopkins University Center for Health Security, said it’s not surprising that Trump tested positive, given that so many of his close associates – including his national security adviser and Secret Service officers – have also been infected by the virus.

“When you look at the number of social contacts and travel schedules, it’s not surprising,” Adalja said.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

President Donald Trump’s COVID-19 diagnosis is raising fresh questions about the White House’s strategy for testing and containing the virus for a president whose cavalier attitude about the coronavirus has persisted since it landed on American shores.

The president has said others are tested before getting close to him, appearing to hold it as an iron shield of safety. He has largely eschewed mask-wearing and social distancing in meetings, travel and public events, while holding rallies for thousands of often maskless supporters.

The Trump administration has increasingly pinned its coronavirus testing strategy for the nation on antigen tests, which do not need a traditional lab for processing and quickly return results to patients. But the results are less accurate than those of the slower PCR tests. 

An early antigen test used by the White House was woefully inaccurate. But the new antigen test the White House is using has not been independently evaluated for accuracy and reliability. Moreover, this is the kit the Trump administration is pushing out to thousands of nursing homes to test residents and staff.

Testing “isn’t a ‘get out of jail free card,’” said Dr. Alan Wells, medical director of clinical labs at the University of Pittsburgh Medical Center and creator of its test for the novel coronavirus. In general, antigen tests can miss up to half the cases that are detected by polymerase chain reaction tests, depending on the population of patients tested, he said.

The White House said the president’s diagnosis was confirmed with a PCR test but declined to say which test delivered his initial result. The White House has been using a new antigen test from Abbott Laboratories to screen its staff for COVID-19, according to two administration officials. 

The test, known as BinaxNOW, received an emergency use authorization from the Food and Drug Administration in August. It produces results in 15 minutes. Yet little is independently known about how effective it is. According to the company, the test is 97% accurate in detecting positives and 98.5% accurate in identifying those without disease. Abbott’s stated performance of its antigen test was based on examining people within 7 days of COVID symptoms appearing.

The president and first lady have both had symptoms, according to White House chief of staff Mark Meadows and the first lady’s Twitter account. The president was admitted to Walter Reed National Military Medical Center on Friday evening “out of an abundance of caution,” White House press secretary Kayleigh McEnany said in a statement.

Vice President Mike Pence is also tested daily for the virus and tested negative, spokesperson Devin O’Malley said Friday, but he did not respond to a follow-up question about which test was used.

Trump heavily promoted another Abbott rapid testing device, the ID NOW, earlier this year. But that test relies on different technology than the newer Abbott antigen test.

“I have not seen any independent evaluation of the Binax assay in the literature or in the blogs,” Wells said. “It is an unknown.”

The Department of Health and Human Services announced in August that it had signed a $760 million contract with Abbott for 150 million BinaxNOW antigen tests, which are now being distributed to nursing homes and historically black colleges and universities, as well as to governors to help inform decisions about opening and closing schools. The Big Ten football conference has also pinned playing hopes on the deployment of antigen tests following Trump’s political pressure.

However, even senior federal officials concede that a test alone isn’t likely to stop the spread of a virus that has sickened more than 7 million Americans.

“Testing does not substitute for avoiding crowded indoor spaces, washing hands, or wearing a mask when you can’t physically distance; further, a negative test today does not mean that you won’t be positive tomorrow,” Adm. Brett Giroir, the senior HHS official helming the administration’s testing effort, said in a statement at the time.

Trump could be part of a “super-spreading event,” said Dr. Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

Given the timing of Trump’s positive test — which he announced on Twitter early Friday – his infection “likely happened 5 or more days ago,” Osterholm said. “If so, then he was widely infectious as early as Tuesday,” the day of the first presidential debate in Cleveland.

At least seven people who attended a Rose Garden announcement last Saturday, when Trump announced his nomination of Judge Amy Coney Barrett to the Supreme Court, have since tested positive for the coronavirus. They include Trump’s former adviser Kellyanne Conway, Republican Sens. Mike Lee and Thom Tillis, and the president of the University of Notre Dame, the Rev. John Jenkins.

“Having that many infected people there all at one time, we’re still going to see transmission coming off that event for a couple days,” Osterholm said.

Osterholm notes that about 20% of infected people lead to 80% of COVID-19 cases, because “super spreaders” can infect so many people at once.

He notes that participants and audience members at Tuesday’s debate were separated by at least 6 feet. But 6 feet isn’t always enough to prevent infection, he said.

While many COVID-19 infections appear to be spread by respiratory droplets, which usually fall to the ground within 6 feet, people who are singing or speaking loudly can project virus much further. Evidence also suggests that the novel coronavirus can spread through aerosols, floating in the air like a speck of dust.

“I wonder how much virus was floating in that room that night,” Osterholm said.

Other experts say it’s too soon to say whether Trump was infected in a super-spreader event. “The president and his wife have had many exposures to many people in enclosed venues without protection,” so they could have been infected at any number of places, said Dr. William Schaffner, an infectious disease specialist at the Vanderbilt University School of Medicine. 

Although Democratic presidential candidate and former Vice President Joe Biden tested negative for the virus with a PCR test Friday, experts note that false-negative results are common in the first few days after infection. Test results over the next several days will yield more useful information.

It can take more than a week for the virus to reproduce enough to be detected, Wells said: “You are probably not detectable for 3, 5, 7, even 10 days after you’re exposed.”

In Minnesota, where Trump held an outdoor campaign rally in Duluth with hundreds of attendees Wednesday, health officials warned that a 14-day quarantine is necessary, regardless of test results.

“Anyone who was a direct contact of President Trump or known COVID-19 cases needs to quarantine and should get tested,” the Minnesota Department of Health said.

Ongoing lapses in test result reporting could hamper efforts to track and isolate sick people. As of Sept. 10, 21 states and the District of Columbia were not reporting all antigen test results, according to a KHN investigation, a lapse in reporting that officials say leaves them blind to disease spread. Since then, public health departments in Arizona, North Carolina and South Dakota all have announced plans to add antigen testing to their case reporting.

Requests for comment to the D.C. Department of Health were referred to Mayor Muriel Bowser’s office, which did not respond. District health officials told KHN in early September that the White House does not report antigen test results to them – a potential violation of federal law under the CARES Act, which says any institution performing tests to diagnose COVID-19 must report all results to local or state public health departments.

Dr. Amesh Adalja, a senior scholar at the Johns Hopkins University Center for Health Security, said it’s not surprising that Trump tested positive, given that so many of his close associates – including his national security adviser and Secret Service officers – have also been infected by the virus.

“When you look at the number of social contacts and travel schedules, it’s not surprising,” Adalja said.

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

The DAPA-CKD trial results, which proved dapagliflozin’s efficacy for slowing chronic kidney disease progression in patients selected for signs of worsening renal function, also have important messages for cardiologists, especially heart failure physicians.

Catherine Hackett/MDedge News

Those messages include findings that were “consistent” with the results of the earlier DAPA-HF trial, which tested the same sodium-glucose transporter 2 (SGLT2) inhibitor in patients selected for having heart failure with reduced ejection fraction (HFrEF). In addition, a specific action of dapagliflozin (Farxiga) on the patients in DAPA-CKD, which enrolled patients based on markers of chronic kidney disease (CKD), was prevention of first and recurrent heart failure hospitalizations, John J.V. McMurray, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America, further highlighting the role that dapagliflozin has in reducing both heart failure and renal events.
 

What DAPA-CKD means for heart failure

The main findings from the DAPA-CKD trial, published in September in the New England Journal of Medicine, included as a secondary outcome the combined rate of death from cardiovascular causes or hospitalization for heart failure (HHF). Treatment with dapagliflozin linked with a significant 29% relative reduction in this endpoint, compared with placebo-treated patients. At the HFSA meeting, Dr. McMurray reported for the first time the specific HHF numbers, a prespecified secondary endpoint for the study.

Patients on dapagliflozin had 37 total HHF events (1.7%), including both first-time and subsequent hospitalizations, while patients in the placebo arm had a total of 71 HHF events (3.3%) during the study’s median 2.4 years of follow-up, an absolute reduction of 1.6% that translated into a relative risk reduction of 49%.

The HHF findings from DAPA-CKD importantly showed that SGLT2 inhibition in patients with signs of renal dysfunction “will not only slow progression of kidney disease but will also reduce the risk of developing heart failure, crucially in patients with or without type 2 diabetes,” explained Dr. McMurray in an interview. “Cardiologists often consult in the kidney wards and advise on management of patients with chronic kidney disease, even those without heart failure.”

The DAPA-CKD findings carry another important message for heart failure management regarding the minimum level of renal function a patient can have and still safely receive dapagliflozin or possibly another agent from the same SGLT2 inhibitor class. In DAPA-CKD, patients safely received dapagliflozin with an estimated glomerular filtration rate (eGFR) as low as 25 mL/min per 1.73 m²; 14% of enrolled patients had an eGFR of 25-29 mL/min per 1.73 m².

“Typically, about 40%-50% of patients with heart failure have chronic kidney disease,” which makes this safety finding important to clinicians who care for heart failure patients, but it’s also important for any patient who might be a candidate for dapagliflozin or another drug from its class. “We had no strong evidence before this trial that SGLT2 inhibition could reduce hard renal endpoints,” specifically need for chronic dialysis, renal transplant, or renal death, “in patients with or without diabetes,” Dr. McMurray said.
 

DAPA-CKD grows the pool of eligible heart failure patients

A further consequence of the DAPA-CKD findings is that when, as expected, regulatory bodies give dapagliflozin an indication for treating the types of CKD patients enrolled in the trial, it will functionally expand this treatment to an even larger swath of heart failure patients who currently don’t qualify for this treatment, specifically patients with CKD who also have heart failure with preserved ejection fraction (HFpEF). On Oct. 2, 2020, the Food and Drug Administration fast-tracked dapagliflozin for the CKD indication by granting it Breakthrough Therapy Designation based on the DAPA-CKD results.

Results first reported in 2019 from the DAPA-HF trial led to dapagliflozin receiving a labeled indication for treating HFrEF, the types of heart failure patients enrolled in the trial. Direct evidence on the efficacy of SGLT2 inhibitors for patients with HFpEF will not be available until results from a few trials now in progress become available during the next 12 months.

In the meantime, nearly half of patients with HFpEF also have CKD, noted Dr. McMurray, and another large portion of HFpEF patients have type 2 diabetes and hence qualify for SGLT2 inhibitor treatment that way. “Obviously, we would like to know specifically about heart failure outcomes in patients with HFpEF” on SGLT2 inhibitor treatment, he acknowledged. But the recent approval of dapagliflozin for patients with HFrEF and the likely indication coming soon for treating CKD means that the number of patients with heart failure who are not eligible for SGLT2 inhibitor treatment is dwindling down to some extent.
 

New DAPA-HF results show no drug, device interactions

In a separate session at the HFSA virtual meeting, Dr. McMurray and several collaborators on the DAPA-HF trial presented results from some new analyses. Dr. McMurray looked at the impact of dapagliflozin treatment on the primary endpoint when patients were stratified by the diuretic dosage they received at study entry. The results showed that “the benefits from dapagliflozin were irrespective of the use of background diuretic therapy or the diuretic dose,” he reported. Study findings also showed that roughly three-quarters of patients in the study had no change in their diuretic dosage during the course of the trial, that the fraction of patients who had an increase in their dosage was about the same as those whose diuretic dosage decreased, and that this pattern was similar in both the patients on dapagliflozin and in those randomized to placebo.

Another set of new analyses from DAPA-HF looked at the impact on dapagliflozin efficacy of background medical and device therapies for heart failure, as well as background diabetes therapies. The findings showed no signal of an interaction with background therapies. “The effects of dapagliflozin are incremental and complimentary to conventional therapies for HFrEF,” concluded Lars Kober, MD, a professor and heart failure physician at Copenhagen University Hospital.

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. McMurray’s employer, Glasgow University, has received payments from AstraZeneca and several other companies to compensate for his time overseeing various clinical trials. Dr. Kober has received honoraria for speaking on behalf of several companies including AstraZeneca.

[email protected]

The DAPA-CKD trial results, which proved dapagliflozin’s efficacy for slowing chronic kidney disease progression in patients selected for signs of worsening renal function, also have important messages for cardiologists, especially heart failure physicians.

Catherine Hackett/MDedge News

Those messages include findings that were “consistent” with the results of the earlier DAPA-HF trial, which tested the same sodium-glucose transporter 2 (SGLT2) inhibitor in patients selected for having heart failure with reduced ejection fraction (HFrEF). In addition, a specific action of dapagliflozin (Farxiga) on the patients in DAPA-CKD, which enrolled patients based on markers of chronic kidney disease (CKD), was prevention of first and recurrent heart failure hospitalizations, John J.V. McMurray, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America, further highlighting the role that dapagliflozin has in reducing both heart failure and renal events.
 

What DAPA-CKD means for heart failure

The main findings from the DAPA-CKD trial, published in September in the New England Journal of Medicine, included as a secondary outcome the combined rate of death from cardiovascular causes or hospitalization for heart failure (HHF). Treatment with dapagliflozin linked with a significant 29% relative reduction in this endpoint, compared with placebo-treated patients. At the HFSA meeting, Dr. McMurray reported for the first time the specific HHF numbers, a prespecified secondary endpoint for the study.

Patients on dapagliflozin had 37 total HHF events (1.7%), including both first-time and subsequent hospitalizations, while patients in the placebo arm had a total of 71 HHF events (3.3%) during the study’s median 2.4 years of follow-up, an absolute reduction of 1.6% that translated into a relative risk reduction of 49%.

The HHF findings from DAPA-CKD importantly showed that SGLT2 inhibition in patients with signs of renal dysfunction “will not only slow progression of kidney disease but will also reduce the risk of developing heart failure, crucially in patients with or without type 2 diabetes,” explained Dr. McMurray in an interview. “Cardiologists often consult in the kidney wards and advise on management of patients with chronic kidney disease, even those without heart failure.”

The DAPA-CKD findings carry another important message for heart failure management regarding the minimum level of renal function a patient can have and still safely receive dapagliflozin or possibly another agent from the same SGLT2 inhibitor class. In DAPA-CKD, patients safely received dapagliflozin with an estimated glomerular filtration rate (eGFR) as low as 25 mL/min per 1.73 m²; 14% of enrolled patients had an eGFR of 25-29 mL/min per 1.73 m².

“Typically, about 40%-50% of patients with heart failure have chronic kidney disease,” which makes this safety finding important to clinicians who care for heart failure patients, but it’s also important for any patient who might be a candidate for dapagliflozin or another drug from its class. “We had no strong evidence before this trial that SGLT2 inhibition could reduce hard renal endpoints,” specifically need for chronic dialysis, renal transplant, or renal death, “in patients with or without diabetes,” Dr. McMurray said.
 

DAPA-CKD grows the pool of eligible heart failure patients

A further consequence of the DAPA-CKD findings is that when, as expected, regulatory bodies give dapagliflozin an indication for treating the types of CKD patients enrolled in the trial, it will functionally expand this treatment to an even larger swath of heart failure patients who currently don’t qualify for this treatment, specifically patients with CKD who also have heart failure with preserved ejection fraction (HFpEF). On Oct. 2, 2020, the Food and Drug Administration fast-tracked dapagliflozin for the CKD indication by granting it Breakthrough Therapy Designation based on the DAPA-CKD results.

Results first reported in 2019 from the DAPA-HF trial led to dapagliflozin receiving a labeled indication for treating HFrEF, the types of heart failure patients enrolled in the trial. Direct evidence on the efficacy of SGLT2 inhibitors for patients with HFpEF will not be available until results from a few trials now in progress become available during the next 12 months.

In the meantime, nearly half of patients with HFpEF also have CKD, noted Dr. McMurray, and another large portion of HFpEF patients have type 2 diabetes and hence qualify for SGLT2 inhibitor treatment that way. “Obviously, we would like to know specifically about heart failure outcomes in patients with HFpEF” on SGLT2 inhibitor treatment, he acknowledged. But the recent approval of dapagliflozin for patients with HFrEF and the likely indication coming soon for treating CKD means that the number of patients with heart failure who are not eligible for SGLT2 inhibitor treatment is dwindling down to some extent.
 

New DAPA-HF results show no drug, device interactions

In a separate session at the HFSA virtual meeting, Dr. McMurray and several collaborators on the DAPA-HF trial presented results from some new analyses. Dr. McMurray looked at the impact of dapagliflozin treatment on the primary endpoint when patients were stratified by the diuretic dosage they received at study entry. The results showed that “the benefits from dapagliflozin were irrespective of the use of background diuretic therapy or the diuretic dose,” he reported. Study findings also showed that roughly three-quarters of patients in the study had no change in their diuretic dosage during the course of the trial, that the fraction of patients who had an increase in their dosage was about the same as those whose diuretic dosage decreased, and that this pattern was similar in both the patients on dapagliflozin and in those randomized to placebo.

Another set of new analyses from DAPA-HF looked at the impact on dapagliflozin efficacy of background medical and device therapies for heart failure, as well as background diabetes therapies. The findings showed no signal of an interaction with background therapies. “The effects of dapagliflozin are incremental and complimentary to conventional therapies for HFrEF,” concluded Lars Kober, MD, a professor and heart failure physician at Copenhagen University Hospital.

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. McMurray’s employer, Glasgow University, has received payments from AstraZeneca and several other companies to compensate for his time overseeing various clinical trials. Dr. Kober has received honoraria for speaking on behalf of several companies including AstraZeneca.

[email protected]

The DAPA-CKD trial results, which proved dapagliflozin’s efficacy for slowing chronic kidney disease progression in patients selected for signs of worsening renal function, also have important messages for cardiologists, especially heart failure physicians.

Catherine Hackett/MDedge News

Those messages include findings that were “consistent” with the results of the earlier DAPA-HF trial, which tested the same sodium-glucose transporter 2 (SGLT2) inhibitor in patients selected for having heart failure with reduced ejection fraction (HFrEF). In addition, a specific action of dapagliflozin (Farxiga) on the patients in DAPA-CKD, which enrolled patients based on markers of chronic kidney disease (CKD), was prevention of first and recurrent heart failure hospitalizations, John J.V. McMurray, MD, said at the virtual annual scientific meeting of the Heart Failure Society of America, further highlighting the role that dapagliflozin has in reducing both heart failure and renal events.
 

What DAPA-CKD means for heart failure

The main findings from the DAPA-CKD trial, published in September in the New England Journal of Medicine, included as a secondary outcome the combined rate of death from cardiovascular causes or hospitalization for heart failure (HHF). Treatment with dapagliflozin linked with a significant 29% relative reduction in this endpoint, compared with placebo-treated patients. At the HFSA meeting, Dr. McMurray reported for the first time the specific HHF numbers, a prespecified secondary endpoint for the study.

Patients on dapagliflozin had 37 total HHF events (1.7%), including both first-time and subsequent hospitalizations, while patients in the placebo arm had a total of 71 HHF events (3.3%) during the study’s median 2.4 years of follow-up, an absolute reduction of 1.6% that translated into a relative risk reduction of 49%.

The HHF findings from DAPA-CKD importantly showed that SGLT2 inhibition in patients with signs of renal dysfunction “will not only slow progression of kidney disease but will also reduce the risk of developing heart failure, crucially in patients with or without type 2 diabetes,” explained Dr. McMurray in an interview. “Cardiologists often consult in the kidney wards and advise on management of patients with chronic kidney disease, even those without heart failure.”

The DAPA-CKD findings carry another important message for heart failure management regarding the minimum level of renal function a patient can have and still safely receive dapagliflozin or possibly another agent from the same SGLT2 inhibitor class. In DAPA-CKD, patients safely received dapagliflozin with an estimated glomerular filtration rate (eGFR) as low as 25 mL/min per 1.73 m²; 14% of enrolled patients had an eGFR of 25-29 mL/min per 1.73 m².

“Typically, about 40%-50% of patients with heart failure have chronic kidney disease,” which makes this safety finding important to clinicians who care for heart failure patients, but it’s also important for any patient who might be a candidate for dapagliflozin or another drug from its class. “We had no strong evidence before this trial that SGLT2 inhibition could reduce hard renal endpoints,” specifically need for chronic dialysis, renal transplant, or renal death, “in patients with or without diabetes,” Dr. McMurray said.
 

DAPA-CKD grows the pool of eligible heart failure patients

A further consequence of the DAPA-CKD findings is that when, as expected, regulatory bodies give dapagliflozin an indication for treating the types of CKD patients enrolled in the trial, it will functionally expand this treatment to an even larger swath of heart failure patients who currently don’t qualify for this treatment, specifically patients with CKD who also have heart failure with preserved ejection fraction (HFpEF). On Oct. 2, 2020, the Food and Drug Administration fast-tracked dapagliflozin for the CKD indication by granting it Breakthrough Therapy Designation based on the DAPA-CKD results.

Results first reported in 2019 from the DAPA-HF trial led to dapagliflozin receiving a labeled indication for treating HFrEF, the types of heart failure patients enrolled in the trial. Direct evidence on the efficacy of SGLT2 inhibitors for patients with HFpEF will not be available until results from a few trials now in progress become available during the next 12 months.

In the meantime, nearly half of patients with HFpEF also have CKD, noted Dr. McMurray, and another large portion of HFpEF patients have type 2 diabetes and hence qualify for SGLT2 inhibitor treatment that way. “Obviously, we would like to know specifically about heart failure outcomes in patients with HFpEF” on SGLT2 inhibitor treatment, he acknowledged. But the recent approval of dapagliflozin for patients with HFrEF and the likely indication coming soon for treating CKD means that the number of patients with heart failure who are not eligible for SGLT2 inhibitor treatment is dwindling down to some extent.
 

New DAPA-HF results show no drug, device interactions

In a separate session at the HFSA virtual meeting, Dr. McMurray and several collaborators on the DAPA-HF trial presented results from some new analyses. Dr. McMurray looked at the impact of dapagliflozin treatment on the primary endpoint when patients were stratified by the diuretic dosage they received at study entry. The results showed that “the benefits from dapagliflozin were irrespective of the use of background diuretic therapy or the diuretic dose,” he reported. Study findings also showed that roughly three-quarters of patients in the study had no change in their diuretic dosage during the course of the trial, that the fraction of patients who had an increase in their dosage was about the same as those whose diuretic dosage decreased, and that this pattern was similar in both the patients on dapagliflozin and in those randomized to placebo.

Another set of new analyses from DAPA-HF looked at the impact on dapagliflozin efficacy of background medical and device therapies for heart failure, as well as background diabetes therapies. The findings showed no signal of an interaction with background therapies. “The effects of dapagliflozin are incremental and complimentary to conventional therapies for HFrEF,” concluded Lars Kober, MD, a professor and heart failure physician at Copenhagen University Hospital.

DAPA-CKD was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). Dr. McMurray’s employer, Glasgow University, has received payments from AstraZeneca and several other companies to compensate for his time overseeing various clinical trials. Dr. Kober has received honoraria for speaking on behalf of several companies including AstraZeneca.

[email protected]

The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.

jarun011/thinkstock

A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.

The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.

Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.

At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.

Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.

The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.

This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.

SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.

The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.

jarun011/thinkstock

A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.

The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.

Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.

At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.

Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.

The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.

This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.

SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.

The adjuvanted recombinant zoster vaccine Shingrix appears to be effective in older adults with autoimmune diseases who are not receiving treatment regimens that suppress the immune system, according to a post hoc analysis of patients in two clinical trials.

jarun011/thinkstock

A two-dose regimen of Shingrix was effective in 90.5% of a subset of patients in two phase 3 clinical trials of adults who were aged at least 50 years, according to Alemnew F. Dagnew, MD, of GlaxoSmithKline and colleagues. The lowest rates of effectiveness with Shingrix, for patients aged between 70-79 years, was 84.4%, the researchers reported in Rheumatology.

The CDC recommends adults aged at least 50 years receive two doses of Shingrix to help prevent reoccurrence of herpes zoster, or Zostavax (zoster vaccine live) if adults are allergic to components of the Shingrix vaccine or have tested negative for varicella zoster virus immunity.

Dr. Dagnew and colleagues evaluated Shingrix in 983 patients who received two doses of Shingrix and 960 patients who received placebo from the ZOE-50 and ZOE-70 trials, where each dose was administered at least 2 months apart. The mean age of patients in both groups was 68.8 years in the Shingrix group and 69.4 years in the placebo group, and more than half of patients in both Shingrix (59.9%) and placebo groups (60.8%) were women. About 7% of the patients in two clinical trial had a pIMD.

At enrollment, the most common preexisting immune-mediated disorders (pIMDs) were psoriasis (215 patients taking Shingrix vs. 239 patients on placebo), spondyloarthropathy (109 patients taking Shingrix vs. 89 patients on placebo), rheumatoid arthritis (96 patients taking Shingrix vs. 94 patients on placebo), and celiac disease (41 patients taking Shingrix vs. 34 patients on placebo). Dr. Dagnew and colleagues examined the subgroup of patients with pIMDs for safety and vaccine efficacy, which was defined as not developing herpes zoster before the second dose.

Overall, the efficacy of Shingrix was 90.5% across all age groups (95% confidence interval, 73.5%-97.5%), with the group aged between 70-79 years having the lowest rate of effectiveness (95% CI, 30.8%-98.3%). The rate of severe adverse events was 14.6% in the Shingrix group and 11.7% in the placebo group between the first Shingrix dose and for up to 1 year after the second dose. The most common adverse events were infections and infestations as well as cardiac disorders. “Our data show a balance between study groups in the frequency and nature of SAEs, confirming the favorable safety profile of [Shingrix] in populations with pIMDs,” Dr. Dagnew and colleagues wrote.

The researchers acknowledged that the ZOE-50/70 studies were underpowered to detect the efficacy and safety of Shingrix in individuals with pIMDs but said that the large number of participants in the studies let them estimate efficacy and adverse events for this subgroup. They also noted there was no randomization of pIMDs at enrollment, even though pIMDs occurred at similar rates between Shingrix and placebo groups.

This study was funded by GlaxoSmithKline; the company helped with conducting and analyzing the study and also provided the costs associated with publishing it. Five authors reported being an employee of GlaxoSmithKline during the time the work was conducted, and four of the five own stock in the company. One author is now an employee of UCB. One author reported having served on the advisory boards for Merck Sharp & Dohme, GlaxoSmithKline, and Curevo.

SOURCE: Dagnew AF et al. Rheumatology. 2020 Sep 10. doi: 10.1093/rheumatology/keaa424.

The Food and Drug Administration has approved combination nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) to be used as first-line treatment of adult patients with unresectable malignant pleural mesothelioma.

This is the first drug regimen to receive regulatory approval for mesothelioma in 16 years and only the second systemic therapy to be approved for this indication.

“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.

“In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen,” Dr. Pazdur added.
 

Improved overall survival

The approval is based on efficacy results from the CheckMate 743 trial, which compared immunotherapy with a chemotherapy regimen in a cohort of more than 600 treatment-naive patients (no systemic therapies) with unresectable mesothelioma.

Patients were randomized 1:1 to nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of combination chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302).

The study results were initially presented during the presidential symposium of the World Congress on Lung Cancer 2020.

The combined immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive versus 27% in the chemotherapy group.

Overall, the trial demonstrated a statistically significant improvement in overall survival for patients who received nivolumab plus ipilimumab versus those treated with chemotherapy. Median overall survival was 18.1 months versus 14.1 months (hazard ratio, 0.74; P = .002).

Median progression-free survival per blinded independent central review was 6.8 months in the nivolumab plus ipilimumab arm and 7.2 months in the chemotherapy arm (HR, 1.0). The confirmed overall response rate was 40% versus 43% in the immunotherapy and chemotherapy arms, respectively.

Median response duration was 11.0 months in the nivolumab plus ipilimumab arm and 6.7 months in the chemotherapy arm. At 24 months, 32% of the immunotherapy patients were still experiencing a response, compared with 8% of those in the chemotherapy arm.

The recommended doses for unresectable malignant pleural mesothelioma are nivolumab 360 mg every 3 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

The most common adverse reactions (incidence ≥20%) in patients receiving combination immunotherapy were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus.
 

New standard of care?

The CheckMate 743 trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported study author Paul Baas, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, at the time of its presentation.

He suggested that combination nivolumab and ipilimumab should therefore “be considered as a new standard of care.”

This article first appeared on Medscape.com.

The Food and Drug Administration has approved combination nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) to be used as first-line treatment of adult patients with unresectable malignant pleural mesothelioma.

This is the first drug regimen to receive regulatory approval for mesothelioma in 16 years and only the second systemic therapy to be approved for this indication.

“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.

“In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen,” Dr. Pazdur added.
 

Improved overall survival

The approval is based on efficacy results from the CheckMate 743 trial, which compared immunotherapy with a chemotherapy regimen in a cohort of more than 600 treatment-naive patients (no systemic therapies) with unresectable mesothelioma.

Patients were randomized 1:1 to nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of combination chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302).

The study results were initially presented during the presidential symposium of the World Congress on Lung Cancer 2020.

The combined immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive versus 27% in the chemotherapy group.

Overall, the trial demonstrated a statistically significant improvement in overall survival for patients who received nivolumab plus ipilimumab versus those treated with chemotherapy. Median overall survival was 18.1 months versus 14.1 months (hazard ratio, 0.74; P = .002).

Median progression-free survival per blinded independent central review was 6.8 months in the nivolumab plus ipilimumab arm and 7.2 months in the chemotherapy arm (HR, 1.0). The confirmed overall response rate was 40% versus 43% in the immunotherapy and chemotherapy arms, respectively.

Median response duration was 11.0 months in the nivolumab plus ipilimumab arm and 6.7 months in the chemotherapy arm. At 24 months, 32% of the immunotherapy patients were still experiencing a response, compared with 8% of those in the chemotherapy arm.

The recommended doses for unresectable malignant pleural mesothelioma are nivolumab 360 mg every 3 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

The most common adverse reactions (incidence ≥20%) in patients receiving combination immunotherapy were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus.
 

New standard of care?

The CheckMate 743 trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported study author Paul Baas, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, at the time of its presentation.

He suggested that combination nivolumab and ipilimumab should therefore “be considered as a new standard of care.”

This article first appeared on Medscape.com.

The Food and Drug Administration has approved combination nivolumab (Opdivo, Bristol-Myers Squibb) and ipilimumab (Yervoy, Bristol-Myers Squibb) to be used as first-line treatment of adult patients with unresectable malignant pleural mesothelioma.

This is the first drug regimen to receive regulatory approval for mesothelioma in 16 years and only the second systemic therapy to be approved for this indication.

“Today’s approval of nivolumab plus ipilimumab provides a new treatment that has demonstrated an improvement in overall survival for patients with malignant pleural mesothelioma,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.

“In 2004, FDA approved pemetrexed in combination with cisplatin for this indication, and now patients have an important, additional treatment option after more than a decade with only one FDA-approved drug regimen,” Dr. Pazdur added.
 

Improved overall survival

The approval is based on efficacy results from the CheckMate 743 trial, which compared immunotherapy with a chemotherapy regimen in a cohort of more than 600 treatment-naive patients (no systemic therapies) with unresectable mesothelioma.

Patients were randomized 1:1 to nivolumab and ipilimumab for up to 2 years (n = 303) or six cycles of combination chemotherapy with cisplatin or carboplatin plus pemetrexed (n = 302).

The study results were initially presented during the presidential symposium of the World Congress on Lung Cancer 2020.

The combined immunotherapy regimen was associated with a 26% improvement in overall survival. At 2 years, 41% of patients in the immunotherapy arm were still alive versus 27% in the chemotherapy group.

Overall, the trial demonstrated a statistically significant improvement in overall survival for patients who received nivolumab plus ipilimumab versus those treated with chemotherapy. Median overall survival was 18.1 months versus 14.1 months (hazard ratio, 0.74; P = .002).

Median progression-free survival per blinded independent central review was 6.8 months in the nivolumab plus ipilimumab arm and 7.2 months in the chemotherapy arm (HR, 1.0). The confirmed overall response rate was 40% versus 43% in the immunotherapy and chemotherapy arms, respectively.

Median response duration was 11.0 months in the nivolumab plus ipilimumab arm and 6.7 months in the chemotherapy arm. At 24 months, 32% of the immunotherapy patients were still experiencing a response, compared with 8% of those in the chemotherapy arm.

The recommended doses for unresectable malignant pleural mesothelioma are nivolumab 360 mg every 3 weeks and ipilimumab 1 mg/kg every 6 weeks until disease progression or unacceptable toxicity, or up to 2 years in patients without disease progression.

The most common adverse reactions (incidence ≥20%) in patients receiving combination immunotherapy were fatigue, musculoskeletal pain, rash, diarrhea, dyspnea, nausea, decreased appetite, cough, and pruritus.
 

New standard of care?

The CheckMate 743 trial “met its primary endpoint of statistically improving overall survival for the experimental arm vs chemotherapy in a prespecified interim analysis,” reported study author Paul Baas, MD, PhD, of the Netherlands Cancer Institute, Amsterdam, at the time of its presentation.

He suggested that combination nivolumab and ipilimumab should therefore “be considered as a new standard of care.”

This article first appeared on Medscape.com.

A higher dose of thoracic radiotherapy (TRT) may improve overall survival in limited-stage small-cell lung cancer (LS-SCLC), but it’s not clear if this dose should become the new standard of care.

In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.

The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.

However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.

Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.

“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
 

Study details

Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.

The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.

All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.

Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).

The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
 

Efficacy

There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).

Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).

Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).

Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.

Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
 

Safety

There were no significant differences in toxicity between the treatment arms.

Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.

Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).

There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.

“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.

“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.

Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.

The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.

“There are some important missing data, in terms of interpretation of results,” she said.

Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.

“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.

The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.

[email protected]

SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.

A higher dose of thoracic radiotherapy (TRT) may improve overall survival in limited-stage small-cell lung cancer (LS-SCLC), but it’s not clear if this dose should become the new standard of care.

In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.

The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.

However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.

Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.

“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
 

Study details

Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.

The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.

All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.

Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).

The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
 

Efficacy

There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).

Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).

Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).

Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.

Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
 

Safety

There were no significant differences in toxicity between the treatment arms.

Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.

Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).

There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.

“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.

“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.

Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.

The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.

“There are some important missing data, in terms of interpretation of results,” she said.

Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.

“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.

The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.

[email protected]

SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.

A higher dose of thoracic radiotherapy (TRT) may improve overall survival in limited-stage small-cell lung cancer (LS-SCLC), but it’s not clear if this dose should become the new standard of care.

In a phase 2 trial, the 2-year overall survival rate was 51.3% when twice-daily TRT was given at a dose of 45 Gy in 30 fractions and 75% when it was given at a dose of 60 Gy in 40 fractions in patients with LS-SCLC. The two treatment arms had similar safety and quality of life outcomes.

The higher dose “did not add toxicity,” a significant concern with higher radiation doses, said Bjorn Gronberg, MD, PhD, of the Norwegian University of Science and Technology in Trondheim, when presenting this study at the European Society for Medical Oncology Virtual Congress 2020.

However, the discussant for this study pointed out several limitations of the trial and concluded that the 45 Gy dose should remain the standard of care.

Dr. Gonberg explained that concurrent platinum/etoposide (PE) chemotherapy and TRT is the standard treatment for LS-SCLC, and the most recommended schedule for TRT is twice daily at 45 Gy in 30 fractions. He noted, however, that “there’s clearly a need for better treatment” because less than 30% of patients are cured.

“We hypothesized that increasing the dose of radiotherapy might improve survival,” he said.
 

Study details

Dr. Gonberg and colleagues conducted a phase 2 trial of patients with stage I-III SCLC confined to one hemithorax plus regional lymph nodes. The trial enrolled 176 patients and randomized 170 of them.

The patients received four courses of PE 3 weeks apart. For TRT, 81 patients were randomized to 45 Gy in 30 fractions, and 89 patients were randomized to 60 Gy in 40 fractions, with 10 fractions per week starting with the second PE course.

All patients who responded to chemoradiotherapy were offered prophylactic cranial irradiation at 25 Gy in 10 fractions or 30 Gy in 15 fractions.

Baseline characteristics were well balanced between the treatment arms. The median age was 65 years in both arms, and most patients were women (60.5% in the 45 Gy arm and 56% in the 60 Gy arm).

The mean number of chemotherapy courses was 3.8 in each arm, about 85% of patients received prophylactic cranial radiation, and roughly half received second-line chemotherapy. Overall, 73 patients completed TRT in the 45 Gy arm, and 81 completed TRT in the 60 Gy arm.
 

Efficacy

There was no significant difference in overall response rate between the treatment arms. It was 81.6% in the 45 Gy arm and 82.1% in the 60 Gy arm (P = .81).

Similarly, there was no significant difference in progression-free survival. The median progression-free survival was 11.1 months in the lower-dose arm and 18.7 months in the higher-dose arm (P = .22).

Still, there was a significant difference in overall survival between the arms. The 2-year overall survival rate was 51.3% in the lower-dose arm and 75% in the higher-dose arm (P = .002). The median overall survival was 24 months and 37.2 months, respectively (P = .034).

Discussant Corinne Faivre-Finn, MD, PhD, of the University of Manchester (England), cautioned that the lower-dose arm appeared to underperform, compared with prior research.

Additionally, “the survival curves separate at about 9 months, [with a] significant difference at 2 years, but the survival curves are coming back together at around 5 years, and that shows that there is a small difference in terms of long-term cure,” she said.
 

Safety

There were no significant differences in toxicity between the treatment arms.

Dr. Gronberg noted that esophagitis is considered the main dose-limiting toxicity with TRT, but there was no difference in incidence between the two arms (P = .916). Grade 3 esophagitis occurred in 18.4% of patients in the lower-dose arm and 19% of those in the higher-dose arm. There was no grade 4 esophagitis.

Rates of grade 3 and 4 neutropenic infections were higher in the lower-dose arm than in the higher-dose arm, but the difference was not statistically significant (P = .08).

There were also no significant differences in quality of life surveys that patients filled out periodically from baseline until week 52.

“Not so surprisingly,” Dr. Gronberg said, dysphagia was more common at the end of TRT. However, patients had recovered to baseline levels at week 22.

“There’s no difference in the maximum dysphagia reported between the treatment arms, but ... patients in the high-dose arm needed longer time to recover from dysphagia,” Dr. Gronberg said.

Scores for dyspnea, physical function, and global quality of life were similar between the treatment arms.

The similar toxicity between the arms “is quite puzzling,” Dr. Faivre-Finn said, given the 33% increase in radiation dose in the experimental arm. She said this “probably points out an imbalance in some of the factors” between the groups, including tumor volume and doses to organs at risk, which were not reported.

“There are some important missing data, in terms of interpretation of results,” she said.

Given the limitations, and the fact that the study population was relatively small, Dr. Faivre-Finn said “the results cannot be considered definitive and practice changing,” pending additional study.

“So my final conclusion is that twice-a-day radiotherapy at a dose of 45 Gy remains the standard of care, as recommended in the recently published ASTRO [American Society for Radiation Oncology] guidelines,” Dr. Faivre-Finn said.

The study was funded by the Norwegian Cancer Society, the Nordic Cancer Union, and the Norwegian University of Science and Technology. Dr. Gronberg disclosed relationships with Pfizer, Roche, Eli Lilly, and other companies. Dr. Faivre-Finn disclosed relationships with AstraZeneca, Merck, Pfizer, Elekta, and Boehringer Ingelheim.

[email protected]

SOURCE: Gronberg B et al. ESMO 2020, Abstract 1783O.

Quadrivalent human papillomavirus (HPV) vaccination was associated with a substantial reduction in the incidence of cervical cancer in a Swedish review of more than 1 million girls and women vaccinated from 2006 to 2017.

It’s been shown that the vaccine (Gardasil) helps prevent genital warts and high-grade cervical lesions, but until now, data on the ability of the vaccine to prevent cervical cancer, although widely assumed, had been lacking.

“Our results extend [the] knowledge base by showing that quadrivalent HPV vaccination is also associated with a substantially reduced risk of invasive cervical cancer, which is the ultimate intent of HPV vaccination programs,” said investigators led by Jiayao Lei, PhD, a researcher in the department of medical epidemiology and biostatistics at the Karolinska Institute, Stockholm.

The study was published online Oct. 1 in the New England Journal of Medicine.

“This work provides evidence of actual cancer prevention,” commented Diane Harper, MD, an HPV expert and professor in the departments of family medicine and obstetrics & gynecology at the University of Michigan, Ann Arbor. She was the principal investigator on the original Gardasil trial.

This study “shows that the quadrivalent HPV vaccine provides prevention from the sexually transmitted HPV infection that actually reduces the incidence of cervical cancer in young women up to 30 years of age,” she said when approached for comment.

However, she also added a note of caution. These new results show “that vaccinated women still develop cervical cancer, but at a slower rate. This makes the connection between early-age vaccination and continued adult life screening incredibly important,” Dr. Harper said in an interview

Cervical cancer was diagnosed in 19 of the 527,871 women (0.004%) who had received at least one dose of the vaccine versus 538 among the 1,145,112 women (0.05%) who had not.

The cumulative incidence was 47 cases per 100,000 vaccinated women and 94 cases per 100,000 unvaccinated women. The cervical cancer incidence rate ratio for the comparison of vaccinated versus unvaccinated women was 0.37 (95% confidence interval, 0.21-0.57).

The risk reduction was even greater among women who had been vaccinated before the age of 17, with a cumulative incidence of 4 versus 54 cases per 100,000 for women vaccinated after age 17. The incidence rate ratio was 0.12 (95% CI, 0.00-0.34) for women who had been vaccinated before age 17 versus 0.47 (95% CI, 0.27-0.75) among those vaccinated from age 17 to 30 years.

Overall, “the risk of cervical cancer among participants who had initiated vaccination before the age of 17 years was 88% lower than among those who had never been vaccinated,” the investigators noted.

These results “support the recommendation to administer quadrivalent HPV vaccine before exposure to HPV infection to achieve the most substantial benefit,” the investigators wrote.
 

Details of the Swedish review

For their review, Dr. Lei and colleagues used several Swedish demographic and health registries to connect vaccination status to incident cervical cancers, using the personal identification numbers Sweden issues to residents.

Participants were followed starting either on their 10th birthday or on Jan. 1, 2006, whichever came later. They were followed until, among other things, diagnosis of invasive cervical cancer; their 31st birthday; or until Dec. 31, 2017, whichever came first.

The quadrivalent HPV vaccine, approved in Sweden in 2006, was used almost exclusively during the study period. Participants were considered vaccinated if they had received only one shot, but the investigators set out to analyze a relationship between the incidence of invasive cervical cancer and the number of shots given.

Among other things, the team controlled for age at follow-up, calendar year, county of residence, maternal disease history, and parental characteristics, including education and household income.

The investigators commented that it’s possible that HPV-vaccinated women could have been generally healthier than unvaccinated women and so would have been at lower risk for cervical cancer.

“Confounding by lifestyle and health factors in the women (such as smoking status, sexual activity, oral contraceptive use, and obesity) cannot be excluded; these factors are known to be associated with a risk of cervical cancer,” the investigators wrote.

HPV is also associated with other types of cancer, including anal and oropharyngeal cancers. But these cancers develop over a longer period than cervical cancer.

Dr. Harper noted that the “probability of HPV 16 cancer by time since infection peaks at 40 years after infection for anal cancers and nearly 50 years after infection for oropharyngeal cancers. This means that registries, such as in Sweden, for the next 40 years will record the evidence to say whether HPV vaccination lasts long enough to prevent [these] other HPV 16–associated cancers occurring at a much later time in life.”

The work was funded by the Swedish Foundation for Strategic Research, the Swedish Cancer Society, and the Swedish Research Council and by the China Scholarship Council. Dr. Lei and two other investigators reported HPV vaccine research funding from Merck, the maker of Gardasil. Harper disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Quadrivalent human papillomavirus (HPV) vaccination was associated with a substantial reduction in the incidence of cervical cancer in a Swedish review of more than 1 million girls and women vaccinated from 2006 to 2017.

It’s been shown that the vaccine (Gardasil) helps prevent genital warts and high-grade cervical lesions, but until now, data on the ability of the vaccine to prevent cervical cancer, although widely assumed, had been lacking.

“Our results extend [the] knowledge base by showing that quadrivalent HPV vaccination is also associated with a substantially reduced risk of invasive cervical cancer, which is the ultimate intent of HPV vaccination programs,” said investigators led by Jiayao Lei, PhD, a researcher in the department of medical epidemiology and biostatistics at the Karolinska Institute, Stockholm.

The study was published online Oct. 1 in the New England Journal of Medicine.

“This work provides evidence of actual cancer prevention,” commented Diane Harper, MD, an HPV expert and professor in the departments of family medicine and obstetrics & gynecology at the University of Michigan, Ann Arbor. She was the principal investigator on the original Gardasil trial.

This study “shows that the quadrivalent HPV vaccine provides prevention from the sexually transmitted HPV infection that actually reduces the incidence of cervical cancer in young women up to 30 years of age,” she said when approached for comment.

However, she also added a note of caution. These new results show “that vaccinated women still develop cervical cancer, but at a slower rate. This makes the connection between early-age vaccination and continued adult life screening incredibly important,” Dr. Harper said in an interview

Cervical cancer was diagnosed in 19 of the 527,871 women (0.004%) who had received at least one dose of the vaccine versus 538 among the 1,145,112 women (0.05%) who had not.

The cumulative incidence was 47 cases per 100,000 vaccinated women and 94 cases per 100,000 unvaccinated women. The cervical cancer incidence rate ratio for the comparison of vaccinated versus unvaccinated women was 0.37 (95% confidence interval, 0.21-0.57).

The risk reduction was even greater among women who had been vaccinated before the age of 17, with a cumulative incidence of 4 versus 54 cases per 100,000 for women vaccinated after age 17. The incidence rate ratio was 0.12 (95% CI, 0.00-0.34) for women who had been vaccinated before age 17 versus 0.47 (95% CI, 0.27-0.75) among those vaccinated from age 17 to 30 years.

Overall, “the risk of cervical cancer among participants who had initiated vaccination before the age of 17 years was 88% lower than among those who had never been vaccinated,” the investigators noted.

These results “support the recommendation to administer quadrivalent HPV vaccine before exposure to HPV infection to achieve the most substantial benefit,” the investigators wrote.
 

Details of the Swedish review

For their review, Dr. Lei and colleagues used several Swedish demographic and health registries to connect vaccination status to incident cervical cancers, using the personal identification numbers Sweden issues to residents.

Participants were followed starting either on their 10th birthday or on Jan. 1, 2006, whichever came later. They were followed until, among other things, diagnosis of invasive cervical cancer; their 31st birthday; or until Dec. 31, 2017, whichever came first.

The quadrivalent HPV vaccine, approved in Sweden in 2006, was used almost exclusively during the study period. Participants were considered vaccinated if they had received only one shot, but the investigators set out to analyze a relationship between the incidence of invasive cervical cancer and the number of shots given.

Among other things, the team controlled for age at follow-up, calendar year, county of residence, maternal disease history, and parental characteristics, including education and household income.

The investigators commented that it’s possible that HPV-vaccinated women could have been generally healthier than unvaccinated women and so would have been at lower risk for cervical cancer.

“Confounding by lifestyle and health factors in the women (such as smoking status, sexual activity, oral contraceptive use, and obesity) cannot be excluded; these factors are known to be associated with a risk of cervical cancer,” the investigators wrote.

HPV is also associated with other types of cancer, including anal and oropharyngeal cancers. But these cancers develop over a longer period than cervical cancer.

Dr. Harper noted that the “probability of HPV 16 cancer by time since infection peaks at 40 years after infection for anal cancers and nearly 50 years after infection for oropharyngeal cancers. This means that registries, such as in Sweden, for the next 40 years will record the evidence to say whether HPV vaccination lasts long enough to prevent [these] other HPV 16–associated cancers occurring at a much later time in life.”

The work was funded by the Swedish Foundation for Strategic Research, the Swedish Cancer Society, and the Swedish Research Council and by the China Scholarship Council. Dr. Lei and two other investigators reported HPV vaccine research funding from Merck, the maker of Gardasil. Harper disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Quadrivalent human papillomavirus (HPV) vaccination was associated with a substantial reduction in the incidence of cervical cancer in a Swedish review of more than 1 million girls and women vaccinated from 2006 to 2017.

It’s been shown that the vaccine (Gardasil) helps prevent genital warts and high-grade cervical lesions, but until now, data on the ability of the vaccine to prevent cervical cancer, although widely assumed, had been lacking.

“Our results extend [the] knowledge base by showing that quadrivalent HPV vaccination is also associated with a substantially reduced risk of invasive cervical cancer, which is the ultimate intent of HPV vaccination programs,” said investigators led by Jiayao Lei, PhD, a researcher in the department of medical epidemiology and biostatistics at the Karolinska Institute, Stockholm.

The study was published online Oct. 1 in the New England Journal of Medicine.

“This work provides evidence of actual cancer prevention,” commented Diane Harper, MD, an HPV expert and professor in the departments of family medicine and obstetrics & gynecology at the University of Michigan, Ann Arbor. She was the principal investigator on the original Gardasil trial.

This study “shows that the quadrivalent HPV vaccine provides prevention from the sexually transmitted HPV infection that actually reduces the incidence of cervical cancer in young women up to 30 years of age,” she said when approached for comment.

However, she also added a note of caution. These new results show “that vaccinated women still develop cervical cancer, but at a slower rate. This makes the connection between early-age vaccination and continued adult life screening incredibly important,” Dr. Harper said in an interview

Cervical cancer was diagnosed in 19 of the 527,871 women (0.004%) who had received at least one dose of the vaccine versus 538 among the 1,145,112 women (0.05%) who had not.

The cumulative incidence was 47 cases per 100,000 vaccinated women and 94 cases per 100,000 unvaccinated women. The cervical cancer incidence rate ratio for the comparison of vaccinated versus unvaccinated women was 0.37 (95% confidence interval, 0.21-0.57).

The risk reduction was even greater among women who had been vaccinated before the age of 17, with a cumulative incidence of 4 versus 54 cases per 100,000 for women vaccinated after age 17. The incidence rate ratio was 0.12 (95% CI, 0.00-0.34) for women who had been vaccinated before age 17 versus 0.47 (95% CI, 0.27-0.75) among those vaccinated from age 17 to 30 years.

Overall, “the risk of cervical cancer among participants who had initiated vaccination before the age of 17 years was 88% lower than among those who had never been vaccinated,” the investigators noted.

These results “support the recommendation to administer quadrivalent HPV vaccine before exposure to HPV infection to achieve the most substantial benefit,” the investigators wrote.
 

Details of the Swedish review

For their review, Dr. Lei and colleagues used several Swedish demographic and health registries to connect vaccination status to incident cervical cancers, using the personal identification numbers Sweden issues to residents.

Participants were followed starting either on their 10th birthday or on Jan. 1, 2006, whichever came later. They were followed until, among other things, diagnosis of invasive cervical cancer; their 31st birthday; or until Dec. 31, 2017, whichever came first.

The quadrivalent HPV vaccine, approved in Sweden in 2006, was used almost exclusively during the study period. Participants were considered vaccinated if they had received only one shot, but the investigators set out to analyze a relationship between the incidence of invasive cervical cancer and the number of shots given.

Among other things, the team controlled for age at follow-up, calendar year, county of residence, maternal disease history, and parental characteristics, including education and household income.

The investigators commented that it’s possible that HPV-vaccinated women could have been generally healthier than unvaccinated women and so would have been at lower risk for cervical cancer.

“Confounding by lifestyle and health factors in the women (such as smoking status, sexual activity, oral contraceptive use, and obesity) cannot be excluded; these factors are known to be associated with a risk of cervical cancer,” the investigators wrote.

HPV is also associated with other types of cancer, including anal and oropharyngeal cancers. But these cancers develop over a longer period than cervical cancer.

Dr. Harper noted that the “probability of HPV 16 cancer by time since infection peaks at 40 years after infection for anal cancers and nearly 50 years after infection for oropharyngeal cancers. This means that registries, such as in Sweden, for the next 40 years will record the evidence to say whether HPV vaccination lasts long enough to prevent [these] other HPV 16–associated cancers occurring at a much later time in life.”

The work was funded by the Swedish Foundation for Strategic Research, the Swedish Cancer Society, and the Swedish Research Council and by the China Scholarship Council. Dr. Lei and two other investigators reported HPV vaccine research funding from Merck, the maker of Gardasil. Harper disclosed no relevant financial relationships.

This article first appeared on Medscape.com.