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Opioid deaths in North America predicted to soar
“Over the past quarter-century, the opioid epidemic has taken nearly 600,000 lives and triggered a cascade of public health catastrophes such as disability, family breakdown, unemployment, and child neglect in North America,” commission chair Keith Humphreys, PhD, said in a news release.
“If no action is taken, by the end of this decade, we are predicting the number of deaths to be twice as high as it has been over the last 20 years,” said Dr. Humphreys, professor of psychiatry and behavioral sciences at Stanford (Calif.) University.
The report was published online Feb. 2, 2022, in The Lancet.
Blame it on COVID-19?
The COVID-19 pandemic has both overshadowed and exacerbated the opioid crisis in North America, the commission pointed out in their report.
Their analysis suggests that 2020 was the worst year on record for overdose deaths in the United States and Canada in terms of both the total number of deaths and percentage annual increase.
In the United States, opioid overdose deaths increased by 37%, from 51,133 in 2019 to 70,168 in 2020, bringing the total number of deaths since 1999 to 583,000.
In Canada, opioid overdose deaths jumped by 72%, from 3,668 in 2019 to 6,306 in 2020, with a further 3,515 deaths reported in the first 6 months of 2021.
Although the 2020 spikes might be partly caused by the effects of the COVID-19 pandemic, a rising trajectory of deaths was evident in both the United States and Canada before the pandemic hit, the Stanford-Lancet Commission said.
Profit motives, lack of regulation
The commission blames the opioid epidemic on a lack of adequate regulation and oversight coupled with profit motives of the pharmaceutical and health care industry.
“To ensure safeguards are in place to curb the opioid addiction epidemic and prevent future ones involving other addictive drugs, we must end the pharmaceutical and health care industry’s undue influence on the government and its unregulated push for opioid use,” commission member Howard Koh, MD, MPH, said in the news release.
“This includes insulating the medical community from pharmaceutical company influence and closing the constantly revolving door between regulators and industry,” said Dr. Koh, with the Harvard School of Public Health, Boston.
In addition to regulation and policy reform, the commission said prevention efforts that focus on treating addiction as a chronic condition are key.
The United States in particular lacks accessible, high-quality, nonstigmatizing, and integrated health and social care services for people experiencing opioid use disorder, the Commission notes.
Addiction-related services must become a permanent feature of health and social care systems in the United States and Canada, in line with established chronic disease management models that are financed and organized as a core public health commitment, the commission said.
“Addiction is an enduring part of population health and should not be treated as a moral failing that needs punishment but as a chronic health condition that requires ongoing treatment and long-term support,” commission member Yasmin Hurd, PhD, director of the Addiction Institute at Icahn School of Medicine at Mount Sinai, New York, said in the release.
Investing in young people to reduce the risk of addiction will also be important going forward.
“Preventing drug addiction should be part of a comprehensive public health strategy that starts in childhood and lays the foundation for long-term declines in addiction,” said commission member Chelsea Shover, PhD, with the University of California, Los Angeles.
‘Audacious but achievable goal’
The commission calls for a nuanced approach to pain management that prioritizes innovation both in society’s response to drug addiction through policy reform and by supporting the development of new, nonaddictive pain management options.
“Opioids should not be viewed as good or bad, but instead as a class of medications essential to the management of pain. However, opioids also come with serious risks, some of which can be difficult to recognize,” commission member David Juurlink, MD, PhD, said in the release.
“Clinicians should begin learning about responsible pain management prescribing in medical school and continue to learn about it as part of their commitment to continued medical education throughout their careers,” said Dr. Juurlink, with Sunnybrook Health Sciences Centre in Toronto.
Humphreys said ending the opioid epidemic in North America and preventing its global spread is “an audacious but achievable goal” that will require a “dramatic shift in policy and culture where innovation, collaboration, and regulation are encouraged.
“We can save and improve lives by summoning the resources and political will necessary to eliminate the sources of addiction and boldly implement policies that will maximize efforts to treat it,” Dr. Humphreys added.
The study was funded by Stanford University.
A version of this article first appeared on Medscape.com.
“Over the past quarter-century, the opioid epidemic has taken nearly 600,000 lives and triggered a cascade of public health catastrophes such as disability, family breakdown, unemployment, and child neglect in North America,” commission chair Keith Humphreys, PhD, said in a news release.
“If no action is taken, by the end of this decade, we are predicting the number of deaths to be twice as high as it has been over the last 20 years,” said Dr. Humphreys, professor of psychiatry and behavioral sciences at Stanford (Calif.) University.
The report was published online Feb. 2, 2022, in The Lancet.
Blame it on COVID-19?
The COVID-19 pandemic has both overshadowed and exacerbated the opioid crisis in North America, the commission pointed out in their report.
Their analysis suggests that 2020 was the worst year on record for overdose deaths in the United States and Canada in terms of both the total number of deaths and percentage annual increase.
In the United States, opioid overdose deaths increased by 37%, from 51,133 in 2019 to 70,168 in 2020, bringing the total number of deaths since 1999 to 583,000.
In Canada, opioid overdose deaths jumped by 72%, from 3,668 in 2019 to 6,306 in 2020, with a further 3,515 deaths reported in the first 6 months of 2021.
Although the 2020 spikes might be partly caused by the effects of the COVID-19 pandemic, a rising trajectory of deaths was evident in both the United States and Canada before the pandemic hit, the Stanford-Lancet Commission said.
Profit motives, lack of regulation
The commission blames the opioid epidemic on a lack of adequate regulation and oversight coupled with profit motives of the pharmaceutical and health care industry.
“To ensure safeguards are in place to curb the opioid addiction epidemic and prevent future ones involving other addictive drugs, we must end the pharmaceutical and health care industry’s undue influence on the government and its unregulated push for opioid use,” commission member Howard Koh, MD, MPH, said in the news release.
“This includes insulating the medical community from pharmaceutical company influence and closing the constantly revolving door between regulators and industry,” said Dr. Koh, with the Harvard School of Public Health, Boston.
In addition to regulation and policy reform, the commission said prevention efforts that focus on treating addiction as a chronic condition are key.
The United States in particular lacks accessible, high-quality, nonstigmatizing, and integrated health and social care services for people experiencing opioid use disorder, the Commission notes.
Addiction-related services must become a permanent feature of health and social care systems in the United States and Canada, in line with established chronic disease management models that are financed and organized as a core public health commitment, the commission said.
“Addiction is an enduring part of population health and should not be treated as a moral failing that needs punishment but as a chronic health condition that requires ongoing treatment and long-term support,” commission member Yasmin Hurd, PhD, director of the Addiction Institute at Icahn School of Medicine at Mount Sinai, New York, said in the release.
Investing in young people to reduce the risk of addiction will also be important going forward.
“Preventing drug addiction should be part of a comprehensive public health strategy that starts in childhood and lays the foundation for long-term declines in addiction,” said commission member Chelsea Shover, PhD, with the University of California, Los Angeles.
‘Audacious but achievable goal’
The commission calls for a nuanced approach to pain management that prioritizes innovation both in society’s response to drug addiction through policy reform and by supporting the development of new, nonaddictive pain management options.
“Opioids should not be viewed as good or bad, but instead as a class of medications essential to the management of pain. However, opioids also come with serious risks, some of which can be difficult to recognize,” commission member David Juurlink, MD, PhD, said in the release.
“Clinicians should begin learning about responsible pain management prescribing in medical school and continue to learn about it as part of their commitment to continued medical education throughout their careers,” said Dr. Juurlink, with Sunnybrook Health Sciences Centre in Toronto.
Humphreys said ending the opioid epidemic in North America and preventing its global spread is “an audacious but achievable goal” that will require a “dramatic shift in policy and culture where innovation, collaboration, and regulation are encouraged.
“We can save and improve lives by summoning the resources and political will necessary to eliminate the sources of addiction and boldly implement policies that will maximize efforts to treat it,” Dr. Humphreys added.
The study was funded by Stanford University.
A version of this article first appeared on Medscape.com.
“Over the past quarter-century, the opioid epidemic has taken nearly 600,000 lives and triggered a cascade of public health catastrophes such as disability, family breakdown, unemployment, and child neglect in North America,” commission chair Keith Humphreys, PhD, said in a news release.
“If no action is taken, by the end of this decade, we are predicting the number of deaths to be twice as high as it has been over the last 20 years,” said Dr. Humphreys, professor of psychiatry and behavioral sciences at Stanford (Calif.) University.
The report was published online Feb. 2, 2022, in The Lancet.
Blame it on COVID-19?
The COVID-19 pandemic has both overshadowed and exacerbated the opioid crisis in North America, the commission pointed out in their report.
Their analysis suggests that 2020 was the worst year on record for overdose deaths in the United States and Canada in terms of both the total number of deaths and percentage annual increase.
In the United States, opioid overdose deaths increased by 37%, from 51,133 in 2019 to 70,168 in 2020, bringing the total number of deaths since 1999 to 583,000.
In Canada, opioid overdose deaths jumped by 72%, from 3,668 in 2019 to 6,306 in 2020, with a further 3,515 deaths reported in the first 6 months of 2021.
Although the 2020 spikes might be partly caused by the effects of the COVID-19 pandemic, a rising trajectory of deaths was evident in both the United States and Canada before the pandemic hit, the Stanford-Lancet Commission said.
Profit motives, lack of regulation
The commission blames the opioid epidemic on a lack of adequate regulation and oversight coupled with profit motives of the pharmaceutical and health care industry.
“To ensure safeguards are in place to curb the opioid addiction epidemic and prevent future ones involving other addictive drugs, we must end the pharmaceutical and health care industry’s undue influence on the government and its unregulated push for opioid use,” commission member Howard Koh, MD, MPH, said in the news release.
“This includes insulating the medical community from pharmaceutical company influence and closing the constantly revolving door between regulators and industry,” said Dr. Koh, with the Harvard School of Public Health, Boston.
In addition to regulation and policy reform, the commission said prevention efforts that focus on treating addiction as a chronic condition are key.
The United States in particular lacks accessible, high-quality, nonstigmatizing, and integrated health and social care services for people experiencing opioid use disorder, the Commission notes.
Addiction-related services must become a permanent feature of health and social care systems in the United States and Canada, in line with established chronic disease management models that are financed and organized as a core public health commitment, the commission said.
“Addiction is an enduring part of population health and should not be treated as a moral failing that needs punishment but as a chronic health condition that requires ongoing treatment and long-term support,” commission member Yasmin Hurd, PhD, director of the Addiction Institute at Icahn School of Medicine at Mount Sinai, New York, said in the release.
Investing in young people to reduce the risk of addiction will also be important going forward.
“Preventing drug addiction should be part of a comprehensive public health strategy that starts in childhood and lays the foundation for long-term declines in addiction,” said commission member Chelsea Shover, PhD, with the University of California, Los Angeles.
‘Audacious but achievable goal’
The commission calls for a nuanced approach to pain management that prioritizes innovation both in society’s response to drug addiction through policy reform and by supporting the development of new, nonaddictive pain management options.
“Opioids should not be viewed as good or bad, but instead as a class of medications essential to the management of pain. However, opioids also come with serious risks, some of which can be difficult to recognize,” commission member David Juurlink, MD, PhD, said in the release.
“Clinicians should begin learning about responsible pain management prescribing in medical school and continue to learn about it as part of their commitment to continued medical education throughout their careers,” said Dr. Juurlink, with Sunnybrook Health Sciences Centre in Toronto.
Humphreys said ending the opioid epidemic in North America and preventing its global spread is “an audacious but achievable goal” that will require a “dramatic shift in policy and culture where innovation, collaboration, and regulation are encouraged.
“We can save and improve lives by summoning the resources and political will necessary to eliminate the sources of addiction and boldly implement policies that will maximize efforts to treat it,” Dr. Humphreys added.
The study was funded by Stanford University.
A version of this article first appeared on Medscape.com.
FROM THE LANCET
Merits of short DAPT, de-escalation in ACS challenge guidelines
Standard dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor for 12 months after stenting for an acute coronary syndrome (ACS) is under increasing fire from studies showing that varying the duration and intensity of DAPT can reduce bleeding risk without compromising ischemic protection.
A novel meta-analysis of 29 studies indirectly compares short DAPT and de-escalation in 50,602 patients, providing new insights into the relative safety and efficacy of the two strategies and further challenging current guideline recommendations.
Results show no difference in the risk of death between short DAPT with aspirin or P2Y12 inhibitor discontinuation 1-6 months after percutaneous coronary intervention and de-escalation to clopidogrel (Plavix) or lower-dose prasugrel (Effient) or ticagrelor (Brilinta) after the initial high-risk period for ischemic events (risk ratio, 0.98).
“However, there are some differentiating characteristics between the two. De-escalation seems to reduce NACE – net adverse cardiovascular events – likely because of a reduction in major adverse cardiac events, while short DAPT decreases bleeding,” senior author Davide Capodanno, MD, PhD, University of Catania (Italy) told this news organization.
The findings, published in JACC: Cardiovascular Interventions, are clinically plausible because patients remain on two antiplatelet drugs with de-escalation, but are on only one drug at the point of shortening DAPT, he said. “So, of course, if you have only one antiplatelet drug instead of two, you reduce bleeding. On the other hand, having two antiplatelets probably reduces the thrombotic and ischemic events.”
The study failed to show statistically significant differences in ischemic endpoints between strategies, likely because of few events and wide confidence intervals, Dr. Capodanno said. “In fact, when we look at each single component of this NACE, we see a directional difference in favor of de-escalation, which is what you would expect from two drugs.”
All-cause death was also similar among strategies in an alternative five-node analysis that split short DAPT and de-escalation into four groups and included standard DAPT.
Compared with short DAPT with P2Y12 inhibitor discontinuation, both de-escalation to clopidogrel and to half-dose prasugrel or ticagrelor reduced the risk for NACE. De-escalation to half dose also reduced the risk for minor bleeding, compared with short DAPT with aspirin discontinuation.
The overall results were similar in multiple sensitivity analyses and a Bayesian meta-analysis, according to the authors, led by Claudio Laudani, MD, also with the University of Catania.
The Bayesian analysis suggested a greater than 95% probability that de-escalation is the best strategy for NACE, MI, stroke, stent thrombosis, and minor bleeding, whereas short DAPT ranks first for major bleeding with a greater than 95% probability.
Guidelines upside down?
In the absence of a head-to-head comparison, the authors say the results warrant a change in current guidelines, which give a class 2a recommendation for short DAPT and a weak class 2b for de-escalation.
“The two strategies have both merits and caveats but, overall, they are very similar; so this is why we believe they should be similar [in status],” Dr. Capodanno said.
In an accompanying editorial, Dean Kereiakes, MD, Christ Hospital Heart and Vascular Center, Cincinnati, and Robert Yeh, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, suggest the guideline recommendations are upside down.
“The class 1 recommendation should be for short DAPT or DAPT de-escalation vs. standard DAPT based on this meta-analysis and, frankly, based on the independent analyses from Bangalore [et al.] and from Shoji [et al.],” Dr. Kereiakes told this news organization.
“When you look at the meta-analyses that have been done, what you see is a reduction of bleeding and either no change or a slight numeric reduction in ischemic events, which magnifies the net clinical benefit, favoring short DAPT or DAPT de-escalation in comparison to standard 12-month, guideline-compliant DAPT,” he said. “So for me, it’s kind of like, game over. When will the guidelines catch up?”
In a comment, Gregg Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an email that “both approaches warrant a class 1 recommendation in patients at high bleeding risk, and both a 2a in non–high bleeding risk patients. With contemporary drug-eluting stents, the prognosis is more strongly determined by bleeding risk and the occurrence of hemorrhagic complications than ischemic risk.”
Not all strategies are ‘created equal’
The editorialists caution that, while viable, not all short DAPT or de-escalation strategies are “created equal.” In the five-node analysis, for example, the relative risk of stent thrombosis is highest following a short DAPT regimen with extended aspirin monotherapy (RR, 1.45) and lowest following de-escalation to half-dose prasugrel/ticagrelor (RR, 0.45).
Although not universally observed, the signal of harm with aspirin is consistent with studies such as TWILIGHT, HOST EXAM, and a 2020 meta-analysis, in which stopping aspirin 1-3 months after PCI cut bleeding by 50%, compared with DAPT in patients with ACS, noted Dr. Kereiakes.
He also hinted that more data are forthcoming showing that short DAPT followed by aspirin single-antiplatelet therapy (SAPT) has relatively higher ischemic and bleeding event rates, compared with short DAPT followed by P2Y12 SAPT, with or without an anticoagulant on board.
The key going forward, all agree, is to formally incorporate ischemic/bleeding risk stratification tools into practice guidelines to allow personalized antiplatelet therapy. To that end, Dr. Kereiakes and Dr. Yeh offer a detailed graphic of rank-order recommendations for each strategy by clinical risk strata, with de-escalation generally best for those at greatest ischemic risk and short DAPT best applied to those at greatest bleeding risk.
“The biggest incremental knowledge provided by Davide and Laudani is that they gave us more insight into the granularity of platelet inhibition strategies,” Dr. Kereiakes said. “And it is mechanistically possible to be applied in clinical practice. It’s what I personally see in high-volume clinical practice.”
Before it can be determined which of these strategies is safer and/or more effective, a large, direct head-to-head comparative randomized trial is necessary, Dr. Stone cautioned.
“There are still many variables that were not adjusted for in this excellent study, including the timing of DAPT discontinuation or de-escalation, the specific agent used, etc.,” he added. “Finally, as implied by these results, the optimal regimen may vary based on the balance of ischemic and bleeding risk. Thus, the specific population enrolled in such a randomized trial might importantly affect its outcome.”
As a man “who likes science and statistics,” Dr. Capodanno said he’d also like a large, randomized trial directly comparing the two strategies to confirm these indirect findings. “But it’s very difficult to imagine the power for a trial like that, so it’s not something that’s easy to do.”
Dr. Capodanno reports consulting and speaker fees from Amgen, Arena, Biotronik, Daiichi-Sankyo, and Sanofi outside the present work. Coauthor disclosures are listed in the original article. Dr. Kereiakes reports consulting fees from SINO Medical Sciences Technologies, Svelte Medical Systems, Elixir Medical, and Caliber Therapeutics/Orchestra Biomed. Dr. Yeh reports consulting fees and grant support from Abbott Vascular, AstraZeneca, Boston Scientific, and Medtronic. Dr. Stone reported having no disclosures relevant to the study.
A version of this article first appeared on Medscape.com.
Standard dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor for 12 months after stenting for an acute coronary syndrome (ACS) is under increasing fire from studies showing that varying the duration and intensity of DAPT can reduce bleeding risk without compromising ischemic protection.
A novel meta-analysis of 29 studies indirectly compares short DAPT and de-escalation in 50,602 patients, providing new insights into the relative safety and efficacy of the two strategies and further challenging current guideline recommendations.
Results show no difference in the risk of death between short DAPT with aspirin or P2Y12 inhibitor discontinuation 1-6 months after percutaneous coronary intervention and de-escalation to clopidogrel (Plavix) or lower-dose prasugrel (Effient) or ticagrelor (Brilinta) after the initial high-risk period for ischemic events (risk ratio, 0.98).
“However, there are some differentiating characteristics between the two. De-escalation seems to reduce NACE – net adverse cardiovascular events – likely because of a reduction in major adverse cardiac events, while short DAPT decreases bleeding,” senior author Davide Capodanno, MD, PhD, University of Catania (Italy) told this news organization.
The findings, published in JACC: Cardiovascular Interventions, are clinically plausible because patients remain on two antiplatelet drugs with de-escalation, but are on only one drug at the point of shortening DAPT, he said. “So, of course, if you have only one antiplatelet drug instead of two, you reduce bleeding. On the other hand, having two antiplatelets probably reduces the thrombotic and ischemic events.”
The study failed to show statistically significant differences in ischemic endpoints between strategies, likely because of few events and wide confidence intervals, Dr. Capodanno said. “In fact, when we look at each single component of this NACE, we see a directional difference in favor of de-escalation, which is what you would expect from two drugs.”
All-cause death was also similar among strategies in an alternative five-node analysis that split short DAPT and de-escalation into four groups and included standard DAPT.
Compared with short DAPT with P2Y12 inhibitor discontinuation, both de-escalation to clopidogrel and to half-dose prasugrel or ticagrelor reduced the risk for NACE. De-escalation to half dose also reduced the risk for minor bleeding, compared with short DAPT with aspirin discontinuation.
The overall results were similar in multiple sensitivity analyses and a Bayesian meta-analysis, according to the authors, led by Claudio Laudani, MD, also with the University of Catania.
The Bayesian analysis suggested a greater than 95% probability that de-escalation is the best strategy for NACE, MI, stroke, stent thrombosis, and minor bleeding, whereas short DAPT ranks first for major bleeding with a greater than 95% probability.
Guidelines upside down?
In the absence of a head-to-head comparison, the authors say the results warrant a change in current guidelines, which give a class 2a recommendation for short DAPT and a weak class 2b for de-escalation.
“The two strategies have both merits and caveats but, overall, they are very similar; so this is why we believe they should be similar [in status],” Dr. Capodanno said.
In an accompanying editorial, Dean Kereiakes, MD, Christ Hospital Heart and Vascular Center, Cincinnati, and Robert Yeh, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, suggest the guideline recommendations are upside down.
“The class 1 recommendation should be for short DAPT or DAPT de-escalation vs. standard DAPT based on this meta-analysis and, frankly, based on the independent analyses from Bangalore [et al.] and from Shoji [et al.],” Dr. Kereiakes told this news organization.
“When you look at the meta-analyses that have been done, what you see is a reduction of bleeding and either no change or a slight numeric reduction in ischemic events, which magnifies the net clinical benefit, favoring short DAPT or DAPT de-escalation in comparison to standard 12-month, guideline-compliant DAPT,” he said. “So for me, it’s kind of like, game over. When will the guidelines catch up?”
In a comment, Gregg Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an email that “both approaches warrant a class 1 recommendation in patients at high bleeding risk, and both a 2a in non–high bleeding risk patients. With contemporary drug-eluting stents, the prognosis is more strongly determined by bleeding risk and the occurrence of hemorrhagic complications than ischemic risk.”
Not all strategies are ‘created equal’
The editorialists caution that, while viable, not all short DAPT or de-escalation strategies are “created equal.” In the five-node analysis, for example, the relative risk of stent thrombosis is highest following a short DAPT regimen with extended aspirin monotherapy (RR, 1.45) and lowest following de-escalation to half-dose prasugrel/ticagrelor (RR, 0.45).
Although not universally observed, the signal of harm with aspirin is consistent with studies such as TWILIGHT, HOST EXAM, and a 2020 meta-analysis, in which stopping aspirin 1-3 months after PCI cut bleeding by 50%, compared with DAPT in patients with ACS, noted Dr. Kereiakes.
He also hinted that more data are forthcoming showing that short DAPT followed by aspirin single-antiplatelet therapy (SAPT) has relatively higher ischemic and bleeding event rates, compared with short DAPT followed by P2Y12 SAPT, with or without an anticoagulant on board.
The key going forward, all agree, is to formally incorporate ischemic/bleeding risk stratification tools into practice guidelines to allow personalized antiplatelet therapy. To that end, Dr. Kereiakes and Dr. Yeh offer a detailed graphic of rank-order recommendations for each strategy by clinical risk strata, with de-escalation generally best for those at greatest ischemic risk and short DAPT best applied to those at greatest bleeding risk.
“The biggest incremental knowledge provided by Davide and Laudani is that they gave us more insight into the granularity of platelet inhibition strategies,” Dr. Kereiakes said. “And it is mechanistically possible to be applied in clinical practice. It’s what I personally see in high-volume clinical practice.”
Before it can be determined which of these strategies is safer and/or more effective, a large, direct head-to-head comparative randomized trial is necessary, Dr. Stone cautioned.
“There are still many variables that were not adjusted for in this excellent study, including the timing of DAPT discontinuation or de-escalation, the specific agent used, etc.,” he added. “Finally, as implied by these results, the optimal regimen may vary based on the balance of ischemic and bleeding risk. Thus, the specific population enrolled in such a randomized trial might importantly affect its outcome.”
As a man “who likes science and statistics,” Dr. Capodanno said he’d also like a large, randomized trial directly comparing the two strategies to confirm these indirect findings. “But it’s very difficult to imagine the power for a trial like that, so it’s not something that’s easy to do.”
Dr. Capodanno reports consulting and speaker fees from Amgen, Arena, Biotronik, Daiichi-Sankyo, and Sanofi outside the present work. Coauthor disclosures are listed in the original article. Dr. Kereiakes reports consulting fees from SINO Medical Sciences Technologies, Svelte Medical Systems, Elixir Medical, and Caliber Therapeutics/Orchestra Biomed. Dr. Yeh reports consulting fees and grant support from Abbott Vascular, AstraZeneca, Boston Scientific, and Medtronic. Dr. Stone reported having no disclosures relevant to the study.
A version of this article first appeared on Medscape.com.
Standard dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor for 12 months after stenting for an acute coronary syndrome (ACS) is under increasing fire from studies showing that varying the duration and intensity of DAPT can reduce bleeding risk without compromising ischemic protection.
A novel meta-analysis of 29 studies indirectly compares short DAPT and de-escalation in 50,602 patients, providing new insights into the relative safety and efficacy of the two strategies and further challenging current guideline recommendations.
Results show no difference in the risk of death between short DAPT with aspirin or P2Y12 inhibitor discontinuation 1-6 months after percutaneous coronary intervention and de-escalation to clopidogrel (Plavix) or lower-dose prasugrel (Effient) or ticagrelor (Brilinta) after the initial high-risk period for ischemic events (risk ratio, 0.98).
“However, there are some differentiating characteristics between the two. De-escalation seems to reduce NACE – net adverse cardiovascular events – likely because of a reduction in major adverse cardiac events, while short DAPT decreases bleeding,” senior author Davide Capodanno, MD, PhD, University of Catania (Italy) told this news organization.
The findings, published in JACC: Cardiovascular Interventions, are clinically plausible because patients remain on two antiplatelet drugs with de-escalation, but are on only one drug at the point of shortening DAPT, he said. “So, of course, if you have only one antiplatelet drug instead of two, you reduce bleeding. On the other hand, having two antiplatelets probably reduces the thrombotic and ischemic events.”
The study failed to show statistically significant differences in ischemic endpoints between strategies, likely because of few events and wide confidence intervals, Dr. Capodanno said. “In fact, when we look at each single component of this NACE, we see a directional difference in favor of de-escalation, which is what you would expect from two drugs.”
All-cause death was also similar among strategies in an alternative five-node analysis that split short DAPT and de-escalation into four groups and included standard DAPT.
Compared with short DAPT with P2Y12 inhibitor discontinuation, both de-escalation to clopidogrel and to half-dose prasugrel or ticagrelor reduced the risk for NACE. De-escalation to half dose also reduced the risk for minor bleeding, compared with short DAPT with aspirin discontinuation.
The overall results were similar in multiple sensitivity analyses and a Bayesian meta-analysis, according to the authors, led by Claudio Laudani, MD, also with the University of Catania.
The Bayesian analysis suggested a greater than 95% probability that de-escalation is the best strategy for NACE, MI, stroke, stent thrombosis, and minor bleeding, whereas short DAPT ranks first for major bleeding with a greater than 95% probability.
Guidelines upside down?
In the absence of a head-to-head comparison, the authors say the results warrant a change in current guidelines, which give a class 2a recommendation for short DAPT and a weak class 2b for de-escalation.
“The two strategies have both merits and caveats but, overall, they are very similar; so this is why we believe they should be similar [in status],” Dr. Capodanno said.
In an accompanying editorial, Dean Kereiakes, MD, Christ Hospital Heart and Vascular Center, Cincinnati, and Robert Yeh, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, suggest the guideline recommendations are upside down.
“The class 1 recommendation should be for short DAPT or DAPT de-escalation vs. standard DAPT based on this meta-analysis and, frankly, based on the independent analyses from Bangalore [et al.] and from Shoji [et al.],” Dr. Kereiakes told this news organization.
“When you look at the meta-analyses that have been done, what you see is a reduction of bleeding and either no change or a slight numeric reduction in ischemic events, which magnifies the net clinical benefit, favoring short DAPT or DAPT de-escalation in comparison to standard 12-month, guideline-compliant DAPT,” he said. “So for me, it’s kind of like, game over. When will the guidelines catch up?”
In a comment, Gregg Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an email that “both approaches warrant a class 1 recommendation in patients at high bleeding risk, and both a 2a in non–high bleeding risk patients. With contemporary drug-eluting stents, the prognosis is more strongly determined by bleeding risk and the occurrence of hemorrhagic complications than ischemic risk.”
Not all strategies are ‘created equal’
The editorialists caution that, while viable, not all short DAPT or de-escalation strategies are “created equal.” In the five-node analysis, for example, the relative risk of stent thrombosis is highest following a short DAPT regimen with extended aspirin monotherapy (RR, 1.45) and lowest following de-escalation to half-dose prasugrel/ticagrelor (RR, 0.45).
Although not universally observed, the signal of harm with aspirin is consistent with studies such as TWILIGHT, HOST EXAM, and a 2020 meta-analysis, in which stopping aspirin 1-3 months after PCI cut bleeding by 50%, compared with DAPT in patients with ACS, noted Dr. Kereiakes.
He also hinted that more data are forthcoming showing that short DAPT followed by aspirin single-antiplatelet therapy (SAPT) has relatively higher ischemic and bleeding event rates, compared with short DAPT followed by P2Y12 SAPT, with or without an anticoagulant on board.
The key going forward, all agree, is to formally incorporate ischemic/bleeding risk stratification tools into practice guidelines to allow personalized antiplatelet therapy. To that end, Dr. Kereiakes and Dr. Yeh offer a detailed graphic of rank-order recommendations for each strategy by clinical risk strata, with de-escalation generally best for those at greatest ischemic risk and short DAPT best applied to those at greatest bleeding risk.
“The biggest incremental knowledge provided by Davide and Laudani is that they gave us more insight into the granularity of platelet inhibition strategies,” Dr. Kereiakes said. “And it is mechanistically possible to be applied in clinical practice. It’s what I personally see in high-volume clinical practice.”
Before it can be determined which of these strategies is safer and/or more effective, a large, direct head-to-head comparative randomized trial is necessary, Dr. Stone cautioned.
“There are still many variables that were not adjusted for in this excellent study, including the timing of DAPT discontinuation or de-escalation, the specific agent used, etc.,” he added. “Finally, as implied by these results, the optimal regimen may vary based on the balance of ischemic and bleeding risk. Thus, the specific population enrolled in such a randomized trial might importantly affect its outcome.”
As a man “who likes science and statistics,” Dr. Capodanno said he’d also like a large, randomized trial directly comparing the two strategies to confirm these indirect findings. “But it’s very difficult to imagine the power for a trial like that, so it’s not something that’s easy to do.”
Dr. Capodanno reports consulting and speaker fees from Amgen, Arena, Biotronik, Daiichi-Sankyo, and Sanofi outside the present work. Coauthor disclosures are listed in the original article. Dr. Kereiakes reports consulting fees from SINO Medical Sciences Technologies, Svelte Medical Systems, Elixir Medical, and Caliber Therapeutics/Orchestra Biomed. Dr. Yeh reports consulting fees and grant support from Abbott Vascular, AstraZeneca, Boston Scientific, and Medtronic. Dr. Stone reported having no disclosures relevant to the study.
A version of this article first appeared on Medscape.com.
FROM JACC: CARDIOVASCULAR INTERVENTIONS
SCAI refines cardiogenic shock classification system
The Society for Cardiovascular Angiography and Interventions (SCAI) has refined its cardiogenic shock (CS) classification system based on the literature and clinician feedback from real-world experience.
“In the 2 years since publication in 2019, the initial definition has been broadly accepted and eagerly appreciated, allowing a very intuitive way to stage these patients for better communication, triage, and treatment,” Srihari S. Naidu, MD, professor of medicine, New York Medical College, Valhalla, said in an interview.
“But the initial definition was based on consensus opinion, with a lack of real fundamental data on segregating patients into different stages. Now we have a lot more data utilizing the definition, and it became very clear that there were a couple of limitations in the initial definition,” Dr. Naidu explained.
The refined CS classification system – authored by Dr. Naidu and a multidisciplinary panel of experts from specialties that included cardiac critical care, interventional cardiology, surgery, nursing, emergency medicine, and heart failure – was published online Jan. 31 in the Journal of the Society for Cardiovascular Angiography and Interventions, with simultaneous publication in the Journal of the American College of Cardiology.
It maintains the five-stage pyramid of CS, starting with “at risk” and moving through “beginning,” “classic,” “deteriorating,” and “extremis” but now includes gradations of severity within each stage and pathways by which patients progress or recover.
“Progression across the SCAI shock stage continuum is a dynamic process, incorporating new information as available, and patient trajectories are important both for communication among clinicians and for decisionmaking regarding the next level of care and therapeutics,” the panel writes.
The second iteration adds a streamlined table incorporating commonly seen variables, based on lessons learned from validation studies and clinician experience.
“While keeping the same initial framework of looking at the three components of staging – the physical exam, the biochemical markers, and hemodynamics – we’ve made it very clear that there are some factors in each of these that are most typically seen. And then there are other factors that are consistent with that stage but don’t necessarily have to be seen, ... are not typically seen in that stage, or [are] not always present at that stage,” Dr. Naidu told this news organization.
The refined CS classification system provides more granularity on cardiac arrest as a risk modifier, which now excludes very brief episodes with rapid response to defibrillation and comprises only those patients who have impaired mental status with unknown neurologic recovery status after cardiopulmonary resuscitation.
Lactate level and thresholds have been highlighted to detect hypoperfusion but may be dissociated from hemodynamics in cases such as chronic heart failure.
In addition, patients may have other manifestations of end-organ hypoperfusion with a normal lactate level, and there are also important causes of an elevated lactate level other than shock.
The revision proposes a three-axis model of CS evaluation and prognostication that integrates shock severity, clinical phenotype, and risk modifiers as distinct elements that should be applied to individualize patient management.
The revision also places more emphasis on the trajectory of the patient with CS through hospitalization, including a “hub and spoke” model for transfer of higher-risk patients, including those with a deteriorating SCAI shock stage.
“It is our desire and belief that the revised SCAI SHOCK stage classification system will enhance both clinical care and CS research trial design,” the panel writes.
This statement has been endorsed by the American College of Cardiology, American College of Emergency Physicians, American Heart Association, European Society of Cardiology Association for Acute Cardiovascular Care, International Society for Heart and Lung Transplantation, Society of Critical Care Medicine, and Society of Thoracic Surgeons.
This research had no commercial funding. Dr. Naidu has disclosed no relevant financial relationships. A complete list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
The Society for Cardiovascular Angiography and Interventions (SCAI) has refined its cardiogenic shock (CS) classification system based on the literature and clinician feedback from real-world experience.
“In the 2 years since publication in 2019, the initial definition has been broadly accepted and eagerly appreciated, allowing a very intuitive way to stage these patients for better communication, triage, and treatment,” Srihari S. Naidu, MD, professor of medicine, New York Medical College, Valhalla, said in an interview.
“But the initial definition was based on consensus opinion, with a lack of real fundamental data on segregating patients into different stages. Now we have a lot more data utilizing the definition, and it became very clear that there were a couple of limitations in the initial definition,” Dr. Naidu explained.
The refined CS classification system – authored by Dr. Naidu and a multidisciplinary panel of experts from specialties that included cardiac critical care, interventional cardiology, surgery, nursing, emergency medicine, and heart failure – was published online Jan. 31 in the Journal of the Society for Cardiovascular Angiography and Interventions, with simultaneous publication in the Journal of the American College of Cardiology.
It maintains the five-stage pyramid of CS, starting with “at risk” and moving through “beginning,” “classic,” “deteriorating,” and “extremis” but now includes gradations of severity within each stage and pathways by which patients progress or recover.
“Progression across the SCAI shock stage continuum is a dynamic process, incorporating new information as available, and patient trajectories are important both for communication among clinicians and for decisionmaking regarding the next level of care and therapeutics,” the panel writes.
The second iteration adds a streamlined table incorporating commonly seen variables, based on lessons learned from validation studies and clinician experience.
“While keeping the same initial framework of looking at the three components of staging – the physical exam, the biochemical markers, and hemodynamics – we’ve made it very clear that there are some factors in each of these that are most typically seen. And then there are other factors that are consistent with that stage but don’t necessarily have to be seen, ... are not typically seen in that stage, or [are] not always present at that stage,” Dr. Naidu told this news organization.
The refined CS classification system provides more granularity on cardiac arrest as a risk modifier, which now excludes very brief episodes with rapid response to defibrillation and comprises only those patients who have impaired mental status with unknown neurologic recovery status after cardiopulmonary resuscitation.
Lactate level and thresholds have been highlighted to detect hypoperfusion but may be dissociated from hemodynamics in cases such as chronic heart failure.
In addition, patients may have other manifestations of end-organ hypoperfusion with a normal lactate level, and there are also important causes of an elevated lactate level other than shock.
The revision proposes a three-axis model of CS evaluation and prognostication that integrates shock severity, clinical phenotype, and risk modifiers as distinct elements that should be applied to individualize patient management.
The revision also places more emphasis on the trajectory of the patient with CS through hospitalization, including a “hub and spoke” model for transfer of higher-risk patients, including those with a deteriorating SCAI shock stage.
“It is our desire and belief that the revised SCAI SHOCK stage classification system will enhance both clinical care and CS research trial design,” the panel writes.
This statement has been endorsed by the American College of Cardiology, American College of Emergency Physicians, American Heart Association, European Society of Cardiology Association for Acute Cardiovascular Care, International Society for Heart and Lung Transplantation, Society of Critical Care Medicine, and Society of Thoracic Surgeons.
This research had no commercial funding. Dr. Naidu has disclosed no relevant financial relationships. A complete list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
The Society for Cardiovascular Angiography and Interventions (SCAI) has refined its cardiogenic shock (CS) classification system based on the literature and clinician feedback from real-world experience.
“In the 2 years since publication in 2019, the initial definition has been broadly accepted and eagerly appreciated, allowing a very intuitive way to stage these patients for better communication, triage, and treatment,” Srihari S. Naidu, MD, professor of medicine, New York Medical College, Valhalla, said in an interview.
“But the initial definition was based on consensus opinion, with a lack of real fundamental data on segregating patients into different stages. Now we have a lot more data utilizing the definition, and it became very clear that there were a couple of limitations in the initial definition,” Dr. Naidu explained.
The refined CS classification system – authored by Dr. Naidu and a multidisciplinary panel of experts from specialties that included cardiac critical care, interventional cardiology, surgery, nursing, emergency medicine, and heart failure – was published online Jan. 31 in the Journal of the Society for Cardiovascular Angiography and Interventions, with simultaneous publication in the Journal of the American College of Cardiology.
It maintains the five-stage pyramid of CS, starting with “at risk” and moving through “beginning,” “classic,” “deteriorating,” and “extremis” but now includes gradations of severity within each stage and pathways by which patients progress or recover.
“Progression across the SCAI shock stage continuum is a dynamic process, incorporating new information as available, and patient trajectories are important both for communication among clinicians and for decisionmaking regarding the next level of care and therapeutics,” the panel writes.
The second iteration adds a streamlined table incorporating commonly seen variables, based on lessons learned from validation studies and clinician experience.
“While keeping the same initial framework of looking at the three components of staging – the physical exam, the biochemical markers, and hemodynamics – we’ve made it very clear that there are some factors in each of these that are most typically seen. And then there are other factors that are consistent with that stage but don’t necessarily have to be seen, ... are not typically seen in that stage, or [are] not always present at that stage,” Dr. Naidu told this news organization.
The refined CS classification system provides more granularity on cardiac arrest as a risk modifier, which now excludes very brief episodes with rapid response to defibrillation and comprises only those patients who have impaired mental status with unknown neurologic recovery status after cardiopulmonary resuscitation.
Lactate level and thresholds have been highlighted to detect hypoperfusion but may be dissociated from hemodynamics in cases such as chronic heart failure.
In addition, patients may have other manifestations of end-organ hypoperfusion with a normal lactate level, and there are also important causes of an elevated lactate level other than shock.
The revision proposes a three-axis model of CS evaluation and prognostication that integrates shock severity, clinical phenotype, and risk modifiers as distinct elements that should be applied to individualize patient management.
The revision also places more emphasis on the trajectory of the patient with CS through hospitalization, including a “hub and spoke” model for transfer of higher-risk patients, including those with a deteriorating SCAI shock stage.
“It is our desire and belief that the revised SCAI SHOCK stage classification system will enhance both clinical care and CS research trial design,” the panel writes.
This statement has been endorsed by the American College of Cardiology, American College of Emergency Physicians, American Heart Association, European Society of Cardiology Association for Acute Cardiovascular Care, International Society for Heart and Lung Transplantation, Society of Critical Care Medicine, and Society of Thoracic Surgeons.
This research had no commercial funding. Dr. Naidu has disclosed no relevant financial relationships. A complete list of author disclosures is available with the original article.
A version of this article first appeared on Medscape.com.
Improved follow-up needed to find late-stage pancreatic cancers
A relatively large number of late-stage pancreatic ductal adenocarcinomas (PDACs) are detected during follow-up surveillance, yet no single patient- or protocol-specific factor appears to be significantly associated with detecting late-stage disease during this period, according to a new systematic literature review and meta-analysis.
The researchers, led by Ankit Chhoda, MD, of Yale University, New Haven, Conn., wrote in Gastroenterology that interval progression in high-risk individuals “highlights the need for improved follow-up methodology with higher accuracy to detect prognostically significant and treatable lesions.”
Individuals at high risk for PDAC are encouraged to undergo routine surveillance for the disease because early detection and resection of T1N0M0 PDAC and high-grade precursors may improve survival outcomes. According to Dr. Chhoda and colleagues, challenges of interval progression of cancers during the surveillance period for gastrointestinal malignancies have been well described in the general and at-risk patient populations. Previous studies, the authors explained, have not scrutinized the issues associated with late-stage PDACs detected during follow-up surveillance.
“Late-stage PDACs necessitate critical appraisal of current follow-up strategies to detect successful targets and perform timely resections,” the authors wrote. The researchers added that the diagnosis of late-stage PDACs during follow-up emphasizes the need for implementing “quality measures to avoid preventable causes, including surveillance adherence and diagnostic errors.”
To understand the incidence rates of late-stage PDACs during follow-up in high-risk individuals, Dr. Chhoda and researchers performed a systematic literature review and meta-analysis of data that included follow-up strategies for early PDAC detection among a high-risk population.
Outcomes of interest for the analysis included the overall diagnosis of advanced neoplasia as well as surveillance-detected/interval late-stage PDACs (T2–4N0M0/metastatic stage PDAC) during follow-up. The investigators defined surveillance-detected and interval late-stage PDACs as late-stage PDACs that were detected during surveillance and as those presenting symptomatically between visits, respectively.
The researchers also performed metaregression of the incidence rates of late-stage PDACs to examine the relationship with clinicoradiologic features in high-risk individuals.
A total of 13 studies on surveillance in 2,169 high-risk individuals were included in the systematic review, while 12 studies were included in the meta-analysis. Across studies, high-risk individuals were followed for over 7,302.72 patient-years for the purposes of detecting incident lesions or progression of preexisting pancreatic abnormalities.
In all high-risk individuals who underwent follow-up, the investigators identified a total yield of advanced neoplasia of 53. This total yield consisted of 7 high-grade pancreatic intraepithelial neoplasms, 7 high-grade intraductal papillary mucinous neoplasms, and 39 PDACs. According to the meta-analysis, the cumulative incidence of advanced neoplasia was 3.3 (95% confidence interval, 0.6-7.4; P < .001) per 1,000 patient-years. During follow-up, the cumulative incidence of surveillance-detected/interval late-stage PDACs was 1.7 per 1,000 patient-years (95% CI, 0.2-4.0; P = .03).
In a separate analysis, the investigators sought to identify the relationship between the modality of follow-up imaging and late-stage PDAC incidence. Imaging modalities used during follow-up were mostly cross-sectional imaging, such as computed tomography or magnetic resonance imaging with cholangiopancreatography (n = 4) or endoscopic ultrasound and cross-sectional modalities (n = 8).
The investigators found no significant associations between late-stage PDACs and surveillance imaging, baseline pancreatic morphology, study location, genetic background, gender, or age. Incidence of late-stage PDACs in studies with mostly cross-sectional imaging was 0.7 per 1,000 patient-years (95% CI, 0.0-8.0). This incidence rate was lower than that reported with EUS and cross-sectional modalities (2.5 per 1,000 patient-years; 95% CI, 0.6-5.4), but this difference was not statistically significant (P = .2).
No significant difference was found during follow-up in the incidence of late-stage PDACs between high-risk individuals with baseline pancreatic abnormalities (0.0 no significant difference; 95% CI, 0.0-0.3) vs. high-risk individuals with normal baseline (0.9 per 1,000 patient-years; 95% CI, 0.0-2.8) (P = .9).
Most studies included in the analysis did not report on diagnostic errors and surveillance adherence, the researchers wrote. Nonadherence to surveillance as well as delays in surveillance accounted for four late-stage PDACs, and surveillance cessation and/or delays were reported in 4 out of 19 high-risk individuals. There was limited information on symptoms, presentation timing, site of lesion, and surveillance adherence, which the investigators indicated prevented a formal meta-analysis.
In their summary, the study authors noted that in clinical practice there is a need for improved quality measures and adherence to surveillance programs to reduce the risk of diagnostic errors. The authors stated that evidence on the impact of these quality measures “on surveillance outcomes will not only improve quality of surveillance practices, but also enrich our communication with patients who undergo surveillance.”
The researchers reported no conflicts of interest with the pharmaceutical industry, and the study did not receive any funding.
Surveillance of individuals at increased risk of pancreatic ductal adenocarcinoma (PDAC) offers an opportunity to improve disease mortality through detection of premalignant lesions and earlier stage PDAC. Emerging data suggest that outcomes in surveillance-detected PDAC are superior to those diagnosed after onset of signs and symptoms. This study by Chhoda et al. highlights a potential quality gap in current surveillance programs, namely the diagnosis of interval cancers and late-stage metastatic PDAC.
Investigators report a cumulative incidence of late-stage PDAC of 1.7 per 1,000 patient-years in surveillance, while the incidence of any advanced neoplasia (high-grade PanIN, high-grade IPMN, NET > 1 cm and any stage PDAC) was 3.3 per 1,000 patient-years. Importantly, late-stage PDAC was defined as T2-4N0-1M0-1 in this study. This is based on the 2013 International Cancer of the Pancreas Screening definition of “success of a screening program” as treatment of T1N0M0 PDAC, which was later updated to include a resected PDAC confined to the pancreas. The cumulative incidence of resectable lesions was 2.2 per 1,000 patient-years, while the incidence of unresectable PDAC was 0.6 per 1,000 patient-years in surveillance. Unfortunately, clinical features were unable to predict the onset of these 11 unresectable PDACs.
Aimee Lucas, MD, is associate professor of medicine, division of gastroenterology, Icahn School of Medicine at Mount Sinai, New York. She reports receiving research support and consulting from Immunovia, who developed a blood-based biomarker for early PDAC detection.
Surveillance of individuals at increased risk of pancreatic ductal adenocarcinoma (PDAC) offers an opportunity to improve disease mortality through detection of premalignant lesions and earlier stage PDAC. Emerging data suggest that outcomes in surveillance-detected PDAC are superior to those diagnosed after onset of signs and symptoms. This study by Chhoda et al. highlights a potential quality gap in current surveillance programs, namely the diagnosis of interval cancers and late-stage metastatic PDAC.
Investigators report a cumulative incidence of late-stage PDAC of 1.7 per 1,000 patient-years in surveillance, while the incidence of any advanced neoplasia (high-grade PanIN, high-grade IPMN, NET > 1 cm and any stage PDAC) was 3.3 per 1,000 patient-years. Importantly, late-stage PDAC was defined as T2-4N0-1M0-1 in this study. This is based on the 2013 International Cancer of the Pancreas Screening definition of “success of a screening program” as treatment of T1N0M0 PDAC, which was later updated to include a resected PDAC confined to the pancreas. The cumulative incidence of resectable lesions was 2.2 per 1,000 patient-years, while the incidence of unresectable PDAC was 0.6 per 1,000 patient-years in surveillance. Unfortunately, clinical features were unable to predict the onset of these 11 unresectable PDACs.
Aimee Lucas, MD, is associate professor of medicine, division of gastroenterology, Icahn School of Medicine at Mount Sinai, New York. She reports receiving research support and consulting from Immunovia, who developed a blood-based biomarker for early PDAC detection.
Surveillance of individuals at increased risk of pancreatic ductal adenocarcinoma (PDAC) offers an opportunity to improve disease mortality through detection of premalignant lesions and earlier stage PDAC. Emerging data suggest that outcomes in surveillance-detected PDAC are superior to those diagnosed after onset of signs and symptoms. This study by Chhoda et al. highlights a potential quality gap in current surveillance programs, namely the diagnosis of interval cancers and late-stage metastatic PDAC.
Investigators report a cumulative incidence of late-stage PDAC of 1.7 per 1,000 patient-years in surveillance, while the incidence of any advanced neoplasia (high-grade PanIN, high-grade IPMN, NET > 1 cm and any stage PDAC) was 3.3 per 1,000 patient-years. Importantly, late-stage PDAC was defined as T2-4N0-1M0-1 in this study. This is based on the 2013 International Cancer of the Pancreas Screening definition of “success of a screening program” as treatment of T1N0M0 PDAC, which was later updated to include a resected PDAC confined to the pancreas. The cumulative incidence of resectable lesions was 2.2 per 1,000 patient-years, while the incidence of unresectable PDAC was 0.6 per 1,000 patient-years in surveillance. Unfortunately, clinical features were unable to predict the onset of these 11 unresectable PDACs.
Aimee Lucas, MD, is associate professor of medicine, division of gastroenterology, Icahn School of Medicine at Mount Sinai, New York. She reports receiving research support and consulting from Immunovia, who developed a blood-based biomarker for early PDAC detection.
A relatively large number of late-stage pancreatic ductal adenocarcinomas (PDACs) are detected during follow-up surveillance, yet no single patient- or protocol-specific factor appears to be significantly associated with detecting late-stage disease during this period, according to a new systematic literature review and meta-analysis.
The researchers, led by Ankit Chhoda, MD, of Yale University, New Haven, Conn., wrote in Gastroenterology that interval progression in high-risk individuals “highlights the need for improved follow-up methodology with higher accuracy to detect prognostically significant and treatable lesions.”
Individuals at high risk for PDAC are encouraged to undergo routine surveillance for the disease because early detection and resection of T1N0M0 PDAC and high-grade precursors may improve survival outcomes. According to Dr. Chhoda and colleagues, challenges of interval progression of cancers during the surveillance period for gastrointestinal malignancies have been well described in the general and at-risk patient populations. Previous studies, the authors explained, have not scrutinized the issues associated with late-stage PDACs detected during follow-up surveillance.
“Late-stage PDACs necessitate critical appraisal of current follow-up strategies to detect successful targets and perform timely resections,” the authors wrote. The researchers added that the diagnosis of late-stage PDACs during follow-up emphasizes the need for implementing “quality measures to avoid preventable causes, including surveillance adherence and diagnostic errors.”
To understand the incidence rates of late-stage PDACs during follow-up in high-risk individuals, Dr. Chhoda and researchers performed a systematic literature review and meta-analysis of data that included follow-up strategies for early PDAC detection among a high-risk population.
Outcomes of interest for the analysis included the overall diagnosis of advanced neoplasia as well as surveillance-detected/interval late-stage PDACs (T2–4N0M0/metastatic stage PDAC) during follow-up. The investigators defined surveillance-detected and interval late-stage PDACs as late-stage PDACs that were detected during surveillance and as those presenting symptomatically between visits, respectively.
The researchers also performed metaregression of the incidence rates of late-stage PDACs to examine the relationship with clinicoradiologic features in high-risk individuals.
A total of 13 studies on surveillance in 2,169 high-risk individuals were included in the systematic review, while 12 studies were included in the meta-analysis. Across studies, high-risk individuals were followed for over 7,302.72 patient-years for the purposes of detecting incident lesions or progression of preexisting pancreatic abnormalities.
In all high-risk individuals who underwent follow-up, the investigators identified a total yield of advanced neoplasia of 53. This total yield consisted of 7 high-grade pancreatic intraepithelial neoplasms, 7 high-grade intraductal papillary mucinous neoplasms, and 39 PDACs. According to the meta-analysis, the cumulative incidence of advanced neoplasia was 3.3 (95% confidence interval, 0.6-7.4; P < .001) per 1,000 patient-years. During follow-up, the cumulative incidence of surveillance-detected/interval late-stage PDACs was 1.7 per 1,000 patient-years (95% CI, 0.2-4.0; P = .03).
In a separate analysis, the investigators sought to identify the relationship between the modality of follow-up imaging and late-stage PDAC incidence. Imaging modalities used during follow-up were mostly cross-sectional imaging, such as computed tomography or magnetic resonance imaging with cholangiopancreatography (n = 4) or endoscopic ultrasound and cross-sectional modalities (n = 8).
The investigators found no significant associations between late-stage PDACs and surveillance imaging, baseline pancreatic morphology, study location, genetic background, gender, or age. Incidence of late-stage PDACs in studies with mostly cross-sectional imaging was 0.7 per 1,000 patient-years (95% CI, 0.0-8.0). This incidence rate was lower than that reported with EUS and cross-sectional modalities (2.5 per 1,000 patient-years; 95% CI, 0.6-5.4), but this difference was not statistically significant (P = .2).
No significant difference was found during follow-up in the incidence of late-stage PDACs between high-risk individuals with baseline pancreatic abnormalities (0.0 no significant difference; 95% CI, 0.0-0.3) vs. high-risk individuals with normal baseline (0.9 per 1,000 patient-years; 95% CI, 0.0-2.8) (P = .9).
Most studies included in the analysis did not report on diagnostic errors and surveillance adherence, the researchers wrote. Nonadherence to surveillance as well as delays in surveillance accounted for four late-stage PDACs, and surveillance cessation and/or delays were reported in 4 out of 19 high-risk individuals. There was limited information on symptoms, presentation timing, site of lesion, and surveillance adherence, which the investigators indicated prevented a formal meta-analysis.
In their summary, the study authors noted that in clinical practice there is a need for improved quality measures and adherence to surveillance programs to reduce the risk of diagnostic errors. The authors stated that evidence on the impact of these quality measures “on surveillance outcomes will not only improve quality of surveillance practices, but also enrich our communication with patients who undergo surveillance.”
The researchers reported no conflicts of interest with the pharmaceutical industry, and the study did not receive any funding.
A relatively large number of late-stage pancreatic ductal adenocarcinomas (PDACs) are detected during follow-up surveillance, yet no single patient- or protocol-specific factor appears to be significantly associated with detecting late-stage disease during this period, according to a new systematic literature review and meta-analysis.
The researchers, led by Ankit Chhoda, MD, of Yale University, New Haven, Conn., wrote in Gastroenterology that interval progression in high-risk individuals “highlights the need for improved follow-up methodology with higher accuracy to detect prognostically significant and treatable lesions.”
Individuals at high risk for PDAC are encouraged to undergo routine surveillance for the disease because early detection and resection of T1N0M0 PDAC and high-grade precursors may improve survival outcomes. According to Dr. Chhoda and colleagues, challenges of interval progression of cancers during the surveillance period for gastrointestinal malignancies have been well described in the general and at-risk patient populations. Previous studies, the authors explained, have not scrutinized the issues associated with late-stage PDACs detected during follow-up surveillance.
“Late-stage PDACs necessitate critical appraisal of current follow-up strategies to detect successful targets and perform timely resections,” the authors wrote. The researchers added that the diagnosis of late-stage PDACs during follow-up emphasizes the need for implementing “quality measures to avoid preventable causes, including surveillance adherence and diagnostic errors.”
To understand the incidence rates of late-stage PDACs during follow-up in high-risk individuals, Dr. Chhoda and researchers performed a systematic literature review and meta-analysis of data that included follow-up strategies for early PDAC detection among a high-risk population.
Outcomes of interest for the analysis included the overall diagnosis of advanced neoplasia as well as surveillance-detected/interval late-stage PDACs (T2–4N0M0/metastatic stage PDAC) during follow-up. The investigators defined surveillance-detected and interval late-stage PDACs as late-stage PDACs that were detected during surveillance and as those presenting symptomatically between visits, respectively.
The researchers also performed metaregression of the incidence rates of late-stage PDACs to examine the relationship with clinicoradiologic features in high-risk individuals.
A total of 13 studies on surveillance in 2,169 high-risk individuals were included in the systematic review, while 12 studies were included in the meta-analysis. Across studies, high-risk individuals were followed for over 7,302.72 patient-years for the purposes of detecting incident lesions or progression of preexisting pancreatic abnormalities.
In all high-risk individuals who underwent follow-up, the investigators identified a total yield of advanced neoplasia of 53. This total yield consisted of 7 high-grade pancreatic intraepithelial neoplasms, 7 high-grade intraductal papillary mucinous neoplasms, and 39 PDACs. According to the meta-analysis, the cumulative incidence of advanced neoplasia was 3.3 (95% confidence interval, 0.6-7.4; P < .001) per 1,000 patient-years. During follow-up, the cumulative incidence of surveillance-detected/interval late-stage PDACs was 1.7 per 1,000 patient-years (95% CI, 0.2-4.0; P = .03).
In a separate analysis, the investigators sought to identify the relationship between the modality of follow-up imaging and late-stage PDAC incidence. Imaging modalities used during follow-up were mostly cross-sectional imaging, such as computed tomography or magnetic resonance imaging with cholangiopancreatography (n = 4) or endoscopic ultrasound and cross-sectional modalities (n = 8).
The investigators found no significant associations between late-stage PDACs and surveillance imaging, baseline pancreatic morphology, study location, genetic background, gender, or age. Incidence of late-stage PDACs in studies with mostly cross-sectional imaging was 0.7 per 1,000 patient-years (95% CI, 0.0-8.0). This incidence rate was lower than that reported with EUS and cross-sectional modalities (2.5 per 1,000 patient-years; 95% CI, 0.6-5.4), but this difference was not statistically significant (P = .2).
No significant difference was found during follow-up in the incidence of late-stage PDACs between high-risk individuals with baseline pancreatic abnormalities (0.0 no significant difference; 95% CI, 0.0-0.3) vs. high-risk individuals with normal baseline (0.9 per 1,000 patient-years; 95% CI, 0.0-2.8) (P = .9).
Most studies included in the analysis did not report on diagnostic errors and surveillance adherence, the researchers wrote. Nonadherence to surveillance as well as delays in surveillance accounted for four late-stage PDACs, and surveillance cessation and/or delays were reported in 4 out of 19 high-risk individuals. There was limited information on symptoms, presentation timing, site of lesion, and surveillance adherence, which the investigators indicated prevented a formal meta-analysis.
In their summary, the study authors noted that in clinical practice there is a need for improved quality measures and adherence to surveillance programs to reduce the risk of diagnostic errors. The authors stated that evidence on the impact of these quality measures “on surveillance outcomes will not only improve quality of surveillance practices, but also enrich our communication with patients who undergo surveillance.”
The researchers reported no conflicts of interest with the pharmaceutical industry, and the study did not receive any funding.
FROM GASTROENTEROLOGY
‘Substantial’ CVD risks, burden up to a year after COVID-19
People who have had COVID-19 have an increased risk for, and 12-month burden of, cardiovascular disease (CVD) that is substantial and spans an array of cardiovascular disorders, a deep dive into federal data suggests.
“I went into this thinking that this is most likely happening in people to start with who have a higher risk of cardiovascular disorders, smokers, people with high BMI, diabetes, but what we found is something different,” Ziyad Al-Aly, MD, said in an interview. “It’s evident in people at high risk, but it was also as clear as the sun even in people who have no cardiovascular risk whatsoever.”
Rates were increased in younger adults, never smokers, White and Black people, and males and females, he said. “So the risk confirmed by the SARS-CoV-2 virus seems to spare almost no one.”
Although cardiovascular outcomes increased with the severity of the acute infection, the excess risks and burdens were also evident in those who never required hospitalization, a group that represents the majority of people with COVID-19, observed Dr. Al-Aly, who directs the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System.
“This study is very important because it underscores not just the acute cardiovascular risk associated with COVID but the increased risk of chronic cardiovascular outcomes as well,” cardiologist C. Michael Gibson, MD, professor of medicine, Harvard Medical School, Boston, said in an interview. “Given the number of patients in the U.S. who have been infected with COVID, this could represent a significant chronic burden on the health care system, particularly as health care professionals leave the profession.”
For the study, the investigators used national VA databases to build a cohort of 153,760 veterans who were alive 30 days after testing positive for COVID-19 between March 1, 2020, and January 2021. They were compared with a contemporary cohort of 5.6 million veterans with no evidence of SARS-CoV-2 infection and a historical cohort of 5.8 million veterans using the system in 2017 prior to the pandemic. Median follow-up was 347, 348, and 347 days, respectively.
As reported in Nature Medicine, the risk for a major adverse cardiovascular event, a composite of myocardial infarction, stroke, and all-cause mortality, was 4% higher in people who had been infected with COVID-19 than in those who had not.
“People say 4% is small, but actually it’s really, really big if you think about it in the context of the huge number of people who have had COVID-19 in the United States, and also globally,” Dr. Al-Aly said.
Compared with the contemporary control group, people who had COVID-19 had an increased risk (hazard ratio [HR]) and burden per 1,000 people at 1 year for the following cardiovascular outcomes:
- Stroke: HR, 1.52; burden, 4.03
- Transient ischemic attack: HR, 1.49; burden, 1.84
- Dysrhythmias: HR, 1.69; burden, 19.86
- Ischemic heart disease: HR, 1.66; burden, 7.28
- Heart failure: HR, 1.72; burden, 11.61
- Nonischemic cardiomyopathy: HR, 1.62; burden 3.56
- Pulmonary embolism: HR, 2.93; burden, 5.47
- Deep vein thrombosis: HR, 2.09; burden, 4.18
- Pericarditis: HR, 1.85, burden, 0.98
- Myocarditis: HR, 5.38; burden, 0.31
Recent reports have raised concerns about an association between COVID-19 vaccines and myocarditis and pericarditis, particularly in young males. Although very few of the participants were vaccinated prior to becoming infected, as vaccines were not yet widely available, the researchers performed two analyses censoring participants at the time of the first dose of any COVID-19 vaccine and adjusting for vaccination as a time-varying covariate.
The absolute numbers of myocarditis and pericarditis were still higher than the contemporary and historical cohorts. These numbers are much larger than those reported for myocarditis after vaccines, which are generally around 40 cases per 1 million people, observed Dr. Al-Aly.
The overall results were also consistent when compared with the historical control subjects.
“What we’re seeing in our report and others is that SARS-CoV-2 can leave a sort of scar or imprint on people, and some of these conditions are likely chronic conditions,” Dr. Al-Aly said. “So you’re going to have a generation of people who will bear the scar of COVID for their lifetime and I think that requires recognition and attention, so we’re aware of the magnitude of the problem and prepared to deal with it.”
With more than 76 million COVID-19 cases in the United States, that effort will likely have to be at the federal level, similar to President Joe Biden’s recent relaunch of the “Cancer Moonshot,” he added. “We need a greater and broader recognition at the federal level to try and recognize that when you have an earthquake, you don’t just deal with the earthquake when the earth is shaking, but you also need to deal with the aftermath.”
Dr. Gibson pointed out that this was a study of predominantly males and, thus, it’s unclear if the results can be extended to females. Nevertheless, he added, “long COVID may include outcomes beyond the central nervous system and we should educate patients about the risk of late cardiovascular outcomes.”
The authors noted the largely White, male cohort may limit generalizability of the findings. Other limitations include the possibility that some people may have had COVID-19 but were not tested, the datasets lacked information on cause of death, and possible residual confounding not accounted for in the adjusted analyses.
The research was funded by the U.S. Department of Veterans Affairs and two American Society of Nephrology and Kidney Cure fellowship awards. The authors declared no competing interests. Dr. Gibson reports having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
People who have had COVID-19 have an increased risk for, and 12-month burden of, cardiovascular disease (CVD) that is substantial and spans an array of cardiovascular disorders, a deep dive into federal data suggests.
“I went into this thinking that this is most likely happening in people to start with who have a higher risk of cardiovascular disorders, smokers, people with high BMI, diabetes, but what we found is something different,” Ziyad Al-Aly, MD, said in an interview. “It’s evident in people at high risk, but it was also as clear as the sun even in people who have no cardiovascular risk whatsoever.”
Rates were increased in younger adults, never smokers, White and Black people, and males and females, he said. “So the risk confirmed by the SARS-CoV-2 virus seems to spare almost no one.”
Although cardiovascular outcomes increased with the severity of the acute infection, the excess risks and burdens were also evident in those who never required hospitalization, a group that represents the majority of people with COVID-19, observed Dr. Al-Aly, who directs the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System.
“This study is very important because it underscores not just the acute cardiovascular risk associated with COVID but the increased risk of chronic cardiovascular outcomes as well,” cardiologist C. Michael Gibson, MD, professor of medicine, Harvard Medical School, Boston, said in an interview. “Given the number of patients in the U.S. who have been infected with COVID, this could represent a significant chronic burden on the health care system, particularly as health care professionals leave the profession.”
For the study, the investigators used national VA databases to build a cohort of 153,760 veterans who were alive 30 days after testing positive for COVID-19 between March 1, 2020, and January 2021. They were compared with a contemporary cohort of 5.6 million veterans with no evidence of SARS-CoV-2 infection and a historical cohort of 5.8 million veterans using the system in 2017 prior to the pandemic. Median follow-up was 347, 348, and 347 days, respectively.
As reported in Nature Medicine, the risk for a major adverse cardiovascular event, a composite of myocardial infarction, stroke, and all-cause mortality, was 4% higher in people who had been infected with COVID-19 than in those who had not.
“People say 4% is small, but actually it’s really, really big if you think about it in the context of the huge number of people who have had COVID-19 in the United States, and also globally,” Dr. Al-Aly said.
Compared with the contemporary control group, people who had COVID-19 had an increased risk (hazard ratio [HR]) and burden per 1,000 people at 1 year for the following cardiovascular outcomes:
- Stroke: HR, 1.52; burden, 4.03
- Transient ischemic attack: HR, 1.49; burden, 1.84
- Dysrhythmias: HR, 1.69; burden, 19.86
- Ischemic heart disease: HR, 1.66; burden, 7.28
- Heart failure: HR, 1.72; burden, 11.61
- Nonischemic cardiomyopathy: HR, 1.62; burden 3.56
- Pulmonary embolism: HR, 2.93; burden, 5.47
- Deep vein thrombosis: HR, 2.09; burden, 4.18
- Pericarditis: HR, 1.85, burden, 0.98
- Myocarditis: HR, 5.38; burden, 0.31
Recent reports have raised concerns about an association between COVID-19 vaccines and myocarditis and pericarditis, particularly in young males. Although very few of the participants were vaccinated prior to becoming infected, as vaccines were not yet widely available, the researchers performed two analyses censoring participants at the time of the first dose of any COVID-19 vaccine and adjusting for vaccination as a time-varying covariate.
The absolute numbers of myocarditis and pericarditis were still higher than the contemporary and historical cohorts. These numbers are much larger than those reported for myocarditis after vaccines, which are generally around 40 cases per 1 million people, observed Dr. Al-Aly.
The overall results were also consistent when compared with the historical control subjects.
“What we’re seeing in our report and others is that SARS-CoV-2 can leave a sort of scar or imprint on people, and some of these conditions are likely chronic conditions,” Dr. Al-Aly said. “So you’re going to have a generation of people who will bear the scar of COVID for their lifetime and I think that requires recognition and attention, so we’re aware of the magnitude of the problem and prepared to deal with it.”
With more than 76 million COVID-19 cases in the United States, that effort will likely have to be at the federal level, similar to President Joe Biden’s recent relaunch of the “Cancer Moonshot,” he added. “We need a greater and broader recognition at the federal level to try and recognize that when you have an earthquake, you don’t just deal with the earthquake when the earth is shaking, but you also need to deal with the aftermath.”
Dr. Gibson pointed out that this was a study of predominantly males and, thus, it’s unclear if the results can be extended to females. Nevertheless, he added, “long COVID may include outcomes beyond the central nervous system and we should educate patients about the risk of late cardiovascular outcomes.”
The authors noted the largely White, male cohort may limit generalizability of the findings. Other limitations include the possibility that some people may have had COVID-19 but were not tested, the datasets lacked information on cause of death, and possible residual confounding not accounted for in the adjusted analyses.
The research was funded by the U.S. Department of Veterans Affairs and two American Society of Nephrology and Kidney Cure fellowship awards. The authors declared no competing interests. Dr. Gibson reports having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
People who have had COVID-19 have an increased risk for, and 12-month burden of, cardiovascular disease (CVD) that is substantial and spans an array of cardiovascular disorders, a deep dive into federal data suggests.
“I went into this thinking that this is most likely happening in people to start with who have a higher risk of cardiovascular disorders, smokers, people with high BMI, diabetes, but what we found is something different,” Ziyad Al-Aly, MD, said in an interview. “It’s evident in people at high risk, but it was also as clear as the sun even in people who have no cardiovascular risk whatsoever.”
Rates were increased in younger adults, never smokers, White and Black people, and males and females, he said. “So the risk confirmed by the SARS-CoV-2 virus seems to spare almost no one.”
Although cardiovascular outcomes increased with the severity of the acute infection, the excess risks and burdens were also evident in those who never required hospitalization, a group that represents the majority of people with COVID-19, observed Dr. Al-Aly, who directs the Clinical Epidemiology Center at the Veterans Affairs St. Louis Health Care System.
“This study is very important because it underscores not just the acute cardiovascular risk associated with COVID but the increased risk of chronic cardiovascular outcomes as well,” cardiologist C. Michael Gibson, MD, professor of medicine, Harvard Medical School, Boston, said in an interview. “Given the number of patients in the U.S. who have been infected with COVID, this could represent a significant chronic burden on the health care system, particularly as health care professionals leave the profession.”
For the study, the investigators used national VA databases to build a cohort of 153,760 veterans who were alive 30 days after testing positive for COVID-19 between March 1, 2020, and January 2021. They were compared with a contemporary cohort of 5.6 million veterans with no evidence of SARS-CoV-2 infection and a historical cohort of 5.8 million veterans using the system in 2017 prior to the pandemic. Median follow-up was 347, 348, and 347 days, respectively.
As reported in Nature Medicine, the risk for a major adverse cardiovascular event, a composite of myocardial infarction, stroke, and all-cause mortality, was 4% higher in people who had been infected with COVID-19 than in those who had not.
“People say 4% is small, but actually it’s really, really big if you think about it in the context of the huge number of people who have had COVID-19 in the United States, and also globally,” Dr. Al-Aly said.
Compared with the contemporary control group, people who had COVID-19 had an increased risk (hazard ratio [HR]) and burden per 1,000 people at 1 year for the following cardiovascular outcomes:
- Stroke: HR, 1.52; burden, 4.03
- Transient ischemic attack: HR, 1.49; burden, 1.84
- Dysrhythmias: HR, 1.69; burden, 19.86
- Ischemic heart disease: HR, 1.66; burden, 7.28
- Heart failure: HR, 1.72; burden, 11.61
- Nonischemic cardiomyopathy: HR, 1.62; burden 3.56
- Pulmonary embolism: HR, 2.93; burden, 5.47
- Deep vein thrombosis: HR, 2.09; burden, 4.18
- Pericarditis: HR, 1.85, burden, 0.98
- Myocarditis: HR, 5.38; burden, 0.31
Recent reports have raised concerns about an association between COVID-19 vaccines and myocarditis and pericarditis, particularly in young males. Although very few of the participants were vaccinated prior to becoming infected, as vaccines were not yet widely available, the researchers performed two analyses censoring participants at the time of the first dose of any COVID-19 vaccine and adjusting for vaccination as a time-varying covariate.
The absolute numbers of myocarditis and pericarditis were still higher than the contemporary and historical cohorts. These numbers are much larger than those reported for myocarditis after vaccines, which are generally around 40 cases per 1 million people, observed Dr. Al-Aly.
The overall results were also consistent when compared with the historical control subjects.
“What we’re seeing in our report and others is that SARS-CoV-2 can leave a sort of scar or imprint on people, and some of these conditions are likely chronic conditions,” Dr. Al-Aly said. “So you’re going to have a generation of people who will bear the scar of COVID for their lifetime and I think that requires recognition and attention, so we’re aware of the magnitude of the problem and prepared to deal with it.”
With more than 76 million COVID-19 cases in the United States, that effort will likely have to be at the federal level, similar to President Joe Biden’s recent relaunch of the “Cancer Moonshot,” he added. “We need a greater and broader recognition at the federal level to try and recognize that when you have an earthquake, you don’t just deal with the earthquake when the earth is shaking, but you also need to deal with the aftermath.”
Dr. Gibson pointed out that this was a study of predominantly males and, thus, it’s unclear if the results can be extended to females. Nevertheless, he added, “long COVID may include outcomes beyond the central nervous system and we should educate patients about the risk of late cardiovascular outcomes.”
The authors noted the largely White, male cohort may limit generalizability of the findings. Other limitations include the possibility that some people may have had COVID-19 but were not tested, the datasets lacked information on cause of death, and possible residual confounding not accounted for in the adjusted analyses.
The research was funded by the U.S. Department of Veterans Affairs and two American Society of Nephrology and Kidney Cure fellowship awards. The authors declared no competing interests. Dr. Gibson reports having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Dupilumab under FDA review for atopic dermatitis in children aged 6 months to 5 years
The and Sanofi.
If approved, dupilumab would be the first biologic approved for children in this age group in the United States, according to the statement. The proposed indication is as add-on therapy for children with moderate to severe AD not adequately controlled with topical prescription therapies or for whom topical therapies are not advised. The FDA granted breakthrough therapy designation for dupilumab for the treatment of severe AD in children aged 6 months to 11 years in 2016.
Approximately 85%-95% of atopic dermatitis patients develop symptoms before 5 years of age, and these symptoms often continue into adulthood, with an increased risk of skin infections and a significant impact on quality of life, according to the statement.
The sBLA is based on data from a phase 3 pivotal study of 162 children aged 6 months to 5 years in which dupilumab was added to standard-of-care topical corticosteroids, presented in December 2021. In the study, dupilumab plus standard of care significantly improved skin clearance and reduced overall disease severity and itch at 16 weeks compared with standard of care alone. Overall, 28% of the children randomized to dupilumab achieved the primary endpoint of clear or almost-clear skin, compared with 4% with those on standard of care alone (P < .0001), according to the manufacturers. Patients in the dupilumab group received either 200 mg (for children weighing ≥ 5 to < 15 kg) or 300 mg (for children weighing ≥ 15 to < 30 kg) every 4 weeks. Safety results were similar to those seen with dupilumab for children aged 6 years and older.
Conjunctivitis and herpes infections were among the most common adverse events associated with dupilumab in the study, according to the statement.
The target action date for the FDA decision on this application is June 9, 2022.
The and Sanofi.
If approved, dupilumab would be the first biologic approved for children in this age group in the United States, according to the statement. The proposed indication is as add-on therapy for children with moderate to severe AD not adequately controlled with topical prescription therapies or for whom topical therapies are not advised. The FDA granted breakthrough therapy designation for dupilumab for the treatment of severe AD in children aged 6 months to 11 years in 2016.
Approximately 85%-95% of atopic dermatitis patients develop symptoms before 5 years of age, and these symptoms often continue into adulthood, with an increased risk of skin infections and a significant impact on quality of life, according to the statement.
The sBLA is based on data from a phase 3 pivotal study of 162 children aged 6 months to 5 years in which dupilumab was added to standard-of-care topical corticosteroids, presented in December 2021. In the study, dupilumab plus standard of care significantly improved skin clearance and reduced overall disease severity and itch at 16 weeks compared with standard of care alone. Overall, 28% of the children randomized to dupilumab achieved the primary endpoint of clear or almost-clear skin, compared with 4% with those on standard of care alone (P < .0001), according to the manufacturers. Patients in the dupilumab group received either 200 mg (for children weighing ≥ 5 to < 15 kg) or 300 mg (for children weighing ≥ 15 to < 30 kg) every 4 weeks. Safety results were similar to those seen with dupilumab for children aged 6 years and older.
Conjunctivitis and herpes infections were among the most common adverse events associated with dupilumab in the study, according to the statement.
The target action date for the FDA decision on this application is June 9, 2022.
The and Sanofi.
If approved, dupilumab would be the first biologic approved for children in this age group in the United States, according to the statement. The proposed indication is as add-on therapy for children with moderate to severe AD not adequately controlled with topical prescription therapies or for whom topical therapies are not advised. The FDA granted breakthrough therapy designation for dupilumab for the treatment of severe AD in children aged 6 months to 11 years in 2016.
Approximately 85%-95% of atopic dermatitis patients develop symptoms before 5 years of age, and these symptoms often continue into adulthood, with an increased risk of skin infections and a significant impact on quality of life, according to the statement.
The sBLA is based on data from a phase 3 pivotal study of 162 children aged 6 months to 5 years in which dupilumab was added to standard-of-care topical corticosteroids, presented in December 2021. In the study, dupilumab plus standard of care significantly improved skin clearance and reduced overall disease severity and itch at 16 weeks compared with standard of care alone. Overall, 28% of the children randomized to dupilumab achieved the primary endpoint of clear or almost-clear skin, compared with 4% with those on standard of care alone (P < .0001), according to the manufacturers. Patients in the dupilumab group received either 200 mg (for children weighing ≥ 5 to < 15 kg) or 300 mg (for children weighing ≥ 15 to < 30 kg) every 4 weeks. Safety results were similar to those seen with dupilumab for children aged 6 years and older.
Conjunctivitis and herpes infections were among the most common adverse events associated with dupilumab in the study, according to the statement.
The target action date for the FDA decision on this application is June 9, 2022.
FROM THE FDA
E-cigarettes don’t help smokers quit, suggests new research
From 2013 to 2017, e-cigarette sales in the United States nearly doubled, driven by a rapid uptake of use by adolescents, wrote Riufeng Chen, MD, of the University of California, San Diego, and colleagues, in their paper published in Tobacco Control. However, the subsequent effect of increased e-cigarette use on smoking cessation have not been examined, they said.
In their study, Dr. Chen and colleagues analyzed data from 3,578 previous-year smokers with a recent quit attempt and 1,323 recent former smokers who were part of the PATH cohort in 2017. The participants reported using e-cigarettes or other products to quit cigarette smoking. The primary outcomes were at least 12 months of cigarette abstinence, and tobacco abstinence in 2019. In 2017, 32.8% of established smokers reported trying to quit. Of these, 12.6% used e-cigarettes to help them quit. Cigarette abstinence for at least 12 months for these individuals was 9.9%, which was lower than for those who used either nicotine replacement therapy or a pharmaceutical aid only (15.2%), and about half of the 18.6% abstinence in those who used no products to help them quit.
“In our study, e-cigarettes resulted in seven fewer successful quitters than those who used pharmaceutical aids,” emphasized corresponding author, John P. Pierce, PhD, of the University of California, San Diego.
Among smokers attempting to quit, the adjusted risk difference for cigarette abstinence for a least 12 months with e-cigarettes vs. pharmaceutical aids was –7.3%, and –7.7% for e-cigarettes vs. other smoking cessation methods.
*“Among recent former smokers who had switched to daily use of e-cigarettes in 2017, 43.2% had successfully quit cigarette smoking by 2019, which was similar to those who used e-cigarettes on a nondaily basis (34.6%) or to those who switched to another tobacco product, whether daily (43.6%) or nondaily (44.7%),” the researchers wrote.
The rapid growth in e-cigarette use between 2014 and 2017 has been attributed in part to aggressive marketing of high-nicotine e-cigarettes, they said. “The high-nicotine JUUL e-cigarette has been noted as the closest match to cigarettes in both nicotine delivery and user satisfaction, which should make it one of the best candidates as a product to which smokers could switch in order to maintain their nicotine habit,” they said in their discussion of the findings.
More research needed
The researchers acknowledged the need to review more recent data.
“When we looked ahead to 2019, recent former smokers had started using high-nicotine e-cigarettes. The effectiveness of high-nicotine e-cigarettes at preventing relapse will require another follow-up PATH survey,” they said.
Among recent former smokers, 2.2% reported switching to a high-nicotine e-cigarette. Although individuals who switched to e-cigarettes showed a higher rate of relapse to cigarettes than those who did not switch to other tobacco or e-cigarette products, this difference was not significant.
The study findings were limited by several factors including the observational design and inability to control for all potential confounding factors, the researchers noted. However, the results were strengthened by the use of a large and representative study population, and the inclusion of biological samples to validate self-reported smoking, they said.
Several findings surprised study author
Dr. Pierce said he was surprised by several aspects of the study findings.
“First of all, contrary to what we expected, there was a 25% decline in using e-cigarettes to quit, compared to the previous year (not the 40% increase that was expected from the increase in e-cigarette sales) and almost no smokers were using high-nicotine JUUL products to help them quit,” he said. “In this study, e-cigarettes were much less helpful (7 less successful quitters per 100) than pharmaceutical cessation aids in helping people quit,” he added.
“The fact that the proportion of smokers using e-cigarettes for cessation dropped from 17% to 12% was unexpected, and it suggests that the belief that they are a cessation aid is declining,” he said.
The implication for clinical practice is that e-cigarettes are not a useful tool for smoking cessation, Dr. Pierce said. “We are not finding any evidence in this very large nationally representative study that smokers who switch to getting their nicotine from e-cigarettes are less likely to relapse back to cigarette smoking,” he said.
“We don’t know about the high-nicotine versions,” he added.
New review advises against e-cigarettes for cessation
A recent review article published in JAMA supported the use of pharmacotherapy and behavioral support for smokers wanting to quit. In the review, Nancy A. Rigotti, MD, of Massachusetts General Hospital, Boston, and colleagues summarized the evidence for managing tobacco smoking in clinical practice.
“The health risk from cigarette smoking is primarily due to chemicals produced by the burning of tobacco and not to nicotine,” they noted. However, the physical dependence on nicotine makes quitting a challenge, but it is one worth pursuing, the authors said.
The authors of this review identified 30 reviews, 12 randomized clinical trials, and 7 recent guidelines and evidence reviews. Their key message: Pharmacotherapy and behavioral support are effective when used alone, but even more effective when combined. Pharmacotherapy helps reduce the symptoms of nicotine withdrawal, while behavioral intervention tackles the challenge of changing learned behaviors associated with smoking, the researchers said.
Although combining medications, such as varenicline and nicotine replacement therapy or bupropion might improve successful quit rates, these combinations have not been well studied, they noted.
With regard to e-cigarettes, the researchers cited a 2021 Cochrane review of 16,759 individuals who used e-cigarettes for smoking cessation, which found no evidence of harm, but insufficient evidence to asses the balance of risks vs. benefits.
In addition to the lack of randomized trials, “the FDA regulates e-cigarettes as tobacco products, not as medical products and has not evaluated any e-cigarette for medical use as a cessation aid,” the authors of the new review noted.
The review was limited by several factors, including the lack of quality assessment for the selected studies and the exclusion of pharmacotherapy not licensed in the United States.
Commenting on the JAMA paper, Dr. Pierce said, “This review looks like a number of Cochrane Reports that have been published recently. Of course, it only considers randomized trials and not population evidence.”
“If public health had limited itself to this form of evidence, then we still would not know that smoking caused cancer,” he noted. “Randomized trials are very important for testing new drugs; they use selected populations and provide considerable support that is not available in the real world. Sometimes they do not generalize to the population.”
Findings may guide patient conversations
The Tobacco Control study was important, because few studies on e-cigarettes have been conducted, said Linda Girgis, MD, a family physician in private practice in South River, N.J., in an interview.
“As clinicians, we do not have a lot of data available in order to make clinical decisions that are evidence based. Also, getting patients to quit smoking is often very difficult, and having more tools available is a great benefit; however, we need to have the evidence that these tools are effective,” she said.
Dr. Girgis also said she was not surprised by the findings.
“Patients still have the same concerns from e-cigarettes regarding nicotine exposure, but just to a lesser degree; and we still don’t know the long-term effects of e-cigarette use, she said. Based on these studies, recommending e-cigarettes for smokers looking to quit may not be the best method, she noted.
“While it may seem reasonable that exposing lungs to lower doses of nicotine will reduce harm, we need to see actual evidence of this. Also, we also need to study the additives that are frequently used in e-cigs, such as artificial flavorings, to see what harms they may pose, she emphasized.
With regard to the JAMA review, Dr. Girgis said she agreed with the recommendations for pharmacotherapy and behavior therapy as first-line treatments for smoking cessation. “There is evidence regarding the efficacy and safety of these methods, and they have been used for decades,” she said.
Dr. Girgis added that there is a role for e-cigarettes in smoking cessation strategies as a method of harm reduction, but pointed out the problem of many people thinking these products are safe and not understanding the hazards they pose.
“They think they can replace smoking with e-cigarettes and be safe from the health risks associated with smoking. I think if the plan were to switch to e-cigarettes for a short period and then quit, there would be a role,” Dr. Girgis said. “However, replacing one risk for another may reduce harm, but doesn’t eliminate it.”
“To continue to use e-cigarettes indefinitely should not be the goal,” she added.
The Tobacco Control study was funded by the National Institutes of Health and the Tobacco-Related Disease Research Program of the University of California. The researchers had no financial conflicts to disclose.
The JAMA study was funded in part by a grant from the National Institute for Health Research, via Cochrane Infrastructure funds to the Cochrane Tobacco Addiction Group. Lead author Dr. Rigotti disclosed funding from the National Heart, Lung, and Blood Institute and Achieve Life Sciences and personal fees from UpToDate and Achieve Life Sciences. Dr. Girgis had no financial conflicts to disclose.
*This article was updated on 2/28/2022.
From 2013 to 2017, e-cigarette sales in the United States nearly doubled, driven by a rapid uptake of use by adolescents, wrote Riufeng Chen, MD, of the University of California, San Diego, and colleagues, in their paper published in Tobacco Control. However, the subsequent effect of increased e-cigarette use on smoking cessation have not been examined, they said.
In their study, Dr. Chen and colleagues analyzed data from 3,578 previous-year smokers with a recent quit attempt and 1,323 recent former smokers who were part of the PATH cohort in 2017. The participants reported using e-cigarettes or other products to quit cigarette smoking. The primary outcomes were at least 12 months of cigarette abstinence, and tobacco abstinence in 2019. In 2017, 32.8% of established smokers reported trying to quit. Of these, 12.6% used e-cigarettes to help them quit. Cigarette abstinence for at least 12 months for these individuals was 9.9%, which was lower than for those who used either nicotine replacement therapy or a pharmaceutical aid only (15.2%), and about half of the 18.6% abstinence in those who used no products to help them quit.
“In our study, e-cigarettes resulted in seven fewer successful quitters than those who used pharmaceutical aids,” emphasized corresponding author, John P. Pierce, PhD, of the University of California, San Diego.
Among smokers attempting to quit, the adjusted risk difference for cigarette abstinence for a least 12 months with e-cigarettes vs. pharmaceutical aids was –7.3%, and –7.7% for e-cigarettes vs. other smoking cessation methods.
*“Among recent former smokers who had switched to daily use of e-cigarettes in 2017, 43.2% had successfully quit cigarette smoking by 2019, which was similar to those who used e-cigarettes on a nondaily basis (34.6%) or to those who switched to another tobacco product, whether daily (43.6%) or nondaily (44.7%),” the researchers wrote.
The rapid growth in e-cigarette use between 2014 and 2017 has been attributed in part to aggressive marketing of high-nicotine e-cigarettes, they said. “The high-nicotine JUUL e-cigarette has been noted as the closest match to cigarettes in both nicotine delivery and user satisfaction, which should make it one of the best candidates as a product to which smokers could switch in order to maintain their nicotine habit,” they said in their discussion of the findings.
More research needed
The researchers acknowledged the need to review more recent data.
“When we looked ahead to 2019, recent former smokers had started using high-nicotine e-cigarettes. The effectiveness of high-nicotine e-cigarettes at preventing relapse will require another follow-up PATH survey,” they said.
Among recent former smokers, 2.2% reported switching to a high-nicotine e-cigarette. Although individuals who switched to e-cigarettes showed a higher rate of relapse to cigarettes than those who did not switch to other tobacco or e-cigarette products, this difference was not significant.
The study findings were limited by several factors including the observational design and inability to control for all potential confounding factors, the researchers noted. However, the results were strengthened by the use of a large and representative study population, and the inclusion of biological samples to validate self-reported smoking, they said.
Several findings surprised study author
Dr. Pierce said he was surprised by several aspects of the study findings.
“First of all, contrary to what we expected, there was a 25% decline in using e-cigarettes to quit, compared to the previous year (not the 40% increase that was expected from the increase in e-cigarette sales) and almost no smokers were using high-nicotine JUUL products to help them quit,” he said. “In this study, e-cigarettes were much less helpful (7 less successful quitters per 100) than pharmaceutical cessation aids in helping people quit,” he added.
“The fact that the proportion of smokers using e-cigarettes for cessation dropped from 17% to 12% was unexpected, and it suggests that the belief that they are a cessation aid is declining,” he said.
The implication for clinical practice is that e-cigarettes are not a useful tool for smoking cessation, Dr. Pierce said. “We are not finding any evidence in this very large nationally representative study that smokers who switch to getting their nicotine from e-cigarettes are less likely to relapse back to cigarette smoking,” he said.
“We don’t know about the high-nicotine versions,” he added.
New review advises against e-cigarettes for cessation
A recent review article published in JAMA supported the use of pharmacotherapy and behavioral support for smokers wanting to quit. In the review, Nancy A. Rigotti, MD, of Massachusetts General Hospital, Boston, and colleagues summarized the evidence for managing tobacco smoking in clinical practice.
“The health risk from cigarette smoking is primarily due to chemicals produced by the burning of tobacco and not to nicotine,” they noted. However, the physical dependence on nicotine makes quitting a challenge, but it is one worth pursuing, the authors said.
The authors of this review identified 30 reviews, 12 randomized clinical trials, and 7 recent guidelines and evidence reviews. Their key message: Pharmacotherapy and behavioral support are effective when used alone, but even more effective when combined. Pharmacotherapy helps reduce the symptoms of nicotine withdrawal, while behavioral intervention tackles the challenge of changing learned behaviors associated with smoking, the researchers said.
Although combining medications, such as varenicline and nicotine replacement therapy or bupropion might improve successful quit rates, these combinations have not been well studied, they noted.
With regard to e-cigarettes, the researchers cited a 2021 Cochrane review of 16,759 individuals who used e-cigarettes for smoking cessation, which found no evidence of harm, but insufficient evidence to asses the balance of risks vs. benefits.
In addition to the lack of randomized trials, “the FDA regulates e-cigarettes as tobacco products, not as medical products and has not evaluated any e-cigarette for medical use as a cessation aid,” the authors of the new review noted.
The review was limited by several factors, including the lack of quality assessment for the selected studies and the exclusion of pharmacotherapy not licensed in the United States.
Commenting on the JAMA paper, Dr. Pierce said, “This review looks like a number of Cochrane Reports that have been published recently. Of course, it only considers randomized trials and not population evidence.”
“If public health had limited itself to this form of evidence, then we still would not know that smoking caused cancer,” he noted. “Randomized trials are very important for testing new drugs; they use selected populations and provide considerable support that is not available in the real world. Sometimes they do not generalize to the population.”
Findings may guide patient conversations
The Tobacco Control study was important, because few studies on e-cigarettes have been conducted, said Linda Girgis, MD, a family physician in private practice in South River, N.J., in an interview.
“As clinicians, we do not have a lot of data available in order to make clinical decisions that are evidence based. Also, getting patients to quit smoking is often very difficult, and having more tools available is a great benefit; however, we need to have the evidence that these tools are effective,” she said.
Dr. Girgis also said she was not surprised by the findings.
“Patients still have the same concerns from e-cigarettes regarding nicotine exposure, but just to a lesser degree; and we still don’t know the long-term effects of e-cigarette use, she said. Based on these studies, recommending e-cigarettes for smokers looking to quit may not be the best method, she noted.
“While it may seem reasonable that exposing lungs to lower doses of nicotine will reduce harm, we need to see actual evidence of this. Also, we also need to study the additives that are frequently used in e-cigs, such as artificial flavorings, to see what harms they may pose, she emphasized.
With regard to the JAMA review, Dr. Girgis said she agreed with the recommendations for pharmacotherapy and behavior therapy as first-line treatments for smoking cessation. “There is evidence regarding the efficacy and safety of these methods, and they have been used for decades,” she said.
Dr. Girgis added that there is a role for e-cigarettes in smoking cessation strategies as a method of harm reduction, but pointed out the problem of many people thinking these products are safe and not understanding the hazards they pose.
“They think they can replace smoking with e-cigarettes and be safe from the health risks associated with smoking. I think if the plan were to switch to e-cigarettes for a short period and then quit, there would be a role,” Dr. Girgis said. “However, replacing one risk for another may reduce harm, but doesn’t eliminate it.”
“To continue to use e-cigarettes indefinitely should not be the goal,” she added.
The Tobacco Control study was funded by the National Institutes of Health and the Tobacco-Related Disease Research Program of the University of California. The researchers had no financial conflicts to disclose.
The JAMA study was funded in part by a grant from the National Institute for Health Research, via Cochrane Infrastructure funds to the Cochrane Tobacco Addiction Group. Lead author Dr. Rigotti disclosed funding from the National Heart, Lung, and Blood Institute and Achieve Life Sciences and personal fees from UpToDate and Achieve Life Sciences. Dr. Girgis had no financial conflicts to disclose.
*This article was updated on 2/28/2022.
From 2013 to 2017, e-cigarette sales in the United States nearly doubled, driven by a rapid uptake of use by adolescents, wrote Riufeng Chen, MD, of the University of California, San Diego, and colleagues, in their paper published in Tobacco Control. However, the subsequent effect of increased e-cigarette use on smoking cessation have not been examined, they said.
In their study, Dr. Chen and colleagues analyzed data from 3,578 previous-year smokers with a recent quit attempt and 1,323 recent former smokers who were part of the PATH cohort in 2017. The participants reported using e-cigarettes or other products to quit cigarette smoking. The primary outcomes were at least 12 months of cigarette abstinence, and tobacco abstinence in 2019. In 2017, 32.8% of established smokers reported trying to quit. Of these, 12.6% used e-cigarettes to help them quit. Cigarette abstinence for at least 12 months for these individuals was 9.9%, which was lower than for those who used either nicotine replacement therapy or a pharmaceutical aid only (15.2%), and about half of the 18.6% abstinence in those who used no products to help them quit.
“In our study, e-cigarettes resulted in seven fewer successful quitters than those who used pharmaceutical aids,” emphasized corresponding author, John P. Pierce, PhD, of the University of California, San Diego.
Among smokers attempting to quit, the adjusted risk difference for cigarette abstinence for a least 12 months with e-cigarettes vs. pharmaceutical aids was –7.3%, and –7.7% for e-cigarettes vs. other smoking cessation methods.
*“Among recent former smokers who had switched to daily use of e-cigarettes in 2017, 43.2% had successfully quit cigarette smoking by 2019, which was similar to those who used e-cigarettes on a nondaily basis (34.6%) or to those who switched to another tobacco product, whether daily (43.6%) or nondaily (44.7%),” the researchers wrote.
The rapid growth in e-cigarette use between 2014 and 2017 has been attributed in part to aggressive marketing of high-nicotine e-cigarettes, they said. “The high-nicotine JUUL e-cigarette has been noted as the closest match to cigarettes in both nicotine delivery and user satisfaction, which should make it one of the best candidates as a product to which smokers could switch in order to maintain their nicotine habit,” they said in their discussion of the findings.
More research needed
The researchers acknowledged the need to review more recent data.
“When we looked ahead to 2019, recent former smokers had started using high-nicotine e-cigarettes. The effectiveness of high-nicotine e-cigarettes at preventing relapse will require another follow-up PATH survey,” they said.
Among recent former smokers, 2.2% reported switching to a high-nicotine e-cigarette. Although individuals who switched to e-cigarettes showed a higher rate of relapse to cigarettes than those who did not switch to other tobacco or e-cigarette products, this difference was not significant.
The study findings were limited by several factors including the observational design and inability to control for all potential confounding factors, the researchers noted. However, the results were strengthened by the use of a large and representative study population, and the inclusion of biological samples to validate self-reported smoking, they said.
Several findings surprised study author
Dr. Pierce said he was surprised by several aspects of the study findings.
“First of all, contrary to what we expected, there was a 25% decline in using e-cigarettes to quit, compared to the previous year (not the 40% increase that was expected from the increase in e-cigarette sales) and almost no smokers were using high-nicotine JUUL products to help them quit,” he said. “In this study, e-cigarettes were much less helpful (7 less successful quitters per 100) than pharmaceutical cessation aids in helping people quit,” he added.
“The fact that the proportion of smokers using e-cigarettes for cessation dropped from 17% to 12% was unexpected, and it suggests that the belief that they are a cessation aid is declining,” he said.
The implication for clinical practice is that e-cigarettes are not a useful tool for smoking cessation, Dr. Pierce said. “We are not finding any evidence in this very large nationally representative study that smokers who switch to getting their nicotine from e-cigarettes are less likely to relapse back to cigarette smoking,” he said.
“We don’t know about the high-nicotine versions,” he added.
New review advises against e-cigarettes for cessation
A recent review article published in JAMA supported the use of pharmacotherapy and behavioral support for smokers wanting to quit. In the review, Nancy A. Rigotti, MD, of Massachusetts General Hospital, Boston, and colleagues summarized the evidence for managing tobacco smoking in clinical practice.
“The health risk from cigarette smoking is primarily due to chemicals produced by the burning of tobacco and not to nicotine,” they noted. However, the physical dependence on nicotine makes quitting a challenge, but it is one worth pursuing, the authors said.
The authors of this review identified 30 reviews, 12 randomized clinical trials, and 7 recent guidelines and evidence reviews. Their key message: Pharmacotherapy and behavioral support are effective when used alone, but even more effective when combined. Pharmacotherapy helps reduce the symptoms of nicotine withdrawal, while behavioral intervention tackles the challenge of changing learned behaviors associated with smoking, the researchers said.
Although combining medications, such as varenicline and nicotine replacement therapy or bupropion might improve successful quit rates, these combinations have not been well studied, they noted.
With regard to e-cigarettes, the researchers cited a 2021 Cochrane review of 16,759 individuals who used e-cigarettes for smoking cessation, which found no evidence of harm, but insufficient evidence to asses the balance of risks vs. benefits.
In addition to the lack of randomized trials, “the FDA regulates e-cigarettes as tobacco products, not as medical products and has not evaluated any e-cigarette for medical use as a cessation aid,” the authors of the new review noted.
The review was limited by several factors, including the lack of quality assessment for the selected studies and the exclusion of pharmacotherapy not licensed in the United States.
Commenting on the JAMA paper, Dr. Pierce said, “This review looks like a number of Cochrane Reports that have been published recently. Of course, it only considers randomized trials and not population evidence.”
“If public health had limited itself to this form of evidence, then we still would not know that smoking caused cancer,” he noted. “Randomized trials are very important for testing new drugs; they use selected populations and provide considerable support that is not available in the real world. Sometimes they do not generalize to the population.”
Findings may guide patient conversations
The Tobacco Control study was important, because few studies on e-cigarettes have been conducted, said Linda Girgis, MD, a family physician in private practice in South River, N.J., in an interview.
“As clinicians, we do not have a lot of data available in order to make clinical decisions that are evidence based. Also, getting patients to quit smoking is often very difficult, and having more tools available is a great benefit; however, we need to have the evidence that these tools are effective,” she said.
Dr. Girgis also said she was not surprised by the findings.
“Patients still have the same concerns from e-cigarettes regarding nicotine exposure, but just to a lesser degree; and we still don’t know the long-term effects of e-cigarette use, she said. Based on these studies, recommending e-cigarettes for smokers looking to quit may not be the best method, she noted.
“While it may seem reasonable that exposing lungs to lower doses of nicotine will reduce harm, we need to see actual evidence of this. Also, we also need to study the additives that are frequently used in e-cigs, such as artificial flavorings, to see what harms they may pose, she emphasized.
With regard to the JAMA review, Dr. Girgis said she agreed with the recommendations for pharmacotherapy and behavior therapy as first-line treatments for smoking cessation. “There is evidence regarding the efficacy and safety of these methods, and they have been used for decades,” she said.
Dr. Girgis added that there is a role for e-cigarettes in smoking cessation strategies as a method of harm reduction, but pointed out the problem of many people thinking these products are safe and not understanding the hazards they pose.
“They think they can replace smoking with e-cigarettes and be safe from the health risks associated with smoking. I think if the plan were to switch to e-cigarettes for a short period and then quit, there would be a role,” Dr. Girgis said. “However, replacing one risk for another may reduce harm, but doesn’t eliminate it.”
“To continue to use e-cigarettes indefinitely should not be the goal,” she added.
The Tobacco Control study was funded by the National Institutes of Health and the Tobacco-Related Disease Research Program of the University of California. The researchers had no financial conflicts to disclose.
The JAMA study was funded in part by a grant from the National Institute for Health Research, via Cochrane Infrastructure funds to the Cochrane Tobacco Addiction Group. Lead author Dr. Rigotti disclosed funding from the National Heart, Lung, and Blood Institute and Achieve Life Sciences and personal fees from UpToDate and Achieve Life Sciences. Dr. Girgis had no financial conflicts to disclose.
*This article was updated on 2/28/2022.
FROM TOBACCO CONTROL
Dietary recommendations for inflammatory rheumatic diseases
This interview is a translation of a video blog that first appeared on Medscape France. It has been edited for clarity.
Weight loss, omega-3 supplements, the Mediterranean diet? What about exclusion diets? Jérémie Sellam, MD, PhD, from Saint-Antoine Hospital in Paris, summarizes the key points of the first set of dietary recommendations of the French Society for Rheumatology.
Transcript
Jérémie Sellam, MD, PhD: Hello, everyone. I’m Professor Jérémie Sellam. I’m a rheumatologist at Saint-Antoine Hospital, which is affiliated with the Sorbonne University in Paris. And I was fortunate enough to coordinate France’s first set of dietary recommendations – in fact, the world’s first set of dietary recommendations – for patients with chronic inflammatory rheumatic diseases. I worked on this project with Claire Daien, MD, PhD, who’s a rheumatologist at Montpellier University Hospital.
The idea of coming up with dietary recommendations for patients with inflammatory rheumatic diseases came, quite simply, from our clinical practice. We see that when patients learn they have polyarthritis or spondyloarthritis, they start to experiment with different diets. Many patients start exclusion diets and experiment in all sorts of ways with the food they eat. And although rheumatologists have been able to find some information here and there in the literature, they’ve been pretty much on their own when trying to come up with advice to give their patients. It was to address this issue that [Dr.] Daien and I set out to form a working group. Because when patients aren’t able to get sound advice and authoritative guidance from their doctors, medical associations, or patient advocacy organizations, they often look for information online, and that information is not always reliable or validated.
This group was made up of rheumatologists, some who work at hospitals and others in private practice. Also involved were physician nutrition specialists and registered dietitians. Operating under the auspices of the French Society for Rheumatology, these multidisciplinary experts conducted out a systematic literature review for the purpose of establishing and drafting recommendations. The result was a declaration of eight general principles and nine recommendations.
General principles
The first of the general principles states that nutritional advice is not a substitute for the pharmacologic treatment of chronic inflammatory rheumatic diseases. As you know, whether it’s methotrexate or biologics, pharmacologic treatments are essential for the proper management of chronic inflammatory rheumatic diseases. We know that these medications have an anti-inflammatory effect, reduce pain, and – particularly in the case of rheumatoid arthritis – have a structural effect. In other words, they prevent joint deterioration and destruction. Now, I can tell you that there’s currently no diet, and no dietary supplement, that has proven to be structurally effective. So, yes, dietary intervention might turn out to be promising for patients with chronic inflammatory rheumatic diseases, but pharmacologic treatment must still be part of the picture.
Another general principle emphasizes that dietary intervention is a way for patients to be actively involved in the overall care of their disease, beyond just taking their medication. We know that patients, when they suffer from chronic diseases, are looking for something more, beyond just taking medications. Encouraging them to take an interest in their diet, asking them about what they eat, giving them advice, and supporting their desire to become involved in this aspect of their treatment plan can give them a sense of empowerment.
Dietary interventions can have articular effects, and I’m going to speak about which interventions you can propose, but also which can be beneficial in terms of cardiovascular health and bone health. All of this is based on the literature. In these recommendations, we’ve taken into account not only laboratory experiments – where this or that diet is given to a mouse with arthritis – but also reviewed randomized controlled trials that compare an intervention group with a control group. This is the benchmark we used to determine whether or not a diet should be recommended.
The recommendations
As for the recommendations themselves, we wanted to start off by emphasizing weight loss and what can be called weight-loss support. There’s a link between obesity and the risk of developing rheumatoid arthritis, and also psoriatic arthropathy. And the more overweight a patient is, the more active their disease. In other words, patients with obesity are going to experience more pain, more instances of wakefulness, and more morning stiffness than their normal-weight peers. They’re also going to show symptoms that suggest that disease activity is not controlled well.
Several randomized controlled studies have shown that weight loss will improve systemic joint symptoms. In one particular study, patients with psoriatic arthropathy were started on [tumor necrosis factor] inhibitor therapy and one group followed a prescribed diet and the other had no restrictions on eating. More patients in the diet group than in the no-diet group achieved minimal disease activity. Of course, in some cases – for example, patients with complicated morbid obesity – it might be necessary to have a discussion about bariatric surgery.
But practically speaking, how does one proceed? First of all, patients should be weighed at each visit and, if they’re overweight or obese, the subject should be broached. But even after that conversation, the reality remains that it’s not easy to lose weight. So in the recommendations, we focused on the fact that it shouldn’t be left to the rheumatologist or treating physician alone to handle this challenging aspect of treatment. They should incorporate dietary and nutritional care by reaching out to a dietician or, in the case of complicated obesity – especially when the BMI is higher than 35 kg/m2 – they can refer patients to a nutrition expert who can manage the patient’s obesity, come up with a weight-loss plan, and handle any complications that might arise.
We don’t speak about a low-calorie diet in the recommendations because a diet has a beginning and an end and, quite often, patients regain weight after stopping a diet. Instead, we speak about weight-loss support to point out that weight loss maintained through dietary changes brings about long-term control of disease activity.
In addition, we make two positive recommendations, which overlap, that can help patients control their disease: a Mediterranean diet and omega-3 supplements. One study showed that after participants with rheumatoid arthritis followed the Mediterranean diet for 1 year, those who also took omega-3 fish oil supplements were twice as likely to achieve remission (40% vs. 20%). This explains the interest in having omega-3 as part of the diet. Other studies have shown a broad benefit of the Mediterranean diet.
We know this diet: Fish, especially fatty fish; meat, but not every day, and white meat is best; and fruits and vegetables. In addition, exercise and stay hydrated. All of this can help patients who want to use diet as a means to control their disease. And, as I said earlier, studies have shown that omega-3 supplements have beneficial effects. These are essential polyunsaturated fatty acids, which can help control the disease and joint symptoms.
We also provide some exclusionary recommendations. Not all studies are done well, but it’s clear that there are no major benefits – in fact, no benefit at all – from vegan diets, gluten-free diets, or dairy-free diets. And with these diets, patients run the risk of developing deficiencies, so it’s important that patients are aware of this. We also have to keep in mind that exclusion diets can increase social isolation. Patients need to take part in meals; such gatherings are times for sharing and having social interactions. And I would say that they must be told that there are no data in the literature in support of these diets. But if they ever insist on this kind of intervention, I think that it’s better to advise them to do it under the supervision of a dietician and nutritionist, especially to prevent the development of deficiencies. We’re talking about deficiencies in things like calcium, vitamin B12, and selenium.
Conclusion
As you can see, we have positive recommendations when the patient wants to do something beyond pharmacologic treatment: the Mediterranean diet and omega-3 supplements. And we have negative recommendations, marked by a warning about the risk of developing deficiencies. But I think we all understand the importance of paying close attention to how our patients are experimenting with food. Their diets and eating habits can give us ideas for research and reviews that could allow us to deepen our understanding of the effect of diet on disease, because currently, the quality of the data on some of the diets and types of dietary interventions out there is rather tenuous.
Thank you for listening. I’d also like to thank Claire Daien, MD, PhD, for conducting this project with me so that we could come up with all of these recommendations. I’m also grateful to the following nutrition societies and associations who were our partners: the French Society of Nutrition, the French-Speaking Society of Clinical Nutrition and Metabolism, the French Association for the Study of Obesity, and the French Association of Dieticians and Nutritionists. And patient associations, too, must be recognized, as some of their members participated: the French National Association Against Rheumatoid Arthritis, the French Spondyloarthritis Association, and the French Association for Polyarthritis and Chronic Inflammatory Rheumatic Diseases.
This interview is a translation of a video blog that first appeared on Medscape France. It has been edited for clarity.
Weight loss, omega-3 supplements, the Mediterranean diet? What about exclusion diets? Jérémie Sellam, MD, PhD, from Saint-Antoine Hospital in Paris, summarizes the key points of the first set of dietary recommendations of the French Society for Rheumatology.
Transcript
Jérémie Sellam, MD, PhD: Hello, everyone. I’m Professor Jérémie Sellam. I’m a rheumatologist at Saint-Antoine Hospital, which is affiliated with the Sorbonne University in Paris. And I was fortunate enough to coordinate France’s first set of dietary recommendations – in fact, the world’s first set of dietary recommendations – for patients with chronic inflammatory rheumatic diseases. I worked on this project with Claire Daien, MD, PhD, who’s a rheumatologist at Montpellier University Hospital.
The idea of coming up with dietary recommendations for patients with inflammatory rheumatic diseases came, quite simply, from our clinical practice. We see that when patients learn they have polyarthritis or spondyloarthritis, they start to experiment with different diets. Many patients start exclusion diets and experiment in all sorts of ways with the food they eat. And although rheumatologists have been able to find some information here and there in the literature, they’ve been pretty much on their own when trying to come up with advice to give their patients. It was to address this issue that [Dr.] Daien and I set out to form a working group. Because when patients aren’t able to get sound advice and authoritative guidance from their doctors, medical associations, or patient advocacy organizations, they often look for information online, and that information is not always reliable or validated.
This group was made up of rheumatologists, some who work at hospitals and others in private practice. Also involved were physician nutrition specialists and registered dietitians. Operating under the auspices of the French Society for Rheumatology, these multidisciplinary experts conducted out a systematic literature review for the purpose of establishing and drafting recommendations. The result was a declaration of eight general principles and nine recommendations.
General principles
The first of the general principles states that nutritional advice is not a substitute for the pharmacologic treatment of chronic inflammatory rheumatic diseases. As you know, whether it’s methotrexate or biologics, pharmacologic treatments are essential for the proper management of chronic inflammatory rheumatic diseases. We know that these medications have an anti-inflammatory effect, reduce pain, and – particularly in the case of rheumatoid arthritis – have a structural effect. In other words, they prevent joint deterioration and destruction. Now, I can tell you that there’s currently no diet, and no dietary supplement, that has proven to be structurally effective. So, yes, dietary intervention might turn out to be promising for patients with chronic inflammatory rheumatic diseases, but pharmacologic treatment must still be part of the picture.
Another general principle emphasizes that dietary intervention is a way for patients to be actively involved in the overall care of their disease, beyond just taking their medication. We know that patients, when they suffer from chronic diseases, are looking for something more, beyond just taking medications. Encouraging them to take an interest in their diet, asking them about what they eat, giving them advice, and supporting their desire to become involved in this aspect of their treatment plan can give them a sense of empowerment.
Dietary interventions can have articular effects, and I’m going to speak about which interventions you can propose, but also which can be beneficial in terms of cardiovascular health and bone health. All of this is based on the literature. In these recommendations, we’ve taken into account not only laboratory experiments – where this or that diet is given to a mouse with arthritis – but also reviewed randomized controlled trials that compare an intervention group with a control group. This is the benchmark we used to determine whether or not a diet should be recommended.
The recommendations
As for the recommendations themselves, we wanted to start off by emphasizing weight loss and what can be called weight-loss support. There’s a link between obesity and the risk of developing rheumatoid arthritis, and also psoriatic arthropathy. And the more overweight a patient is, the more active their disease. In other words, patients with obesity are going to experience more pain, more instances of wakefulness, and more morning stiffness than their normal-weight peers. They’re also going to show symptoms that suggest that disease activity is not controlled well.
Several randomized controlled studies have shown that weight loss will improve systemic joint symptoms. In one particular study, patients with psoriatic arthropathy were started on [tumor necrosis factor] inhibitor therapy and one group followed a prescribed diet and the other had no restrictions on eating. More patients in the diet group than in the no-diet group achieved minimal disease activity. Of course, in some cases – for example, patients with complicated morbid obesity – it might be necessary to have a discussion about bariatric surgery.
But practically speaking, how does one proceed? First of all, patients should be weighed at each visit and, if they’re overweight or obese, the subject should be broached. But even after that conversation, the reality remains that it’s not easy to lose weight. So in the recommendations, we focused on the fact that it shouldn’t be left to the rheumatologist or treating physician alone to handle this challenging aspect of treatment. They should incorporate dietary and nutritional care by reaching out to a dietician or, in the case of complicated obesity – especially when the BMI is higher than 35 kg/m2 – they can refer patients to a nutrition expert who can manage the patient’s obesity, come up with a weight-loss plan, and handle any complications that might arise.
We don’t speak about a low-calorie diet in the recommendations because a diet has a beginning and an end and, quite often, patients regain weight after stopping a diet. Instead, we speak about weight-loss support to point out that weight loss maintained through dietary changes brings about long-term control of disease activity.
In addition, we make two positive recommendations, which overlap, that can help patients control their disease: a Mediterranean diet and omega-3 supplements. One study showed that after participants with rheumatoid arthritis followed the Mediterranean diet for 1 year, those who also took omega-3 fish oil supplements were twice as likely to achieve remission (40% vs. 20%). This explains the interest in having omega-3 as part of the diet. Other studies have shown a broad benefit of the Mediterranean diet.
We know this diet: Fish, especially fatty fish; meat, but not every day, and white meat is best; and fruits and vegetables. In addition, exercise and stay hydrated. All of this can help patients who want to use diet as a means to control their disease. And, as I said earlier, studies have shown that omega-3 supplements have beneficial effects. These are essential polyunsaturated fatty acids, which can help control the disease and joint symptoms.
We also provide some exclusionary recommendations. Not all studies are done well, but it’s clear that there are no major benefits – in fact, no benefit at all – from vegan diets, gluten-free diets, or dairy-free diets. And with these diets, patients run the risk of developing deficiencies, so it’s important that patients are aware of this. We also have to keep in mind that exclusion diets can increase social isolation. Patients need to take part in meals; such gatherings are times for sharing and having social interactions. And I would say that they must be told that there are no data in the literature in support of these diets. But if they ever insist on this kind of intervention, I think that it’s better to advise them to do it under the supervision of a dietician and nutritionist, especially to prevent the development of deficiencies. We’re talking about deficiencies in things like calcium, vitamin B12, and selenium.
Conclusion
As you can see, we have positive recommendations when the patient wants to do something beyond pharmacologic treatment: the Mediterranean diet and omega-3 supplements. And we have negative recommendations, marked by a warning about the risk of developing deficiencies. But I think we all understand the importance of paying close attention to how our patients are experimenting with food. Their diets and eating habits can give us ideas for research and reviews that could allow us to deepen our understanding of the effect of diet on disease, because currently, the quality of the data on some of the diets and types of dietary interventions out there is rather tenuous.
Thank you for listening. I’d also like to thank Claire Daien, MD, PhD, for conducting this project with me so that we could come up with all of these recommendations. I’m also grateful to the following nutrition societies and associations who were our partners: the French Society of Nutrition, the French-Speaking Society of Clinical Nutrition and Metabolism, the French Association for the Study of Obesity, and the French Association of Dieticians and Nutritionists. And patient associations, too, must be recognized, as some of their members participated: the French National Association Against Rheumatoid Arthritis, the French Spondyloarthritis Association, and the French Association for Polyarthritis and Chronic Inflammatory Rheumatic Diseases.
This interview is a translation of a video blog that first appeared on Medscape France. It has been edited for clarity.
Weight loss, omega-3 supplements, the Mediterranean diet? What about exclusion diets? Jérémie Sellam, MD, PhD, from Saint-Antoine Hospital in Paris, summarizes the key points of the first set of dietary recommendations of the French Society for Rheumatology.
Transcript
Jérémie Sellam, MD, PhD: Hello, everyone. I’m Professor Jérémie Sellam. I’m a rheumatologist at Saint-Antoine Hospital, which is affiliated with the Sorbonne University in Paris. And I was fortunate enough to coordinate France’s first set of dietary recommendations – in fact, the world’s first set of dietary recommendations – for patients with chronic inflammatory rheumatic diseases. I worked on this project with Claire Daien, MD, PhD, who’s a rheumatologist at Montpellier University Hospital.
The idea of coming up with dietary recommendations for patients with inflammatory rheumatic diseases came, quite simply, from our clinical practice. We see that when patients learn they have polyarthritis or spondyloarthritis, they start to experiment with different diets. Many patients start exclusion diets and experiment in all sorts of ways with the food they eat. And although rheumatologists have been able to find some information here and there in the literature, they’ve been pretty much on their own when trying to come up with advice to give their patients. It was to address this issue that [Dr.] Daien and I set out to form a working group. Because when patients aren’t able to get sound advice and authoritative guidance from their doctors, medical associations, or patient advocacy organizations, they often look for information online, and that information is not always reliable or validated.
This group was made up of rheumatologists, some who work at hospitals and others in private practice. Also involved were physician nutrition specialists and registered dietitians. Operating under the auspices of the French Society for Rheumatology, these multidisciplinary experts conducted out a systematic literature review for the purpose of establishing and drafting recommendations. The result was a declaration of eight general principles and nine recommendations.
General principles
The first of the general principles states that nutritional advice is not a substitute for the pharmacologic treatment of chronic inflammatory rheumatic diseases. As you know, whether it’s methotrexate or biologics, pharmacologic treatments are essential for the proper management of chronic inflammatory rheumatic diseases. We know that these medications have an anti-inflammatory effect, reduce pain, and – particularly in the case of rheumatoid arthritis – have a structural effect. In other words, they prevent joint deterioration and destruction. Now, I can tell you that there’s currently no diet, and no dietary supplement, that has proven to be structurally effective. So, yes, dietary intervention might turn out to be promising for patients with chronic inflammatory rheumatic diseases, but pharmacologic treatment must still be part of the picture.
Another general principle emphasizes that dietary intervention is a way for patients to be actively involved in the overall care of their disease, beyond just taking their medication. We know that patients, when they suffer from chronic diseases, are looking for something more, beyond just taking medications. Encouraging them to take an interest in their diet, asking them about what they eat, giving them advice, and supporting their desire to become involved in this aspect of their treatment plan can give them a sense of empowerment.
Dietary interventions can have articular effects, and I’m going to speak about which interventions you can propose, but also which can be beneficial in terms of cardiovascular health and bone health. All of this is based on the literature. In these recommendations, we’ve taken into account not only laboratory experiments – where this or that diet is given to a mouse with arthritis – but also reviewed randomized controlled trials that compare an intervention group with a control group. This is the benchmark we used to determine whether or not a diet should be recommended.
The recommendations
As for the recommendations themselves, we wanted to start off by emphasizing weight loss and what can be called weight-loss support. There’s a link between obesity and the risk of developing rheumatoid arthritis, and also psoriatic arthropathy. And the more overweight a patient is, the more active their disease. In other words, patients with obesity are going to experience more pain, more instances of wakefulness, and more morning stiffness than their normal-weight peers. They’re also going to show symptoms that suggest that disease activity is not controlled well.
Several randomized controlled studies have shown that weight loss will improve systemic joint symptoms. In one particular study, patients with psoriatic arthropathy were started on [tumor necrosis factor] inhibitor therapy and one group followed a prescribed diet and the other had no restrictions on eating. More patients in the diet group than in the no-diet group achieved minimal disease activity. Of course, in some cases – for example, patients with complicated morbid obesity – it might be necessary to have a discussion about bariatric surgery.
But practically speaking, how does one proceed? First of all, patients should be weighed at each visit and, if they’re overweight or obese, the subject should be broached. But even after that conversation, the reality remains that it’s not easy to lose weight. So in the recommendations, we focused on the fact that it shouldn’t be left to the rheumatologist or treating physician alone to handle this challenging aspect of treatment. They should incorporate dietary and nutritional care by reaching out to a dietician or, in the case of complicated obesity – especially when the BMI is higher than 35 kg/m2 – they can refer patients to a nutrition expert who can manage the patient’s obesity, come up with a weight-loss plan, and handle any complications that might arise.
We don’t speak about a low-calorie diet in the recommendations because a diet has a beginning and an end and, quite often, patients regain weight after stopping a diet. Instead, we speak about weight-loss support to point out that weight loss maintained through dietary changes brings about long-term control of disease activity.
In addition, we make two positive recommendations, which overlap, that can help patients control their disease: a Mediterranean diet and omega-3 supplements. One study showed that after participants with rheumatoid arthritis followed the Mediterranean diet for 1 year, those who also took omega-3 fish oil supplements were twice as likely to achieve remission (40% vs. 20%). This explains the interest in having omega-3 as part of the diet. Other studies have shown a broad benefit of the Mediterranean diet.
We know this diet: Fish, especially fatty fish; meat, but not every day, and white meat is best; and fruits and vegetables. In addition, exercise and stay hydrated. All of this can help patients who want to use diet as a means to control their disease. And, as I said earlier, studies have shown that omega-3 supplements have beneficial effects. These are essential polyunsaturated fatty acids, which can help control the disease and joint symptoms.
We also provide some exclusionary recommendations. Not all studies are done well, but it’s clear that there are no major benefits – in fact, no benefit at all – from vegan diets, gluten-free diets, or dairy-free diets. And with these diets, patients run the risk of developing deficiencies, so it’s important that patients are aware of this. We also have to keep in mind that exclusion diets can increase social isolation. Patients need to take part in meals; such gatherings are times for sharing and having social interactions. And I would say that they must be told that there are no data in the literature in support of these diets. But if they ever insist on this kind of intervention, I think that it’s better to advise them to do it under the supervision of a dietician and nutritionist, especially to prevent the development of deficiencies. We’re talking about deficiencies in things like calcium, vitamin B12, and selenium.
Conclusion
As you can see, we have positive recommendations when the patient wants to do something beyond pharmacologic treatment: the Mediterranean diet and omega-3 supplements. And we have negative recommendations, marked by a warning about the risk of developing deficiencies. But I think we all understand the importance of paying close attention to how our patients are experimenting with food. Their diets and eating habits can give us ideas for research and reviews that could allow us to deepen our understanding of the effect of diet on disease, because currently, the quality of the data on some of the diets and types of dietary interventions out there is rather tenuous.
Thank you for listening. I’d also like to thank Claire Daien, MD, PhD, for conducting this project with me so that we could come up with all of these recommendations. I’m also grateful to the following nutrition societies and associations who were our partners: the French Society of Nutrition, the French-Speaking Society of Clinical Nutrition and Metabolism, the French Association for the Study of Obesity, and the French Association of Dieticians and Nutritionists. And patient associations, too, must be recognized, as some of their members participated: the French National Association Against Rheumatoid Arthritis, the French Spondyloarthritis Association, and the French Association for Polyarthritis and Chronic Inflammatory Rheumatic Diseases.
Scientists see hope in new therapy for COVID-19 brain fog patients
People with long-COVID “brain fog” may be able to recover mental abilities that were dulled or stolen from them by the virus through an approach that has improved the effects of stroke, traumatic brain injury, and other post-viral disorders, doctors and scientists say.
For a lucky portion of the population, COVID-19 lasts a handful of days with minor symptoms. But for an estimated 37% who contract the virus, symptoms can linger for weeks, months, or even years. One of the most common symptoms of long COVID is brain fog: a life-altering condition characterized by slow thinking, confusion, difficulty remembering things, and poor concentration.
The approaches are based on the concept of neuroplasticity: The ability of neural networks in the brain to change, adapt, and strengthen, much like a muscle in the body that has been trained and exercised.
“The brain’s ability to bounce back from injury is what neuroplasticity is, and I’ve worked with people in our rehab clinic who have had brain tumors or suffer the effects of surgery or radiation on the brain, and people who have had West Nile virus, HIV, and meningitis,” said Tom Bergquist, PhD, clinical neuropsychologist at Mayo Clinic in Rochester, Minn. “There’s not a week that goes by that I don’t see someone recovering from COVID-19.”
One of the approaches used in the clinic is errorless learning, or having a patient with memory problems repeat information a certain number of times without error. The repetition helps rebuild those memory skills that were weakened during infection, Dr. Bergquist says.
People who have experienced brain fog after other viral infections have seen improvements with these approaches. Ben Ahrens, co-founder and CEO of re-origin – a company that offers neuroplasticity therapy – says he had long-term cognitive issues after a Lyme disease infection. Posttreatment Lyme disease syndrome, or chronic Lyme disease, occurs in about 1 in 10 people who are infected.
Mr. Ahrens says he was struck with Lyme 10 years ago and had brain fog, joint pain, and brain lesions detectable on scans for several years after infection.
According to Mr. Ahrens, neuroplasticity-based therapies help combat what researchers have found may be a lingering memory of past infections that lead to a heightened immune response, causing lingering symptoms.
“Essentially, what we believe is happening here, is the brain has learned that these symptoms are life-threatening – because, in fact, they can be,” Mr. Ahrens said. “The brain’s one job is to protect the body, and once it’s learned to associate these symptoms with that potentially very dangerous pathogen, even after it’s gone, things like a normal headache can trigger an immune cascade.”
Studies are underway at the University of Alabama at Birmingham to examine whether constraint-induced therapy – an approach rooted in neuroplasticity and historically used for loss of limb and speech function – is also effective for cognitive impairments like brain fog.
One technique they use is called shaping, which requires a person to repeatedly carry out their personal best function of impaired use – for example, remembering household tasks they have previously forgotten. That is done multiple times over several weeks in the clinic, and patients are given ways to transfer those skills to real-life use.
So far, the results are promising, said Edward Taub, PhD, researcher and professor of psychology at the University of Alabama at Birmingham.
When used in the past for physical impairments, researchers have noted not just clinical improvements, but structural changes. It led to an increase in the brain’s gray matter – which allows individuals to control movement, memory, and emotions – and improved white matter, which helps communication between gray matter areas.
Though results of the cognitive studies have not been published, Dr. Taub said patients with brain fog have shown improvement after just 35 hours of therapy and are nearly 100% improved after 6 months.
“The idea behind this is that the brain is responsive to use,” Dr. Taub said. “The amount of brain territory that’s dedicated to supporting or mediating a given behavioral function depends on the demands placed on the brain.”
A version of this article first appeared on WebMD.com.
People with long-COVID “brain fog” may be able to recover mental abilities that were dulled or stolen from them by the virus through an approach that has improved the effects of stroke, traumatic brain injury, and other post-viral disorders, doctors and scientists say.
For a lucky portion of the population, COVID-19 lasts a handful of days with minor symptoms. But for an estimated 37% who contract the virus, symptoms can linger for weeks, months, or even years. One of the most common symptoms of long COVID is brain fog: a life-altering condition characterized by slow thinking, confusion, difficulty remembering things, and poor concentration.
The approaches are based on the concept of neuroplasticity: The ability of neural networks in the brain to change, adapt, and strengthen, much like a muscle in the body that has been trained and exercised.
“The brain’s ability to bounce back from injury is what neuroplasticity is, and I’ve worked with people in our rehab clinic who have had brain tumors or suffer the effects of surgery or radiation on the brain, and people who have had West Nile virus, HIV, and meningitis,” said Tom Bergquist, PhD, clinical neuropsychologist at Mayo Clinic in Rochester, Minn. “There’s not a week that goes by that I don’t see someone recovering from COVID-19.”
One of the approaches used in the clinic is errorless learning, or having a patient with memory problems repeat information a certain number of times without error. The repetition helps rebuild those memory skills that were weakened during infection, Dr. Bergquist says.
People who have experienced brain fog after other viral infections have seen improvements with these approaches. Ben Ahrens, co-founder and CEO of re-origin – a company that offers neuroplasticity therapy – says he had long-term cognitive issues after a Lyme disease infection. Posttreatment Lyme disease syndrome, or chronic Lyme disease, occurs in about 1 in 10 people who are infected.
Mr. Ahrens says he was struck with Lyme 10 years ago and had brain fog, joint pain, and brain lesions detectable on scans for several years after infection.
According to Mr. Ahrens, neuroplasticity-based therapies help combat what researchers have found may be a lingering memory of past infections that lead to a heightened immune response, causing lingering symptoms.
“Essentially, what we believe is happening here, is the brain has learned that these symptoms are life-threatening – because, in fact, they can be,” Mr. Ahrens said. “The brain’s one job is to protect the body, and once it’s learned to associate these symptoms with that potentially very dangerous pathogen, even after it’s gone, things like a normal headache can trigger an immune cascade.”
Studies are underway at the University of Alabama at Birmingham to examine whether constraint-induced therapy – an approach rooted in neuroplasticity and historically used for loss of limb and speech function – is also effective for cognitive impairments like brain fog.
One technique they use is called shaping, which requires a person to repeatedly carry out their personal best function of impaired use – for example, remembering household tasks they have previously forgotten. That is done multiple times over several weeks in the clinic, and patients are given ways to transfer those skills to real-life use.
So far, the results are promising, said Edward Taub, PhD, researcher and professor of psychology at the University of Alabama at Birmingham.
When used in the past for physical impairments, researchers have noted not just clinical improvements, but structural changes. It led to an increase in the brain’s gray matter – which allows individuals to control movement, memory, and emotions – and improved white matter, which helps communication between gray matter areas.
Though results of the cognitive studies have not been published, Dr. Taub said patients with brain fog have shown improvement after just 35 hours of therapy and are nearly 100% improved after 6 months.
“The idea behind this is that the brain is responsive to use,” Dr. Taub said. “The amount of brain territory that’s dedicated to supporting or mediating a given behavioral function depends on the demands placed on the brain.”
A version of this article first appeared on WebMD.com.
People with long-COVID “brain fog” may be able to recover mental abilities that were dulled or stolen from them by the virus through an approach that has improved the effects of stroke, traumatic brain injury, and other post-viral disorders, doctors and scientists say.
For a lucky portion of the population, COVID-19 lasts a handful of days with minor symptoms. But for an estimated 37% who contract the virus, symptoms can linger for weeks, months, or even years. One of the most common symptoms of long COVID is brain fog: a life-altering condition characterized by slow thinking, confusion, difficulty remembering things, and poor concentration.
The approaches are based on the concept of neuroplasticity: The ability of neural networks in the brain to change, adapt, and strengthen, much like a muscle in the body that has been trained and exercised.
“The brain’s ability to bounce back from injury is what neuroplasticity is, and I’ve worked with people in our rehab clinic who have had brain tumors or suffer the effects of surgery or radiation on the brain, and people who have had West Nile virus, HIV, and meningitis,” said Tom Bergquist, PhD, clinical neuropsychologist at Mayo Clinic in Rochester, Minn. “There’s not a week that goes by that I don’t see someone recovering from COVID-19.”
One of the approaches used in the clinic is errorless learning, or having a patient with memory problems repeat information a certain number of times without error. The repetition helps rebuild those memory skills that were weakened during infection, Dr. Bergquist says.
People who have experienced brain fog after other viral infections have seen improvements with these approaches. Ben Ahrens, co-founder and CEO of re-origin – a company that offers neuroplasticity therapy – says he had long-term cognitive issues after a Lyme disease infection. Posttreatment Lyme disease syndrome, or chronic Lyme disease, occurs in about 1 in 10 people who are infected.
Mr. Ahrens says he was struck with Lyme 10 years ago and had brain fog, joint pain, and brain lesions detectable on scans for several years after infection.
According to Mr. Ahrens, neuroplasticity-based therapies help combat what researchers have found may be a lingering memory of past infections that lead to a heightened immune response, causing lingering symptoms.
“Essentially, what we believe is happening here, is the brain has learned that these symptoms are life-threatening – because, in fact, they can be,” Mr. Ahrens said. “The brain’s one job is to protect the body, and once it’s learned to associate these symptoms with that potentially very dangerous pathogen, even after it’s gone, things like a normal headache can trigger an immune cascade.”
Studies are underway at the University of Alabama at Birmingham to examine whether constraint-induced therapy – an approach rooted in neuroplasticity and historically used for loss of limb and speech function – is also effective for cognitive impairments like brain fog.
One technique they use is called shaping, which requires a person to repeatedly carry out their personal best function of impaired use – for example, remembering household tasks they have previously forgotten. That is done multiple times over several weeks in the clinic, and patients are given ways to transfer those skills to real-life use.
So far, the results are promising, said Edward Taub, PhD, researcher and professor of psychology at the University of Alabama at Birmingham.
When used in the past for physical impairments, researchers have noted not just clinical improvements, but structural changes. It led to an increase in the brain’s gray matter – which allows individuals to control movement, memory, and emotions – and improved white matter, which helps communication between gray matter areas.
Though results of the cognitive studies have not been published, Dr. Taub said patients with brain fog have shown improvement after just 35 hours of therapy and are nearly 100% improved after 6 months.
“The idea behind this is that the brain is responsive to use,” Dr. Taub said. “The amount of brain territory that’s dedicated to supporting or mediating a given behavioral function depends on the demands placed on the brain.”
A version of this article first appeared on WebMD.com.
Does endovascular therapy benefit strokes with larger ischemic cores?
The RESCUE-JAPAN LIMIT trial was presented at the International Stroke Conference by Shinichi Yoshimura, MD, Hyogo College of Medicine, Nishinomiya, Japan. The study was also published online in the New England Journal of Medicine to coincide with its presentation at the ISC meeting.
The trial showed that among patients with acute stroke and a large ischemic brain region, functional outcomes at 90 days were better with endovascular therapy and medical care than with medical care alone.
Patients who received endovascular therapy were more than twice as likely to have a good functional outcome, defined as a modified Rankin scale (mRS) score of 0-3 at 90 days, than those who received medical care alone.
While the rate of intracranial hemorrhage increased with endovascular therapy, authors of the study and outside commentators suggested that the benefit appeared to outweigh the risk. “Our results provide strong evidence that endovascular therapy improves patient outcomes when the infarct area is large,” Dr. Yoshimura concluded at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Commenting on the study at an ISC press conference, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “The question of strokes with a large core stroke being an exclusion criteria for endovascular therapy is arguably one of the hottest topics the field is facing at this time. There are several randomized trials ongoing aiming to answer this question.”
“The RESCUE-JAPAN trial is the first of these trials to report and shed some light on this issue,” Dr. Jovin added. “The results appear to show that these patients with large core infarcts have just as much benefit from endovascular therapy as patients with smaller infarcts.”
Dr. Jovin described these findings as encouraging but also surprising. “When these large core randomized trials were planned, there was a belief that there would be benefit at some level. But what is surprising to me is that in this trial the benefit was similar to that seen in trials in patients with moderate or small core infarcts. This begs the question of whether we should care about the size of the infarct when we are considering taking these patients for thrombectomy,” he said.
Confirmation needed
On whether this will change practice, Dr. Jovin cautioned that this was just one study with a relatively small number of patients. “I think it is important that all the other randomized trials ongoing should continue so that we have a definitive answer to this question,” he said.
In his presentation, Dr. Yoshimura explained that current guidelines recommended endovascular therapy for patients with large cerebral vessel occlusion and a small or moderate infarct size – an ASPECTS score (Alberta Stroke Program Early Computed Tomographic Score) of 6 or higher. The ASPECTS score has a scale of 1-10, with lower values indicating larger infarction.
The RESCUE-JAPAN LIMIT study included 203 patients with occlusion of large cerebral vessels and sizable strokes on imaging, as indicated by an ASPECTS score of 3 to 5.
Patients were randomly assigned to receive endovascular therapy with medical care (endovascular-therapy group) or medical therapy alone (medical-care group) within 6 hours after they were last known to be well or within 24 hours if there was no early change on fluid-attenuated inversion recovery images indicating that the infarction was recent.
The percentage of patients with a good outcome as defined by an mRS score of 0 to 3 at 90 days, the primary outcome, was 31.0% in the endovascular-therapy group and 12.7% in the medical-care group (relative risk, 2.43; 95% confidence interval, 1.35 to 4.37; P = .002).
Secondary outcomes were mRS scores of 0 to 2 and 0 to 1, an ordinal shift across the range of mRS scores toward a better outcome at 90 days, and an improvement of at least 8 points in the National Institutes of Health Stroke Scale (NIHSS) score (range, 0 to 42, with higher scores indicating greater deficit) at 48 hours.
An mRS score of 0 to 2 was seen in 14% of patients in the endovascular-therapy group and 6.9% in the medical-care group (RR, 2.04; 95% CI, 0.86 to 4.84), and an mRS score of 0 to 1 was reported in 5% of the endovascular group versus 2.9% of the medical group (RR, 1.70; 95% CI, 0.42 to 6.93).
The ordinal shift across the range of mRS scores also favored endovascular therapy (common odds ratio, 2.42; 95% CI, 1.46 to 4.01).
An improvement of at least 8 points on the NIHSS score at 48 hours was observed in 31.0% of the patients in the endovascular-therapy group and 8.8% of those in the medical-care group (RR, 3.51; 95% CI, 1.76 to 7.00).
In terms of safety, any intracranial hemorrhage occurred in 58.0% of patients in the endovascular group and 31.4% of those in the medical therapy group (RR, 1.85; 95% CI, 1.33 to 2.58; P < .001).
There was also a trend toward an increase in symptomatic intracranial hemorrhage in the endovascular group (9% vs. 4.9%), but this did not reach significance (RR, 1.84; 95% CI, 0.64 to 5.29; P = .25).
In the NEJM paper, the authors pointed out that the ASPECTS value in most of the patients in this study was determined with the use of diffusion-weighted MRI, as MRI is widely used in Japan for the diagnosis of acute ischemic stroke. They noted that differences between ASPECTS values based on CT results and those based on diffusion-weighted MRI results should be considered in the interpretation of the results and that previous studies have suggested that an ASPECTS value determined with the use of diffusion-weighted MRI may be one level lower than that determined with the use of CT.
They also noted that there was a relatively low use of thrombolysis in the trial (27% to 29%), which may have altered the outcomes in both groups and disadvantaged the medical-care group. However, they add that most guidelines recommend against the use of thrombolysis when there is extensive ischemic change on imaging.
Risk/benefit trade-off
Commenting on the trade-off between benefits and risks in the study, Dr. Jovin said the increase in intracranial hemorrhage seen in the endovascular group was similar to that seen in other situations.
“This is not really any different from what is seen when giving tPA [tissue plasminogen activator] to stroke patients or when performing thrombectomy in small or moderate core strokes – we know that intracranial hemorrhage is the price to pay,” he stated.
“While the increase in symptomatic intracranial hemorrhage was nonsignificant, the trend is very clear, and I believe it is real,” Dr. Jovin said. “But I think what matters – and what matters to patients – is that there is a much higher chance of having a good outcome with endovascular therapy. I think most patients will accept the extra risk of intracranial hemorrhage if there is an even higher chance of having a better neurological outcome. This is no different to the approach that we take when we treat patients with IV tPA.”
Dr. Jovin pointed out that the RESCUE-JAPAN study did not include the largest core infarcts (ASPECTS score 0-1), but he added that these very large core infarcts are quite rare – especially in patients in the early time window.
He concluded that the study provided important information but cautioned that, with just 200 patients, the findings needed confirmation from other randomized trials that are ongoing.
Also speaking at the ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association, and professor of neurology at Columbia University, New York, said previous trials had established endovascular therapy for patients with large cerebral artery occlusions who have primarily preserved brain tissue and small infarct cores.
“We have picked off the low-lying fruit – the patients with small areas of infarcted brain. But perhaps most patients do not fit into this category and now we are seeing trials addressing these groups,” he said. “This initial study suggests that these patients with larger core infarcts can indeed still benefit from this therapy tremendously.”
The RESCUE-JAPAN LIMIT study was supported in part by the Mihara Cerebrovascular Disorder Research Promotion Fund and the Japanese Society for Neuroendovascular Therapy. There was no industry involvement. Dr. Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol-Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, and CSL Behring; and lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer-Ingelheim, Daiichi Sankyo, Bayer, and Bristol-Meyers Squibb.
A version of this article first appeared on Medscape.com.
The RESCUE-JAPAN LIMIT trial was presented at the International Stroke Conference by Shinichi Yoshimura, MD, Hyogo College of Medicine, Nishinomiya, Japan. The study was also published online in the New England Journal of Medicine to coincide with its presentation at the ISC meeting.
The trial showed that among patients with acute stroke and a large ischemic brain region, functional outcomes at 90 days were better with endovascular therapy and medical care than with medical care alone.
Patients who received endovascular therapy were more than twice as likely to have a good functional outcome, defined as a modified Rankin scale (mRS) score of 0-3 at 90 days, than those who received medical care alone.
While the rate of intracranial hemorrhage increased with endovascular therapy, authors of the study and outside commentators suggested that the benefit appeared to outweigh the risk. “Our results provide strong evidence that endovascular therapy improves patient outcomes when the infarct area is large,” Dr. Yoshimura concluded at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Commenting on the study at an ISC press conference, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “The question of strokes with a large core stroke being an exclusion criteria for endovascular therapy is arguably one of the hottest topics the field is facing at this time. There are several randomized trials ongoing aiming to answer this question.”
“The RESCUE-JAPAN trial is the first of these trials to report and shed some light on this issue,” Dr. Jovin added. “The results appear to show that these patients with large core infarcts have just as much benefit from endovascular therapy as patients with smaller infarcts.”
Dr. Jovin described these findings as encouraging but also surprising. “When these large core randomized trials were planned, there was a belief that there would be benefit at some level. But what is surprising to me is that in this trial the benefit was similar to that seen in trials in patients with moderate or small core infarcts. This begs the question of whether we should care about the size of the infarct when we are considering taking these patients for thrombectomy,” he said.
Confirmation needed
On whether this will change practice, Dr. Jovin cautioned that this was just one study with a relatively small number of patients. “I think it is important that all the other randomized trials ongoing should continue so that we have a definitive answer to this question,” he said.
In his presentation, Dr. Yoshimura explained that current guidelines recommended endovascular therapy for patients with large cerebral vessel occlusion and a small or moderate infarct size – an ASPECTS score (Alberta Stroke Program Early Computed Tomographic Score) of 6 or higher. The ASPECTS score has a scale of 1-10, with lower values indicating larger infarction.
The RESCUE-JAPAN LIMIT study included 203 patients with occlusion of large cerebral vessels and sizable strokes on imaging, as indicated by an ASPECTS score of 3 to 5.
Patients were randomly assigned to receive endovascular therapy with medical care (endovascular-therapy group) or medical therapy alone (medical-care group) within 6 hours after they were last known to be well or within 24 hours if there was no early change on fluid-attenuated inversion recovery images indicating that the infarction was recent.
The percentage of patients with a good outcome as defined by an mRS score of 0 to 3 at 90 days, the primary outcome, was 31.0% in the endovascular-therapy group and 12.7% in the medical-care group (relative risk, 2.43; 95% confidence interval, 1.35 to 4.37; P = .002).
Secondary outcomes were mRS scores of 0 to 2 and 0 to 1, an ordinal shift across the range of mRS scores toward a better outcome at 90 days, and an improvement of at least 8 points in the National Institutes of Health Stroke Scale (NIHSS) score (range, 0 to 42, with higher scores indicating greater deficit) at 48 hours.
An mRS score of 0 to 2 was seen in 14% of patients in the endovascular-therapy group and 6.9% in the medical-care group (RR, 2.04; 95% CI, 0.86 to 4.84), and an mRS score of 0 to 1 was reported in 5% of the endovascular group versus 2.9% of the medical group (RR, 1.70; 95% CI, 0.42 to 6.93).
The ordinal shift across the range of mRS scores also favored endovascular therapy (common odds ratio, 2.42; 95% CI, 1.46 to 4.01).
An improvement of at least 8 points on the NIHSS score at 48 hours was observed in 31.0% of the patients in the endovascular-therapy group and 8.8% of those in the medical-care group (RR, 3.51; 95% CI, 1.76 to 7.00).
In terms of safety, any intracranial hemorrhage occurred in 58.0% of patients in the endovascular group and 31.4% of those in the medical therapy group (RR, 1.85; 95% CI, 1.33 to 2.58; P < .001).
There was also a trend toward an increase in symptomatic intracranial hemorrhage in the endovascular group (9% vs. 4.9%), but this did not reach significance (RR, 1.84; 95% CI, 0.64 to 5.29; P = .25).
In the NEJM paper, the authors pointed out that the ASPECTS value in most of the patients in this study was determined with the use of diffusion-weighted MRI, as MRI is widely used in Japan for the diagnosis of acute ischemic stroke. They noted that differences between ASPECTS values based on CT results and those based on diffusion-weighted MRI results should be considered in the interpretation of the results and that previous studies have suggested that an ASPECTS value determined with the use of diffusion-weighted MRI may be one level lower than that determined with the use of CT.
They also noted that there was a relatively low use of thrombolysis in the trial (27% to 29%), which may have altered the outcomes in both groups and disadvantaged the medical-care group. However, they add that most guidelines recommend against the use of thrombolysis when there is extensive ischemic change on imaging.
Risk/benefit trade-off
Commenting on the trade-off between benefits and risks in the study, Dr. Jovin said the increase in intracranial hemorrhage seen in the endovascular group was similar to that seen in other situations.
“This is not really any different from what is seen when giving tPA [tissue plasminogen activator] to stroke patients or when performing thrombectomy in small or moderate core strokes – we know that intracranial hemorrhage is the price to pay,” he stated.
“While the increase in symptomatic intracranial hemorrhage was nonsignificant, the trend is very clear, and I believe it is real,” Dr. Jovin said. “But I think what matters – and what matters to patients – is that there is a much higher chance of having a good outcome with endovascular therapy. I think most patients will accept the extra risk of intracranial hemorrhage if there is an even higher chance of having a better neurological outcome. This is no different to the approach that we take when we treat patients with IV tPA.”
Dr. Jovin pointed out that the RESCUE-JAPAN study did not include the largest core infarcts (ASPECTS score 0-1), but he added that these very large core infarcts are quite rare – especially in patients in the early time window.
He concluded that the study provided important information but cautioned that, with just 200 patients, the findings needed confirmation from other randomized trials that are ongoing.
Also speaking at the ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association, and professor of neurology at Columbia University, New York, said previous trials had established endovascular therapy for patients with large cerebral artery occlusions who have primarily preserved brain tissue and small infarct cores.
“We have picked off the low-lying fruit – the patients with small areas of infarcted brain. But perhaps most patients do not fit into this category and now we are seeing trials addressing these groups,” he said. “This initial study suggests that these patients with larger core infarcts can indeed still benefit from this therapy tremendously.”
The RESCUE-JAPAN LIMIT study was supported in part by the Mihara Cerebrovascular Disorder Research Promotion Fund and the Japanese Society for Neuroendovascular Therapy. There was no industry involvement. Dr. Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol-Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, and CSL Behring; and lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer-Ingelheim, Daiichi Sankyo, Bayer, and Bristol-Meyers Squibb.
A version of this article first appeared on Medscape.com.
The RESCUE-JAPAN LIMIT trial was presented at the International Stroke Conference by Shinichi Yoshimura, MD, Hyogo College of Medicine, Nishinomiya, Japan. The study was also published online in the New England Journal of Medicine to coincide with its presentation at the ISC meeting.
The trial showed that among patients with acute stroke and a large ischemic brain region, functional outcomes at 90 days were better with endovascular therapy and medical care than with medical care alone.
Patients who received endovascular therapy were more than twice as likely to have a good functional outcome, defined as a modified Rankin scale (mRS) score of 0-3 at 90 days, than those who received medical care alone.
While the rate of intracranial hemorrhage increased with endovascular therapy, authors of the study and outside commentators suggested that the benefit appeared to outweigh the risk. “Our results provide strong evidence that endovascular therapy improves patient outcomes when the infarct area is large,” Dr. Yoshimura concluded at the meeting, presented by the American Stroke Association, a division of the American Heart Association.
Commenting on the study at an ISC press conference, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, New Jersey, said: “The question of strokes with a large core stroke being an exclusion criteria for endovascular therapy is arguably one of the hottest topics the field is facing at this time. There are several randomized trials ongoing aiming to answer this question.”
“The RESCUE-JAPAN trial is the first of these trials to report and shed some light on this issue,” Dr. Jovin added. “The results appear to show that these patients with large core infarcts have just as much benefit from endovascular therapy as patients with smaller infarcts.”
Dr. Jovin described these findings as encouraging but also surprising. “When these large core randomized trials were planned, there was a belief that there would be benefit at some level. But what is surprising to me is that in this trial the benefit was similar to that seen in trials in patients with moderate or small core infarcts. This begs the question of whether we should care about the size of the infarct when we are considering taking these patients for thrombectomy,” he said.
Confirmation needed
On whether this will change practice, Dr. Jovin cautioned that this was just one study with a relatively small number of patients. “I think it is important that all the other randomized trials ongoing should continue so that we have a definitive answer to this question,” he said.
In his presentation, Dr. Yoshimura explained that current guidelines recommended endovascular therapy for patients with large cerebral vessel occlusion and a small or moderate infarct size – an ASPECTS score (Alberta Stroke Program Early Computed Tomographic Score) of 6 or higher. The ASPECTS score has a scale of 1-10, with lower values indicating larger infarction.
The RESCUE-JAPAN LIMIT study included 203 patients with occlusion of large cerebral vessels and sizable strokes on imaging, as indicated by an ASPECTS score of 3 to 5.
Patients were randomly assigned to receive endovascular therapy with medical care (endovascular-therapy group) or medical therapy alone (medical-care group) within 6 hours after they were last known to be well or within 24 hours if there was no early change on fluid-attenuated inversion recovery images indicating that the infarction was recent.
The percentage of patients with a good outcome as defined by an mRS score of 0 to 3 at 90 days, the primary outcome, was 31.0% in the endovascular-therapy group and 12.7% in the medical-care group (relative risk, 2.43; 95% confidence interval, 1.35 to 4.37; P = .002).
Secondary outcomes were mRS scores of 0 to 2 and 0 to 1, an ordinal shift across the range of mRS scores toward a better outcome at 90 days, and an improvement of at least 8 points in the National Institutes of Health Stroke Scale (NIHSS) score (range, 0 to 42, with higher scores indicating greater deficit) at 48 hours.
An mRS score of 0 to 2 was seen in 14% of patients in the endovascular-therapy group and 6.9% in the medical-care group (RR, 2.04; 95% CI, 0.86 to 4.84), and an mRS score of 0 to 1 was reported in 5% of the endovascular group versus 2.9% of the medical group (RR, 1.70; 95% CI, 0.42 to 6.93).
The ordinal shift across the range of mRS scores also favored endovascular therapy (common odds ratio, 2.42; 95% CI, 1.46 to 4.01).
An improvement of at least 8 points on the NIHSS score at 48 hours was observed in 31.0% of the patients in the endovascular-therapy group and 8.8% of those in the medical-care group (RR, 3.51; 95% CI, 1.76 to 7.00).
In terms of safety, any intracranial hemorrhage occurred in 58.0% of patients in the endovascular group and 31.4% of those in the medical therapy group (RR, 1.85; 95% CI, 1.33 to 2.58; P < .001).
There was also a trend toward an increase in symptomatic intracranial hemorrhage in the endovascular group (9% vs. 4.9%), but this did not reach significance (RR, 1.84; 95% CI, 0.64 to 5.29; P = .25).
In the NEJM paper, the authors pointed out that the ASPECTS value in most of the patients in this study was determined with the use of diffusion-weighted MRI, as MRI is widely used in Japan for the diagnosis of acute ischemic stroke. They noted that differences between ASPECTS values based on CT results and those based on diffusion-weighted MRI results should be considered in the interpretation of the results and that previous studies have suggested that an ASPECTS value determined with the use of diffusion-weighted MRI may be one level lower than that determined with the use of CT.
They also noted that there was a relatively low use of thrombolysis in the trial (27% to 29%), which may have altered the outcomes in both groups and disadvantaged the medical-care group. However, they add that most guidelines recommend against the use of thrombolysis when there is extensive ischemic change on imaging.
Risk/benefit trade-off
Commenting on the trade-off between benefits and risks in the study, Dr. Jovin said the increase in intracranial hemorrhage seen in the endovascular group was similar to that seen in other situations.
“This is not really any different from what is seen when giving tPA [tissue plasminogen activator] to stroke patients or when performing thrombectomy in small or moderate core strokes – we know that intracranial hemorrhage is the price to pay,” he stated.
“While the increase in symptomatic intracranial hemorrhage was nonsignificant, the trend is very clear, and I believe it is real,” Dr. Jovin said. “But I think what matters – and what matters to patients – is that there is a much higher chance of having a good outcome with endovascular therapy. I think most patients will accept the extra risk of intracranial hemorrhage if there is an even higher chance of having a better neurological outcome. This is no different to the approach that we take when we treat patients with IV tPA.”
Dr. Jovin pointed out that the RESCUE-JAPAN study did not include the largest core infarcts (ASPECTS score 0-1), but he added that these very large core infarcts are quite rare – especially in patients in the early time window.
He concluded that the study provided important information but cautioned that, with just 200 patients, the findings needed confirmation from other randomized trials that are ongoing.
Also speaking at the ISC press conference, Mitchell Elkind, MD, immediate past president of the American Heart Association/American Stroke Association, and professor of neurology at Columbia University, New York, said previous trials had established endovascular therapy for patients with large cerebral artery occlusions who have primarily preserved brain tissue and small infarct cores.
“We have picked off the low-lying fruit – the patients with small areas of infarcted brain. But perhaps most patients do not fit into this category and now we are seeing trials addressing these groups,” he said. “This initial study suggests that these patients with larger core infarcts can indeed still benefit from this therapy tremendously.”
The RESCUE-JAPAN LIMIT study was supported in part by the Mihara Cerebrovascular Disorder Research Promotion Fund and the Japanese Society for Neuroendovascular Therapy. There was no industry involvement. Dr. Yoshimura reported research grants from Stryker, Siemens Healthineers, Bristol-Myers Squibb, Sanofi, Eisai, Daiichi Sankyo, Teijin Pharma, Chugai Pharmaceutical, HEALIOS, Asahi Kasei Medical, Kowa, and CSL Behring; and lecturer fees from Stryker, Medtronic, Johnson & Johnson, Kaneka, Terumo, Biomedical Solutions, Boehringer-Ingelheim, Daiichi Sankyo, Bayer, and Bristol-Meyers Squibb.
A version of this article first appeared on Medscape.com.
FROM ISC 2022