Federal Practitioner

More than HIV, more than malaria. The death toll worldwide from bacterial antimicrobial resistance (AMR) in 2019 exceeded 1.2 million people, according to a new study.

In terms of preventable deaths, 1.27 million people could have been saved if drug-resistant infections were replaced with infections susceptible to current antibiotics. Furthermore, 4.95 million fewer people would have died if drug-resistant infections were replaced by no infections, researchers estimated.

Although the COVID-19 pandemic took some focus off the AMR burden worldwide over the past 2 years, the urgency to address risk to public health did not ebb. In fact, based on the findings, the researchers noted that AMR is now a leading cause of death worldwide.

“If left unchecked, the spread of AMR could make many bacterial pathogens much more lethal in the future than they are today,” the researchers noted in the study, published online Jan. 20, 2022, in The Lancet.

“These findings are a warning signal that antibiotic resistance is placing pressure on health care systems and leading to significant health loss,” study author Kevin Ikuta, MD, MPH, told this news organization.

“We need to continue to adhere to and support infection prevention and control programs, be thoughtful about our antibiotic use, and advocate for increased funding to vaccine discovery and the antibiotic development pipeline,” added Dr. Ikuta, health sciences assistant clinical professor of medicine at the University of California, Los Angeles.

Although many investigators have studied AMR, this study is the largest in scope, covering 204 countries and territories and incorporating data on a comprehensive range of pathogens and pathogen-drug combinations.

Dr. Ikuta, lead author Christopher J.L. Murray, DPhil, and colleagues estimated the global burden of AMR using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. They specifically looked at rates of death directly attributed to and separately those associated with resistance.
 

Regional differences

Broken down by 21 regions, Australasia had 6.5 deaths per 100,000 people attributable to AMR, the lowest rate reported. This region also had 28 deaths per 100,000 associated with AMR.

Researchers found the highest rates in western sub-Saharan Africa. Deaths attributable to AMR were 27.3 per 100,000 and associated death rate was 114.8 per 100,000.

Lower- and middle-income regions had the highest AMR death rates, although resistance remains a high-priority issue for high-income countries as well.

“It’s important to take a global perspective on resistant infections because we can learn about regions and countries that are experiencing the greatest burden, information that was previously unknown,” Dr. Ikuta said. “With these estimates policy makers can prioritize regions that are hotspots and would most benefit from additional interventions.”

Furthermore, the study emphasized the global nature of AMR. “We’ve seen over the last 2 years with COVID-19 that this sort of problem doesn’t respect country borders, and high rates of resistance in one location can spread across a region or spread globally pretty quickly,” Dr. Ikuta said.
 

Leading resistant infections

Lower respiratory and thorax infections, bloodstream infections, and intra-abdominal infections together accounted for almost 79% of such deaths linked to AMR.

The six leading pathogens are likely household names among infectious disease specialists. The researchers found Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, each responsible for more than 250,000 AMR-associated deaths.

The study also revealed that resistance to several first-line antibiotic agents often used empirically to treat infections accounted for more than 70% of the AMR-attributable deaths. These included fluoroquinolones and beta-lactam antibiotics such as carbapenems, cephalosporins, and penicillins.

Courtesy The Lancet

Potential solutions offered

Dr. Murray and colleagues outlined five strategies to address the challenge of bacterial AMR:

• Infection prevention and control remain paramount in minimizing infections in general and AMR infections in particular.
• More vaccines are needed to reduce the need for antibiotics. “Vaccines are available for only one of the six leading pathogens (S. pneumoniae), although new vaccine programs are underway for S. aureus, E. coli, and others,” the researchers wrote.
• Reduce antibiotic use unrelated to treatment of human disease.
• Avoid using antibiotics for viral infections and other unnecessary indications.
• Invest in new antibiotic development and ensure access to second-line agents in areas without widespread access.

“Identifying strategies that can work to reduce the burden of bacterial AMR – either across a wide range of settings or those that are specifically tailored to the resources available and leading pathogen-drug combinations in a particular setting – is an urgent priority,” the researchers noted.
 

Admirable AMR research

The results of the study are “startling, but not surprising,” said Dr. Fowler, professor of medicine at Duke University, Durham, N.C.

The authors did a “nice job” of addressing both deaths attributable and associated with AMR, Dr. Fowler added. “Those two categories unlock applications, not just in terms of how you interpret it but also what you do about it.”

The deaths attributable to AMR show that there is more work to be done regarding infection control and prevention, Dr. Fowler said, including in areas of the world like lower- and middle-income countries where infection resistance is most pronounced.

The deaths associated with AMR can be more challenging to calculate – people with infections can die for multiple reasons. However, Dr. Fowler applauded the researchers for doing “as good a job as you can” in estimating the extent of associated mortality.
 

‘The overlooked pandemic of antimicrobial resistance’

In an accompanying editorial in The Lancet, Ramanan Laxminarayan, PhD, MPH, wrote: “As COVID-19 rages on, the pandemic of antimicrobial resistance continues in the shadows. The toll taken by AMR on patients and their families is largely invisible but is reflected in prolonged bacterial infections that extend hospital stays and cause needless deaths.”

Dr. Laxminarayan pointed out an irony with AMR in different regions. Some of the AMR burden in sub-Saharan Africa is “probably due to inadequate access to antibiotics and high infection levels, albeit at low levels of resistance, whereas in south Asia and Latin America, it is because of high resistance even with good access to antibiotics.”

More funding to address AMR is needed, Dr. Laxminarayan noted. “Even the lower end of 911,000 deaths estimated by Murray and colleagues is higher than the number of deaths from HIV, which attracts close to U.S. $50 billion each year. However, global spending on addressing AMR is probably much lower than that.” Dr. Laxminarayan is an economist and epidemiologist affiliated with the Center for Disease Dynamics, Economics & Policy in Washington, D.C., and the Global Antibiotic Research and Development Partnership in Geneva.
 

An overlap with COVID-19

The Lancet report is likely “to bring more attention to AMR, especially since so many people have been distracted by COVID, and rightly so,” Dr. Fowler predicted. “The world has had its hands full with COVID.”

The two infections interact in direct ways, Dr. Fowler added. For example, some people hospitalized for COVID-19 for an extended time could develop progressively drug-resistant bacteria – leading to a superinfection.

The overlap could be illustrated by a Venn diagram, he said. A yellow circle could illustrate people with COVID-19 who are asymptomatic or who remain outpatients. Next to that would be a blue circle showing people who develop AMR infections. Where the two circles overlap would be green for those hospitalized who – because of receiving steroids, being on a ventilator, or getting a central line – develop a superinfection.
 

Official guidance continues

The study comes in the context of recent guidance and federal action on AMR. For example, the Infectious Diseases Society of America released new guidelines for AMR in November 2021 as part of ongoing advice on prevention and treatment of this “ongoing crisis.”

This most recent IDSA guidance addresses three pathogens in particular: AmpC beta-lactamase–producing Enterobacterales, carbapenem-resistant A. baumannii, and Stenotrophomonas maltophilia.

Also in November, the World Health Organization released an updated fact sheet on antimicrobial resistance. The WHO declared AMR one of the world’s top 10 global public health threats. The agency emphasized that misuse and overuse of antimicrobials are the main drivers in the development of drug-resistant pathogens. The WHO also pointed out that lack of clean water and sanitation in many areas of the world contribute to spread of microbes, including those resistant to current treatment options.

In September 2021, the Biden administration acknowledged the threat of AMR with allocation of more than $2 billion of the American Rescue Plan money for prevention and treatment of these infections.

Asked if there are any reasons for hope or optimism at this point, Dr. Ikuta said: “Definitely. We know what needs to be done to combat the spread of resistance. COVID-19 has demonstrated the importance of global commitment to infection control measures, such as hand washing and surveillance, and rapid investments in treatments, which can all be applied to antimicrobial resistance.”

The Bill & Melinda Gates Foundation, the Wellcome Trust, and the U.K. Department of Health and Social Care using U.K. aid funding managed by the Fleming Fund and other organizations provided funding for the study. Dr. Ikuta and Dr. Laxminarayan have disclosed no relevant financial relationships. Dr. Fowler reported receiving grants or honoraria, as well as serving as a consultant, for numerous sources. He also reported a patent pending in sepsis diagnostics and serving as chair of the V710 Scientific Advisory Committee (Merck).

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

More than HIV, more than malaria. The death toll worldwide from bacterial antimicrobial resistance (AMR) in 2019 exceeded 1.2 million people, according to a new study.

In terms of preventable deaths, 1.27 million people could have been saved if drug-resistant infections were replaced with infections susceptible to current antibiotics. Furthermore, 4.95 million fewer people would have died if drug-resistant infections were replaced by no infections, researchers estimated.

Although the COVID-19 pandemic took some focus off the AMR burden worldwide over the past 2 years, the urgency to address risk to public health did not ebb. In fact, based on the findings, the researchers noted that AMR is now a leading cause of death worldwide.

“If left unchecked, the spread of AMR could make many bacterial pathogens much more lethal in the future than they are today,” the researchers noted in the study, published online Jan. 20, 2022, in The Lancet.

“These findings are a warning signal that antibiotic resistance is placing pressure on health care systems and leading to significant health loss,” study author Kevin Ikuta, MD, MPH, told this news organization.

“We need to continue to adhere to and support infection prevention and control programs, be thoughtful about our antibiotic use, and advocate for increased funding to vaccine discovery and the antibiotic development pipeline,” added Dr. Ikuta, health sciences assistant clinical professor of medicine at the University of California, Los Angeles.

Although many investigators have studied AMR, this study is the largest in scope, covering 204 countries and territories and incorporating data on a comprehensive range of pathogens and pathogen-drug combinations.

Dr. Ikuta, lead author Christopher J.L. Murray, DPhil, and colleagues estimated the global burden of AMR using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. They specifically looked at rates of death directly attributed to and separately those associated with resistance.
 

Regional differences

Broken down by 21 regions, Australasia had 6.5 deaths per 100,000 people attributable to AMR, the lowest rate reported. This region also had 28 deaths per 100,000 associated with AMR.

Researchers found the highest rates in western sub-Saharan Africa. Deaths attributable to AMR were 27.3 per 100,000 and associated death rate was 114.8 per 100,000.

Lower- and middle-income regions had the highest AMR death rates, although resistance remains a high-priority issue for high-income countries as well.

“It’s important to take a global perspective on resistant infections because we can learn about regions and countries that are experiencing the greatest burden, information that was previously unknown,” Dr. Ikuta said. “With these estimates policy makers can prioritize regions that are hotspots and would most benefit from additional interventions.”

Furthermore, the study emphasized the global nature of AMR. “We’ve seen over the last 2 years with COVID-19 that this sort of problem doesn’t respect country borders, and high rates of resistance in one location can spread across a region or spread globally pretty quickly,” Dr. Ikuta said.
 

Leading resistant infections

Lower respiratory and thorax infections, bloodstream infections, and intra-abdominal infections together accounted for almost 79% of such deaths linked to AMR.

The six leading pathogens are likely household names among infectious disease specialists. The researchers found Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, each responsible for more than 250,000 AMR-associated deaths.

The study also revealed that resistance to several first-line antibiotic agents often used empirically to treat infections accounted for more than 70% of the AMR-attributable deaths. These included fluoroquinolones and beta-lactam antibiotics such as carbapenems, cephalosporins, and penicillins.

Courtesy The Lancet

Potential solutions offered

Dr. Murray and colleagues outlined five strategies to address the challenge of bacterial AMR:

• Infection prevention and control remain paramount in minimizing infections in general and AMR infections in particular.
• More vaccines are needed to reduce the need for antibiotics. “Vaccines are available for only one of the six leading pathogens (S. pneumoniae), although new vaccine programs are underway for S. aureus, E. coli, and others,” the researchers wrote.
• Reduce antibiotic use unrelated to treatment of human disease.
• Avoid using antibiotics for viral infections and other unnecessary indications.
• Invest in new antibiotic development and ensure access to second-line agents in areas without widespread access.

“Identifying strategies that can work to reduce the burden of bacterial AMR – either across a wide range of settings or those that are specifically tailored to the resources available and leading pathogen-drug combinations in a particular setting – is an urgent priority,” the researchers noted.
 

Admirable AMR research

The results of the study are “startling, but not surprising,” said Dr. Fowler, professor of medicine at Duke University, Durham, N.C.

The authors did a “nice job” of addressing both deaths attributable and associated with AMR, Dr. Fowler added. “Those two categories unlock applications, not just in terms of how you interpret it but also what you do about it.”

The deaths attributable to AMR show that there is more work to be done regarding infection control and prevention, Dr. Fowler said, including in areas of the world like lower- and middle-income countries where infection resistance is most pronounced.

The deaths associated with AMR can be more challenging to calculate – people with infections can die for multiple reasons. However, Dr. Fowler applauded the researchers for doing “as good a job as you can” in estimating the extent of associated mortality.
 

‘The overlooked pandemic of antimicrobial resistance’

In an accompanying editorial in The Lancet, Ramanan Laxminarayan, PhD, MPH, wrote: “As COVID-19 rages on, the pandemic of antimicrobial resistance continues in the shadows. The toll taken by AMR on patients and their families is largely invisible but is reflected in prolonged bacterial infections that extend hospital stays and cause needless deaths.”

Dr. Laxminarayan pointed out an irony with AMR in different regions. Some of the AMR burden in sub-Saharan Africa is “probably due to inadequate access to antibiotics and high infection levels, albeit at low levels of resistance, whereas in south Asia and Latin America, it is because of high resistance even with good access to antibiotics.”

More funding to address AMR is needed, Dr. Laxminarayan noted. “Even the lower end of 911,000 deaths estimated by Murray and colleagues is higher than the number of deaths from HIV, which attracts close to U.S. $50 billion each year. However, global spending on addressing AMR is probably much lower than that.” Dr. Laxminarayan is an economist and epidemiologist affiliated with the Center for Disease Dynamics, Economics & Policy in Washington, D.C., and the Global Antibiotic Research and Development Partnership in Geneva.
 

An overlap with COVID-19

The Lancet report is likely “to bring more attention to AMR, especially since so many people have been distracted by COVID, and rightly so,” Dr. Fowler predicted. “The world has had its hands full with COVID.”

The two infections interact in direct ways, Dr. Fowler added. For example, some people hospitalized for COVID-19 for an extended time could develop progressively drug-resistant bacteria – leading to a superinfection.

The overlap could be illustrated by a Venn diagram, he said. A yellow circle could illustrate people with COVID-19 who are asymptomatic or who remain outpatients. Next to that would be a blue circle showing people who develop AMR infections. Where the two circles overlap would be green for those hospitalized who – because of receiving steroids, being on a ventilator, or getting a central line – develop a superinfection.
 

Official guidance continues

The study comes in the context of recent guidance and federal action on AMR. For example, the Infectious Diseases Society of America released new guidelines for AMR in November 2021 as part of ongoing advice on prevention and treatment of this “ongoing crisis.”

This most recent IDSA guidance addresses three pathogens in particular: AmpC beta-lactamase–producing Enterobacterales, carbapenem-resistant A. baumannii, and Stenotrophomonas maltophilia.

Also in November, the World Health Organization released an updated fact sheet on antimicrobial resistance. The WHO declared AMR one of the world’s top 10 global public health threats. The agency emphasized that misuse and overuse of antimicrobials are the main drivers in the development of drug-resistant pathogens. The WHO also pointed out that lack of clean water and sanitation in many areas of the world contribute to spread of microbes, including those resistant to current treatment options.

In September 2021, the Biden administration acknowledged the threat of AMR with allocation of more than $2 billion of the American Rescue Plan money for prevention and treatment of these infections.

Asked if there are any reasons for hope or optimism at this point, Dr. Ikuta said: “Definitely. We know what needs to be done to combat the spread of resistance. COVID-19 has demonstrated the importance of global commitment to infection control measures, such as hand washing and surveillance, and rapid investments in treatments, which can all be applied to antimicrobial resistance.”

The Bill & Melinda Gates Foundation, the Wellcome Trust, and the U.K. Department of Health and Social Care using U.K. aid funding managed by the Fleming Fund and other organizations provided funding for the study. Dr. Ikuta and Dr. Laxminarayan have disclosed no relevant financial relationships. Dr. Fowler reported receiving grants or honoraria, as well as serving as a consultant, for numerous sources. He also reported a patent pending in sepsis diagnostics and serving as chair of the V710 Scientific Advisory Committee (Merck).

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

More than HIV, more than malaria. The death toll worldwide from bacterial antimicrobial resistance (AMR) in 2019 exceeded 1.2 million people, according to a new study.

In terms of preventable deaths, 1.27 million people could have been saved if drug-resistant infections were replaced with infections susceptible to current antibiotics. Furthermore, 4.95 million fewer people would have died if drug-resistant infections were replaced by no infections, researchers estimated.

Although the COVID-19 pandemic took some focus off the AMR burden worldwide over the past 2 years, the urgency to address risk to public health did not ebb. In fact, based on the findings, the researchers noted that AMR is now a leading cause of death worldwide.

“If left unchecked, the spread of AMR could make many bacterial pathogens much more lethal in the future than they are today,” the researchers noted in the study, published online Jan. 20, 2022, in The Lancet.

“These findings are a warning signal that antibiotic resistance is placing pressure on health care systems and leading to significant health loss,” study author Kevin Ikuta, MD, MPH, told this news organization.

“We need to continue to adhere to and support infection prevention and control programs, be thoughtful about our antibiotic use, and advocate for increased funding to vaccine discovery and the antibiotic development pipeline,” added Dr. Ikuta, health sciences assistant clinical professor of medicine at the University of California, Los Angeles.

Although many investigators have studied AMR, this study is the largest in scope, covering 204 countries and territories and incorporating data on a comprehensive range of pathogens and pathogen-drug combinations.

Dr. Ikuta, lead author Christopher J.L. Murray, DPhil, and colleagues estimated the global burden of AMR using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. They specifically looked at rates of death directly attributed to and separately those associated with resistance.
 

Regional differences

Broken down by 21 regions, Australasia had 6.5 deaths per 100,000 people attributable to AMR, the lowest rate reported. This region also had 28 deaths per 100,000 associated with AMR.

Researchers found the highest rates in western sub-Saharan Africa. Deaths attributable to AMR were 27.3 per 100,000 and associated death rate was 114.8 per 100,000.

Lower- and middle-income regions had the highest AMR death rates, although resistance remains a high-priority issue for high-income countries as well.

“It’s important to take a global perspective on resistant infections because we can learn about regions and countries that are experiencing the greatest burden, information that was previously unknown,” Dr. Ikuta said. “With these estimates policy makers can prioritize regions that are hotspots and would most benefit from additional interventions.”

Furthermore, the study emphasized the global nature of AMR. “We’ve seen over the last 2 years with COVID-19 that this sort of problem doesn’t respect country borders, and high rates of resistance in one location can spread across a region or spread globally pretty quickly,” Dr. Ikuta said.
 

Leading resistant infections

Lower respiratory and thorax infections, bloodstream infections, and intra-abdominal infections together accounted for almost 79% of such deaths linked to AMR.

The six leading pathogens are likely household names among infectious disease specialists. The researchers found Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, each responsible for more than 250,000 AMR-associated deaths.

The study also revealed that resistance to several first-line antibiotic agents often used empirically to treat infections accounted for more than 70% of the AMR-attributable deaths. These included fluoroquinolones and beta-lactam antibiotics such as carbapenems, cephalosporins, and penicillins.

Courtesy The Lancet

Potential solutions offered

Dr. Murray and colleagues outlined five strategies to address the challenge of bacterial AMR:

• Infection prevention and control remain paramount in minimizing infections in general and AMR infections in particular.
• More vaccines are needed to reduce the need for antibiotics. “Vaccines are available for only one of the six leading pathogens (S. pneumoniae), although new vaccine programs are underway for S. aureus, E. coli, and others,” the researchers wrote.
• Reduce antibiotic use unrelated to treatment of human disease.
• Avoid using antibiotics for viral infections and other unnecessary indications.
• Invest in new antibiotic development and ensure access to second-line agents in areas without widespread access.

“Identifying strategies that can work to reduce the burden of bacterial AMR – either across a wide range of settings or those that are specifically tailored to the resources available and leading pathogen-drug combinations in a particular setting – is an urgent priority,” the researchers noted.
 

Admirable AMR research

The results of the study are “startling, but not surprising,” said Dr. Fowler, professor of medicine at Duke University, Durham, N.C.

The authors did a “nice job” of addressing both deaths attributable and associated with AMR, Dr. Fowler added. “Those two categories unlock applications, not just in terms of how you interpret it but also what you do about it.”

The deaths attributable to AMR show that there is more work to be done regarding infection control and prevention, Dr. Fowler said, including in areas of the world like lower- and middle-income countries where infection resistance is most pronounced.

The deaths associated with AMR can be more challenging to calculate – people with infections can die for multiple reasons. However, Dr. Fowler applauded the researchers for doing “as good a job as you can” in estimating the extent of associated mortality.
 

‘The overlooked pandemic of antimicrobial resistance’

In an accompanying editorial in The Lancet, Ramanan Laxminarayan, PhD, MPH, wrote: “As COVID-19 rages on, the pandemic of antimicrobial resistance continues in the shadows. The toll taken by AMR on patients and their families is largely invisible but is reflected in prolonged bacterial infections that extend hospital stays and cause needless deaths.”

Dr. Laxminarayan pointed out an irony with AMR in different regions. Some of the AMR burden in sub-Saharan Africa is “probably due to inadequate access to antibiotics and high infection levels, albeit at low levels of resistance, whereas in south Asia and Latin America, it is because of high resistance even with good access to antibiotics.”

More funding to address AMR is needed, Dr. Laxminarayan noted. “Even the lower end of 911,000 deaths estimated by Murray and colleagues is higher than the number of deaths from HIV, which attracts close to U.S. $50 billion each year. However, global spending on addressing AMR is probably much lower than that.” Dr. Laxminarayan is an economist and epidemiologist affiliated with the Center for Disease Dynamics, Economics & Policy in Washington, D.C., and the Global Antibiotic Research and Development Partnership in Geneva.
 

An overlap with COVID-19

The Lancet report is likely “to bring more attention to AMR, especially since so many people have been distracted by COVID, and rightly so,” Dr. Fowler predicted. “The world has had its hands full with COVID.”

The two infections interact in direct ways, Dr. Fowler added. For example, some people hospitalized for COVID-19 for an extended time could develop progressively drug-resistant bacteria – leading to a superinfection.

The overlap could be illustrated by a Venn diagram, he said. A yellow circle could illustrate people with COVID-19 who are asymptomatic or who remain outpatients. Next to that would be a blue circle showing people who develop AMR infections. Where the two circles overlap would be green for those hospitalized who – because of receiving steroids, being on a ventilator, or getting a central line – develop a superinfection.
 

Official guidance continues

The study comes in the context of recent guidance and federal action on AMR. For example, the Infectious Diseases Society of America released new guidelines for AMR in November 2021 as part of ongoing advice on prevention and treatment of this “ongoing crisis.”

This most recent IDSA guidance addresses three pathogens in particular: AmpC beta-lactamase–producing Enterobacterales, carbapenem-resistant A. baumannii, and Stenotrophomonas maltophilia.

Also in November, the World Health Organization released an updated fact sheet on antimicrobial resistance. The WHO declared AMR one of the world’s top 10 global public health threats. The agency emphasized that misuse and overuse of antimicrobials are the main drivers in the development of drug-resistant pathogens. The WHO also pointed out that lack of clean water and sanitation in many areas of the world contribute to spread of microbes, including those resistant to current treatment options.

In September 2021, the Biden administration acknowledged the threat of AMR with allocation of more than $2 billion of the American Rescue Plan money for prevention and treatment of these infections.

Asked if there are any reasons for hope or optimism at this point, Dr. Ikuta said: “Definitely. We know what needs to be done to combat the spread of resistance. COVID-19 has demonstrated the importance of global commitment to infection control measures, such as hand washing and surveillance, and rapid investments in treatments, which can all be applied to antimicrobial resistance.”

The Bill & Melinda Gates Foundation, the Wellcome Trust, and the U.K. Department of Health and Social Care using U.K. aid funding managed by the Fleming Fund and other organizations provided funding for the study. Dr. Ikuta and Dr. Laxminarayan have disclosed no relevant financial relationships. Dr. Fowler reported receiving grants or honoraria, as well as serving as a consultant, for numerous sources. He also reported a patent pending in sepsis diagnostics and serving as chair of the V710 Scientific Advisory Committee (Merck).

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

BUENOS AIRES – The Latin American Association of Cardiac and Endovascular Surgery (LACES) has demanded “urgent reconsideration” of the decision to downgrade the strength of the recommendation for revascularization or coronary artery bypass graft (CABG) surgery for multivessel disease in the new guideline on coronary artery revascularization, putting it in the same class as the recommendation for percutaneous coronary intervention, which has no apparent advantage over optimal medical therapy.

With the prevalence of stable ischemic heart disease in patients with multivessel disease, the contradiction between the evidence and the new recommendation “may affect the lives and survival of millions of patients worldwide and have a major socio-economic impact,” the association warned in a public letter.

In the 2011 guideline, CABG for patients with multivessel coronary artery disease was given a class I recommendation, which means that it is considered useful and effective and should be performed in the majority of patients in most circumstances. But the new, much weaker class IIb recommendation suggests that the benefit only marginally exceeds the risk and that it should be used selectively and only after careful consideration.

“It is an incomprehensible rollercoaster drop in the recommendation level. We totally disagree. In the absence of evidence, a IIb level provides equal freedom to send a patient to surgery or not. And in patients who are not being sent to surgery, it could take years of survival before we can be sure that we are doing the right thing,” said LACES president Víctor Dayan, MD, PhD, from the cardiovascular center at the Hospital de Clínicas “Dr. Manuel Quintela”, which is part of the School of Medicine at the University of the Republic, Montevideo, Uruguay.

The change in the recommendation for this indication “reflects new evidence showing no advantage of coronary artery bypass grafting over medical therapy alone to improve survival in patients with three-vessel coronary disease with preserved left ventricular function and no left main disease,” according to the authors of the guideline, issued jointly by the American College of Cardiology (ACC), the American Heart Association, and the Society for Cardiovascular Angiography and Interventions (SCAI). In particular, they cite the 2019 ISCHEMIA clinical study that failed to show that an early invasive strategy reduces major adverse cardiovascular events, compared with optimal medical therapy and a handful of meta-analyses.

However, ISCHEMIA did not discriminate between the two types of invasive strategy – CABG and percutaneous coronary intervention (PCI) – so cannot be considered as a basis to downgrade the CABG recommendation, Dr. Dayan explained.

“Furthermore, the authors neglected previous RCTs that have shown the survival benefit of CABG in these patients and decided to put PCI in the same [class of recommendation], although no RCT has been able to show any survival advantage of PCI compared to optimal medical treatment,” the LACES letter states.

Basis should be evidence, ‘not inferences’

Three large randomized clinical trials and a 1994 meta-analysis with individual patient data from seven studies firmly established that survival is better with CABG than with medical treatment, the letter continues. However, the guideline authors did not provide any additional randomized clinical trials that refute this evidence.

“Furthermore, the committee disregarded data from the Ten-Year Follow-up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II) randomized control[led] trial, which showed a lower incidence of cardiac mortality (as part of its secondary outcomes) following CABG compared to optimal medical therapy and PCI,” the letter explains.

The guideline authors might have judged current optimal medical therapy to be better than what existed 10, 15, or 30 years ago, diluting the relative benefits of surgery, but the “recommendation in a guideline must act on evidence, not inferences. And there is no evidence to support this drop in recommendation class,” Dr. Dayan said.

Other experts have drawn attention to the fact that two surgical societies – the American Association for Thoracic Surgery (AAST) and the Society of Thoracic Surgeons (STS) – did not endorse the final document, despite having participated in its review, reported this news organization.

“This is a very disappointing update that will negatively affect the lives of many people,” tweeted Marc Pelletier, MD, head of cardiac surgery at University Hospitals, Case Western Reserve University, Cleveland.

Contradictions in the text that examines the evidence and the final recommendations, are “unclear” and “open to various interpretations, when they should be a pillar for decisionmaking,” said Javier Ferrari Ayarragaray, MD, president of the Argentine College of Cardiovascular Surgeons (CACCV) and vice president of LACES.

The new guidelines “show no additional randomized controlled trial to support this downgrade in the level of evidence,” according to a recent CACCV statement. “The inclusion, approval and endorsement of this type of [recommendation,] including [other] international surgical scientific societies, such as STS, AATS, EACTS, LACES[,] is necessary to obtain a better understanding and agreement on the current evidence.”

In a Dec. 17, 2021 response to LACES, Patrick O’Gara, MD, who was chair of the ACC/AHA Joint Committee on Clinical Practice Guidelines at the time, and his successor, Joshua Beckman, MD, explained that both organizations approved the guideline for publication and support its authors “in their interpretation of the published evidence and findings.”

The pair pointed out that the drafting committee members, who have extensive clinical judgment and experience, deliberated extensively on the issue and that the change from a class I to a class IIb recommendation was “carefully considered after a review of the entire available and relevant evidence.”

“When we bring together multiple organizations to review and summarize the evidence, we work collaboratively to interpret the extensive catalog of published and peer-reviewed literature and create clinical practice recommendations,” said Thomas Getchius, director of guideline strategy and operations at the AHA.

“The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed upon by the ACC, AHA, SCAI, and the full drafting committee,” Mr. Getchius said.

Dr. Dayan and Dr. Ferrari Ayarragaray have disclosed no relevant financial relationships. Mr. Getchius is an employee of the American Heart Association.

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

BUENOS AIRES – The Latin American Association of Cardiac and Endovascular Surgery (LACES) has demanded “urgent reconsideration” of the decision to downgrade the strength of the recommendation for revascularization or coronary artery bypass graft (CABG) surgery for multivessel disease in the new guideline on coronary artery revascularization, putting it in the same class as the recommendation for percutaneous coronary intervention, which has no apparent advantage over optimal medical therapy.

With the prevalence of stable ischemic heart disease in patients with multivessel disease, the contradiction between the evidence and the new recommendation “may affect the lives and survival of millions of patients worldwide and have a major socio-economic impact,” the association warned in a public letter.

In the 2011 guideline, CABG for patients with multivessel coronary artery disease was given a class I recommendation, which means that it is considered useful and effective and should be performed in the majority of patients in most circumstances. But the new, much weaker class IIb recommendation suggests that the benefit only marginally exceeds the risk and that it should be used selectively and only after careful consideration.

“It is an incomprehensible rollercoaster drop in the recommendation level. We totally disagree. In the absence of evidence, a IIb level provides equal freedom to send a patient to surgery or not. And in patients who are not being sent to surgery, it could take years of survival before we can be sure that we are doing the right thing,” said LACES president Víctor Dayan, MD, PhD, from the cardiovascular center at the Hospital de Clínicas “Dr. Manuel Quintela”, which is part of the School of Medicine at the University of the Republic, Montevideo, Uruguay.

The change in the recommendation for this indication “reflects new evidence showing no advantage of coronary artery bypass grafting over medical therapy alone to improve survival in patients with three-vessel coronary disease with preserved left ventricular function and no left main disease,” according to the authors of the guideline, issued jointly by the American College of Cardiology (ACC), the American Heart Association, and the Society for Cardiovascular Angiography and Interventions (SCAI). In particular, they cite the 2019 ISCHEMIA clinical study that failed to show that an early invasive strategy reduces major adverse cardiovascular events, compared with optimal medical therapy and a handful of meta-analyses.

However, ISCHEMIA did not discriminate between the two types of invasive strategy – CABG and percutaneous coronary intervention (PCI) – so cannot be considered as a basis to downgrade the CABG recommendation, Dr. Dayan explained.

“Furthermore, the authors neglected previous RCTs that have shown the survival benefit of CABG in these patients and decided to put PCI in the same [class of recommendation], although no RCT has been able to show any survival advantage of PCI compared to optimal medical treatment,” the LACES letter states.

Basis should be evidence, ‘not inferences’

Three large randomized clinical trials and a 1994 meta-analysis with individual patient data from seven studies firmly established that survival is better with CABG than with medical treatment, the letter continues. However, the guideline authors did not provide any additional randomized clinical trials that refute this evidence.

“Furthermore, the committee disregarded data from the Ten-Year Follow-up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II) randomized control[led] trial, which showed a lower incidence of cardiac mortality (as part of its secondary outcomes) following CABG compared to optimal medical therapy and PCI,” the letter explains.

The guideline authors might have judged current optimal medical therapy to be better than what existed 10, 15, or 30 years ago, diluting the relative benefits of surgery, but the “recommendation in a guideline must act on evidence, not inferences. And there is no evidence to support this drop in recommendation class,” Dr. Dayan said.

Other experts have drawn attention to the fact that two surgical societies – the American Association for Thoracic Surgery (AAST) and the Society of Thoracic Surgeons (STS) – did not endorse the final document, despite having participated in its review, reported this news organization.

“This is a very disappointing update that will negatively affect the lives of many people,” tweeted Marc Pelletier, MD, head of cardiac surgery at University Hospitals, Case Western Reserve University, Cleveland.

Contradictions in the text that examines the evidence and the final recommendations, are “unclear” and “open to various interpretations, when they should be a pillar for decisionmaking,” said Javier Ferrari Ayarragaray, MD, president of the Argentine College of Cardiovascular Surgeons (CACCV) and vice president of LACES.

The new guidelines “show no additional randomized controlled trial to support this downgrade in the level of evidence,” according to a recent CACCV statement. “The inclusion, approval and endorsement of this type of [recommendation,] including [other] international surgical scientific societies, such as STS, AATS, EACTS, LACES[,] is necessary to obtain a better understanding and agreement on the current evidence.”

In a Dec. 17, 2021 response to LACES, Patrick O’Gara, MD, who was chair of the ACC/AHA Joint Committee on Clinical Practice Guidelines at the time, and his successor, Joshua Beckman, MD, explained that both organizations approved the guideline for publication and support its authors “in their interpretation of the published evidence and findings.”

The pair pointed out that the drafting committee members, who have extensive clinical judgment and experience, deliberated extensively on the issue and that the change from a class I to a class IIb recommendation was “carefully considered after a review of the entire available and relevant evidence.”

“When we bring together multiple organizations to review and summarize the evidence, we work collaboratively to interpret the extensive catalog of published and peer-reviewed literature and create clinical practice recommendations,” said Thomas Getchius, director of guideline strategy and operations at the AHA.

“The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed upon by the ACC, AHA, SCAI, and the full drafting committee,” Mr. Getchius said.

Dr. Dayan and Dr. Ferrari Ayarragaray have disclosed no relevant financial relationships. Mr. Getchius is an employee of the American Heart Association.

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

BUENOS AIRES – The Latin American Association of Cardiac and Endovascular Surgery (LACES) has demanded “urgent reconsideration” of the decision to downgrade the strength of the recommendation for revascularization or coronary artery bypass graft (CABG) surgery for multivessel disease in the new guideline on coronary artery revascularization, putting it in the same class as the recommendation for percutaneous coronary intervention, which has no apparent advantage over optimal medical therapy.

With the prevalence of stable ischemic heart disease in patients with multivessel disease, the contradiction between the evidence and the new recommendation “may affect the lives and survival of millions of patients worldwide and have a major socio-economic impact,” the association warned in a public letter.

In the 2011 guideline, CABG for patients with multivessel coronary artery disease was given a class I recommendation, which means that it is considered useful and effective and should be performed in the majority of patients in most circumstances. But the new, much weaker class IIb recommendation suggests that the benefit only marginally exceeds the risk and that it should be used selectively and only after careful consideration.

“It is an incomprehensible rollercoaster drop in the recommendation level. We totally disagree. In the absence of evidence, a IIb level provides equal freedom to send a patient to surgery or not. And in patients who are not being sent to surgery, it could take years of survival before we can be sure that we are doing the right thing,” said LACES president Víctor Dayan, MD, PhD, from the cardiovascular center at the Hospital de Clínicas “Dr. Manuel Quintela”, which is part of the School of Medicine at the University of the Republic, Montevideo, Uruguay.

The change in the recommendation for this indication “reflects new evidence showing no advantage of coronary artery bypass grafting over medical therapy alone to improve survival in patients with three-vessel coronary disease with preserved left ventricular function and no left main disease,” according to the authors of the guideline, issued jointly by the American College of Cardiology (ACC), the American Heart Association, and the Society for Cardiovascular Angiography and Interventions (SCAI). In particular, they cite the 2019 ISCHEMIA clinical study that failed to show that an early invasive strategy reduces major adverse cardiovascular events, compared with optimal medical therapy and a handful of meta-analyses.

However, ISCHEMIA did not discriminate between the two types of invasive strategy – CABG and percutaneous coronary intervention (PCI) – so cannot be considered as a basis to downgrade the CABG recommendation, Dr. Dayan explained.

“Furthermore, the authors neglected previous RCTs that have shown the survival benefit of CABG in these patients and decided to put PCI in the same [class of recommendation], although no RCT has been able to show any survival advantage of PCI compared to optimal medical treatment,” the LACES letter states.

Basis should be evidence, ‘not inferences’

Three large randomized clinical trials and a 1994 meta-analysis with individual patient data from seven studies firmly established that survival is better with CABG than with medical treatment, the letter continues. However, the guideline authors did not provide any additional randomized clinical trials that refute this evidence.

“Furthermore, the committee disregarded data from the Ten-Year Follow-up Survival of the Medicine, Angioplasty, or Surgery Study (MASS II) randomized control[led] trial, which showed a lower incidence of cardiac mortality (as part of its secondary outcomes) following CABG compared to optimal medical therapy and PCI,” the letter explains.

The guideline authors might have judged current optimal medical therapy to be better than what existed 10, 15, or 30 years ago, diluting the relative benefits of surgery, but the “recommendation in a guideline must act on evidence, not inferences. And there is no evidence to support this drop in recommendation class,” Dr. Dayan said.

Other experts have drawn attention to the fact that two surgical societies – the American Association for Thoracic Surgery (AAST) and the Society of Thoracic Surgeons (STS) – did not endorse the final document, despite having participated in its review, reported this news organization.

“This is a very disappointing update that will negatively affect the lives of many people,” tweeted Marc Pelletier, MD, head of cardiac surgery at University Hospitals, Case Western Reserve University, Cleveland.

Contradictions in the text that examines the evidence and the final recommendations, are “unclear” and “open to various interpretations, when they should be a pillar for decisionmaking,” said Javier Ferrari Ayarragaray, MD, president of the Argentine College of Cardiovascular Surgeons (CACCV) and vice president of LACES.

The new guidelines “show no additional randomized controlled trial to support this downgrade in the level of evidence,” according to a recent CACCV statement. “The inclusion, approval and endorsement of this type of [recommendation,] including [other] international surgical scientific societies, such as STS, AATS, EACTS, LACES[,] is necessary to obtain a better understanding and agreement on the current evidence.”

In a Dec. 17, 2021 response to LACES, Patrick O’Gara, MD, who was chair of the ACC/AHA Joint Committee on Clinical Practice Guidelines at the time, and his successor, Joshua Beckman, MD, explained that both organizations approved the guideline for publication and support its authors “in their interpretation of the published evidence and findings.”

The pair pointed out that the drafting committee members, who have extensive clinical judgment and experience, deliberated extensively on the issue and that the change from a class I to a class IIb recommendation was “carefully considered after a review of the entire available and relevant evidence.”

“When we bring together multiple organizations to review and summarize the evidence, we work collaboratively to interpret the extensive catalog of published and peer-reviewed literature and create clinical practice recommendations,” said Thomas Getchius, director of guideline strategy and operations at the AHA.

“The final guideline reflects the latest evidence-based recommendations for coronary artery revascularization, as agreed upon by the ACC, AHA, SCAI, and the full drafting committee,” Mr. Getchius said.

Dr. Dayan and Dr. Ferrari Ayarragaray have disclosed no relevant financial relationships. Mr. Getchius is an employee of the American Heart Association.

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

New research suggests serial coronary CT angiography (CCTA) can provide novel insights into the association between lipoprotein(a) and plaque progression over time in patients with advanced coronary artery disease.

Researchers examined data from 191 individuals with multivessel coronary disease receiving preventive statin (95%) and antiplatelet (100%) therapy in the single-center Scottish DIAMOND trial and compared CCTA at baseline and 12 months available for 160 patients.

As reported in the Journal of the American College of Cardiology, patients with high Lp(a), defined as at least 70 mg/dL, had higher baseline high-density lipoprotein cholesterol and ASSIGN scores than those with low Lp(a) but had comparable coronary artery calcium (CAC) scores and total, calcific, noncalcific, and low-attenuation plaque (LAP) volumes.

At 1 year, however, LAP volume – a marker for necrotic core – increased by 26.2 mm3 in the high-Lp(a) group and decreased by –0.7 mm3 in the low-Lp(a) group (P = .020).

There was no significant difference in change in total, calcific, and noncalcific plaque volumes between groups.

In multivariate linear regression analysis adjusting for body mass index, ASSIGN score, and segment involvement score, LAP volume increased by 10.5% for each 50 mg/dL increment in Lp(a) (P = .034).

“It’s an exciting observation, because we’ve done previous studies where we’ve demonstrated the association of that particular plaque type with future myocardial infarction,” senior author Marc R. Dweck, MD, PhD, University of Amsterdam, told this news organization. “So, you’ve potentially got an explanation for the adverse prognosis associated with high lipoprotein(a) and its link to cardiovascular events and, in particular, myocardial infarction.”

The team’s recent SCOT-HEART analysis found that LAP burden was a stronger predictor of myocardial infarction (MI) than cardiovascular risk scores, stenosis severity, and CAC scoring, with MI risk nearly five-fold higher if LAP was above 4%.

As to why total, calcific, and noncalcific plaque volumes didn’t change significantly on repeat CCTA in the present study, Dr. Dweck said it’s possible that the sample was too small and follow-up too short but also that “total plaque volume is really dominated by the fibrous plaque, which doesn’t appear affected by Lp(a).” Nevertheless, Lp(a)’s effect on low-attenuation plaque was clearly present and supported by the change in fibro-fatty plaque, the next-most unstable plaque type.

At 1 year, fibro-fatty plaque volume was 55.0 mm3 in the high-Lp(a) group versus –25.0 mm3 in the low-Lp(a) group (P = .020).

Lp(a) was associated with fibro-fatty plaque progression in univariate analysis (β = 6.7%; P = .034) and showed a trend in multivariable analysis (β = 6.0%; P = .062).

“This study shows you can track changes in plaque over time and highlight important disease mechanisms and use them to understand the pathology of the disease,” Dr. Dweck said. “I’m very encouraged by this.”

What’s novel in the present study is that “it represents the beginning of our understanding of the role of Lp(a) in plaque progression,” Sotirios Tsimikas, MD, University of California, San Diego, and Jagat Narula, MD, PhD, Icahn School of Medicine at Mount Sinai, New York, say in an accompanying commentary.

They note that prior studies, including the Dallas Heart Study, have struggled to find a strong association between Lp(a) with the extent or progression of CAC, despite elevated Lp(a) and CAC identifying higher-risk patients.

Similarly, a meta-analysis of intravascular ultrasound trials turned up only a 1.2% absolute difference in atheroma volume in patients with elevated Lp(a), and a recent optical coherence tomography study found an association of Lp(a) with thin-cap fibroatheromas but not lipid core.

With just 36 patients with elevated Lp(a), however, the current findings need validation in a larger data set, Dr. Tsimikas and Dr. Narula say.

Although Lp(a) is genetically elevated in about one in five individuals and measurement is recommended in European dyslipidemia guidelines, testing rates are low, in part because the argument has been that there are no Lp(a)-lowering therapies available, Dr. Dweck observed. That may change with the phase 3 cardiovascular outcomes Lp(a)HORIZON trial, which follows strong phase 2 results with the antisense agent AKCEA-APO(a)-LRx and is enrolling patients similar to the current cohort.

“Ultimately it comes down to that fundamental thing, that you need an action once you’ve done the test and then insurers will be happy to pay for it and clinicians will ask for it. That’s why that trial is so important,” Dr. Dweck said.

Dr. Tsimikas and Dr. Narula also point to the eagerly awaited results of that trial, expected in 2025. “A positive trial is likely to lead to additional trials and new drugs that may reinvigorate the use of imaging modalities that could go beyond plaque volume and atherosclerosis to also predict clinically relevant inflammation and atherothrombosis,” they conclude.

Dr. Dweck is supported by the British Heart Foundation and is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015; has received speaker fees from Pfizer and Novartis; and has received consultancy fees from Novartis, Jupiter Bioventures, and Silence Therapeutics. Coauthor disclosures are listed in the paper. Dr. Tsimikas has a dual appointment at the University of California, San Diego, (UCSD) and Ionis Pharmaceuticals; is a coinventor and receives royalties from patents owned by UCSD; and is a cofounder and has an equity interest in Oxitope and its affiliates, Kleanthi Diagnostics, and Covicept Therapeutics. Dr. Narula reports having no relevant financial relationships.

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

New research suggests serial coronary CT angiography (CCTA) can provide novel insights into the association between lipoprotein(a) and plaque progression over time in patients with advanced coronary artery disease.

Researchers examined data from 191 individuals with multivessel coronary disease receiving preventive statin (95%) and antiplatelet (100%) therapy in the single-center Scottish DIAMOND trial and compared CCTA at baseline and 12 months available for 160 patients.

As reported in the Journal of the American College of Cardiology, patients with high Lp(a), defined as at least 70 mg/dL, had higher baseline high-density lipoprotein cholesterol and ASSIGN scores than those with low Lp(a) but had comparable coronary artery calcium (CAC) scores and total, calcific, noncalcific, and low-attenuation plaque (LAP) volumes.

At 1 year, however, LAP volume – a marker for necrotic core – increased by 26.2 mm3 in the high-Lp(a) group and decreased by –0.7 mm3 in the low-Lp(a) group (P = .020).

There was no significant difference in change in total, calcific, and noncalcific plaque volumes between groups.

In multivariate linear regression analysis adjusting for body mass index, ASSIGN score, and segment involvement score, LAP volume increased by 10.5% for each 50 mg/dL increment in Lp(a) (P = .034).

“It’s an exciting observation, because we’ve done previous studies where we’ve demonstrated the association of that particular plaque type with future myocardial infarction,” senior author Marc R. Dweck, MD, PhD, University of Amsterdam, told this news organization. “So, you’ve potentially got an explanation for the adverse prognosis associated with high lipoprotein(a) and its link to cardiovascular events and, in particular, myocardial infarction.”

The team’s recent SCOT-HEART analysis found that LAP burden was a stronger predictor of myocardial infarction (MI) than cardiovascular risk scores, stenosis severity, and CAC scoring, with MI risk nearly five-fold higher if LAP was above 4%.

As to why total, calcific, and noncalcific plaque volumes didn’t change significantly on repeat CCTA in the present study, Dr. Dweck said it’s possible that the sample was too small and follow-up too short but also that “total plaque volume is really dominated by the fibrous plaque, which doesn’t appear affected by Lp(a).” Nevertheless, Lp(a)’s effect on low-attenuation plaque was clearly present and supported by the change in fibro-fatty plaque, the next-most unstable plaque type.

At 1 year, fibro-fatty plaque volume was 55.0 mm3 in the high-Lp(a) group versus –25.0 mm3 in the low-Lp(a) group (P = .020).

Lp(a) was associated with fibro-fatty plaque progression in univariate analysis (β = 6.7%; P = .034) and showed a trend in multivariable analysis (β = 6.0%; P = .062).

“This study shows you can track changes in plaque over time and highlight important disease mechanisms and use them to understand the pathology of the disease,” Dr. Dweck said. “I’m very encouraged by this.”

What’s novel in the present study is that “it represents the beginning of our understanding of the role of Lp(a) in plaque progression,” Sotirios Tsimikas, MD, University of California, San Diego, and Jagat Narula, MD, PhD, Icahn School of Medicine at Mount Sinai, New York, say in an accompanying commentary.

They note that prior studies, including the Dallas Heart Study, have struggled to find a strong association between Lp(a) with the extent or progression of CAC, despite elevated Lp(a) and CAC identifying higher-risk patients.

Similarly, a meta-analysis of intravascular ultrasound trials turned up only a 1.2% absolute difference in atheroma volume in patients with elevated Lp(a), and a recent optical coherence tomography study found an association of Lp(a) with thin-cap fibroatheromas but not lipid core.

With just 36 patients with elevated Lp(a), however, the current findings need validation in a larger data set, Dr. Tsimikas and Dr. Narula say.

Although Lp(a) is genetically elevated in about one in five individuals and measurement is recommended in European dyslipidemia guidelines, testing rates are low, in part because the argument has been that there are no Lp(a)-lowering therapies available, Dr. Dweck observed. That may change with the phase 3 cardiovascular outcomes Lp(a)HORIZON trial, which follows strong phase 2 results with the antisense agent AKCEA-APO(a)-LRx and is enrolling patients similar to the current cohort.

“Ultimately it comes down to that fundamental thing, that you need an action once you’ve done the test and then insurers will be happy to pay for it and clinicians will ask for it. That’s why that trial is so important,” Dr. Dweck said.

Dr. Tsimikas and Dr. Narula also point to the eagerly awaited results of that trial, expected in 2025. “A positive trial is likely to lead to additional trials and new drugs that may reinvigorate the use of imaging modalities that could go beyond plaque volume and atherosclerosis to also predict clinically relevant inflammation and atherothrombosis,” they conclude.

Dr. Dweck is supported by the British Heart Foundation and is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015; has received speaker fees from Pfizer and Novartis; and has received consultancy fees from Novartis, Jupiter Bioventures, and Silence Therapeutics. Coauthor disclosures are listed in the paper. Dr. Tsimikas has a dual appointment at the University of California, San Diego, (UCSD) and Ionis Pharmaceuticals; is a coinventor and receives royalties from patents owned by UCSD; and is a cofounder and has an equity interest in Oxitope and its affiliates, Kleanthi Diagnostics, and Covicept Therapeutics. Dr. Narula reports having no relevant financial relationships.

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

New research suggests serial coronary CT angiography (CCTA) can provide novel insights into the association between lipoprotein(a) and plaque progression over time in patients with advanced coronary artery disease.

Researchers examined data from 191 individuals with multivessel coronary disease receiving preventive statin (95%) and antiplatelet (100%) therapy in the single-center Scottish DIAMOND trial and compared CCTA at baseline and 12 months available for 160 patients.

As reported in the Journal of the American College of Cardiology, patients with high Lp(a), defined as at least 70 mg/dL, had higher baseline high-density lipoprotein cholesterol and ASSIGN scores than those with low Lp(a) but had comparable coronary artery calcium (CAC) scores and total, calcific, noncalcific, and low-attenuation plaque (LAP) volumes.

At 1 year, however, LAP volume – a marker for necrotic core – increased by 26.2 mm3 in the high-Lp(a) group and decreased by –0.7 mm3 in the low-Lp(a) group (P = .020).

There was no significant difference in change in total, calcific, and noncalcific plaque volumes between groups.

In multivariate linear regression analysis adjusting for body mass index, ASSIGN score, and segment involvement score, LAP volume increased by 10.5% for each 50 mg/dL increment in Lp(a) (P = .034).

“It’s an exciting observation, because we’ve done previous studies where we’ve demonstrated the association of that particular plaque type with future myocardial infarction,” senior author Marc R. Dweck, MD, PhD, University of Amsterdam, told this news organization. “So, you’ve potentially got an explanation for the adverse prognosis associated with high lipoprotein(a) and its link to cardiovascular events and, in particular, myocardial infarction.”

The team’s recent SCOT-HEART analysis found that LAP burden was a stronger predictor of myocardial infarction (MI) than cardiovascular risk scores, stenosis severity, and CAC scoring, with MI risk nearly five-fold higher if LAP was above 4%.

As to why total, calcific, and noncalcific plaque volumes didn’t change significantly on repeat CCTA in the present study, Dr. Dweck said it’s possible that the sample was too small and follow-up too short but also that “total plaque volume is really dominated by the fibrous plaque, which doesn’t appear affected by Lp(a).” Nevertheless, Lp(a)’s effect on low-attenuation plaque was clearly present and supported by the change in fibro-fatty plaque, the next-most unstable plaque type.

At 1 year, fibro-fatty plaque volume was 55.0 mm3 in the high-Lp(a) group versus –25.0 mm3 in the low-Lp(a) group (P = .020).

Lp(a) was associated with fibro-fatty plaque progression in univariate analysis (β = 6.7%; P = .034) and showed a trend in multivariable analysis (β = 6.0%; P = .062).

“This study shows you can track changes in plaque over time and highlight important disease mechanisms and use them to understand the pathology of the disease,” Dr. Dweck said. “I’m very encouraged by this.”

What’s novel in the present study is that “it represents the beginning of our understanding of the role of Lp(a) in plaque progression,” Sotirios Tsimikas, MD, University of California, San Diego, and Jagat Narula, MD, PhD, Icahn School of Medicine at Mount Sinai, New York, say in an accompanying commentary.

They note that prior studies, including the Dallas Heart Study, have struggled to find a strong association between Lp(a) with the extent or progression of CAC, despite elevated Lp(a) and CAC identifying higher-risk patients.

Similarly, a meta-analysis of intravascular ultrasound trials turned up only a 1.2% absolute difference in atheroma volume in patients with elevated Lp(a), and a recent optical coherence tomography study found an association of Lp(a) with thin-cap fibroatheromas but not lipid core.

With just 36 patients with elevated Lp(a), however, the current findings need validation in a larger data set, Dr. Tsimikas and Dr. Narula say.

Although Lp(a) is genetically elevated in about one in five individuals and measurement is recommended in European dyslipidemia guidelines, testing rates are low, in part because the argument has been that there are no Lp(a)-lowering therapies available, Dr. Dweck observed. That may change with the phase 3 cardiovascular outcomes Lp(a)HORIZON trial, which follows strong phase 2 results with the antisense agent AKCEA-APO(a)-LRx and is enrolling patients similar to the current cohort.

“Ultimately it comes down to that fundamental thing, that you need an action once you’ve done the test and then insurers will be happy to pay for it and clinicians will ask for it. That’s why that trial is so important,” Dr. Dweck said.

Dr. Tsimikas and Dr. Narula also point to the eagerly awaited results of that trial, expected in 2025. “A positive trial is likely to lead to additional trials and new drugs that may reinvigorate the use of imaging modalities that could go beyond plaque volume and atherosclerosis to also predict clinically relevant inflammation and atherothrombosis,” they conclude.

Dr. Dweck is supported by the British Heart Foundation and is the recipient of the Sir Jules Thorn Award for Biomedical Research 2015; has received speaker fees from Pfizer and Novartis; and has received consultancy fees from Novartis, Jupiter Bioventures, and Silence Therapeutics. Coauthor disclosures are listed in the paper. Dr. Tsimikas has a dual appointment at the University of California, San Diego, (UCSD) and Ionis Pharmaceuticals; is a coinventor and receives royalties from patents owned by UCSD; and is a cofounder and has an equity interest in Oxitope and its affiliates, Kleanthi Diagnostics, and Covicept Therapeutics. Dr. Narula reports having no relevant financial relationships.

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

People with bipolar disorder as well as their unaffected siblings appear to be at increased risk for cancer, particularly of the breast, according to new research from Taiwan.

“To our knowledge, our study is the first to report an increased overall cancer risk as well as increased risks of breast and ectodermal cancer among the unaffected siblings aged < 50 years of patients with bipolar disorder,” Ya-Mei Bai, MD, PhD, of National Yang-Ming University, Taipei, Taiwan, and colleagues write in an article published online in the International Journal of Cancer.

Most, but not all, previous studies have shown a link between bipolar disorder and cancer. Whether the elevated risk of malignancy extends to family members without the mental health condition has not been elucidated.

To investigate, the researchers turned to the National Health Insurance Research Database of Taiwan. They identified 25,356 individuals diagnosed with bipolar disorder by a psychiatrist between 1996 and 2010 and the same number of unaffected siblings, as well as more than 100,000 age-, sex-, income-, and residence-matched controls without severe mental illness.

Compared with the control group, people with bipolar disorder (odds ratio, 1.22) and their unaffected siblings (OR, 1.17) both had a higher risk of developing malignant cancer of any kind. The researchers also found that both groups were at higher risk for breast cancer, with odds ratios of 1.98 in individuals with bipolar disorder and 1.73 in their unaffected siblings.

However, the risk of skin cancer was only high in people with bipolar disorder (OR, 2.70) and not in their siblings (OR, 0.62). And conversely, the risk of kidney cancer was significantly increased in unaffected siblings (OR, 2.45) but not in people with bipolar disorder (OR, 0.47).

When stratified by the embryonic developmental layer from which tumors had originated – ectodermal, mesodermal, or endodermal – the authors observed a significantly increased risk for only ectodermal cancers. In addition, only people under age 50 in both groups (OR, 1.90 for those with bipolar disorder; OR, 1.65 for siblings) were more likely to develop an ectodermal cancer, especially of the breast, compared with the control group. The risks remained elevated after excluding breast cancer but were no longer significant.

When stratified by age, the risk of developing any cancer in both groups also only appeared to be greater for those under age 50 (OR, 1.34 in people with bipolar disorder; OR, 1.32 in siblings) compared with those aged 50 and over (OR, 0.97 and 0.99, respectively). The authors highlighted these figures in the supplemental data set but did not discuss it further in the study beyond a brief mention that “younger patients with bipolar disorder and younger unaffected siblings (< 50 years), but not older ones (≥ 50 years), were more likely to develop any malignancy during the follow-up than matched controls.”

“This paper essentially finds what we have found in our previous work – that people with bipolar disorder have a greater risk of cancer,” said Michael Berk, MBBCh, PhD, a professor of psychiatry at the Deakin University School of Medicine in Geelong, Australia, who published a systematic review and meta-analysis last spring on cancer risk and the role of lithium treatment in bipolar disorder.

“The interesting finding in our work,” Dr. Berk told this news organization, “is that this risk is attenuated by use of lithium but not other agents.”

The Taiwanese researchers propose a “biopsychosocial explanation” for their results, noting that both the nervous system and the breast and skin develop from the ectoderm, and that cancer risk factors such as smoking and obesity are more common in people with bipolar disorder and their unaffected siblings.

“The findings,” they write, “imply a genetic overlap in neurodevelopment and malignancy pathogenesis and may encourage clinicians to closely monitor patients with bipolar disorder and their unaffected siblings for cancer warning signs.”

The authors, however, caution that their study needs validation and had several limitations, including lack of adjustment for drug treatment and lifestyle and environmental factors.

“Our findings may persuade clinicians and researchers to reevaluate the cancer risk among the unaffected siblings of patients with schizophrenia and bipolar disorder because these two severe mental disorders may have a common biopsychosocial pathophysiology,” the team writes.

The study was supported by a grant from Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan.

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

People with bipolar disorder as well as their unaffected siblings appear to be at increased risk for cancer, particularly of the breast, according to new research from Taiwan.

“To our knowledge, our study is the first to report an increased overall cancer risk as well as increased risks of breast and ectodermal cancer among the unaffected siblings aged < 50 years of patients with bipolar disorder,” Ya-Mei Bai, MD, PhD, of National Yang-Ming University, Taipei, Taiwan, and colleagues write in an article published online in the International Journal of Cancer.

Most, but not all, previous studies have shown a link between bipolar disorder and cancer. Whether the elevated risk of malignancy extends to family members without the mental health condition has not been elucidated.

To investigate, the researchers turned to the National Health Insurance Research Database of Taiwan. They identified 25,356 individuals diagnosed with bipolar disorder by a psychiatrist between 1996 and 2010 and the same number of unaffected siblings, as well as more than 100,000 age-, sex-, income-, and residence-matched controls without severe mental illness.

Compared with the control group, people with bipolar disorder (odds ratio, 1.22) and their unaffected siblings (OR, 1.17) both had a higher risk of developing malignant cancer of any kind. The researchers also found that both groups were at higher risk for breast cancer, with odds ratios of 1.98 in individuals with bipolar disorder and 1.73 in their unaffected siblings.

However, the risk of skin cancer was only high in people with bipolar disorder (OR, 2.70) and not in their siblings (OR, 0.62). And conversely, the risk of kidney cancer was significantly increased in unaffected siblings (OR, 2.45) but not in people with bipolar disorder (OR, 0.47).

When stratified by the embryonic developmental layer from which tumors had originated – ectodermal, mesodermal, or endodermal – the authors observed a significantly increased risk for only ectodermal cancers. In addition, only people under age 50 in both groups (OR, 1.90 for those with bipolar disorder; OR, 1.65 for siblings) were more likely to develop an ectodermal cancer, especially of the breast, compared with the control group. The risks remained elevated after excluding breast cancer but were no longer significant.

When stratified by age, the risk of developing any cancer in both groups also only appeared to be greater for those under age 50 (OR, 1.34 in people with bipolar disorder; OR, 1.32 in siblings) compared with those aged 50 and over (OR, 0.97 and 0.99, respectively). The authors highlighted these figures in the supplemental data set but did not discuss it further in the study beyond a brief mention that “younger patients with bipolar disorder and younger unaffected siblings (< 50 years), but not older ones (≥ 50 years), were more likely to develop any malignancy during the follow-up than matched controls.”

“This paper essentially finds what we have found in our previous work – that people with bipolar disorder have a greater risk of cancer,” said Michael Berk, MBBCh, PhD, a professor of psychiatry at the Deakin University School of Medicine in Geelong, Australia, who published a systematic review and meta-analysis last spring on cancer risk and the role of lithium treatment in bipolar disorder.

“The interesting finding in our work,” Dr. Berk told this news organization, “is that this risk is attenuated by use of lithium but not other agents.”

The Taiwanese researchers propose a “biopsychosocial explanation” for their results, noting that both the nervous system and the breast and skin develop from the ectoderm, and that cancer risk factors such as smoking and obesity are more common in people with bipolar disorder and their unaffected siblings.

“The findings,” they write, “imply a genetic overlap in neurodevelopment and malignancy pathogenesis and may encourage clinicians to closely monitor patients with bipolar disorder and their unaffected siblings for cancer warning signs.”

The authors, however, caution that their study needs validation and had several limitations, including lack of adjustment for drug treatment and lifestyle and environmental factors.

“Our findings may persuade clinicians and researchers to reevaluate the cancer risk among the unaffected siblings of patients with schizophrenia and bipolar disorder because these two severe mental disorders may have a common biopsychosocial pathophysiology,” the team writes.

The study was supported by a grant from Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan.

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

People with bipolar disorder as well as their unaffected siblings appear to be at increased risk for cancer, particularly of the breast, according to new research from Taiwan.

“To our knowledge, our study is the first to report an increased overall cancer risk as well as increased risks of breast and ectodermal cancer among the unaffected siblings aged < 50 years of patients with bipolar disorder,” Ya-Mei Bai, MD, PhD, of National Yang-Ming University, Taipei, Taiwan, and colleagues write in an article published online in the International Journal of Cancer.

Most, but not all, previous studies have shown a link between bipolar disorder and cancer. Whether the elevated risk of malignancy extends to family members without the mental health condition has not been elucidated.

To investigate, the researchers turned to the National Health Insurance Research Database of Taiwan. They identified 25,356 individuals diagnosed with bipolar disorder by a psychiatrist between 1996 and 2010 and the same number of unaffected siblings, as well as more than 100,000 age-, sex-, income-, and residence-matched controls without severe mental illness.

Compared with the control group, people with bipolar disorder (odds ratio, 1.22) and their unaffected siblings (OR, 1.17) both had a higher risk of developing malignant cancer of any kind. The researchers also found that both groups were at higher risk for breast cancer, with odds ratios of 1.98 in individuals with bipolar disorder and 1.73 in their unaffected siblings.

However, the risk of skin cancer was only high in people with bipolar disorder (OR, 2.70) and not in their siblings (OR, 0.62). And conversely, the risk of kidney cancer was significantly increased in unaffected siblings (OR, 2.45) but not in people with bipolar disorder (OR, 0.47).

When stratified by the embryonic developmental layer from which tumors had originated – ectodermal, mesodermal, or endodermal – the authors observed a significantly increased risk for only ectodermal cancers. In addition, only people under age 50 in both groups (OR, 1.90 for those with bipolar disorder; OR, 1.65 for siblings) were more likely to develop an ectodermal cancer, especially of the breast, compared with the control group. The risks remained elevated after excluding breast cancer but were no longer significant.

When stratified by age, the risk of developing any cancer in both groups also only appeared to be greater for those under age 50 (OR, 1.34 in people with bipolar disorder; OR, 1.32 in siblings) compared with those aged 50 and over (OR, 0.97 and 0.99, respectively). The authors highlighted these figures in the supplemental data set but did not discuss it further in the study beyond a brief mention that “younger patients with bipolar disorder and younger unaffected siblings (< 50 years), but not older ones (≥ 50 years), were more likely to develop any malignancy during the follow-up than matched controls.”

“This paper essentially finds what we have found in our previous work – that people with bipolar disorder have a greater risk of cancer,” said Michael Berk, MBBCh, PhD, a professor of psychiatry at the Deakin University School of Medicine in Geelong, Australia, who published a systematic review and meta-analysis last spring on cancer risk and the role of lithium treatment in bipolar disorder.

“The interesting finding in our work,” Dr. Berk told this news organization, “is that this risk is attenuated by use of lithium but not other agents.”

The Taiwanese researchers propose a “biopsychosocial explanation” for their results, noting that both the nervous system and the breast and skin develop from the ectoderm, and that cancer risk factors such as smoking and obesity are more common in people with bipolar disorder and their unaffected siblings.

“The findings,” they write, “imply a genetic overlap in neurodevelopment and malignancy pathogenesis and may encourage clinicians to closely monitor patients with bipolar disorder and their unaffected siblings for cancer warning signs.”

The authors, however, caution that their study needs validation and had several limitations, including lack of adjustment for drug treatment and lifestyle and environmental factors.

“Our findings may persuade clinicians and researchers to reevaluate the cancer risk among the unaffected siblings of patients with schizophrenia and bipolar disorder because these two severe mental disorders may have a common biopsychosocial pathophysiology,” the team writes.

The study was supported by a grant from Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan.

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

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Measurement of the rate of cellular amyloid uptake and metabolic production of toxic amyloid species could be used as novel biomarkers for early and/or differential diagnosis of Alzheimer’s disease (AD).
• Estimated beta-amyloid (Aβ42) cellular uptake can be more than two times greater in AD patients compared to cognitively normal subjects. A less pronounced yet increased uptake rate was also observed in patients with late-onset mild cognitive impairment (MCI). This increased uptake may prove to be a key mechanism defining age-related AD progression.
• The increased cellular amyloid uptake in AD and LMCI may lead to quicker disease progression, but early-onset MCI may result from increased production of toxic amyloid metabolites.

Why this matters

• Additional biomarkers for AD could greatly aid diagnosis and course prediction, as they are currently limited to PET scan analysis of amyloid plaque deposits and concentration of Aβ42 in cerebrospinal fluid (CSF).
• Amyloid deposits found by PET have a positive correlation with AD diagnosis. In contrast, CSF-Aβ42 and AD diagnosis or cognitive decline are negatively correlated. Normal cognition (NC) is associated with higher CSF beta-amyloid levels, but previous research has not explained why CSF-Aβ42 levels can be equivalent in patients with NC but high amyloid load and patients with AD and low amyloid load.

Study design

• The authors of this retrospective study used anonymized data obtained from the Alzheimer’s’s Disease Neuroimaging Initiative (ADNI). ADNI’s goal has been to test whether serial MRI scans, PET scans, biomarkers, and clinical/neuropsychological assessment can be combined to measure the progression of MCI and AD.
• Study subjects had either an AD diagnosis or NC and were divided into two groups: low amyloid load and high amyloid load. The fraction of patients with an AD diagnosis was calculated as a function of CSF-Aβ42.
• Calculations and statistical comparisons were performed using Microsoft Excel and custom-written C++ programs.

Key results

• The lowest levels of CSF-Aβ42 correlated with the highest percentage of AD-diagnosed patients, estimated to be 27% in subjects with low amyloid deposit density and 65% in those with high deposit density.
• The relationship between CSF-Aβ42 levels and amyloid load can be described using a simple mathematical model: Amyloid concentration in the interstitial cells is equal to the synthesis rate divided by the density of amyloid deposits plus the sum of the rate of amyloid removal through the CSF and the cellular amyloid uptake rate.
• AD and late-onset MCI patients had a significantly higher amyloid removal rate compared to NC subjects.
• Early-onset MCI patients had Aβ42 turnover similar to that of NC subjects, pointing to a different underlying mechanism such as enzymatic disbalance.

Limitations

• The model used to explain amyloid exchange between the interstitial space and the CSF is oversimplified; the actual process is more complex.
• Synthesis and uptake rates of Aβ42 vary throughout areas of the brain. The model assumes a homogeneous distribution within the interstitial compartment.

Study disclosures

• Research reported in this publication was not supported by any external funding. Data collection and sharing for this project were funded by ADNI.

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

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Measurement of the rate of cellular amyloid uptake and metabolic production of toxic amyloid species could be used as novel biomarkers for early and/or differential diagnosis of Alzheimer’s disease (AD).
• Estimated beta-amyloid (Aβ42) cellular uptake can be more than two times greater in AD patients compared to cognitively normal subjects. A less pronounced yet increased uptake rate was also observed in patients with late-onset mild cognitive impairment (MCI). This increased uptake may prove to be a key mechanism defining age-related AD progression.
• The increased cellular amyloid uptake in AD and LMCI may lead to quicker disease progression, but early-onset MCI may result from increased production of toxic amyloid metabolites.

Why this matters

• Additional biomarkers for AD could greatly aid diagnosis and course prediction, as they are currently limited to PET scan analysis of amyloid plaque deposits and concentration of Aβ42 in cerebrospinal fluid (CSF).
• Amyloid deposits found by PET have a positive correlation with AD diagnosis. In contrast, CSF-Aβ42 and AD diagnosis or cognitive decline are negatively correlated. Normal cognition (NC) is associated with higher CSF beta-amyloid levels, but previous research has not explained why CSF-Aβ42 levels can be equivalent in patients with NC but high amyloid load and patients with AD and low amyloid load.

Study design

• The authors of this retrospective study used anonymized data obtained from the Alzheimer’s’s Disease Neuroimaging Initiative (ADNI). ADNI’s goal has been to test whether serial MRI scans, PET scans, biomarkers, and clinical/neuropsychological assessment can be combined to measure the progression of MCI and AD.
• Study subjects had either an AD diagnosis or NC and were divided into two groups: low amyloid load and high amyloid load. The fraction of patients with an AD diagnosis was calculated as a function of CSF-Aβ42.
• Calculations and statistical comparisons were performed using Microsoft Excel and custom-written C++ programs.

Key results

• The lowest levels of CSF-Aβ42 correlated with the highest percentage of AD-diagnosed patients, estimated to be 27% in subjects with low amyloid deposit density and 65% in those with high deposit density.
• The relationship between CSF-Aβ42 levels and amyloid load can be described using a simple mathematical model: Amyloid concentration in the interstitial cells is equal to the synthesis rate divided by the density of amyloid deposits plus the sum of the rate of amyloid removal through the CSF and the cellular amyloid uptake rate.
• AD and late-onset MCI patients had a significantly higher amyloid removal rate compared to NC subjects.
• Early-onset MCI patients had Aβ42 turnover similar to that of NC subjects, pointing to a different underlying mechanism such as enzymatic disbalance.

Limitations

• The model used to explain amyloid exchange between the interstitial space and the CSF is oversimplified; the actual process is more complex.
• Synthesis and uptake rates of Aβ42 vary throughout areas of the brain. The model assumes a homogeneous distribution within the interstitial compartment.

Study disclosures

• Research reported in this publication was not supported by any external funding. Data collection and sharing for this project were funded by ADNI.

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

The study covered in this summary was published in medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaways

• Measurement of the rate of cellular amyloid uptake and metabolic production of toxic amyloid species could be used as novel biomarkers for early and/or differential diagnosis of Alzheimer’s disease (AD).
• Estimated beta-amyloid (Aβ42) cellular uptake can be more than two times greater in AD patients compared to cognitively normal subjects. A less pronounced yet increased uptake rate was also observed in patients with late-onset mild cognitive impairment (MCI). This increased uptake may prove to be a key mechanism defining age-related AD progression.
• The increased cellular amyloid uptake in AD and LMCI may lead to quicker disease progression, but early-onset MCI may result from increased production of toxic amyloid metabolites.

Why this matters

• Additional biomarkers for AD could greatly aid diagnosis and course prediction, as they are currently limited to PET scan analysis of amyloid plaque deposits and concentration of Aβ42 in cerebrospinal fluid (CSF).
• Amyloid deposits found by PET have a positive correlation with AD diagnosis. In contrast, CSF-Aβ42 and AD diagnosis or cognitive decline are negatively correlated. Normal cognition (NC) is associated with higher CSF beta-amyloid levels, but previous research has not explained why CSF-Aβ42 levels can be equivalent in patients with NC but high amyloid load and patients with AD and low amyloid load.

Study design

• The authors of this retrospective study used anonymized data obtained from the Alzheimer’s’s Disease Neuroimaging Initiative (ADNI). ADNI’s goal has been to test whether serial MRI scans, PET scans, biomarkers, and clinical/neuropsychological assessment can be combined to measure the progression of MCI and AD.
• Study subjects had either an AD diagnosis or NC and were divided into two groups: low amyloid load and high amyloid load. The fraction of patients with an AD diagnosis was calculated as a function of CSF-Aβ42.
• Calculations and statistical comparisons were performed using Microsoft Excel and custom-written C++ programs.

Key results

• The lowest levels of CSF-Aβ42 correlated with the highest percentage of AD-diagnosed patients, estimated to be 27% in subjects with low amyloid deposit density and 65% in those with high deposit density.
• The relationship between CSF-Aβ42 levels and amyloid load can be described using a simple mathematical model: Amyloid concentration in the interstitial cells is equal to the synthesis rate divided by the density of amyloid deposits plus the sum of the rate of amyloid removal through the CSF and the cellular amyloid uptake rate.
• AD and late-onset MCI patients had a significantly higher amyloid removal rate compared to NC subjects.
• Early-onset MCI patients had Aβ42 turnover similar to that of NC subjects, pointing to a different underlying mechanism such as enzymatic disbalance.

Limitations

• The model used to explain amyloid exchange between the interstitial space and the CSF is oversimplified; the actual process is more complex.
• Synthesis and uptake rates of Aβ42 vary throughout areas of the brain. The model assumes a homogeneous distribution within the interstitial compartment.

Study disclosures

• Research reported in this publication was not supported by any external funding. Data collection and sharing for this project were funded by ADNI.

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

Scientists at Newcastle University (England) have identified the mechanism for skin cancer growth.

Their research, published in the British Journal of Dermatology, describes how early-stage melanomas at risk of spreading secrete transforming growth factor beta₂ (TGF-beta₂), which causes the reduction, or down-regulation, of the proteins AMBRA1 and loricrin, both of which are found in the skin overlaying the tumor. TGF-beta₂ also causes the loss of claudin-1, which in turn leads to loss of skin integrity, facilitating ulceration.

Senior author Penny Lovat, PhD, professor of cellular dermatology and oncology at Newcastle University, and chief scientific officer at AMLo Biosciences, explained: “AMBRA1, loricrin, and claudin-1 are all proteins key to maintaining the integrity of the upper layer of the skin,” and that the loss of these proteins causes gaps to develop, allowing the tumor to spread and ulcerate – a process associated with high-risk tumors. Dr. Lovat likened the process to that of “mortar and bricks holding together a wall”, with the loss of these proteins being “like the mortar crumbling away in the wall.”

According to Cancer Research UK, there are over 16,000 new cases of melanoma skin cancer each year in the United Kingdom, with over 2,000 deaths annually. After being surgically removed, primary tumors are histologically staged, with even low-risk cases being followed up for a number of years, a process that can be time-consuming for patients and costly for the NHS.
 

Some reassurance for those with melanoma

The creators of the new test say that it is these low-risk patients that the test is able to identify, offering a degree of reassurance to those diagnosed with the disease, and potentially reducing the number of hospital clinic visits they require.

Dr. Lovat commented: “Our test offers a personalized prognosis as it more accurately predicts if your skin cancer is unlikely to spread.”

She added that the test will aid clinicians to identify genuinely low-risk patients diagnosed with an early-stage melanoma, reducing the number of follow-up appointments for those identified as low risk. It, therefore, offers the opportunity to save the NHS time and money.
 

Excellent news for those with skin cancer

Phil Brady, chief operating officer of the British Skin Foundation, echoed Dr. Lovat’s comments, saying: “The test can alleviate stress and anxiety for patients caused by this potentially deadly skin cancer, whilst increasing efficiency and reducing costs to the NHS.”

Nick Levell, MD, consultant dermatologist & British Skin Foundation spokesperson, who has not been involved in the research, commented how the arrival of the test was “excellent news,” adding that “people at low risk can be reassured and will not have to attend hospital so often for check-ups”.

The development of the new test AMBLor has been led by Dr. Lovat, in association with the university spin-out company AMLo Biosciences, and is accredited by the National Accreditation Body for the United Kingdom. The test involves tissue sections from the standard biopsy being sent in the post to the lab for analysis and costs £293 plus VAT. Currently available through a private referral service, the Newcastle team have applied for the test to be made available on the NHS.

A version of this article first appeared on Medscape UK.

Scientists at Newcastle University (England) have identified the mechanism for skin cancer growth.

Their research, published in the British Journal of Dermatology, describes how early-stage melanomas at risk of spreading secrete transforming growth factor beta₂ (TGF-beta₂), which causes the reduction, or down-regulation, of the proteins AMBRA1 and loricrin, both of which are found in the skin overlaying the tumor. TGF-beta₂ also causes the loss of claudin-1, which in turn leads to loss of skin integrity, facilitating ulceration.

Senior author Penny Lovat, PhD, professor of cellular dermatology and oncology at Newcastle University, and chief scientific officer at AMLo Biosciences, explained: “AMBRA1, loricrin, and claudin-1 are all proteins key to maintaining the integrity of the upper layer of the skin,” and that the loss of these proteins causes gaps to develop, allowing the tumor to spread and ulcerate – a process associated with high-risk tumors. Dr. Lovat likened the process to that of “mortar and bricks holding together a wall”, with the loss of these proteins being “like the mortar crumbling away in the wall.”

According to Cancer Research UK, there are over 16,000 new cases of melanoma skin cancer each year in the United Kingdom, with over 2,000 deaths annually. After being surgically removed, primary tumors are histologically staged, with even low-risk cases being followed up for a number of years, a process that can be time-consuming for patients and costly for the NHS.
 

Some reassurance for those with melanoma

The creators of the new test say that it is these low-risk patients that the test is able to identify, offering a degree of reassurance to those diagnosed with the disease, and potentially reducing the number of hospital clinic visits they require.

Dr. Lovat commented: “Our test offers a personalized prognosis as it more accurately predicts if your skin cancer is unlikely to spread.”

She added that the test will aid clinicians to identify genuinely low-risk patients diagnosed with an early-stage melanoma, reducing the number of follow-up appointments for those identified as low risk. It, therefore, offers the opportunity to save the NHS time and money.
 

Excellent news for those with skin cancer

Phil Brady, chief operating officer of the British Skin Foundation, echoed Dr. Lovat’s comments, saying: “The test can alleviate stress and anxiety for patients caused by this potentially deadly skin cancer, whilst increasing efficiency and reducing costs to the NHS.”

Nick Levell, MD, consultant dermatologist & British Skin Foundation spokesperson, who has not been involved in the research, commented how the arrival of the test was “excellent news,” adding that “people at low risk can be reassured and will not have to attend hospital so often for check-ups”.

The development of the new test AMBLor has been led by Dr. Lovat, in association with the university spin-out company AMLo Biosciences, and is accredited by the National Accreditation Body for the United Kingdom. The test involves tissue sections from the standard biopsy being sent in the post to the lab for analysis and costs £293 plus VAT. Currently available through a private referral service, the Newcastle team have applied for the test to be made available on the NHS.

A version of this article first appeared on Medscape UK.

Scientists at Newcastle University (England) have identified the mechanism for skin cancer growth.

Their research, published in the British Journal of Dermatology, describes how early-stage melanomas at risk of spreading secrete transforming growth factor beta₂ (TGF-beta₂), which causes the reduction, or down-regulation, of the proteins AMBRA1 and loricrin, both of which are found in the skin overlaying the tumor. TGF-beta₂ also causes the loss of claudin-1, which in turn leads to loss of skin integrity, facilitating ulceration.

Senior author Penny Lovat, PhD, professor of cellular dermatology and oncology at Newcastle University, and chief scientific officer at AMLo Biosciences, explained: “AMBRA1, loricrin, and claudin-1 are all proteins key to maintaining the integrity of the upper layer of the skin,” and that the loss of these proteins causes gaps to develop, allowing the tumor to spread and ulcerate – a process associated with high-risk tumors. Dr. Lovat likened the process to that of “mortar and bricks holding together a wall”, with the loss of these proteins being “like the mortar crumbling away in the wall.”

According to Cancer Research UK, there are over 16,000 new cases of melanoma skin cancer each year in the United Kingdom, with over 2,000 deaths annually. After being surgically removed, primary tumors are histologically staged, with even low-risk cases being followed up for a number of years, a process that can be time-consuming for patients and costly for the NHS.
 

Some reassurance for those with melanoma

The creators of the new test say that it is these low-risk patients that the test is able to identify, offering a degree of reassurance to those diagnosed with the disease, and potentially reducing the number of hospital clinic visits they require.

Dr. Lovat commented: “Our test offers a personalized prognosis as it more accurately predicts if your skin cancer is unlikely to spread.”

She added that the test will aid clinicians to identify genuinely low-risk patients diagnosed with an early-stage melanoma, reducing the number of follow-up appointments for those identified as low risk. It, therefore, offers the opportunity to save the NHS time and money.
 

Excellent news for those with skin cancer

Phil Brady, chief operating officer of the British Skin Foundation, echoed Dr. Lovat’s comments, saying: “The test can alleviate stress and anxiety for patients caused by this potentially deadly skin cancer, whilst increasing efficiency and reducing costs to the NHS.”

Nick Levell, MD, consultant dermatologist & British Skin Foundation spokesperson, who has not been involved in the research, commented how the arrival of the test was “excellent news,” adding that “people at low risk can be reassured and will not have to attend hospital so often for check-ups”.

The development of the new test AMBLor has been led by Dr. Lovat, in association with the university spin-out company AMLo Biosciences, and is accredited by the National Accreditation Body for the United Kingdom. The test involves tissue sections from the standard biopsy being sent in the post to the lab for analysis and costs £293 plus VAT. Currently available through a private referral service, the Newcastle team have applied for the test to be made available on the NHS.

A version of this article first appeared on Medscape UK.

Black patients hospitalized with skin and soft-tissue infections were more likely to receive clindamycin and less likely to receive cefazolin – the latter of which is considered a first-line SSTI treatment – in a national cross-sectional study involving over 1,000 patients in 91 hospitals.

The potential racial disparity in management of SSTI was detected after data were adjusted for penicillin allergy history and for MRSA colonization/infection. The data were also adjusted for hospital day (since admission) in order to control for the administration of more empiric therapy early on.

Massachusetts General Hospital

Clindamycin, a beta-lactam alternative, is not recommended as an SSTI treatment given its frequent dosing requirements and high potential for adverse events including Clostridioides difficile infection (DCI). “Clindamycin is an option but it’s considered inferior. ... It covers MRSA but it shouldn’t be a go-to for skin and soft-tissue infections,” said senior author Kimberly Blumenthal, MD, MSc, assistant professor of medicine at Harvard University, and an allergist, immunologist, and drug allergy and epidemiology researcher at Massachusetts General Hospital, both in Boston.

Cefazolin, on the other hand, does not cover MRSA but is “a guideline-recommended first-line antibiotic for cellulitis SSTI in the hospital,” she said in an interview.

The findings, recently published in JAMA Network Open, offer a valuable portrait of the antibiotics being prescribed in the inpatient setting for SSTIs. Vancomycin, which typically is reserved for MRSA, was the most commonly prescribed antibiotic, regardless of race. Piperacillin-tazobactam, a beta-lactam, was the second most commonly prescribed antibiotic, again regardless of race.

Intravenously administered cefazolin was used in 13% of White inpatients versus 5% of Black inpatients. After controlling for kidney disease, diabetes, and ICU location (in addition to hospital day, penicillin allergy history, and MRSA), White inpatients had an increased likelihood of being prescribed cefazolin (adjusted odds ratio, 2.82; 95% confidence interval, 1.41-5.63) and a decreased likelihood of clindamycin use (aOR, 0.54; 95% CI, 0.30-0.96), compared with Black inpatients.

The investigators utilized the Acute Care Hospital Groups network within Vizient, a member-driven health care performance improvement company, to collect data for the study. Most of the hospitals (91%) that submitted data on adult inpatients with cellulitis or SSTIs (without other infections) were in urban settings and 9% were in rural settings; 60% were community hospitals and 40% were academic medical centers. The researchers accounted for “clustering by hospital” – such as the use of internal guidelines – in their methodology.

Black patients hospitalized with skin and soft-tissue infections were more likely to receive clindamycin and less likely to receive cefazolin – the latter of which is considered a first-line SSTI treatment – in a national cross-sectional study involving over 1,000 patients in 91 hospitals.

The potential racial disparity in management of SSTI was detected after data were adjusted for penicillin allergy history and for MRSA colonization/infection. The data were also adjusted for hospital day (since admission) in order to control for the administration of more empiric therapy early on.

Massachusetts General Hospital

Clindamycin, a beta-lactam alternative, is not recommended as an SSTI treatment given its frequent dosing requirements and high potential for adverse events including Clostridioides difficile infection (DCI). “Clindamycin is an option but it’s considered inferior. ... It covers MRSA but it shouldn’t be a go-to for skin and soft-tissue infections,” said senior author Kimberly Blumenthal, MD, MSc, assistant professor of medicine at Harvard University, and an allergist, immunologist, and drug allergy and epidemiology researcher at Massachusetts General Hospital, both in Boston.

Cefazolin, on the other hand, does not cover MRSA but is “a guideline-recommended first-line antibiotic for cellulitis SSTI in the hospital,” she said in an interview.

The findings, recently published in JAMA Network Open, offer a valuable portrait of the antibiotics being prescribed in the inpatient setting for SSTIs. Vancomycin, which typically is reserved for MRSA, was the most commonly prescribed antibiotic, regardless of race. Piperacillin-tazobactam, a beta-lactam, was the second most commonly prescribed antibiotic, again regardless of race.

Intravenously administered cefazolin was used in 13% of White inpatients versus 5% of Black inpatients. After controlling for kidney disease, diabetes, and ICU location (in addition to hospital day, penicillin allergy history, and MRSA), White inpatients had an increased likelihood of being prescribed cefazolin (adjusted odds ratio, 2.82; 95% confidence interval, 1.41-5.63) and a decreased likelihood of clindamycin use (aOR, 0.54; 95% CI, 0.30-0.96), compared with Black inpatients.

The investigators utilized the Acute Care Hospital Groups network within Vizient, a member-driven health care performance improvement company, to collect data for the study. Most of the hospitals (91%) that submitted data on adult inpatients with cellulitis or SSTIs (without other infections) were in urban settings and 9% were in rural settings; 60% were community hospitals and 40% were academic medical centers. The researchers accounted for “clustering by hospital” – such as the use of internal guidelines – in their methodology.

Black patients hospitalized with skin and soft-tissue infections were more likely to receive clindamycin and less likely to receive cefazolin – the latter of which is considered a first-line SSTI treatment – in a national cross-sectional study involving over 1,000 patients in 91 hospitals.

The potential racial disparity in management of SSTI was detected after data were adjusted for penicillin allergy history and for MRSA colonization/infection. The data were also adjusted for hospital day (since admission) in order to control for the administration of more empiric therapy early on.

Massachusetts General Hospital

Clindamycin, a beta-lactam alternative, is not recommended as an SSTI treatment given its frequent dosing requirements and high potential for adverse events including Clostridioides difficile infection (DCI). “Clindamycin is an option but it’s considered inferior. ... It covers MRSA but it shouldn’t be a go-to for skin and soft-tissue infections,” said senior author Kimberly Blumenthal, MD, MSc, assistant professor of medicine at Harvard University, and an allergist, immunologist, and drug allergy and epidemiology researcher at Massachusetts General Hospital, both in Boston.

Cefazolin, on the other hand, does not cover MRSA but is “a guideline-recommended first-line antibiotic for cellulitis SSTI in the hospital,” she said in an interview.

The findings, recently published in JAMA Network Open, offer a valuable portrait of the antibiotics being prescribed in the inpatient setting for SSTIs. Vancomycin, which typically is reserved for MRSA, was the most commonly prescribed antibiotic, regardless of race. Piperacillin-tazobactam, a beta-lactam, was the second most commonly prescribed antibiotic, again regardless of race.

Intravenously administered cefazolin was used in 13% of White inpatients versus 5% of Black inpatients. After controlling for kidney disease, diabetes, and ICU location (in addition to hospital day, penicillin allergy history, and MRSA), White inpatients had an increased likelihood of being prescribed cefazolin (adjusted odds ratio, 2.82; 95% confidence interval, 1.41-5.63) and a decreased likelihood of clindamycin use (aOR, 0.54; 95% CI, 0.30-0.96), compared with Black inpatients.

The investigators utilized the Acute Care Hospital Groups network within Vizient, a member-driven health care performance improvement company, to collect data for the study. Most of the hospitals (91%) that submitted data on adult inpatients with cellulitis or SSTIs (without other infections) were in urban settings and 9% were in rural settings; 60% were community hospitals and 40% were academic medical centers. The researchers accounted for “clustering by hospital” – such as the use of internal guidelines – in their methodology.

Real-World Experience With Automated Insulin Pumps

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• Diabetes Self-Management Education

• SGLT2 Inhibitors, T2DM, and Heart Failure

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• K Pneumoniae-Induced Aortitis

Read now 

Real-World Experience With Automated Insulin Pumps

Continuous Blood Glucose Monitoring for T2DM

Statin-Induced Adverse Effects

Long QT and Cardiac Arrest After Pulmonary Edema

And more online

• Clinical Impact of U-500 Insulin Initiation

• Diabetes Self-Management Education

• SGLT2 Inhibitors, T2DM, and Heart Failure

• Alirocumab Use in Statin-Intolerant Veterans

• K Pneumoniae-Induced Aortitis

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One of the unexpected consequences of the pandemic is that many people are rethinking their priorities and lifestyles, and physicians are no exception.

This year’s Medscape Physician Lifestyle and Happiness Report surveyed more than 10,000 physicians in 29 specialties about how they are prioritizing wellness, work-life balance, and their family lives during this challenging time.

Pets, prayer, and partners

The pandemic has taken a toll on physicians outside of work as well as on the job. Eight in 10 physicians (82% of men and 80% of women) said they were “somewhat” or “very” happy outside of work before the pandemic. This is almost exactly the same result as in last year’s survey.

However, when asked how happy they are outside of work currently, only 6 in 10 (59%) reported being “somewhat” or “very” happy. While the pandemic has made life difficult for everyone, health care professionals face particular stresses even outside of work. Wayne M. Sotile, PhD, founder of the Center for Physician Resilience, says he has counseled doctors who witnessed COVID-related suffering and death at work, then came home to a partner who didn’t believe that the pandemic was real.

Still, physicians reported that spending time with people they love and engaging in favorite activities helps them stay happy. “Spending time with pets” and “religious practice/prayer” were frequent “other” responses to the question, “What do you do to maintain happiness and mental health?” Seven in 10 physicians reported having some kind of religious or spiritual beliefs.

The majority of physicians (83%) are either married or living with a partner, with male physicians edging out their female peers (89% vs. 75%). Among married physicians, 8 in 10 physicians reported that their union is “good” or “very good.” The pandemic may have helped in this respect. Dr. Sotile says he’s heard physicians say that they’ve connected more with their families in the past 18 months. Specialists with the highest rates of happy marriages were otolaryngologists and immunologists (both 91%), followed closely by dermatologists, rheumatologists, and nephrologists (all 90%).

Among physicians balancing a medical career and parenthood, female physicians reported feeling conflicted more often than males (48% vs. 29%). Nicole A. Sparks, MD, an ob.gyn. and a health and lifestyle blogger, cites not being there for her kids as a source of stress. She notes that her two young children notice when she’s not there to help with homework, read bedtime stories, or make their dinner. “Mom guilt can definitely set in if I have to miss important events,” she says.

Work-life balance is an important, if elusive, goal for physicians, and not just females. Sixty percent of female doctors and 53% of male doctors said they would be willing to take a cut in pay if it meant more free time and a better work-life balance. Many doctors do manage to get away from work occasionally, with one-fifth of all physicians taking 5 or more weeks of vacation each year.

Seeking a ‘balanced life’

Alexis Polles, MD, medical director for the Professionals Resource Network, points out the importance of taking time for personal health and wellness. “When we work with professionals who have problems with mental health or substance abuse, they often don’t have a balanced life,” she says. “They are usually in a workaholic mindset and disregard their own needs.”

Few physicians seem to prioritize self-care, with a third indicating they “always” or “most of the time” spend enough time on their own health and wellness. But of those who do, males (38%) are more likely than females (27%) to spend enough time on their own health and wellness. Dr. Polles adds that exercising after a shift can help physicians better make the transition from professional to personal life. Though they did not report when they exercised, about a third of physicians reported doing so four or more times per week. Controlling weight is an issue as well, with 49% of male and 55% of female physicians saying they are currently trying to lose weight.

Of physicians who drink alcohol, about a third have three or more drinks per week. (The CDC defines “heavy drinking” as consuming 15 drinks or more per week for men and eight drinks or more per week for women.)

Of those surveyed, 92% say they do not regularly use cannabidiol or cannabis, and a mere 4% of respondents said they would use at least one of these substances if they were to become legal in their state.

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

One of the unexpected consequences of the pandemic is that many people are rethinking their priorities and lifestyles, and physicians are no exception.

This year’s Medscape Physician Lifestyle and Happiness Report surveyed more than 10,000 physicians in 29 specialties about how they are prioritizing wellness, work-life balance, and their family lives during this challenging time.

Pets, prayer, and partners

The pandemic has taken a toll on physicians outside of work as well as on the job. Eight in 10 physicians (82% of men and 80% of women) said they were “somewhat” or “very” happy outside of work before the pandemic. This is almost exactly the same result as in last year’s survey.

However, when asked how happy they are outside of work currently, only 6 in 10 (59%) reported being “somewhat” or “very” happy. While the pandemic has made life difficult for everyone, health care professionals face particular stresses even outside of work. Wayne M. Sotile, PhD, founder of the Center for Physician Resilience, says he has counseled doctors who witnessed COVID-related suffering and death at work, then came home to a partner who didn’t believe that the pandemic was real.

Still, physicians reported that spending time with people they love and engaging in favorite activities helps them stay happy. “Spending time with pets” and “religious practice/prayer” were frequent “other” responses to the question, “What do you do to maintain happiness and mental health?” Seven in 10 physicians reported having some kind of religious or spiritual beliefs.

The majority of physicians (83%) are either married or living with a partner, with male physicians edging out their female peers (89% vs. 75%). Among married physicians, 8 in 10 physicians reported that their union is “good” or “very good.” The pandemic may have helped in this respect. Dr. Sotile says he’s heard physicians say that they’ve connected more with their families in the past 18 months. Specialists with the highest rates of happy marriages were otolaryngologists and immunologists (both 91%), followed closely by dermatologists, rheumatologists, and nephrologists (all 90%).

Among physicians balancing a medical career and parenthood, female physicians reported feeling conflicted more often than males (48% vs. 29%). Nicole A. Sparks, MD, an ob.gyn. and a health and lifestyle blogger, cites not being there for her kids as a source of stress. She notes that her two young children notice when she’s not there to help with homework, read bedtime stories, or make their dinner. “Mom guilt can definitely set in if I have to miss important events,” she says.

Work-life balance is an important, if elusive, goal for physicians, and not just females. Sixty percent of female doctors and 53% of male doctors said they would be willing to take a cut in pay if it meant more free time and a better work-life balance. Many doctors do manage to get away from work occasionally, with one-fifth of all physicians taking 5 or more weeks of vacation each year.

Seeking a ‘balanced life’

Alexis Polles, MD, medical director for the Professionals Resource Network, points out the importance of taking time for personal health and wellness. “When we work with professionals who have problems with mental health or substance abuse, they often don’t have a balanced life,” she says. “They are usually in a workaholic mindset and disregard their own needs.”

Few physicians seem to prioritize self-care, with a third indicating they “always” or “most of the time” spend enough time on their own health and wellness. But of those who do, males (38%) are more likely than females (27%) to spend enough time on their own health and wellness. Dr. Polles adds that exercising after a shift can help physicians better make the transition from professional to personal life. Though they did not report when they exercised, about a third of physicians reported doing so four or more times per week. Controlling weight is an issue as well, with 49% of male and 55% of female physicians saying they are currently trying to lose weight.

Of physicians who drink alcohol, about a third have three or more drinks per week. (The CDC defines “heavy drinking” as consuming 15 drinks or more per week for men and eight drinks or more per week for women.)

Of those surveyed, 92% say they do not regularly use cannabidiol or cannabis, and a mere 4% of respondents said they would use at least one of these substances if they were to become legal in their state.

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

One of the unexpected consequences of the pandemic is that many people are rethinking their priorities and lifestyles, and physicians are no exception.

This year’s Medscape Physician Lifestyle and Happiness Report surveyed more than 10,000 physicians in 29 specialties about how they are prioritizing wellness, work-life balance, and their family lives during this challenging time.

Pets, prayer, and partners

The pandemic has taken a toll on physicians outside of work as well as on the job. Eight in 10 physicians (82% of men and 80% of women) said they were “somewhat” or “very” happy outside of work before the pandemic. This is almost exactly the same result as in last year’s survey.

However, when asked how happy they are outside of work currently, only 6 in 10 (59%) reported being “somewhat” or “very” happy. While the pandemic has made life difficult for everyone, health care professionals face particular stresses even outside of work. Wayne M. Sotile, PhD, founder of the Center for Physician Resilience, says he has counseled doctors who witnessed COVID-related suffering and death at work, then came home to a partner who didn’t believe that the pandemic was real.

Still, physicians reported that spending time with people they love and engaging in favorite activities helps them stay happy. “Spending time with pets” and “religious practice/prayer” were frequent “other” responses to the question, “What do you do to maintain happiness and mental health?” Seven in 10 physicians reported having some kind of religious or spiritual beliefs.

The majority of physicians (83%) are either married or living with a partner, with male physicians edging out their female peers (89% vs. 75%). Among married physicians, 8 in 10 physicians reported that their union is “good” or “very good.” The pandemic may have helped in this respect. Dr. Sotile says he’s heard physicians say that they’ve connected more with their families in the past 18 months. Specialists with the highest rates of happy marriages were otolaryngologists and immunologists (both 91%), followed closely by dermatologists, rheumatologists, and nephrologists (all 90%).

Among physicians balancing a medical career and parenthood, female physicians reported feeling conflicted more often than males (48% vs. 29%). Nicole A. Sparks, MD, an ob.gyn. and a health and lifestyle blogger, cites not being there for her kids as a source of stress. She notes that her two young children notice when she’s not there to help with homework, read bedtime stories, or make their dinner. “Mom guilt can definitely set in if I have to miss important events,” she says.

Work-life balance is an important, if elusive, goal for physicians, and not just females. Sixty percent of female doctors and 53% of male doctors said they would be willing to take a cut in pay if it meant more free time and a better work-life balance. Many doctors do manage to get away from work occasionally, with one-fifth of all physicians taking 5 or more weeks of vacation each year.

Seeking a ‘balanced life’

Alexis Polles, MD, medical director for the Professionals Resource Network, points out the importance of taking time for personal health and wellness. “When we work with professionals who have problems with mental health or substance abuse, they often don’t have a balanced life,” she says. “They are usually in a workaholic mindset and disregard their own needs.”

Few physicians seem to prioritize self-care, with a third indicating they “always” or “most of the time” spend enough time on their own health and wellness. But of those who do, males (38%) are more likely than females (27%) to spend enough time on their own health and wellness. Dr. Polles adds that exercising after a shift can help physicians better make the transition from professional to personal life. Though they did not report when they exercised, about a third of physicians reported doing so four or more times per week. Controlling weight is an issue as well, with 49% of male and 55% of female physicians saying they are currently trying to lose weight.

Of physicians who drink alcohol, about a third have three or more drinks per week. (The CDC defines “heavy drinking” as consuming 15 drinks or more per week for men and eight drinks or more per week for women.)

Of those surveyed, 92% say they do not regularly use cannabidiol or cannabis, and a mere 4% of respondents said they would use at least one of these substances if they were to become legal in their state.

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

Since Canada legalized marijuana in 2018, there has been a dramatic increase in the number of individuals driving while high, new research shows.

Investigators studied over 4,000 drivers treated after a motor vehicle collision in British Columbia trauma centers and found that, before cannabis was legalized, a THC level greater than 0 ng/mL in the blood was present in roughly 10% of drivers. After the drug was legalized this percentage increased to 18%. The percentages of injured drivers with at least 2 ng/mL, the Canadian legal limit, and at least 5 ng/mL more than doubled.

“It’s concerning that we’re seeing such a dramatic increase,” study investigator Jeffrey Brubacher, MD, associate professor, department of emergency medicine, University of British Columbia, Vancouver, said in a press release.

“There are serious risks associated with driving after cannabis use and our findings suggest more [work] is needed to deter this dangerous behavior in light of legalization,” he said.

The study was published online Jan. 12 in the New England Journal of Medicine.
 

Impact of legalization?

The investigators note that the Canadian government introduced a law aiming to prevent cannabis-impaired driving by establishing penalties and criminal charges for drivers found with a whole-blood THC level of 2 ng/mL, with more severe penalties for those with a THC level of greater than 5 ng/mL or greater than 2.5 ng/mL combined with a blood alcohol level of .05%.

Cannabis use is “associated with cognitive deficits and psychomotor impairment, and there is evidence that it increases the risk of motor vehicle crashes, especially at higher THC levels,” they noted.

“I’m an emergency physician at Vancouver General Hospital’s trauma center. We’ve been measuring drug levels in injured drivers since 2013 here in British Columbia and, in particular, we’ve been measuring THC levels,” Dr. Brubacher said in an interview. “We thought it would be interesting and important to see what would happen after legalization.”

The investigators studied 4,339 drivers – 3,550 whose accident took place before legalization of cannabis, and 789 after legalization – who had been moderately injured in a motor vehicle collision and presented to four British Columbia trauma centers between January 2013 and March 2020.

“Moderately injured drivers had injuries or potential injuries significant enough to have blood work done as part of routine clinical care,” said Dr. Brubacher. Drivers included in the study had excess blood remaining after the clinical testing had been completed, which was then used for drug analysis.
 

Insufficient laws

After legalization there was an increased prevalence of drivers with a THC level greater than 0 ng/mL, a TCH level of at least 2 ng/mL, and a THC level of at least 5 ng/mL.

The largest increases in a THC level of at least 2 ng/mL were in drivers 50 years of age or older and among male drivers (adjusted prevalence ratio, 5.18; 95% confidence interval, 2.49-10.78 and aPR, 2.44; 95% CI, 1.60-3.74, respectively).

“There were no significant changes in the prevalence of drivers testing positive for alcohol,” the authors reported.

Dr. Brubacher said the evidence suggests these new laws “are not enough to stop everyone from driving after using cannabis.”

The findings have implications for clinicians and patients and for policymakers, he said. “My moderately conservative recommendations are that, if you are going to smoke cannabis, wait at least 4 hours after smoking before you drive. Edibles last longer, and patients should wait least 8 hours after ingesting [edibles] before driving. And of course, if you continue to feel the effects of the THC, you should avoid driving altogether until the time has elapsed and you no longer feel any effects.”

Dr. Brubacher hopes policy makers will use the study’s findings to “design public information campaigns and enforcement measures that encourage drivers, especially older drivers, to separate cannabis use from driving.”

Additionally, “policy makers shouldn’t lose sight of drinking and driving because that’s an even bigger problem than the risk of driving under the influence of cannabis.”
 

Focus on older adults

In a comment, Anees Bahji, MD, an International Collaborative Addiction Medicine research fellow at the British Columbia Centre on Substance Use, called the study “interesting and relevant.”

He raised several questions regarding the “correlation between the level of a substance in a person’s system and the degree of impairment.” For example, “does the same level of THC in the blood affect us all the same way? And to what extent do the levels detected at the time of the analysis correlate with the level in the person’s system at the time of driving?”

An additional consideration “is for individuals with cannabis use disorder and for those who have developed tolerance to the psychoactive effects of THC: Does it affect their driving skills in the same way as someone who is cannabis naive?” asked Dr. Bahji, a clinical assistant professor at the University of Calgary (Alta.) who was not involved with the study.

Also commenting, Eric Sevigny, PhD, associate professor of criminal justice and criminology at Georgia State University, Atlanta, described it as a “well-designed study that adds yet another data point for considering appropriate road safety policy responses alongside ongoing cannabis liberalization.”

However, the findings “cannot say much about whether cannabis legalization leads to an increase in cannabis-impaired driving, because current research finds little correlation between biological THC concentrations and driving performance,” said Dr. Sevigny, who was not involved with the study.

The finding of “higher THC prevalence among older adults is also relevant for road safety, as this population has a number of concomitant risk factors, such as cognitive decline and prescription drug use,” Dr. Sevigny added.

The study was supported by the Canadian Institutes of Health Research. Dr. Brubacher and Dr. Sevigny disclosed no relevant financial relationships. Dr. Bahji reported receiving research funding from the Canadian Institutes of Health Research, the Calgary Health Trust, the American Psychiatric Association, NIDA, and the University of Calgary.

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