Hematology News

A raft of new studies that looked at the ability of Omicron to evade an array of currently available vaccines suggest a substantial loss of protection against the highly mutated variant.

Medscape Illustration/Dreamstime

The new studies, from teams of researchers in Germany, South Africa, Sweden, and the drug company Pfizer, showed 25 to 40-fold drops in the ability of antibodies created by two doses of the Pfizer-BioNTech vaccine to neutralize the virus.  

But there seemed to be a bright spot in the studies too. The virus didn’t completely escape the immunity from the vaccines, and giving a third, booster dose appeared to restore antibodies to a level that’s been associated with protection against variants in the past.

“One of the silver linings of this pandemic so far is that mRNA vaccines manufactured based on the ancestral SARS-CoV-2 continue to work in the laboratory and, importantly, in real life against variant strains,” said Hana El Sahly, MD, professor of molecular virology and microbiology at Baylor College of Medicine in Houston. “The strains so far vary by their degree of being neutralized by the antibodies from these vaccines, but they are being neutralized nonetheless.” 

Dr. El Sahly points out that the Beta variant was associated with a 10-fold drop in antibodies, but two doses of the vaccines still protected against it.

President Biden hailed the study results as good news.

“That Pfizer lab report came back saying that the expectation is that the existing vaccines protect against Omicron. But if you get the booster, you’re really in good shape. And so that’s very encouraging,” he said in a press briefing Dec. 8.
 

More research needed

Other scientists, however, stressed that these studies are from lab tests, and don’t necessarily reflect what will happen with Omicron in the real world. They cautioned about a worldwide push for boosters with so many countries still struggling to give first doses of vaccines.

Soumya Swaminathan, MD, chief scientist for the World Health Organization, stressed in a press briefing Dec. 8 that the results from the four studies varied widely, showing dips in neutralizing activity with Omicron that ranged from 5-fold to 40-fold.

The types of lab tests that were run were different, too, and involved small numbers of blood samples from patients.

She stressed that immunity depends not just on neutralizing antibodies, which act as a first line of defense when a virus invades, but also on B cells and T cells, and so far, tests show that these crucial components — which are important for preventing severe disease and death — had been less impacted than antibodies.

“So, I think it’s premature to conclude that this reduction in neutralizing activity would result in a significant reduction in vaccine effectiveness,” she said.

Whether or not these first-generation vaccines will be enough to stop Omicron, though, remains to be seen. A study of the Pfizer, Moderna, and AstraZeneca vaccines, led by German physician Sandra Ciesek, MD, who directs the Institute of Medical Virology at the University of Frankfurt, shows a booster didn’t appear to hold up well over time.

Dr. Ciesek and her team exposed Omicron viruses to the antibodies of volunteers who had been boosted with the Pfizer vaccine 3 months prior.  

She also compared the results to what happened to those same 3-month antibody levels against Delta variant viruses. She found only a 25% neutralization of Omicron compared with a 95% neutralization of Delta. That represented about a 37-fold reduction in the ability of the antibodies to neutralize Omicron vs Delta.

“The data confirm that developing a vaccine adapted for Omicron makes sense,” she tweeted as part of a long thread she posted on her results.
 

Retool the vaccines?

Both Pfizer and Moderna are retooling their vaccines to better match them to the changes in the Omicron variant. In a press release, Pfizer said it could start deliveries of that updated vaccine by March, pending U.S. Food and Drug Administration authorization.

“What the booster really does in neutralizing Omicron right now, they don’t know, they have no idea,” said Peter Palese, PhD, chair of the department of microbiology at the Mount Sinai School of Medicine in New York City.

Dr. Palese said he was definitely concerned about a possible Omicron wave.

“There are four major sites on the spike protein targeted by antibodies from the vaccines, and all four sites have mutations,” he said. “All these important antigenic sites are changed.

“If Omicron becomes the new Delta, and the old vaccines really aren’t good enough, then we have to make new Omicron vaccines. Then we have to revaccinate everybody twice,” he said, and the costs could be staggering. “I am worried.”

Tedros Adhanom Ghebreyesus, PhD, director general of the WHO, urged countries to move quickly.

“Don’t wait. Act now,” he said, even before all the science is in hand. “All of us, every government, every individual should use all the tools we have right now,” to drive down transmission, increase testing and surveillance, and share scientific findings.

“We can prevent Omicron [from] becoming a global crisis right now,” he said.

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

A raft of new studies that looked at the ability of Omicron to evade an array of currently available vaccines suggest a substantial loss of protection against the highly mutated variant.

Medscape Illustration/Dreamstime

The new studies, from teams of researchers in Germany, South Africa, Sweden, and the drug company Pfizer, showed 25 to 40-fold drops in the ability of antibodies created by two doses of the Pfizer-BioNTech vaccine to neutralize the virus.  

But there seemed to be a bright spot in the studies too. The virus didn’t completely escape the immunity from the vaccines, and giving a third, booster dose appeared to restore antibodies to a level that’s been associated with protection against variants in the past.

“One of the silver linings of this pandemic so far is that mRNA vaccines manufactured based on the ancestral SARS-CoV-2 continue to work in the laboratory and, importantly, in real life against variant strains,” said Hana El Sahly, MD, professor of molecular virology and microbiology at Baylor College of Medicine in Houston. “The strains so far vary by their degree of being neutralized by the antibodies from these vaccines, but they are being neutralized nonetheless.” 

Dr. El Sahly points out that the Beta variant was associated with a 10-fold drop in antibodies, but two doses of the vaccines still protected against it.

President Biden hailed the study results as good news.

“That Pfizer lab report came back saying that the expectation is that the existing vaccines protect against Omicron. But if you get the booster, you’re really in good shape. And so that’s very encouraging,” he said in a press briefing Dec. 8.
 

More research needed

Other scientists, however, stressed that these studies are from lab tests, and don’t necessarily reflect what will happen with Omicron in the real world. They cautioned about a worldwide push for boosters with so many countries still struggling to give first doses of vaccines.

Soumya Swaminathan, MD, chief scientist for the World Health Organization, stressed in a press briefing Dec. 8 that the results from the four studies varied widely, showing dips in neutralizing activity with Omicron that ranged from 5-fold to 40-fold.

The types of lab tests that were run were different, too, and involved small numbers of blood samples from patients.

She stressed that immunity depends not just on neutralizing antibodies, which act as a first line of defense when a virus invades, but also on B cells and T cells, and so far, tests show that these crucial components — which are important for preventing severe disease and death — had been less impacted than antibodies.

“So, I think it’s premature to conclude that this reduction in neutralizing activity would result in a significant reduction in vaccine effectiveness,” she said.

Whether or not these first-generation vaccines will be enough to stop Omicron, though, remains to be seen. A study of the Pfizer, Moderna, and AstraZeneca vaccines, led by German physician Sandra Ciesek, MD, who directs the Institute of Medical Virology at the University of Frankfurt, shows a booster didn’t appear to hold up well over time.

Dr. Ciesek and her team exposed Omicron viruses to the antibodies of volunteers who had been boosted with the Pfizer vaccine 3 months prior.  

She also compared the results to what happened to those same 3-month antibody levels against Delta variant viruses. She found only a 25% neutralization of Omicron compared with a 95% neutralization of Delta. That represented about a 37-fold reduction in the ability of the antibodies to neutralize Omicron vs Delta.

“The data confirm that developing a vaccine adapted for Omicron makes sense,” she tweeted as part of a long thread she posted on her results.
 

Retool the vaccines?

Both Pfizer and Moderna are retooling their vaccines to better match them to the changes in the Omicron variant. In a press release, Pfizer said it could start deliveries of that updated vaccine by March, pending U.S. Food and Drug Administration authorization.

“What the booster really does in neutralizing Omicron right now, they don’t know, they have no idea,” said Peter Palese, PhD, chair of the department of microbiology at the Mount Sinai School of Medicine in New York City.

Dr. Palese said he was definitely concerned about a possible Omicron wave.

“There are four major sites on the spike protein targeted by antibodies from the vaccines, and all four sites have mutations,” he said. “All these important antigenic sites are changed.

“If Omicron becomes the new Delta, and the old vaccines really aren’t good enough, then we have to make new Omicron vaccines. Then we have to revaccinate everybody twice,” he said, and the costs could be staggering. “I am worried.”

Tedros Adhanom Ghebreyesus, PhD, director general of the WHO, urged countries to move quickly.

“Don’t wait. Act now,” he said, even before all the science is in hand. “All of us, every government, every individual should use all the tools we have right now,” to drive down transmission, increase testing and surveillance, and share scientific findings.

“We can prevent Omicron [from] becoming a global crisis right now,” he said.

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

A raft of new studies that looked at the ability of Omicron to evade an array of currently available vaccines suggest a substantial loss of protection against the highly mutated variant.

Medscape Illustration/Dreamstime

The new studies, from teams of researchers in Germany, South Africa, Sweden, and the drug company Pfizer, showed 25 to 40-fold drops in the ability of antibodies created by two doses of the Pfizer-BioNTech vaccine to neutralize the virus.  

But there seemed to be a bright spot in the studies too. The virus didn’t completely escape the immunity from the vaccines, and giving a third, booster dose appeared to restore antibodies to a level that’s been associated with protection against variants in the past.

“One of the silver linings of this pandemic so far is that mRNA vaccines manufactured based on the ancestral SARS-CoV-2 continue to work in the laboratory and, importantly, in real life against variant strains,” said Hana El Sahly, MD, professor of molecular virology and microbiology at Baylor College of Medicine in Houston. “The strains so far vary by their degree of being neutralized by the antibodies from these vaccines, but they are being neutralized nonetheless.” 

Dr. El Sahly points out that the Beta variant was associated with a 10-fold drop in antibodies, but two doses of the vaccines still protected against it.

President Biden hailed the study results as good news.

“That Pfizer lab report came back saying that the expectation is that the existing vaccines protect against Omicron. But if you get the booster, you’re really in good shape. And so that’s very encouraging,” he said in a press briefing Dec. 8.
 

More research needed

Other scientists, however, stressed that these studies are from lab tests, and don’t necessarily reflect what will happen with Omicron in the real world. They cautioned about a worldwide push for boosters with so many countries still struggling to give first doses of vaccines.

Soumya Swaminathan, MD, chief scientist for the World Health Organization, stressed in a press briefing Dec. 8 that the results from the four studies varied widely, showing dips in neutralizing activity with Omicron that ranged from 5-fold to 40-fold.

The types of lab tests that were run were different, too, and involved small numbers of blood samples from patients.

She stressed that immunity depends not just on neutralizing antibodies, which act as a first line of defense when a virus invades, but also on B cells and T cells, and so far, tests show that these crucial components — which are important for preventing severe disease and death — had been less impacted than antibodies.

“So, I think it’s premature to conclude that this reduction in neutralizing activity would result in a significant reduction in vaccine effectiveness,” she said.

Whether or not these first-generation vaccines will be enough to stop Omicron, though, remains to be seen. A study of the Pfizer, Moderna, and AstraZeneca vaccines, led by German physician Sandra Ciesek, MD, who directs the Institute of Medical Virology at the University of Frankfurt, shows a booster didn’t appear to hold up well over time.

Dr. Ciesek and her team exposed Omicron viruses to the antibodies of volunteers who had been boosted with the Pfizer vaccine 3 months prior.  

She also compared the results to what happened to those same 3-month antibody levels against Delta variant viruses. She found only a 25% neutralization of Omicron compared with a 95% neutralization of Delta. That represented about a 37-fold reduction in the ability of the antibodies to neutralize Omicron vs Delta.

“The data confirm that developing a vaccine adapted for Omicron makes sense,” she tweeted as part of a long thread she posted on her results.
 

Retool the vaccines?

Both Pfizer and Moderna are retooling their vaccines to better match them to the changes in the Omicron variant. In a press release, Pfizer said it could start deliveries of that updated vaccine by March, pending U.S. Food and Drug Administration authorization.

“What the booster really does in neutralizing Omicron right now, they don’t know, they have no idea,” said Peter Palese, PhD, chair of the department of microbiology at the Mount Sinai School of Medicine in New York City.

Dr. Palese said he was definitely concerned about a possible Omicron wave.

“There are four major sites on the spike protein targeted by antibodies from the vaccines, and all four sites have mutations,” he said. “All these important antigenic sites are changed.

“If Omicron becomes the new Delta, and the old vaccines really aren’t good enough, then we have to make new Omicron vaccines. Then we have to revaccinate everybody twice,” he said, and the costs could be staggering. “I am worried.”

Tedros Adhanom Ghebreyesus, PhD, director general of the WHO, urged countries to move quickly.

“Don’t wait. Act now,” he said, even before all the science is in hand. “All of us, every government, every individual should use all the tools we have right now,” to drive down transmission, increase testing and surveillance, and share scientific findings.

“We can prevent Omicron [from] becoming a global crisis right now,” he said.

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

Adolescents and adults younger than age 21 who develop myocarditis after mRNA COVID-19 vaccination frequently have abnormal findings on cardiac MRI (cMRI) but most have a mild clinical course with rapid resolution of symptoms, a new study concludes.

• Most patients were male (90.6%), White (66.2%) and with a median age of 15.8 years.
• Suspected myocarditis occurred in 136 patients (97.8%) following mRNA vaccine, with 131 (94.2%) following the Pfizer-BioNTech vaccine; 128 cases (91.4%) occurred after the second dose.
• Symptoms started a median of 2 days (range 0 to 22 days) following vaccination administration.
• Chest pain was the most common symptom (99.3%), with fever present in 30.9% of patients and shortness of breath in 27.3%.
• Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%) or no anti-inflammatory therapies (8.6%).
• Twenty-six patients (18.7%) were admitted to the intensive care unit; 2 received inotropic/vasoactive support; none required extracorporeal membrane oxygenation or died.
• Median time spent in the hospital was 2 days.
• A total of 111 patients had elevated troponin I (8.12 ng/mL) and 28 had elevated troponin T (0.61 ng/mL).
• More than two-thirds (69.8%) had abnormal electrocardiograms and/or arrhythmias (7 with nonsustained ventricular tachycardia).
• Twenty-six patients (18.7%) had left ventricular ejection fraction (LVEF) less than 55% on echocardiogram; LVEF had returned to normal in the 25 who returned for follow-up.
• 75 of 97 patients (77.3%) who underwent cMRI at a median of 5 days from symptom onset had abnormal findings; 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria for myocarditis.

“These data suggest that most cases of suspected COVID-19 vaccine–related myocarditis in people younger than 21 are mild and resolve quickly,” corresponding author Dongngan Truong, MD, Division of Pediatric Cardiology, University of Utah and Primary Children’s Hospital, Salt Lake City, said in a statement.

“We were very happy to see that type of recovery. However, we are awaiting further studies to better understand the long-term outcomes of patients who have had COVID-19 vaccination-related myocarditis. We also need to study the risk factors and mechanisms for this rare complication,” Dr. Truong added.

Dr. Lloyd-Jones said these findings support the AHA’s position that COVID-19 vaccines are “safe, highly effective, and fundamental to saving lives, protecting our families and communities against COVID-19, and ending the pandemic.”

The study received no funding. Dr. Truong consults for Pfizer on vaccine-associated myocarditis. A complete list of author disclosures is available with the original article.

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

Adolescents and adults younger than age 21 who develop myocarditis after mRNA COVID-19 vaccination frequently have abnormal findings on cardiac MRI (cMRI) but most have a mild clinical course with rapid resolution of symptoms, a new study concludes.

• Most patients were male (90.6%), White (66.2%) and with a median age of 15.8 years.
• Suspected myocarditis occurred in 136 patients (97.8%) following mRNA vaccine, with 131 (94.2%) following the Pfizer-BioNTech vaccine; 128 cases (91.4%) occurred after the second dose.
• Symptoms started a median of 2 days (range 0 to 22 days) following vaccination administration.
• Chest pain was the most common symptom (99.3%), with fever present in 30.9% of patients and shortness of breath in 27.3%.
• Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%) or no anti-inflammatory therapies (8.6%).
• Twenty-six patients (18.7%) were admitted to the intensive care unit; 2 received inotropic/vasoactive support; none required extracorporeal membrane oxygenation or died.
• Median time spent in the hospital was 2 days.
• A total of 111 patients had elevated troponin I (8.12 ng/mL) and 28 had elevated troponin T (0.61 ng/mL).
• More than two-thirds (69.8%) had abnormal electrocardiograms and/or arrhythmias (7 with nonsustained ventricular tachycardia).
• Twenty-six patients (18.7%) had left ventricular ejection fraction (LVEF) less than 55% on echocardiogram; LVEF had returned to normal in the 25 who returned for follow-up.
• 75 of 97 patients (77.3%) who underwent cMRI at a median of 5 days from symptom onset had abnormal findings; 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria for myocarditis.

“These data suggest that most cases of suspected COVID-19 vaccine–related myocarditis in people younger than 21 are mild and resolve quickly,” corresponding author Dongngan Truong, MD, Division of Pediatric Cardiology, University of Utah and Primary Children’s Hospital, Salt Lake City, said in a statement.

“We were very happy to see that type of recovery. However, we are awaiting further studies to better understand the long-term outcomes of patients who have had COVID-19 vaccination-related myocarditis. We also need to study the risk factors and mechanisms for this rare complication,” Dr. Truong added.

Dr. Lloyd-Jones said these findings support the AHA’s position that COVID-19 vaccines are “safe, highly effective, and fundamental to saving lives, protecting our families and communities against COVID-19, and ending the pandemic.”

The study received no funding. Dr. Truong consults for Pfizer on vaccine-associated myocarditis. A complete list of author disclosures is available with the original article.

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

Adolescents and adults younger than age 21 who develop myocarditis after mRNA COVID-19 vaccination frequently have abnormal findings on cardiac MRI (cMRI) but most have a mild clinical course with rapid resolution of symptoms, a new study concludes.

• Most patients were male (90.6%), White (66.2%) and with a median age of 15.8 years.
• Suspected myocarditis occurred in 136 patients (97.8%) following mRNA vaccine, with 131 (94.2%) following the Pfizer-BioNTech vaccine; 128 cases (91.4%) occurred after the second dose.
• Symptoms started a median of 2 days (range 0 to 22 days) following vaccination administration.
• Chest pain was the most common symptom (99.3%), with fever present in 30.9% of patients and shortness of breath in 27.3%.
• Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%) or no anti-inflammatory therapies (8.6%).
• Twenty-six patients (18.7%) were admitted to the intensive care unit; 2 received inotropic/vasoactive support; none required extracorporeal membrane oxygenation or died.
• Median time spent in the hospital was 2 days.
• A total of 111 patients had elevated troponin I (8.12 ng/mL) and 28 had elevated troponin T (0.61 ng/mL).
• More than two-thirds (69.8%) had abnormal electrocardiograms and/or arrhythmias (7 with nonsustained ventricular tachycardia).
• Twenty-six patients (18.7%) had left ventricular ejection fraction (LVEF) less than 55% on echocardiogram; LVEF had returned to normal in the 25 who returned for follow-up.
• 75 of 97 patients (77.3%) who underwent cMRI at a median of 5 days from symptom onset had abnormal findings; 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria for myocarditis.

“These data suggest that most cases of suspected COVID-19 vaccine–related myocarditis in people younger than 21 are mild and resolve quickly,” corresponding author Dongngan Truong, MD, Division of Pediatric Cardiology, University of Utah and Primary Children’s Hospital, Salt Lake City, said in a statement.

“We were very happy to see that type of recovery. However, we are awaiting further studies to better understand the long-term outcomes of patients who have had COVID-19 vaccination-related myocarditis. We also need to study the risk factors and mechanisms for this rare complication,” Dr. Truong added.

Dr. Lloyd-Jones said these findings support the AHA’s position that COVID-19 vaccines are “safe, highly effective, and fundamental to saving lives, protecting our families and communities against COVID-19, and ending the pandemic.”

The study received no funding. Dr. Truong consults for Pfizer on vaccine-associated myocarditis. A complete list of author disclosures is available with the original article.

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

An abstract and poster presentation questioning the safety of mRNA-based COVID-19 vaccines, embraced by some and lambasted by others, has drawn an “expression of concern” from the American Heart Association, along with a bid for correction.

The abstract in question concludes that COVID vaccines “dramatically increase” levels of certain inflammatory biomarkers, and therefore, the 5-year risk of acute coronary syndromes (ACS), based on pre- and post-vaccination results of an obscure blood panel called the PULS Cardiac Test (GD Biosciences). The findings were presented at the AHA’s 2021 Scientific Sessionsas, an uncontrolled observational study of 566 patients in a preventive cardiology practice.

Some on social media have seized on the abstract as evidence of serious potential harm from the two available mRNA-based SARS-CoV-2 vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). But others contend that the study’s described design and findings are specious and its conclusions overstated.

They also point to the notoriety of its one listed author, Steven R. Gundry, MD, who promotes his diet books and supplements as well as fringe, highly criticized theories about diet and disease on several websites, including drgundry.com. Dr. Gundry has not responded to requests for an interview.

Dr. Gundry’s abstract from the AHA Scientific Sessions 2021, available on the meeting’s program planner, was marked with an “expression of concern” by the AHA that is to stand “until a suitable correction is published, to indicate that the abstract in its current version may not be reliable.”

The expression of concern statement, also published online Nov. 24 in Circulation, says “potential errors in the abstract” were brought to the attention of the meeting planners. “Specifically, there are several typographical errors, there is no data in the abstract regarding myocardial T-cell infiltration, there are no statistical analyses for significance provided, and the author is not clear that only anecdotal data was used.”

The biomarker elevations on which the abstract’s conclusions are based included hepatocyte growth factor, “which serves as a marker for chemotaxis of T-cells into epithelium and cardiac tissue,” it states.

“The expression of concern about the abstract will remain in place until a correction is accepted and published” in Circulation, AHA spokesperson Suzanne Grant told this news organization by email.

“The specific data needed will be up to the abstract author to determine and supply,” she said, noting that Dr. Gundry “has been in communication with the journal throughout this process.”

Submitting researchers “must always attest to the validity of the abstract,” Ms. Grant said. “Abstracts are then curated by independent review panels, blinded to the identities of the abstract authors, and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting.”

Regarding the AHA’s system for vetting abstracts vying for acceptance to the scientific sessions, she said it is not primarily intended to “evaluate scientific validity” and that the organization is “currently reviewing its existing abstract submission processes.”

A recent Reuters report reviews the controversy and provides links to criticisms of the study on social media.

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

An abstract and poster presentation questioning the safety of mRNA-based COVID-19 vaccines, embraced by some and lambasted by others, has drawn an “expression of concern” from the American Heart Association, along with a bid for correction.

The abstract in question concludes that COVID vaccines “dramatically increase” levels of certain inflammatory biomarkers, and therefore, the 5-year risk of acute coronary syndromes (ACS), based on pre- and post-vaccination results of an obscure blood panel called the PULS Cardiac Test (GD Biosciences). The findings were presented at the AHA’s 2021 Scientific Sessionsas, an uncontrolled observational study of 566 patients in a preventive cardiology practice.

Some on social media have seized on the abstract as evidence of serious potential harm from the two available mRNA-based SARS-CoV-2 vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). But others contend that the study’s described design and findings are specious and its conclusions overstated.

They also point to the notoriety of its one listed author, Steven R. Gundry, MD, who promotes his diet books and supplements as well as fringe, highly criticized theories about diet and disease on several websites, including drgundry.com. Dr. Gundry has not responded to requests for an interview.

Dr. Gundry’s abstract from the AHA Scientific Sessions 2021, available on the meeting’s program planner, was marked with an “expression of concern” by the AHA that is to stand “until a suitable correction is published, to indicate that the abstract in its current version may not be reliable.”

The expression of concern statement, also published online Nov. 24 in Circulation, says “potential errors in the abstract” were brought to the attention of the meeting planners. “Specifically, there are several typographical errors, there is no data in the abstract regarding myocardial T-cell infiltration, there are no statistical analyses for significance provided, and the author is not clear that only anecdotal data was used.”

The biomarker elevations on which the abstract’s conclusions are based included hepatocyte growth factor, “which serves as a marker for chemotaxis of T-cells into epithelium and cardiac tissue,” it states.

“The expression of concern about the abstract will remain in place until a correction is accepted and published” in Circulation, AHA spokesperson Suzanne Grant told this news organization by email.

“The specific data needed will be up to the abstract author to determine and supply,” she said, noting that Dr. Gundry “has been in communication with the journal throughout this process.”

Submitting researchers “must always attest to the validity of the abstract,” Ms. Grant said. “Abstracts are then curated by independent review panels, blinded to the identities of the abstract authors, and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting.”

Regarding the AHA’s system for vetting abstracts vying for acceptance to the scientific sessions, she said it is not primarily intended to “evaluate scientific validity” and that the organization is “currently reviewing its existing abstract submission processes.”

A recent Reuters report reviews the controversy and provides links to criticisms of the study on social media.

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

An abstract and poster presentation questioning the safety of mRNA-based COVID-19 vaccines, embraced by some and lambasted by others, has drawn an “expression of concern” from the American Heart Association, along with a bid for correction.

The abstract in question concludes that COVID vaccines “dramatically increase” levels of certain inflammatory biomarkers, and therefore, the 5-year risk of acute coronary syndromes (ACS), based on pre- and post-vaccination results of an obscure blood panel called the PULS Cardiac Test (GD Biosciences). The findings were presented at the AHA’s 2021 Scientific Sessionsas, an uncontrolled observational study of 566 patients in a preventive cardiology practice.

Some on social media have seized on the abstract as evidence of serious potential harm from the two available mRNA-based SARS-CoV-2 vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). But others contend that the study’s described design and findings are specious and its conclusions overstated.

They also point to the notoriety of its one listed author, Steven R. Gundry, MD, who promotes his diet books and supplements as well as fringe, highly criticized theories about diet and disease on several websites, including drgundry.com. Dr. Gundry has not responded to requests for an interview.

Dr. Gundry’s abstract from the AHA Scientific Sessions 2021, available on the meeting’s program planner, was marked with an “expression of concern” by the AHA that is to stand “until a suitable correction is published, to indicate that the abstract in its current version may not be reliable.”

The expression of concern statement, also published online Nov. 24 in Circulation, says “potential errors in the abstract” were brought to the attention of the meeting planners. “Specifically, there are several typographical errors, there is no data in the abstract regarding myocardial T-cell infiltration, there are no statistical analyses for significance provided, and the author is not clear that only anecdotal data was used.”

The biomarker elevations on which the abstract’s conclusions are based included hepatocyte growth factor, “which serves as a marker for chemotaxis of T-cells into epithelium and cardiac tissue,” it states.

“The expression of concern about the abstract will remain in place until a correction is accepted and published” in Circulation, AHA spokesperson Suzanne Grant told this news organization by email.

“The specific data needed will be up to the abstract author to determine and supply,” she said, noting that Dr. Gundry “has been in communication with the journal throughout this process.”

Submitting researchers “must always attest to the validity of the abstract,” Ms. Grant said. “Abstracts are then curated by independent review panels, blinded to the identities of the abstract authors, and are considered based on the potential to add to the diversity of scientific issues and views discussed at the meeting.”

Regarding the AHA’s system for vetting abstracts vying for acceptance to the scientific sessions, she said it is not primarily intended to “evaluate scientific validity” and that the organization is “currently reviewing its existing abstract submission processes.”

A recent Reuters report reviews the controversy and provides links to criticisms of the study on social media.

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

Retrospective data suggest that improvements over time in overall survival (OS) among COVID-19-infected patients with chronic lymphocytic leukemia (CLL) mirror those observed in COVID-19–infected patients in general, but the data also highlight areas for further investigation, according to the researchers.

MSKCC

Specifically, “the data highlight opportunities for further investigation into optimal management of COVID-19, immune response after infection, and effective vaccination strategy for patients with CLL,” Lindsey E. Roeker, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote in a Nov. 4, 2021, letter to the editor of Blood.

The researchers noted that recently reported COVID-19 case fatality rates from two large series of patients with CLL ranged from 31% to 33%, but trends over time were unclear.

“To understand change in outcomes over time, we present this follow-up study, which builds upon a previously reported cohort with extended follow up and addition of more recently diagnosed cases,” they wrote, explaining that “early data from a small series suggest that patients with CLL may not consistently generate anti–SARS-CoV-2 antibodies after infection.”

“This finding, along with previous reports of inadequate response to vaccines in patients with CLL, highlight significant questions regarding COVID-19 vaccine efficacy in this population,” they added.
 

Trends in outcomes

The review of outcomes in 374 CLL patients from 45 centers who were diagnosed with COVID-19 between Feb. 17, 2020, and Feb. 1, 2021, showed an overall case fatality rate (CFR) of 28%. Among the 278 patients (75%) admitted to the hospital, the CFR was 36%; among those not admitted, the CFR was 4.3%.

Independent predictors of poor survival were ages over 75 years (adjusted hazard ratio, 1.6) and Cumulative Illness Rating Scale–Geriatric (CIRS) scores greater than 6 (aHR, 1.6).

Updated data for 254 patients diagnosed from Feb. 17 to April 30, 2020, and 120 diagnosed from May 1, 2020, to Feb. 1, 2021, showed that more patients in the early versus later cohort were admitted to the hospital (85% vs. 55%) and more required ICU admission (32% vs. 11%).

The overall case fatality rates in the early and later cohorts were 35% and 11%, respectively (P < .001), and among those requiring hospitalization, the rates were 40% and 20% (P = .003).

“The proportion of hospitalized patients requiring ICU-level care was lower in the later cohort (37% vs. 29%), whereas the CFR remained high for the subset of patients who required ICU-level care (52% vs. 50%; P = .89),” the investigators wrote, noting that “[a] difference in management of BTKi[Bruton’s tyrosine kinase inhibitor]-treated patients was observed in the early versus the later cohort.”

“In the early cohort, 76% of patients receiving BTKi had their drug therapy suspended or discontinued. In the later cohort, only 20% of BTKi-treated patients had their therapy suspended or discontinued,” they added.

Univariate analyses showed significant associations between use of remdesivir and OS (HR, 0.48) and use of convalescent plasma and OS (HR, 0.50) in patients who were admitted, whereas admitted patients who received corticosteroids or hydroxychloroquine had an increased risk of death (HRs, 1.73 and 1.53, respectively).

“Corticosteroids were associated with increased risk of death when the data were adjusted for admission status (HR, 1.8) and the need for mechanical ventilation (HR, 2.0), although they were not significantly associated with survival when the data were adjusted for use of supplemental oxygen (HR, 1.4),” they wrote, also noting that admitted patients treated with corticosteroids in the later cohort did not experience an OS benefit (HR, 2.6).

The findings mirror population-based studies with decreasing CFR (35% in those diagnosed before May 1, 2020, versus 11% in those diagnosed after that date), they said, adding that “these trends suggest that patients in the later cohort experienced a less severe clinical course and that the observed difference in CFR over time may not just be due to more frequent testing and identification of less symptomatic patients.”

Of note, the outcomes observed for steroid-treated patients in the current cohort contrast with those from the RECOVERY trial as published in July 2020, which “may be an artifact of their use in patients with more severe disease,” they suggested.

They added that these data “are hypothesis generating and suggest that COVID-19 directed interventions, particularly immunomodulatory agents, require prospective study, specifically in immunocompromised populations.”

The investigators also noted that, consistent with a prior single-center study, 60% of patients with CLL developed positive anti–SARS-CoV-2 serology results after polymerase chain reaction diagnosis of COVID-19, adding further evidence of nonuniform antibody production after COVID-19 in patients with CLL.

Study is ongoing to gain understanding of the immune response to SARS-CoV-2 vaccination in patients with CLL, they said.
 

Changing the odds

In a related commentary also published in Blood, Yair Herishanu, MD, and Chava Perry, MD, PhD, of Tel Aviv Sourasky Medical Center called the reduction in mortality over time as reported by Dr. Roeker and colleagues “encouraging and intriguing.”

“One explanation is that the later cohort included a larger proportion of patients with mild symptoms who were diagnosed because of increased awareness of COVID-19 and more extensive screening to detect SARS-CoV-2 over time. That is supported by the lower hospitalization rates and lower rates of hospitalized patients requiring ICU care in the later cohort,” they wrote. “Another possibility is better patient management owing to increasing experience, expanding therapeutic options, and improved capacity of health systems to manage an influx of patients.”

The lower mortality in hospitalized patients over time may reflect better management of patients over time, but it also highlights the significance of “early introduction of various anti–COVID-19 therapies to prevent clinical deterioration to ICU-level care,” they added.

Also intriguing, according to Dr. Herishanu and Dr. Perry, was the finding of increased secondary infections and death rates among corticosteroid-treatment patients.

In the RECOVERY trial, the use of dexamethasone improved survival in patients hospitalized with COVID-19 who received respiratory support. Perhaps the impaired immune reactions in patients with CLL moderate the hyperinflammatory reactions to COVID-19, thus turning corticosteroids beneficial effects to somewhat redundant in this frail population,” they wrote.

Further, the finding that only 60% of patients with CLL seroconvert after the acute phase of SARS-CoV-2 infection suggests CLL patients may be at risk for reinfection, which “justifies vaccinating all patients with CLL who have recovered from COVID-19.”

“Likewise, patients with CLL may develop persistent COVID-19 infection,” they added, explaining that “prolonged shedding of infectious SARS-CoV-2 virus and within-host genomic evolution may eventually lead to emergence of new virus variants.”

Given the high risk of severe COVID-19 disease and impaired antibody-mediated immune response to the virus and its vaccine, a booster dose may be warranted in patients with CLL who fail to achieve seropositivity after 2 vaccine doses, they said.

The available data to date “call for early application of antiviral drugs, [monoclonal antibodies], and convalescent plasma as well as improved vaccination strategy, to improve the odds for patients with CLL confronting COVID-19,” they concluded, adding that large-scale prospective studies on the clinical disease course, outcomes, efficacy of treatments, and vaccination timing and schedule in patients with CLL and COVID-19 are still warranted.

The research was supported by a National Cancer Institute Cancer Center support grant. Dr. Roeker, Dr. Herishanu, and Dr. Perry reported having no financial disclosures.

[email protected]

Retrospective data suggest that improvements over time in overall survival (OS) among COVID-19-infected patients with chronic lymphocytic leukemia (CLL) mirror those observed in COVID-19–infected patients in general, but the data also highlight areas for further investigation, according to the researchers.

MSKCC

Specifically, “the data highlight opportunities for further investigation into optimal management of COVID-19, immune response after infection, and effective vaccination strategy for patients with CLL,” Lindsey E. Roeker, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote in a Nov. 4, 2021, letter to the editor of Blood.

The researchers noted that recently reported COVID-19 case fatality rates from two large series of patients with CLL ranged from 31% to 33%, but trends over time were unclear.

“To understand change in outcomes over time, we present this follow-up study, which builds upon a previously reported cohort with extended follow up and addition of more recently diagnosed cases,” they wrote, explaining that “early data from a small series suggest that patients with CLL may not consistently generate anti–SARS-CoV-2 antibodies after infection.”

“This finding, along with previous reports of inadequate response to vaccines in patients with CLL, highlight significant questions regarding COVID-19 vaccine efficacy in this population,” they added.
 

Trends in outcomes

The review of outcomes in 374 CLL patients from 45 centers who were diagnosed with COVID-19 between Feb. 17, 2020, and Feb. 1, 2021, showed an overall case fatality rate (CFR) of 28%. Among the 278 patients (75%) admitted to the hospital, the CFR was 36%; among those not admitted, the CFR was 4.3%.

Independent predictors of poor survival were ages over 75 years (adjusted hazard ratio, 1.6) and Cumulative Illness Rating Scale–Geriatric (CIRS) scores greater than 6 (aHR, 1.6).

Updated data for 254 patients diagnosed from Feb. 17 to April 30, 2020, and 120 diagnosed from May 1, 2020, to Feb. 1, 2021, showed that more patients in the early versus later cohort were admitted to the hospital (85% vs. 55%) and more required ICU admission (32% vs. 11%).

The overall case fatality rates in the early and later cohorts were 35% and 11%, respectively (P < .001), and among those requiring hospitalization, the rates were 40% and 20% (P = .003).

“The proportion of hospitalized patients requiring ICU-level care was lower in the later cohort (37% vs. 29%), whereas the CFR remained high for the subset of patients who required ICU-level care (52% vs. 50%; P = .89),” the investigators wrote, noting that “[a] difference in management of BTKi[Bruton’s tyrosine kinase inhibitor]-treated patients was observed in the early versus the later cohort.”

“In the early cohort, 76% of patients receiving BTKi had their drug therapy suspended or discontinued. In the later cohort, only 20% of BTKi-treated patients had their therapy suspended or discontinued,” they added.

Univariate analyses showed significant associations between use of remdesivir and OS (HR, 0.48) and use of convalescent plasma and OS (HR, 0.50) in patients who were admitted, whereas admitted patients who received corticosteroids or hydroxychloroquine had an increased risk of death (HRs, 1.73 and 1.53, respectively).

“Corticosteroids were associated with increased risk of death when the data were adjusted for admission status (HR, 1.8) and the need for mechanical ventilation (HR, 2.0), although they were not significantly associated with survival when the data were adjusted for use of supplemental oxygen (HR, 1.4),” they wrote, also noting that admitted patients treated with corticosteroids in the later cohort did not experience an OS benefit (HR, 2.6).

The findings mirror population-based studies with decreasing CFR (35% in those diagnosed before May 1, 2020, versus 11% in those diagnosed after that date), they said, adding that “these trends suggest that patients in the later cohort experienced a less severe clinical course and that the observed difference in CFR over time may not just be due to more frequent testing and identification of less symptomatic patients.”

Of note, the outcomes observed for steroid-treated patients in the current cohort contrast with those from the RECOVERY trial as published in July 2020, which “may be an artifact of their use in patients with more severe disease,” they suggested.

They added that these data “are hypothesis generating and suggest that COVID-19 directed interventions, particularly immunomodulatory agents, require prospective study, specifically in immunocompromised populations.”

The investigators also noted that, consistent with a prior single-center study, 60% of patients with CLL developed positive anti–SARS-CoV-2 serology results after polymerase chain reaction diagnosis of COVID-19, adding further evidence of nonuniform antibody production after COVID-19 in patients with CLL.

Study is ongoing to gain understanding of the immune response to SARS-CoV-2 vaccination in patients with CLL, they said.
 

Changing the odds

In a related commentary also published in Blood, Yair Herishanu, MD, and Chava Perry, MD, PhD, of Tel Aviv Sourasky Medical Center called the reduction in mortality over time as reported by Dr. Roeker and colleagues “encouraging and intriguing.”

“One explanation is that the later cohort included a larger proportion of patients with mild symptoms who were diagnosed because of increased awareness of COVID-19 and more extensive screening to detect SARS-CoV-2 over time. That is supported by the lower hospitalization rates and lower rates of hospitalized patients requiring ICU care in the later cohort,” they wrote. “Another possibility is better patient management owing to increasing experience, expanding therapeutic options, and improved capacity of health systems to manage an influx of patients.”

The lower mortality in hospitalized patients over time may reflect better management of patients over time, but it also highlights the significance of “early introduction of various anti–COVID-19 therapies to prevent clinical deterioration to ICU-level care,” they added.

Also intriguing, according to Dr. Herishanu and Dr. Perry, was the finding of increased secondary infections and death rates among corticosteroid-treatment patients.

In the RECOVERY trial, the use of dexamethasone improved survival in patients hospitalized with COVID-19 who received respiratory support. Perhaps the impaired immune reactions in patients with CLL moderate the hyperinflammatory reactions to COVID-19, thus turning corticosteroids beneficial effects to somewhat redundant in this frail population,” they wrote.

Further, the finding that only 60% of patients with CLL seroconvert after the acute phase of SARS-CoV-2 infection suggests CLL patients may be at risk for reinfection, which “justifies vaccinating all patients with CLL who have recovered from COVID-19.”

“Likewise, patients with CLL may develop persistent COVID-19 infection,” they added, explaining that “prolonged shedding of infectious SARS-CoV-2 virus and within-host genomic evolution may eventually lead to emergence of new virus variants.”

Given the high risk of severe COVID-19 disease and impaired antibody-mediated immune response to the virus and its vaccine, a booster dose may be warranted in patients with CLL who fail to achieve seropositivity after 2 vaccine doses, they said.

The available data to date “call for early application of antiviral drugs, [monoclonal antibodies], and convalescent plasma as well as improved vaccination strategy, to improve the odds for patients with CLL confronting COVID-19,” they concluded, adding that large-scale prospective studies on the clinical disease course, outcomes, efficacy of treatments, and vaccination timing and schedule in patients with CLL and COVID-19 are still warranted.

The research was supported by a National Cancer Institute Cancer Center support grant. Dr. Roeker, Dr. Herishanu, and Dr. Perry reported having no financial disclosures.

[email protected]

Retrospective data suggest that improvements over time in overall survival (OS) among COVID-19-infected patients with chronic lymphocytic leukemia (CLL) mirror those observed in COVID-19–infected patients in general, but the data also highlight areas for further investigation, according to the researchers.

MSKCC

Specifically, “the data highlight opportunities for further investigation into optimal management of COVID-19, immune response after infection, and effective vaccination strategy for patients with CLL,” Lindsey E. Roeker, MD, a hematologic oncologist at Memorial Sloan Kettering Cancer Center, New York, and colleagues wrote in a Nov. 4, 2021, letter to the editor of Blood.

The researchers noted that recently reported COVID-19 case fatality rates from two large series of patients with CLL ranged from 31% to 33%, but trends over time were unclear.

“To understand change in outcomes over time, we present this follow-up study, which builds upon a previously reported cohort with extended follow up and addition of more recently diagnosed cases,” they wrote, explaining that “early data from a small series suggest that patients with CLL may not consistently generate anti–SARS-CoV-2 antibodies after infection.”

“This finding, along with previous reports of inadequate response to vaccines in patients with CLL, highlight significant questions regarding COVID-19 vaccine efficacy in this population,” they added.
 

Trends in outcomes

The review of outcomes in 374 CLL patients from 45 centers who were diagnosed with COVID-19 between Feb. 17, 2020, and Feb. 1, 2021, showed an overall case fatality rate (CFR) of 28%. Among the 278 patients (75%) admitted to the hospital, the CFR was 36%; among those not admitted, the CFR was 4.3%.

Independent predictors of poor survival were ages over 75 years (adjusted hazard ratio, 1.6) and Cumulative Illness Rating Scale–Geriatric (CIRS) scores greater than 6 (aHR, 1.6).

Updated data for 254 patients diagnosed from Feb. 17 to April 30, 2020, and 120 diagnosed from May 1, 2020, to Feb. 1, 2021, showed that more patients in the early versus later cohort were admitted to the hospital (85% vs. 55%) and more required ICU admission (32% vs. 11%).

The overall case fatality rates in the early and later cohorts were 35% and 11%, respectively (P < .001), and among those requiring hospitalization, the rates were 40% and 20% (P = .003).

“The proportion of hospitalized patients requiring ICU-level care was lower in the later cohort (37% vs. 29%), whereas the CFR remained high for the subset of patients who required ICU-level care (52% vs. 50%; P = .89),” the investigators wrote, noting that “[a] difference in management of BTKi[Bruton’s tyrosine kinase inhibitor]-treated patients was observed in the early versus the later cohort.”

“In the early cohort, 76% of patients receiving BTKi had their drug therapy suspended or discontinued. In the later cohort, only 20% of BTKi-treated patients had their therapy suspended or discontinued,” they added.

Univariate analyses showed significant associations between use of remdesivir and OS (HR, 0.48) and use of convalescent plasma and OS (HR, 0.50) in patients who were admitted, whereas admitted patients who received corticosteroids or hydroxychloroquine had an increased risk of death (HRs, 1.73 and 1.53, respectively).

“Corticosteroids were associated with increased risk of death when the data were adjusted for admission status (HR, 1.8) and the need for mechanical ventilation (HR, 2.0), although they were not significantly associated with survival when the data were adjusted for use of supplemental oxygen (HR, 1.4),” they wrote, also noting that admitted patients treated with corticosteroids in the later cohort did not experience an OS benefit (HR, 2.6).

The findings mirror population-based studies with decreasing CFR (35% in those diagnosed before May 1, 2020, versus 11% in those diagnosed after that date), they said, adding that “these trends suggest that patients in the later cohort experienced a less severe clinical course and that the observed difference in CFR over time may not just be due to more frequent testing and identification of less symptomatic patients.”

Of note, the outcomes observed for steroid-treated patients in the current cohort contrast with those from the RECOVERY trial as published in July 2020, which “may be an artifact of their use in patients with more severe disease,” they suggested.

They added that these data “are hypothesis generating and suggest that COVID-19 directed interventions, particularly immunomodulatory agents, require prospective study, specifically in immunocompromised populations.”

The investigators also noted that, consistent with a prior single-center study, 60% of patients with CLL developed positive anti–SARS-CoV-2 serology results after polymerase chain reaction diagnosis of COVID-19, adding further evidence of nonuniform antibody production after COVID-19 in patients with CLL.

Study is ongoing to gain understanding of the immune response to SARS-CoV-2 vaccination in patients with CLL, they said.
 

Changing the odds

In a related commentary also published in Blood, Yair Herishanu, MD, and Chava Perry, MD, PhD, of Tel Aviv Sourasky Medical Center called the reduction in mortality over time as reported by Dr. Roeker and colleagues “encouraging and intriguing.”

“One explanation is that the later cohort included a larger proportion of patients with mild symptoms who were diagnosed because of increased awareness of COVID-19 and more extensive screening to detect SARS-CoV-2 over time. That is supported by the lower hospitalization rates and lower rates of hospitalized patients requiring ICU care in the later cohort,” they wrote. “Another possibility is better patient management owing to increasing experience, expanding therapeutic options, and improved capacity of health systems to manage an influx of patients.”

The lower mortality in hospitalized patients over time may reflect better management of patients over time, but it also highlights the significance of “early introduction of various anti–COVID-19 therapies to prevent clinical deterioration to ICU-level care,” they added.

Also intriguing, according to Dr. Herishanu and Dr. Perry, was the finding of increased secondary infections and death rates among corticosteroid-treatment patients.

In the RECOVERY trial, the use of dexamethasone improved survival in patients hospitalized with COVID-19 who received respiratory support. Perhaps the impaired immune reactions in patients with CLL moderate the hyperinflammatory reactions to COVID-19, thus turning corticosteroids beneficial effects to somewhat redundant in this frail population,” they wrote.

Further, the finding that only 60% of patients with CLL seroconvert after the acute phase of SARS-CoV-2 infection suggests CLL patients may be at risk for reinfection, which “justifies vaccinating all patients with CLL who have recovered from COVID-19.”

“Likewise, patients with CLL may develop persistent COVID-19 infection,” they added, explaining that “prolonged shedding of infectious SARS-CoV-2 virus and within-host genomic evolution may eventually lead to emergence of new virus variants.”

Given the high risk of severe COVID-19 disease and impaired antibody-mediated immune response to the virus and its vaccine, a booster dose may be warranted in patients with CLL who fail to achieve seropositivity after 2 vaccine doses, they said.

The available data to date “call for early application of antiviral drugs, [monoclonal antibodies], and convalescent plasma as well as improved vaccination strategy, to improve the odds for patients with CLL confronting COVID-19,” they concluded, adding that large-scale prospective studies on the clinical disease course, outcomes, efficacy of treatments, and vaccination timing and schedule in patients with CLL and COVID-19 are still warranted.

The research was supported by a National Cancer Institute Cancer Center support grant. Dr. Roeker, Dr. Herishanu, and Dr. Perry reported having no financial disclosures.

[email protected]

Younger patients with two genetic subtypes of diffuse large B cell lymphoma (DLBCL) – specifically MCD and N1 – show substantial improvements in survival with the addition of ibrutinib to standard R-CHOP chemotherapy, compared with R-CHOP alone, new research shows.

The findings, published Nov. 4, 2021, in Cancer Cell, come from a subanalysis of the phase 3 Phoenix trial. They show that patients with DLBCL aged 60 and younger with either the MCD or N1 genetic subtype had 3-year event-free survival rates as high as 100% when treated with ibrutinib plus R-CHOP, whereas with R-CHOP chemotherapy alone, the survival rates were approximately half of that rate.

“A 100% 3-year event-free survival is almost unheard-of in DLBCL and speaks to the intense dependency of these subtypes to constitutive B cell receptor signaling and their vulnerability to ibrutinib,” first author Louis M. Staudt, MD, of the Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md., said in an interview.

“By contrast, in ABC DLBCL, the addition of ibrutinib to R-CHOP increased event-free survival by 12.4% to 76.9% in younger patients,” Dr. Staudt said.

ABC, along with GCB and unclassified, are among three key genetic classifications of DLBCL, which is the most common type of lymphoma. While previous studies have shown the Bruton kinase (BTK) inhibitor ibrutinib to induce very low responses among those with the GCB type, favorable responses are seen with the ABC type, of which MCD and N1 are genetic subtypes.

For the Phoenix trial, 838 previously untreated DLBCL patients of the ABC subtype were randomized to ibrutinib (560 mg per day, orally) or placebo plus R-CHOP, in a 21-day cycle for 6 or 8 cycles.

In the overall population, the study failed to achieve its primary survival endpoint of improved survival with ibrutinib. However, a subset analysis stratifying patients by age revealed significant event-free, progression-free, and overall survival benefits with ibrutinib among patients aged 60 and under, with manageable safety. Unexpectedly, this treatment was associated with a worsening of survival outcomes among patients over 60, due to toxicities.

In the new subanalysis, focusing on patients aged 60 and under, Dr. Staudt and his colleagues found that those with the MCD subtype of ABC DLBCL (n = 31) who were treated with ibrutinib had 3-year event-free survival and overall survival rates as high as 100% each, while these rates were significantly lower with R-CHOP alone (48%; P = .01, and 69.6%; P = .032, respectively).

Likewise, among younger patients with the N1 subtype (n = 13), the addition of ibrutinib was associated 3-year event-free and overall survival of 100%, while the R-CHOP alone patients had a significantly lower event-free- (50%; P = .0161) and overall survival (50%; P = .0134).

In the study in general, younger patients who were neither MCD nor N1 also showed better responses with ibrutinib versus placebo; however, the effects were not as strong as those with the MCD and N1 genetic subtypes.

Older patients over 60 showed no benefit from ibrutinib, regardless of their genetic subtype. And benefits were not observed in younger patients with BN2 DLBCL (n = 21), another ABC subtype.

The results are important – despite being secondary endpoints, Dr. Staudt emphasized.

“The automatic assumption regarding secondary endpoints is that any positive findings might have occurred by chance. In the present study, we show that this is not the case.”

“Rather, two previously defined genetic subtypes of DLBCL had an exceptional benefit from ibrutinib,” he said.

“Our study provides strong biological support for the view that the original Phoenix trial should be viewed as a positive trial for younger patients (under 60) with non-GCB DLBCL,” Dr. Staudt said.

While the responses to ibrutinib among younger ABC patients in general were not as robust as with the MCD and N1 subtypes, those improvements nevertheless suggest important benefit with the added treatment, he noted.

“Overall, MCD and N1 constitute roughly 10% of DLBCLs; however, our conclusion is that ibrutinib should be considered in younger patients with non-GCB DLBCL, which constitutes roughly 43% of all DLBCLs,” he said.

Dr. Staudt and other authors are inventors on NIH patent applications covering the LymphGen algorithm (a genetic predictor tool) and covering the use of BTK inhibitors in genetic subtypes of DLBCL. The Phoenix trial received support from Janssen Global Services.

Younger patients with two genetic subtypes of diffuse large B cell lymphoma (DLBCL) – specifically MCD and N1 – show substantial improvements in survival with the addition of ibrutinib to standard R-CHOP chemotherapy, compared with R-CHOP alone, new research shows.

The findings, published Nov. 4, 2021, in Cancer Cell, come from a subanalysis of the phase 3 Phoenix trial. They show that patients with DLBCL aged 60 and younger with either the MCD or N1 genetic subtype had 3-year event-free survival rates as high as 100% when treated with ibrutinib plus R-CHOP, whereas with R-CHOP chemotherapy alone, the survival rates were approximately half of that rate.

“A 100% 3-year event-free survival is almost unheard-of in DLBCL and speaks to the intense dependency of these subtypes to constitutive B cell receptor signaling and their vulnerability to ibrutinib,” first author Louis M. Staudt, MD, of the Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md., said in an interview.

“By contrast, in ABC DLBCL, the addition of ibrutinib to R-CHOP increased event-free survival by 12.4% to 76.9% in younger patients,” Dr. Staudt said.

ABC, along with GCB and unclassified, are among three key genetic classifications of DLBCL, which is the most common type of lymphoma. While previous studies have shown the Bruton kinase (BTK) inhibitor ibrutinib to induce very low responses among those with the GCB type, favorable responses are seen with the ABC type, of which MCD and N1 are genetic subtypes.

For the Phoenix trial, 838 previously untreated DLBCL patients of the ABC subtype were randomized to ibrutinib (560 mg per day, orally) or placebo plus R-CHOP, in a 21-day cycle for 6 or 8 cycles.

In the overall population, the study failed to achieve its primary survival endpoint of improved survival with ibrutinib. However, a subset analysis stratifying patients by age revealed significant event-free, progression-free, and overall survival benefits with ibrutinib among patients aged 60 and under, with manageable safety. Unexpectedly, this treatment was associated with a worsening of survival outcomes among patients over 60, due to toxicities.

In the new subanalysis, focusing on patients aged 60 and under, Dr. Staudt and his colleagues found that those with the MCD subtype of ABC DLBCL (n = 31) who were treated with ibrutinib had 3-year event-free survival and overall survival rates as high as 100% each, while these rates were significantly lower with R-CHOP alone (48%; P = .01, and 69.6%; P = .032, respectively).

Likewise, among younger patients with the N1 subtype (n = 13), the addition of ibrutinib was associated 3-year event-free and overall survival of 100%, while the R-CHOP alone patients had a significantly lower event-free- (50%; P = .0161) and overall survival (50%; P = .0134).

In the study in general, younger patients who were neither MCD nor N1 also showed better responses with ibrutinib versus placebo; however, the effects were not as strong as those with the MCD and N1 genetic subtypes.

Older patients over 60 showed no benefit from ibrutinib, regardless of their genetic subtype. And benefits were not observed in younger patients with BN2 DLBCL (n = 21), another ABC subtype.

The results are important – despite being secondary endpoints, Dr. Staudt emphasized.

“The automatic assumption regarding secondary endpoints is that any positive findings might have occurred by chance. In the present study, we show that this is not the case.”

“Rather, two previously defined genetic subtypes of DLBCL had an exceptional benefit from ibrutinib,” he said.

“Our study provides strong biological support for the view that the original Phoenix trial should be viewed as a positive trial for younger patients (under 60) with non-GCB DLBCL,” Dr. Staudt said.

While the responses to ibrutinib among younger ABC patients in general were not as robust as with the MCD and N1 subtypes, those improvements nevertheless suggest important benefit with the added treatment, he noted.

“Overall, MCD and N1 constitute roughly 10% of DLBCLs; however, our conclusion is that ibrutinib should be considered in younger patients with non-GCB DLBCL, which constitutes roughly 43% of all DLBCLs,” he said.

Dr. Staudt and other authors are inventors on NIH patent applications covering the LymphGen algorithm (a genetic predictor tool) and covering the use of BTK inhibitors in genetic subtypes of DLBCL. The Phoenix trial received support from Janssen Global Services.

Younger patients with two genetic subtypes of diffuse large B cell lymphoma (DLBCL) – specifically MCD and N1 – show substantial improvements in survival with the addition of ibrutinib to standard R-CHOP chemotherapy, compared with R-CHOP alone, new research shows.

The findings, published Nov. 4, 2021, in Cancer Cell, come from a subanalysis of the phase 3 Phoenix trial. They show that patients with DLBCL aged 60 and younger with either the MCD or N1 genetic subtype had 3-year event-free survival rates as high as 100% when treated with ibrutinib plus R-CHOP, whereas with R-CHOP chemotherapy alone, the survival rates were approximately half of that rate.

“A 100% 3-year event-free survival is almost unheard-of in DLBCL and speaks to the intense dependency of these subtypes to constitutive B cell receptor signaling and their vulnerability to ibrutinib,” first author Louis M. Staudt, MD, of the Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md., said in an interview.

“By contrast, in ABC DLBCL, the addition of ibrutinib to R-CHOP increased event-free survival by 12.4% to 76.9% in younger patients,” Dr. Staudt said.

ABC, along with GCB and unclassified, are among three key genetic classifications of DLBCL, which is the most common type of lymphoma. While previous studies have shown the Bruton kinase (BTK) inhibitor ibrutinib to induce very low responses among those with the GCB type, favorable responses are seen with the ABC type, of which MCD and N1 are genetic subtypes.

For the Phoenix trial, 838 previously untreated DLBCL patients of the ABC subtype were randomized to ibrutinib (560 mg per day, orally) or placebo plus R-CHOP, in a 21-day cycle for 6 or 8 cycles.

In the overall population, the study failed to achieve its primary survival endpoint of improved survival with ibrutinib. However, a subset analysis stratifying patients by age revealed significant event-free, progression-free, and overall survival benefits with ibrutinib among patients aged 60 and under, with manageable safety. Unexpectedly, this treatment was associated with a worsening of survival outcomes among patients over 60, due to toxicities.

In the new subanalysis, focusing on patients aged 60 and under, Dr. Staudt and his colleagues found that those with the MCD subtype of ABC DLBCL (n = 31) who were treated with ibrutinib had 3-year event-free survival and overall survival rates as high as 100% each, while these rates were significantly lower with R-CHOP alone (48%; P = .01, and 69.6%; P = .032, respectively).

Likewise, among younger patients with the N1 subtype (n = 13), the addition of ibrutinib was associated 3-year event-free and overall survival of 100%, while the R-CHOP alone patients had a significantly lower event-free- (50%; P = .0161) and overall survival (50%; P = .0134).

In the study in general, younger patients who were neither MCD nor N1 also showed better responses with ibrutinib versus placebo; however, the effects were not as strong as those with the MCD and N1 genetic subtypes.

Older patients over 60 showed no benefit from ibrutinib, regardless of their genetic subtype. And benefits were not observed in younger patients with BN2 DLBCL (n = 21), another ABC subtype.

The results are important – despite being secondary endpoints, Dr. Staudt emphasized.

“The automatic assumption regarding secondary endpoints is that any positive findings might have occurred by chance. In the present study, we show that this is not the case.”

“Rather, two previously defined genetic subtypes of DLBCL had an exceptional benefit from ibrutinib,” he said.

“Our study provides strong biological support for the view that the original Phoenix trial should be viewed as a positive trial for younger patients (under 60) with non-GCB DLBCL,” Dr. Staudt said.

While the responses to ibrutinib among younger ABC patients in general were not as robust as with the MCD and N1 subtypes, those improvements nevertheless suggest important benefit with the added treatment, he noted.

“Overall, MCD and N1 constitute roughly 10% of DLBCLs; however, our conclusion is that ibrutinib should be considered in younger patients with non-GCB DLBCL, which constitutes roughly 43% of all DLBCLs,” he said.

Dr. Staudt and other authors are inventors on NIH patent applications covering the LymphGen algorithm (a genetic predictor tool) and covering the use of BTK inhibitors in genetic subtypes of DLBCL. The Phoenix trial received support from Janssen Global Services.

Large, physician-owned group practices are gaining ground as a popular form of practice, even as the number of physicians in solo and small practices declines, and employment maintains its appeal.

Ridofranz/Thinkstock

As physicians shift from owning private practices to employment in hospital systems, this countertrend is also taking place. Large group practices are growing in number, even as solo and small practices are in decline.

Do large, physician-owned groups bring benefits that beat employment? And how do large groups compare with smaller practices and new opportunities, such as private equity? You’ll find some answers here.
 

Working in large group practices

Large group practices with 50 or more physicians are enjoying a renaissance, even though physicians are still streaming into hospital systems. The share of physicians in large practices increased from 14.7% in 2018 to 17.2% in 2020, the largest 2-year change for this group, according to the American Medical Association.

“Physicians expect that large groups will treat them better than hospitals do,” says Robert Pearl, MD, former CEO of Permanente Medical Group, the nation’s largest physicians’ group. 

Compared with hospitals, “doctors would prefer working in a group practice, if all other things are equal,” says Dr. Pearl, who is now a professor at Stanford (Calif.) University Medical School.

Large group practices can include both multispecialty groups and single-specialty groups. Groups in specialties like urology, orthopedics, and oncology have been growing in recent years, according to Gregory Mertz, managing director of Physician Strategies Group in Virginia Beach, Va.

A group practice could also be an independent physicians association – a federation of small practices that share functions like negotiations with insurers and management. Physicians can also form larger groups for single purposes like running an accountable care organization.

Some large group practices can have a mix of partners and employees. In these groups, “some doctors either don’t want a partnership or aren’t offered one,” says Nathan Miller, CEO of the Medicus Firm, a physician recruitment company in Dallas. The AMA reports that about 10% of physicians are employees of large practices.

“Large groups like the Permanente Medical Group are not partnerships,” Dr. Pearl says. “They tend to be a corporation with a board of directors, and all the physicians are employees, but it’s a physician-led organization.”

Doctors in these groups can enjoy a great deal of control. While Permanente Medical Group is exclusively affiliated with Kaiser, which runs hospitals and an HMO, the group is an independent corporation run by its doctors, who are both shareholders and employees, Dr. Pearl says.

The Cleveland Clinic and Mayo Clinic are not medical groups in the strict sense of the word. They describe themselves as academic medical centers, but Dr. Pearl says, “Doctors have a tremendous amount of control there, particularly those in the most remunerative specialties.”

Pros of large groups 

Group practices are able to focus more on the physician participants’ needs and priorities, says Mr. Mertz. “In a hospital-based organization, physicians’ needs have to compete with the needs of the hospital. … In a large group, it can be easier to get policies changed and order equipment.”

However, for many physicians, their primary reason for joining a large group is having negotiating leverage with health insurance plans, and this leverage seems even more important today. It typically results in higher reimbursements, which could translate into higher pay. The higher practice income, however, could be negated by higher administrative overhead, which is endemic in large organizations.

Mr. Mertz says large groups also have the resources to recruit new doctors. Small practices, in contrast, often decide not to grow. The practice would at first need to guarantee the salary of a new partner, which could require existing partners to take a pay cut, which they often don’t want to do. “They’ll decide to ride the practice into the ground,” which means closing it down when they retire, he says.

Cons of large groups

One individual doctor may have relatively little input in decision-making in a large group, and strong leadership may be lacking. One study examining the pros and cons of large group practices found that lack of physician cooperation, investment, and leadership were the most frequently cited barriers in large groups.

Physicians in large groups can also divide into competing factions. Mr. Mertz says rifts are more likely to take place in multispecialty groups, where higher-reimbursed proceduralists resent having to financially support lower-reimbursed primary care physicians. But it’s rare that such rifts actually break up the practice, he says.
 

Private practice vs. employment

Even as more physicians enter large groups, physicians continue to flee private practice in general. In 2020, the AMA found that the number of physicians in private practices had dropped nearly 5 percentage points since 2018, the largest 2-year drop recorded by the AMA.

The hardest hit are small groups of 10 physicians or fewer, once the backbone of U.S. medicine. A 2020 survey found that 53.7% of physicians still work in small practices of 10 or fewer physicians, compared with 61.4% in 2012.

Private practices tend to be partnerships, but younger physicians, for their part, often don’t want to become a partner. In a 2016 survey, only 22% of medical residents surveyed said they anticipate owning a stake in a practice someday.

What’s good about private practice?

The obvious advantage of private practice is having control. Physician-owners can choose staff, oversee finances, and decide on the direction the practice should take. They don’t have to worry about being fired, because the partnership agreement virtually guarantees each doctor’s place in the group.

The atmosphere in a small practice is often more relaxed. “Private practices tend to offer a family-like environment,” Mr. Miller says. Owners of small practices tend to have lower burnout than large practices, a 2018 study found.

Unlike hospital-employed doctors, private practitioners get to keep their ancillary income. “Physicians own the equipment and receive income generated from ancillary services, not just professional fees,” says Mr. Miller.

What’s negative about private practice?

Since small groups have little negotiating power with private payers, they can’t get favorable reimbursement rates. And while partners are protected from being fired, the practice could still go bankrupt.

Running a private practice means putting on an entrepreneurial hat. To develop a strong practice, you need to learn about marketing, finance, IT, contract negotiations, and facility management. “Most young doctors have no interest in this work,” Mr. Mertz says.

Value-based contracting has added another disadvantage for small practices. “It can be harder for small, independent groups to compete,” says Mike Belkin, JD, a divisional vice president at Merritt Hawkins, a physician recruitment company based in Dallas. “They don’t have the data and integration of services that are necessary for this.”
 

Employment in hospital systems

More than one-third of all physicians worked for hospitals in 2018, and hospitals’ share has been growing since then. In 2020, for the first time, the AMA found that more than half of all physicians were employed, and employment is mainly a hospital phenomenon.

The trend shows no signs of stopping. In 2019 and 2020, hospitals and other corporate entities acquired 20,900 physician practices, representing 29,800 doctors. “This trend will continue,” Dr. Pearl says. “The bigger will get bigger. It’s all about market control. Everyone wants to be wider, more vertical, and more powerful.”

Pros of hospital employment 

“The advantages of hospital employment are mostly financial,” Mr. Mertz says. Unlike a private practice, “there’s no financial risk to hospital employment because you don’t own it. You won’t be on the tab for any losses.”

“Hospitals usually offer a highly competitive salary with less emphasis on production than in a private practice,” he says. New physicians are typically paid a guaranteed salary in the first 1-3 years of employment.

“You don’t have any management responsibilities, as you would in a practice,” Mr. Mertz says. “The hospital has a professional management team to handle the business side. Most young doctors have no interest in this work.”

“Employed physicians have a built-in referral network at a hospital,” Mr. Miller says. This is especially an advantage for new physicians, who don’t yet have a referral network of their own.”

Cons of hospital employment

Physicians employed by a hospital lack control. “You don’t decide the hours you work, the schedules you follow, and the physical facility you work in, and, for the most part, you don’t pick your staff,” Mr. Mertz says.

Like any big organization, hospitals are bureaucratic. “If you want to purchase a new piece of equipment, your request goes up the chain of command,” Mr. Mertz says. “Your purchase has to fit into the budget.” (This can be the case with large groups, too.)

Many employed doctors chafe under this lack of control. In an earlier survey by Medscape, 45% of employed respondents didn’t like having limited influence in decision-making, and 32% said they had less control over their work or schedule.

It’s no wonder that a large percentage of physicians would rather work in practices than hospitals. According to a 2021 Medicus Firm survey, 23% of physicians are interested in working in hospitals, while 40% would rather work either in multispecialty or single-specialty groups, Mr. Miller reports.
 

Doctors have differing views of hospital employment

New physicians are apt to dismiss any negatives about hospitals. “Lack of autonomy often matters less to younger physicians, who were trained in team-based models,” Mr. Belkin says.

Many young doctors actually like working in a large organization. “Young doctors out of residency are used to having everything at their fingertips – labs and testing is in-house,” Mr. Mertz says.

On the other hand, doctors who were previously self-employed – a group that makes up almost one-third of all hospital-employed doctors – can often be dissatisfied with employment. In a 2014 Medscape survey, 26% of previously self-employed doctors said job satisfaction had not improved with employment.

Mr. Mertz says these doctors remember what it was like to be in charge of a practice. “If you once owned a practice, you can always compare what’s going on now with that experience, and that can make you frustrated.”
 

Hospitals have higher turnover

It’s much easier to leave an organization when you don’t have an ownership stake. The annual physician turnover rate at hospitals is 28%, compared with 7% at medical groups, according to a 2019 report.

Mr. Belkin says changing jobs has become a way of life for many doctors. “Staying at a job for only a few years is no longer a red flag,” he says. “Physicians are exploring different options. They might try group practice and switch to hospitals or vice versa.”

Physicians are now part of a high-turnover culture: Once in a new job, many are already thinking about the next one. A 2018 survey found that 46% of doctors planned to leave their position within 3 years.
 

Private equity ownership of practice

Selling majority control of your practice to a private equity firm is a relatively new phenomenon and accounts for a small share of physicians – just 4% in 2020. This trend was originally limited to certain specialties, such as anesthesiology, emergency medicine, and dermatology, but now many others are courted.

The deals work like this: Physicians sell majority control of their practice to investors in return for shares in the private equity practice, and they become employees of that practice. The private equity firm then adds more physicians to the practice and invests in infrastructure with the intention of selling the practice at a large profit, which is then shared with the original physicians.

Pros of private equity

The original owners of the practice stand to make a substantial profit if they are willing to wait several years for the practice to be built up and sold. “If they are patient, they could earn a bonanza,” Mr. Belkin says.

Private equity investment helps the practice expand. “It’s an alternative to going to the bank and borrowing money,” Mr. Mertz says.

Cons of private equity

Physicians lose control of their practice. A client of Mr. Mertz’s briefly considered a private equity offer and turned it down. “The private equity firm would have veto power over what the doctors wanted to do,” he says.

Mr. Belkin says the selling physicians typically lose income after the sale. “Money they earned from ancillary services now goes to the practice,” Mr. Belkin says. The selling doctors could potentially take up to a 30% cut in their compensation, according to Coker Capital Advisors.

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

Large, physician-owned group practices are gaining ground as a popular form of practice, even as the number of physicians in solo and small practices declines, and employment maintains its appeal.

Ridofranz/Thinkstock

As physicians shift from owning private practices to employment in hospital systems, this countertrend is also taking place. Large group practices are growing in number, even as solo and small practices are in decline.

Do large, physician-owned groups bring benefits that beat employment? And how do large groups compare with smaller practices and new opportunities, such as private equity? You’ll find some answers here.
 

Working in large group practices

Large group practices with 50 or more physicians are enjoying a renaissance, even though physicians are still streaming into hospital systems. The share of physicians in large practices increased from 14.7% in 2018 to 17.2% in 2020, the largest 2-year change for this group, according to the American Medical Association.

“Physicians expect that large groups will treat them better than hospitals do,” says Robert Pearl, MD, former CEO of Permanente Medical Group, the nation’s largest physicians’ group. 

Compared with hospitals, “doctors would prefer working in a group practice, if all other things are equal,” says Dr. Pearl, who is now a professor at Stanford (Calif.) University Medical School.

Large group practices can include both multispecialty groups and single-specialty groups. Groups in specialties like urology, orthopedics, and oncology have been growing in recent years, according to Gregory Mertz, managing director of Physician Strategies Group in Virginia Beach, Va.

A group practice could also be an independent physicians association – a federation of small practices that share functions like negotiations with insurers and management. Physicians can also form larger groups for single purposes like running an accountable care organization.

Some large group practices can have a mix of partners and employees. In these groups, “some doctors either don’t want a partnership or aren’t offered one,” says Nathan Miller, CEO of the Medicus Firm, a physician recruitment company in Dallas. The AMA reports that about 10% of physicians are employees of large practices.

“Large groups like the Permanente Medical Group are not partnerships,” Dr. Pearl says. “They tend to be a corporation with a board of directors, and all the physicians are employees, but it’s a physician-led organization.”

Doctors in these groups can enjoy a great deal of control. While Permanente Medical Group is exclusively affiliated with Kaiser, which runs hospitals and an HMO, the group is an independent corporation run by its doctors, who are both shareholders and employees, Dr. Pearl says.

The Cleveland Clinic and Mayo Clinic are not medical groups in the strict sense of the word. They describe themselves as academic medical centers, but Dr. Pearl says, “Doctors have a tremendous amount of control there, particularly those in the most remunerative specialties.”

Pros of large groups 

Group practices are able to focus more on the physician participants’ needs and priorities, says Mr. Mertz. “In a hospital-based organization, physicians’ needs have to compete with the needs of the hospital. … In a large group, it can be easier to get policies changed and order equipment.”

However, for many physicians, their primary reason for joining a large group is having negotiating leverage with health insurance plans, and this leverage seems even more important today. It typically results in higher reimbursements, which could translate into higher pay. The higher practice income, however, could be negated by higher administrative overhead, which is endemic in large organizations.

Mr. Mertz says large groups also have the resources to recruit new doctors. Small practices, in contrast, often decide not to grow. The practice would at first need to guarantee the salary of a new partner, which could require existing partners to take a pay cut, which they often don’t want to do. “They’ll decide to ride the practice into the ground,” which means closing it down when they retire, he says.

Cons of large groups

One individual doctor may have relatively little input in decision-making in a large group, and strong leadership may be lacking. One study examining the pros and cons of large group practices found that lack of physician cooperation, investment, and leadership were the most frequently cited barriers in large groups.

Physicians in large groups can also divide into competing factions. Mr. Mertz says rifts are more likely to take place in multispecialty groups, where higher-reimbursed proceduralists resent having to financially support lower-reimbursed primary care physicians. But it’s rare that such rifts actually break up the practice, he says.
 

Private practice vs. employment

Even as more physicians enter large groups, physicians continue to flee private practice in general. In 2020, the AMA found that the number of physicians in private practices had dropped nearly 5 percentage points since 2018, the largest 2-year drop recorded by the AMA.

The hardest hit are small groups of 10 physicians or fewer, once the backbone of U.S. medicine. A 2020 survey found that 53.7% of physicians still work in small practices of 10 or fewer physicians, compared with 61.4% in 2012.

Private practices tend to be partnerships, but younger physicians, for their part, often don’t want to become a partner. In a 2016 survey, only 22% of medical residents surveyed said they anticipate owning a stake in a practice someday.

What’s good about private practice?

The obvious advantage of private practice is having control. Physician-owners can choose staff, oversee finances, and decide on the direction the practice should take. They don’t have to worry about being fired, because the partnership agreement virtually guarantees each doctor’s place in the group.

The atmosphere in a small practice is often more relaxed. “Private practices tend to offer a family-like environment,” Mr. Miller says. Owners of small practices tend to have lower burnout than large practices, a 2018 study found.

Unlike hospital-employed doctors, private practitioners get to keep their ancillary income. “Physicians own the equipment and receive income generated from ancillary services, not just professional fees,” says Mr. Miller.

What’s negative about private practice?

Since small groups have little negotiating power with private payers, they can’t get favorable reimbursement rates. And while partners are protected from being fired, the practice could still go bankrupt.

Running a private practice means putting on an entrepreneurial hat. To develop a strong practice, you need to learn about marketing, finance, IT, contract negotiations, and facility management. “Most young doctors have no interest in this work,” Mr. Mertz says.

Value-based contracting has added another disadvantage for small practices. “It can be harder for small, independent groups to compete,” says Mike Belkin, JD, a divisional vice president at Merritt Hawkins, a physician recruitment company based in Dallas. “They don’t have the data and integration of services that are necessary for this.”
 

Employment in hospital systems

More than one-third of all physicians worked for hospitals in 2018, and hospitals’ share has been growing since then. In 2020, for the first time, the AMA found that more than half of all physicians were employed, and employment is mainly a hospital phenomenon.

The trend shows no signs of stopping. In 2019 and 2020, hospitals and other corporate entities acquired 20,900 physician practices, representing 29,800 doctors. “This trend will continue,” Dr. Pearl says. “The bigger will get bigger. It’s all about market control. Everyone wants to be wider, more vertical, and more powerful.”

Pros of hospital employment 

“The advantages of hospital employment are mostly financial,” Mr. Mertz says. Unlike a private practice, “there’s no financial risk to hospital employment because you don’t own it. You won’t be on the tab for any losses.”

“Hospitals usually offer a highly competitive salary with less emphasis on production than in a private practice,” he says. New physicians are typically paid a guaranteed salary in the first 1-3 years of employment.

“You don’t have any management responsibilities, as you would in a practice,” Mr. Mertz says. “The hospital has a professional management team to handle the business side. Most young doctors have no interest in this work.”

“Employed physicians have a built-in referral network at a hospital,” Mr. Miller says. This is especially an advantage for new physicians, who don’t yet have a referral network of their own.”

Cons of hospital employment

Physicians employed by a hospital lack control. “You don’t decide the hours you work, the schedules you follow, and the physical facility you work in, and, for the most part, you don’t pick your staff,” Mr. Mertz says.

Like any big organization, hospitals are bureaucratic. “If you want to purchase a new piece of equipment, your request goes up the chain of command,” Mr. Mertz says. “Your purchase has to fit into the budget.” (This can be the case with large groups, too.)

Many employed doctors chafe under this lack of control. In an earlier survey by Medscape, 45% of employed respondents didn’t like having limited influence in decision-making, and 32% said they had less control over their work or schedule.

It’s no wonder that a large percentage of physicians would rather work in practices than hospitals. According to a 2021 Medicus Firm survey, 23% of physicians are interested in working in hospitals, while 40% would rather work either in multispecialty or single-specialty groups, Mr. Miller reports.
 

Doctors have differing views of hospital employment

New physicians are apt to dismiss any negatives about hospitals. “Lack of autonomy often matters less to younger physicians, who were trained in team-based models,” Mr. Belkin says.

Many young doctors actually like working in a large organization. “Young doctors out of residency are used to having everything at their fingertips – labs and testing is in-house,” Mr. Mertz says.

On the other hand, doctors who were previously self-employed – a group that makes up almost one-third of all hospital-employed doctors – can often be dissatisfied with employment. In a 2014 Medscape survey, 26% of previously self-employed doctors said job satisfaction had not improved with employment.

Mr. Mertz says these doctors remember what it was like to be in charge of a practice. “If you once owned a practice, you can always compare what’s going on now with that experience, and that can make you frustrated.”
 

Hospitals have higher turnover

It’s much easier to leave an organization when you don’t have an ownership stake. The annual physician turnover rate at hospitals is 28%, compared with 7% at medical groups, according to a 2019 report.

Mr. Belkin says changing jobs has become a way of life for many doctors. “Staying at a job for only a few years is no longer a red flag,” he says. “Physicians are exploring different options. They might try group practice and switch to hospitals or vice versa.”

Physicians are now part of a high-turnover culture: Once in a new job, many are already thinking about the next one. A 2018 survey found that 46% of doctors planned to leave their position within 3 years.
 

Private equity ownership of practice

Selling majority control of your practice to a private equity firm is a relatively new phenomenon and accounts for a small share of physicians – just 4% in 2020. This trend was originally limited to certain specialties, such as anesthesiology, emergency medicine, and dermatology, but now many others are courted.

The deals work like this: Physicians sell majority control of their practice to investors in return for shares in the private equity practice, and they become employees of that practice. The private equity firm then adds more physicians to the practice and invests in infrastructure with the intention of selling the practice at a large profit, which is then shared with the original physicians.

Pros of private equity

The original owners of the practice stand to make a substantial profit if they are willing to wait several years for the practice to be built up and sold. “If they are patient, they could earn a bonanza,” Mr. Belkin says.

Private equity investment helps the practice expand. “It’s an alternative to going to the bank and borrowing money,” Mr. Mertz says.

Cons of private equity

Physicians lose control of their practice. A client of Mr. Mertz’s briefly considered a private equity offer and turned it down. “The private equity firm would have veto power over what the doctors wanted to do,” he says.

Mr. Belkin says the selling physicians typically lose income after the sale. “Money they earned from ancillary services now goes to the practice,” Mr. Belkin says. The selling doctors could potentially take up to a 30% cut in their compensation, according to Coker Capital Advisors.

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

Large, physician-owned group practices are gaining ground as a popular form of practice, even as the number of physicians in solo and small practices declines, and employment maintains its appeal.

Ridofranz/Thinkstock

As physicians shift from owning private practices to employment in hospital systems, this countertrend is also taking place. Large group practices are growing in number, even as solo and small practices are in decline.

Do large, physician-owned groups bring benefits that beat employment? And how do large groups compare with smaller practices and new opportunities, such as private equity? You’ll find some answers here.
 

Working in large group practices

Large group practices with 50 or more physicians are enjoying a renaissance, even though physicians are still streaming into hospital systems. The share of physicians in large practices increased from 14.7% in 2018 to 17.2% in 2020, the largest 2-year change for this group, according to the American Medical Association.

“Physicians expect that large groups will treat them better than hospitals do,” says Robert Pearl, MD, former CEO of Permanente Medical Group, the nation’s largest physicians’ group. 

Compared with hospitals, “doctors would prefer working in a group practice, if all other things are equal,” says Dr. Pearl, who is now a professor at Stanford (Calif.) University Medical School.

Large group practices can include both multispecialty groups and single-specialty groups. Groups in specialties like urology, orthopedics, and oncology have been growing in recent years, according to Gregory Mertz, managing director of Physician Strategies Group in Virginia Beach, Va.

A group practice could also be an independent physicians association – a federation of small practices that share functions like negotiations with insurers and management. Physicians can also form larger groups for single purposes like running an accountable care organization.

Some large group practices can have a mix of partners and employees. In these groups, “some doctors either don’t want a partnership or aren’t offered one,” says Nathan Miller, CEO of the Medicus Firm, a physician recruitment company in Dallas. The AMA reports that about 10% of physicians are employees of large practices.

“Large groups like the Permanente Medical Group are not partnerships,” Dr. Pearl says. “They tend to be a corporation with a board of directors, and all the physicians are employees, but it’s a physician-led organization.”

Doctors in these groups can enjoy a great deal of control. While Permanente Medical Group is exclusively affiliated with Kaiser, which runs hospitals and an HMO, the group is an independent corporation run by its doctors, who are both shareholders and employees, Dr. Pearl says.

The Cleveland Clinic and Mayo Clinic are not medical groups in the strict sense of the word. They describe themselves as academic medical centers, but Dr. Pearl says, “Doctors have a tremendous amount of control there, particularly those in the most remunerative specialties.”

Pros of large groups 

Group practices are able to focus more on the physician participants’ needs and priorities, says Mr. Mertz. “In a hospital-based organization, physicians’ needs have to compete with the needs of the hospital. … In a large group, it can be easier to get policies changed and order equipment.”

However, for many physicians, their primary reason for joining a large group is having negotiating leverage with health insurance plans, and this leverage seems even more important today. It typically results in higher reimbursements, which could translate into higher pay. The higher practice income, however, could be negated by higher administrative overhead, which is endemic in large organizations.

Mr. Mertz says large groups also have the resources to recruit new doctors. Small practices, in contrast, often decide not to grow. The practice would at first need to guarantee the salary of a new partner, which could require existing partners to take a pay cut, which they often don’t want to do. “They’ll decide to ride the practice into the ground,” which means closing it down when they retire, he says.

Cons of large groups

One individual doctor may have relatively little input in decision-making in a large group, and strong leadership may be lacking. One study examining the pros and cons of large group practices found that lack of physician cooperation, investment, and leadership were the most frequently cited barriers in large groups.

Physicians in large groups can also divide into competing factions. Mr. Mertz says rifts are more likely to take place in multispecialty groups, where higher-reimbursed proceduralists resent having to financially support lower-reimbursed primary care physicians. But it’s rare that such rifts actually break up the practice, he says.
 

Private practice vs. employment

Even as more physicians enter large groups, physicians continue to flee private practice in general. In 2020, the AMA found that the number of physicians in private practices had dropped nearly 5 percentage points since 2018, the largest 2-year drop recorded by the AMA.

The hardest hit are small groups of 10 physicians or fewer, once the backbone of U.S. medicine. A 2020 survey found that 53.7% of physicians still work in small practices of 10 or fewer physicians, compared with 61.4% in 2012.

Private practices tend to be partnerships, but younger physicians, for their part, often don’t want to become a partner. In a 2016 survey, only 22% of medical residents surveyed said they anticipate owning a stake in a practice someday.

What’s good about private practice?

The obvious advantage of private practice is having control. Physician-owners can choose staff, oversee finances, and decide on the direction the practice should take. They don’t have to worry about being fired, because the partnership agreement virtually guarantees each doctor’s place in the group.

The atmosphere in a small practice is often more relaxed. “Private practices tend to offer a family-like environment,” Mr. Miller says. Owners of small practices tend to have lower burnout than large practices, a 2018 study found.

Unlike hospital-employed doctors, private practitioners get to keep their ancillary income. “Physicians own the equipment and receive income generated from ancillary services, not just professional fees,” says Mr. Miller.

What’s negative about private practice?

Since small groups have little negotiating power with private payers, they can’t get favorable reimbursement rates. And while partners are protected from being fired, the practice could still go bankrupt.

Running a private practice means putting on an entrepreneurial hat. To develop a strong practice, you need to learn about marketing, finance, IT, contract negotiations, and facility management. “Most young doctors have no interest in this work,” Mr. Mertz says.

Value-based contracting has added another disadvantage for small practices. “It can be harder for small, independent groups to compete,” says Mike Belkin, JD, a divisional vice president at Merritt Hawkins, a physician recruitment company based in Dallas. “They don’t have the data and integration of services that are necessary for this.”
 

Employment in hospital systems

More than one-third of all physicians worked for hospitals in 2018, and hospitals’ share has been growing since then. In 2020, for the first time, the AMA found that more than half of all physicians were employed, and employment is mainly a hospital phenomenon.

The trend shows no signs of stopping. In 2019 and 2020, hospitals and other corporate entities acquired 20,900 physician practices, representing 29,800 doctors. “This trend will continue,” Dr. Pearl says. “The bigger will get bigger. It’s all about market control. Everyone wants to be wider, more vertical, and more powerful.”

Pros of hospital employment 

“The advantages of hospital employment are mostly financial,” Mr. Mertz says. Unlike a private practice, “there’s no financial risk to hospital employment because you don’t own it. You won’t be on the tab for any losses.”

“Hospitals usually offer a highly competitive salary with less emphasis on production than in a private practice,” he says. New physicians are typically paid a guaranteed salary in the first 1-3 years of employment.

“You don’t have any management responsibilities, as you would in a practice,” Mr. Mertz says. “The hospital has a professional management team to handle the business side. Most young doctors have no interest in this work.”

“Employed physicians have a built-in referral network at a hospital,” Mr. Miller says. This is especially an advantage for new physicians, who don’t yet have a referral network of their own.”

Cons of hospital employment

Physicians employed by a hospital lack control. “You don’t decide the hours you work, the schedules you follow, and the physical facility you work in, and, for the most part, you don’t pick your staff,” Mr. Mertz says.

Like any big organization, hospitals are bureaucratic. “If you want to purchase a new piece of equipment, your request goes up the chain of command,” Mr. Mertz says. “Your purchase has to fit into the budget.” (This can be the case with large groups, too.)

Many employed doctors chafe under this lack of control. In an earlier survey by Medscape, 45% of employed respondents didn’t like having limited influence in decision-making, and 32% said they had less control over their work or schedule.

It’s no wonder that a large percentage of physicians would rather work in practices than hospitals. According to a 2021 Medicus Firm survey, 23% of physicians are interested in working in hospitals, while 40% would rather work either in multispecialty or single-specialty groups, Mr. Miller reports.
 

Doctors have differing views of hospital employment

New physicians are apt to dismiss any negatives about hospitals. “Lack of autonomy often matters less to younger physicians, who were trained in team-based models,” Mr. Belkin says.

Many young doctors actually like working in a large organization. “Young doctors out of residency are used to having everything at their fingertips – labs and testing is in-house,” Mr. Mertz says.

On the other hand, doctors who were previously self-employed – a group that makes up almost one-third of all hospital-employed doctors – can often be dissatisfied with employment. In a 2014 Medscape survey, 26% of previously self-employed doctors said job satisfaction had not improved with employment.

Mr. Mertz says these doctors remember what it was like to be in charge of a practice. “If you once owned a practice, you can always compare what’s going on now with that experience, and that can make you frustrated.”
 

Hospitals have higher turnover

It’s much easier to leave an organization when you don’t have an ownership stake. The annual physician turnover rate at hospitals is 28%, compared with 7% at medical groups, according to a 2019 report.

Mr. Belkin says changing jobs has become a way of life for many doctors. “Staying at a job for only a few years is no longer a red flag,” he says. “Physicians are exploring different options. They might try group practice and switch to hospitals or vice versa.”

Physicians are now part of a high-turnover culture: Once in a new job, many are already thinking about the next one. A 2018 survey found that 46% of doctors planned to leave their position within 3 years.
 

Private equity ownership of practice

Selling majority control of your practice to a private equity firm is a relatively new phenomenon and accounts for a small share of physicians – just 4% in 2020. This trend was originally limited to certain specialties, such as anesthesiology, emergency medicine, and dermatology, but now many others are courted.

The deals work like this: Physicians sell majority control of their practice to investors in return for shares in the private equity practice, and they become employees of that practice. The private equity firm then adds more physicians to the practice and invests in infrastructure with the intention of selling the practice at a large profit, which is then shared with the original physicians.

Pros of private equity

The original owners of the practice stand to make a substantial profit if they are willing to wait several years for the practice to be built up and sold. “If they are patient, they could earn a bonanza,” Mr. Belkin says.

Private equity investment helps the practice expand. “It’s an alternative to going to the bank and borrowing money,” Mr. Mertz says.

Cons of private equity

Physicians lose control of their practice. A client of Mr. Mertz’s briefly considered a private equity offer and turned it down. “The private equity firm would have veto power over what the doctors wanted to do,” he says.

Mr. Belkin says the selling physicians typically lose income after the sale. “Money they earned from ancillary services now goes to the practice,” Mr. Belkin says. The selling doctors could potentially take up to a 30% cut in their compensation, according to Coker Capital Advisors.

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

Physician practices around the country took an unprecedented financial hit with the arrival of the COVID-19 pandemic in March 2020. Recent research from the American Medical Association reveals an estimated pandemic-related shortfall in Medicare physician fee spending of $13.9 billion, or a 14% reduction, across all states and all major specialties in 2020.

While the report pointed to a “strong recovery” in May and June, that recovery stalled in the second half of 2020, and spending never returned to pre–COVID-19 levels.

“Physicians experienced a significant and sustained drop in Medicare revenue during the first 10 months of the pandemic,” said AMA President Gerald Harmon, MD, in a statement. “Medical practices that have not buckled under financial strain continue to be stretched clinically, emotionally, and fiscally as the pandemic persists. Yet physicians face an array of planned cuts that would reduce Medicare physician payments by nearly 10% for 2022.”

The reduction in the Medicare physician fee schedule payments means providers may face payment cuts of more than 9% starting Jan. 1, 2022, when the cuts take effect. That is, unless Congress makes changes.

Medicare physician fee schedule spending on telehealth stood at $4.1 billion, or 5% of the total Medicare spent in 2020. From March 16 to June 30, $1.8 billion of this amount was on telehealth, while $1.1 billion came in during third and fourth quarters of 2020, respectively, per the report.

According to AMA’s research:

• Medicare physician fee schedule spending for 2020, relative to expected 2020 spending, dipped 32% between March 16 and June 30; spending was down during the last 6 months of the year by between 9% and 10%.
• The care settings hit the worst were ambulatory surgical centers, outpatient hospitals, and physician offices; the next worst off were hospital emergency departments, inpatient hospitals, and skilled nursing facilities.
• The specialties that fared worst included physical therapists (-28%), opthamologists (-19%), podiatrists (-18%), and dermatologists (-18%).
• Cumulative spending was down the most in Minnesota (-22%), Maine (-19%), and New York (-19%); less affected states included Idaho (-9%), Oklahoma (-9%), and South Carolina (9%).

AMA: Budget neutrality hurting physicians’ financial stability

Dr. Harmon is calling for financial stability in Medicare spending. In particular, the AMA is “strongly urging Congress to avert the planned payment cuts,” he said in a statement.

The challenge: The Medicare physician fee schedule is currently “budget neutral,” meaning that the budget is fixed, Dr. Harmon, a family medicine specialist in South Carolina, told this news organization.

“If you rob from Peter to pay Paul, Paul is going to be less efficient or less rewarded. It continues to be that there’s always a ‘pay for’ in these things. So budget neutrality is probably one of the first things we need to address,” he said.
 

Lack of routine care expected to affect health outcomes

The result of reduced screening and treatment during the pandemic could be as many as 10,000 excess deaths due to cancers of the breast and colon during the next 10 years, wrote Norman Sharpless, MD, director of the National Cancer Institute, in Science in June. Combined, breast cancer and colon cancer account for one-sixth of all cancers in the U.S., he wrote.

In addition, blood pressure control has gotten worse since the start of the pandemic, said Michael Rakotz, MD, FAHA, FAAFP, vice president of improving health outcomes at the AMA, in an AMA blog post.

Dr. Harmon’s advice for physician practices on getting patients in for routine care:

• Educate the area’s largest employers to encourage their employees.
• Engage with hospital employees, since hospitals are often the largest employers in many communities.
• Partner with health insurers.
• Show up at athletic events, which is a particularly good fit for “small town America,” said Dr. Harmon.

The AMA’s research doesn’t consider reimbursement from other public and private payers. It also doesn’t account for funding sources such as Provider Relief Fund grants, Paycheck Protection Program loans, and the temporary suspension of the Medicare sequester, per the report.

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

Physician practices around the country took an unprecedented financial hit with the arrival of the COVID-19 pandemic in March 2020. Recent research from the American Medical Association reveals an estimated pandemic-related shortfall in Medicare physician fee spending of $13.9 billion, or a 14% reduction, across all states and all major specialties in 2020.

While the report pointed to a “strong recovery” in May and June, that recovery stalled in the second half of 2020, and spending never returned to pre–COVID-19 levels.

“Physicians experienced a significant and sustained drop in Medicare revenue during the first 10 months of the pandemic,” said AMA President Gerald Harmon, MD, in a statement. “Medical practices that have not buckled under financial strain continue to be stretched clinically, emotionally, and fiscally as the pandemic persists. Yet physicians face an array of planned cuts that would reduce Medicare physician payments by nearly 10% for 2022.”

The reduction in the Medicare physician fee schedule payments means providers may face payment cuts of more than 9% starting Jan. 1, 2022, when the cuts take effect. That is, unless Congress makes changes.

Medicare physician fee schedule spending on telehealth stood at $4.1 billion, or 5% of the total Medicare spent in 2020. From March 16 to June 30, $1.8 billion of this amount was on telehealth, while $1.1 billion came in during third and fourth quarters of 2020, respectively, per the report.

According to AMA’s research:

• Medicare physician fee schedule spending for 2020, relative to expected 2020 spending, dipped 32% between March 16 and June 30; spending was down during the last 6 months of the year by between 9% and 10%.
• The care settings hit the worst were ambulatory surgical centers, outpatient hospitals, and physician offices; the next worst off were hospital emergency departments, inpatient hospitals, and skilled nursing facilities.
• The specialties that fared worst included physical therapists (-28%), opthamologists (-19%), podiatrists (-18%), and dermatologists (-18%).
• Cumulative spending was down the most in Minnesota (-22%), Maine (-19%), and New York (-19%); less affected states included Idaho (-9%), Oklahoma (-9%), and South Carolina (9%).

AMA: Budget neutrality hurting physicians’ financial stability

Dr. Harmon is calling for financial stability in Medicare spending. In particular, the AMA is “strongly urging Congress to avert the planned payment cuts,” he said in a statement.

The challenge: The Medicare physician fee schedule is currently “budget neutral,” meaning that the budget is fixed, Dr. Harmon, a family medicine specialist in South Carolina, told this news organization.

“If you rob from Peter to pay Paul, Paul is going to be less efficient or less rewarded. It continues to be that there’s always a ‘pay for’ in these things. So budget neutrality is probably one of the first things we need to address,” he said.
 

Lack of routine care expected to affect health outcomes

The result of reduced screening and treatment during the pandemic could be as many as 10,000 excess deaths due to cancers of the breast and colon during the next 10 years, wrote Norman Sharpless, MD, director of the National Cancer Institute, in Science in June. Combined, breast cancer and colon cancer account for one-sixth of all cancers in the U.S., he wrote.

In addition, blood pressure control has gotten worse since the start of the pandemic, said Michael Rakotz, MD, FAHA, FAAFP, vice president of improving health outcomes at the AMA, in an AMA blog post.

Dr. Harmon’s advice for physician practices on getting patients in for routine care:

• Educate the area’s largest employers to encourage their employees.
• Engage with hospital employees, since hospitals are often the largest employers in many communities.
• Partner with health insurers.
• Show up at athletic events, which is a particularly good fit for “small town America,” said Dr. Harmon.

The AMA’s research doesn’t consider reimbursement from other public and private payers. It also doesn’t account for funding sources such as Provider Relief Fund grants, Paycheck Protection Program loans, and the temporary suspension of the Medicare sequester, per the report.

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

Physician practices around the country took an unprecedented financial hit with the arrival of the COVID-19 pandemic in March 2020. Recent research from the American Medical Association reveals an estimated pandemic-related shortfall in Medicare physician fee spending of $13.9 billion, or a 14% reduction, across all states and all major specialties in 2020.

While the report pointed to a “strong recovery” in May and June, that recovery stalled in the second half of 2020, and spending never returned to pre–COVID-19 levels.

“Physicians experienced a significant and sustained drop in Medicare revenue during the first 10 months of the pandemic,” said AMA President Gerald Harmon, MD, in a statement. “Medical practices that have not buckled under financial strain continue to be stretched clinically, emotionally, and fiscally as the pandemic persists. Yet physicians face an array of planned cuts that would reduce Medicare physician payments by nearly 10% for 2022.”

The reduction in the Medicare physician fee schedule payments means providers may face payment cuts of more than 9% starting Jan. 1, 2022, when the cuts take effect. That is, unless Congress makes changes.

Medicare physician fee schedule spending on telehealth stood at $4.1 billion, or 5% of the total Medicare spent in 2020. From March 16 to June 30, $1.8 billion of this amount was on telehealth, while $1.1 billion came in during third and fourth quarters of 2020, respectively, per the report.

According to AMA’s research:

• Medicare physician fee schedule spending for 2020, relative to expected 2020 spending, dipped 32% between March 16 and June 30; spending was down during the last 6 months of the year by between 9% and 10%.
• The care settings hit the worst were ambulatory surgical centers, outpatient hospitals, and physician offices; the next worst off were hospital emergency departments, inpatient hospitals, and skilled nursing facilities.
• The specialties that fared worst included physical therapists (-28%), opthamologists (-19%), podiatrists (-18%), and dermatologists (-18%).
• Cumulative spending was down the most in Minnesota (-22%), Maine (-19%), and New York (-19%); less affected states included Idaho (-9%), Oklahoma (-9%), and South Carolina (9%).

AMA: Budget neutrality hurting physicians’ financial stability

Dr. Harmon is calling for financial stability in Medicare spending. In particular, the AMA is “strongly urging Congress to avert the planned payment cuts,” he said in a statement.

The challenge: The Medicare physician fee schedule is currently “budget neutral,” meaning that the budget is fixed, Dr. Harmon, a family medicine specialist in South Carolina, told this news organization.

“If you rob from Peter to pay Paul, Paul is going to be less efficient or less rewarded. It continues to be that there’s always a ‘pay for’ in these things. So budget neutrality is probably one of the first things we need to address,” he said.
 

Lack of routine care expected to affect health outcomes

The result of reduced screening and treatment during the pandemic could be as many as 10,000 excess deaths due to cancers of the breast and colon during the next 10 years, wrote Norman Sharpless, MD, director of the National Cancer Institute, in Science in June. Combined, breast cancer and colon cancer account for one-sixth of all cancers in the U.S., he wrote.

In addition, blood pressure control has gotten worse since the start of the pandemic, said Michael Rakotz, MD, FAHA, FAAFP, vice president of improving health outcomes at the AMA, in an AMA blog post.

Dr. Harmon’s advice for physician practices on getting patients in for routine care:

• Educate the area’s largest employers to encourage their employees.
• Engage with hospital employees, since hospitals are often the largest employers in many communities.
• Partner with health insurers.
• Show up at athletic events, which is a particularly good fit for “small town America,” said Dr. Harmon.

The AMA’s research doesn’t consider reimbursement from other public and private payers. It also doesn’t account for funding sources such as Provider Relief Fund grants, Paycheck Protection Program loans, and the temporary suspension of the Medicare sequester, per the report.

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

Online reviews and star ratings are the most important factor in choosing a new health care provider, according to a new survey from Press Ganey, a provider of patient satisfaction surveys. According to the data, this online information is more important to consumers in selecting a physician than another doctor’s referral and is more than twice as important when choosing a primary care physician.

m-imagephotography/Thinkstock.com

In fact, 83% of respondents said they went online to read reviews of a physician after receiving a referral from another provider.

The online research trend reflects not only the increased familiarity of all generations with the internet but also the growing consumerization of health care, Thomas Jeffrey, president of the Sullivan/Luallin Group, a patient experience consulting firm, told this news organization.

“According to patient satisfaction surveys, people are becoming health care consumers more than in the past,” he noted. “Historically, we didn’t look at health care as a consumer product. But, with high deductibles and copays, doctor visits can represent a pretty significant out-of-pocket expense. As it begins to hit folks’ pocketbooks, they become more savvy shoppers.”

Digital preferences for providers were gaining “positive momentum” even before the COVID-19 pandemic, but the crisis “drove upticks in some consumer digital behaviors,” the Press Ganey report pointed out.

Mr. Jeffrey agreed, noting that this finding matches what Sullivan/Luallin has discovered in its research. “I think the pandemic pushed people to engage more online,” he said. “The highest net promoter score [likelihood to recommend in market surveys] for a pharmacy is the Amazon pharmacy, which is an online-based delivery service. Then you have telehealth visits, which are more convenient in many ways.”
 

How patients search online

In choosing a new primary care doctor, 51.1% go on the web first, 23.8% seek a referral from another health care provider, and 4.4% get information from an insurer or a benefits manager, according to the survey.

The factors that matter most to consumers when they pick any provider, in order, are online ratings and reviews of the physician, referral from a current doctor, ratings and reviews of the facility, and the quality and completeness of a doctor’s profile on a website or online directory. The doctor’s online presence and the quality of their website are also important.

According to Press Ganey, search engines like Google are the most used digital resources, with 65.4% of consumers employing them to find a doctor. However, consumers now use an average of 2.7 sites in their search. The leading destinations are a hospital or a clinic site, WebMD, Healthgrades, and Facebook. (This news organization is owned by WebMD.)

Compared with 2019, the report said, there has been a 22.8% decline in the use of search engines for seeking a doctor and a 53.7% increase in the use of health care review sites such as Healthgrades and Vitals.

When reading provider reviews, consumers look for more recent reviews and want the reviews to be “authentic and informative.” They also value the star ratings. About 84%of respondents said they wouldn’t book an appointment with a referred provider that had a rating of less than four stars.

Overall, the top reasons why people are deterred from making an appointment are difficulty contacting the office, the poor quality of online reviews, and an average online rating of less than four stars.

The vast majority of respondents (77%) said they believe internet reviews reflect their own experience with a provider organization, and only 2.6% said the reviews were inaccurate. Another finding of the survey indicates that this attention of patients to reviews of their own provider doesn’t represent idle curiosity: About 57% of Baby Boomers and 45% of millennials/Gen Z’ers said they’d written online reviews of a doctor or a hospital.
 

Factors in patient loyalty

The Press Ganey survey asked which of several factors, besides excellent care, patients weighed when giving a five-star review to a health care provider.

Quality of customer service was rated first by 70.8% of respondents, followed by cleanliness of facilities (67.5%), communication (63.4%), the provider’s bedside manner (63%), ease of appointment booking (58.8%), ease of patient intake/registration (52.3%), quality and accuracy of information (40.1%), availability of telehealth services (21.7%), and waiting room amenities (21.8%).

The report explained that “quality of customer service” means “demeanor, attentiveness, and helpfulness of staff and practitioners.” “Communication” refers to things like follow-up appointment reminders and annual checkup reminders.

According to Mr. Jeffrey, these factors were considered more important than a doctor’s bedside manner because of the team care approach in most physician offices. “We see a lot more folks derive their notion of quality from continuity of care. And if they feel the physician they love is being supported by a less than competent team, that can impact significantly their sense of the quality of care,” he said.
 

Online appointment booking is a must

To win over the online consumer, Press Ganey emphasized, practices should ensure that provider listings are accurate and complete. In addition, offering online appointment booking can avoid the top challenge in making a new appointment, which is getting through to the office.

Mr. Jeffrey concurred, although he notes that practices have to be careful about how they enable patients to select appointment slots online. He suggests that an appointment request form on a patient portal first ask what the purpose of the visit is and that it offer five or so options. If the request fits into a routine visit category, the provider’s calendar pops up and the patient can select a convenient time slot. If it’s something else, an appointment scheduler calls the patient back.

“There needs to be greater access to standard appointments online,” he said. “While privacy is an issue, you can use the patient portal that most EHRs have to provide online booking. If you want to succeed going forward, that’s going to be a major plus.”

Of course, to do any of this, including reading provider reviews, a consumer needs a good internet connection and a mobile or desktop device. While broadband internet access is still not available in some communities, the breakdown of the survey respondents by demographics shows that low-income people were included.

Mr. Jeffrey doesn’t believe that a lack of internet access or digital devices prevents many Americans from going online today. “Even in poor communities, most people have internet access through their smartphones. Even baby boomers are familiar with smartphones. I haven’t seen internet access be a big barrier for low-income households, because they all have access to phones.”

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

Online reviews and star ratings are the most important factor in choosing a new health care provider, according to a new survey from Press Ganey, a provider of patient satisfaction surveys. According to the data, this online information is more important to consumers in selecting a physician than another doctor’s referral and is more than twice as important when choosing a primary care physician.

m-imagephotography/Thinkstock.com

In fact, 83% of respondents said they went online to read reviews of a physician after receiving a referral from another provider.

The online research trend reflects not only the increased familiarity of all generations with the internet but also the growing consumerization of health care, Thomas Jeffrey, president of the Sullivan/Luallin Group, a patient experience consulting firm, told this news organization.

“According to patient satisfaction surveys, people are becoming health care consumers more than in the past,” he noted. “Historically, we didn’t look at health care as a consumer product. But, with high deductibles and copays, doctor visits can represent a pretty significant out-of-pocket expense. As it begins to hit folks’ pocketbooks, they become more savvy shoppers.”

Digital preferences for providers were gaining “positive momentum” even before the COVID-19 pandemic, but the crisis “drove upticks in some consumer digital behaviors,” the Press Ganey report pointed out.

Mr. Jeffrey agreed, noting that this finding matches what Sullivan/Luallin has discovered in its research. “I think the pandemic pushed people to engage more online,” he said. “The highest net promoter score [likelihood to recommend in market surveys] for a pharmacy is the Amazon pharmacy, which is an online-based delivery service. Then you have telehealth visits, which are more convenient in many ways.”
 

How patients search online

In choosing a new primary care doctor, 51.1% go on the web first, 23.8% seek a referral from another health care provider, and 4.4% get information from an insurer or a benefits manager, according to the survey.

The factors that matter most to consumers when they pick any provider, in order, are online ratings and reviews of the physician, referral from a current doctor, ratings and reviews of the facility, and the quality and completeness of a doctor’s profile on a website or online directory. The doctor’s online presence and the quality of their website are also important.

According to Press Ganey, search engines like Google are the most used digital resources, with 65.4% of consumers employing them to find a doctor. However, consumers now use an average of 2.7 sites in their search. The leading destinations are a hospital or a clinic site, WebMD, Healthgrades, and Facebook. (This news organization is owned by WebMD.)

Compared with 2019, the report said, there has been a 22.8% decline in the use of search engines for seeking a doctor and a 53.7% increase in the use of health care review sites such as Healthgrades and Vitals.

When reading provider reviews, consumers look for more recent reviews and want the reviews to be “authentic and informative.” They also value the star ratings. About 84%of respondents said they wouldn’t book an appointment with a referred provider that had a rating of less than four stars.

Overall, the top reasons why people are deterred from making an appointment are difficulty contacting the office, the poor quality of online reviews, and an average online rating of less than four stars.

The vast majority of respondents (77%) said they believe internet reviews reflect their own experience with a provider organization, and only 2.6% said the reviews were inaccurate. Another finding of the survey indicates that this attention of patients to reviews of their own provider doesn’t represent idle curiosity: About 57% of Baby Boomers and 45% of millennials/Gen Z’ers said they’d written online reviews of a doctor or a hospital.
 

Factors in patient loyalty

The Press Ganey survey asked which of several factors, besides excellent care, patients weighed when giving a five-star review to a health care provider.

Quality of customer service was rated first by 70.8% of respondents, followed by cleanliness of facilities (67.5%), communication (63.4%), the provider’s bedside manner (63%), ease of appointment booking (58.8%), ease of patient intake/registration (52.3%), quality and accuracy of information (40.1%), availability of telehealth services (21.7%), and waiting room amenities (21.8%).

The report explained that “quality of customer service” means “demeanor, attentiveness, and helpfulness of staff and practitioners.” “Communication” refers to things like follow-up appointment reminders and annual checkup reminders.

According to Mr. Jeffrey, these factors were considered more important than a doctor’s bedside manner because of the team care approach in most physician offices. “We see a lot more folks derive their notion of quality from continuity of care. And if they feel the physician they love is being supported by a less than competent team, that can impact significantly their sense of the quality of care,” he said.
 

Online appointment booking is a must

To win over the online consumer, Press Ganey emphasized, practices should ensure that provider listings are accurate and complete. In addition, offering online appointment booking can avoid the top challenge in making a new appointment, which is getting through to the office.

Mr. Jeffrey concurred, although he notes that practices have to be careful about how they enable patients to select appointment slots online. He suggests that an appointment request form on a patient portal first ask what the purpose of the visit is and that it offer five or so options. If the request fits into a routine visit category, the provider’s calendar pops up and the patient can select a convenient time slot. If it’s something else, an appointment scheduler calls the patient back.

“There needs to be greater access to standard appointments online,” he said. “While privacy is an issue, you can use the patient portal that most EHRs have to provide online booking. If you want to succeed going forward, that’s going to be a major plus.”

Of course, to do any of this, including reading provider reviews, a consumer needs a good internet connection and a mobile or desktop device. While broadband internet access is still not available in some communities, the breakdown of the survey respondents by demographics shows that low-income people were included.

Mr. Jeffrey doesn’t believe that a lack of internet access or digital devices prevents many Americans from going online today. “Even in poor communities, most people have internet access through their smartphones. Even baby boomers are familiar with smartphones. I haven’t seen internet access be a big barrier for low-income households, because they all have access to phones.”

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

Online reviews and star ratings are the most important factor in choosing a new health care provider, according to a new survey from Press Ganey, a provider of patient satisfaction surveys. According to the data, this online information is more important to consumers in selecting a physician than another doctor’s referral and is more than twice as important when choosing a primary care physician.

m-imagephotography/Thinkstock.com

In fact, 83% of respondents said they went online to read reviews of a physician after receiving a referral from another provider.

The online research trend reflects not only the increased familiarity of all generations with the internet but also the growing consumerization of health care, Thomas Jeffrey, president of the Sullivan/Luallin Group, a patient experience consulting firm, told this news organization.

“According to patient satisfaction surveys, people are becoming health care consumers more than in the past,” he noted. “Historically, we didn’t look at health care as a consumer product. But, with high deductibles and copays, doctor visits can represent a pretty significant out-of-pocket expense. As it begins to hit folks’ pocketbooks, they become more savvy shoppers.”

Digital preferences for providers were gaining “positive momentum” even before the COVID-19 pandemic, but the crisis “drove upticks in some consumer digital behaviors,” the Press Ganey report pointed out.

Mr. Jeffrey agreed, noting that this finding matches what Sullivan/Luallin has discovered in its research. “I think the pandemic pushed people to engage more online,” he said. “The highest net promoter score [likelihood to recommend in market surveys] for a pharmacy is the Amazon pharmacy, which is an online-based delivery service. Then you have telehealth visits, which are more convenient in many ways.”
 

How patients search online

In choosing a new primary care doctor, 51.1% go on the web first, 23.8% seek a referral from another health care provider, and 4.4% get information from an insurer or a benefits manager, according to the survey.

The factors that matter most to consumers when they pick any provider, in order, are online ratings and reviews of the physician, referral from a current doctor, ratings and reviews of the facility, and the quality and completeness of a doctor’s profile on a website or online directory. The doctor’s online presence and the quality of their website are also important.

According to Press Ganey, search engines like Google are the most used digital resources, with 65.4% of consumers employing them to find a doctor. However, consumers now use an average of 2.7 sites in their search. The leading destinations are a hospital or a clinic site, WebMD, Healthgrades, and Facebook. (This news organization is owned by WebMD.)

Compared with 2019, the report said, there has been a 22.8% decline in the use of search engines for seeking a doctor and a 53.7% increase in the use of health care review sites such as Healthgrades and Vitals.

When reading provider reviews, consumers look for more recent reviews and want the reviews to be “authentic and informative.” They also value the star ratings. About 84%of respondents said they wouldn’t book an appointment with a referred provider that had a rating of less than four stars.

Overall, the top reasons why people are deterred from making an appointment are difficulty contacting the office, the poor quality of online reviews, and an average online rating of less than four stars.

The vast majority of respondents (77%) said they believe internet reviews reflect their own experience with a provider organization, and only 2.6% said the reviews were inaccurate. Another finding of the survey indicates that this attention of patients to reviews of their own provider doesn’t represent idle curiosity: About 57% of Baby Boomers and 45% of millennials/Gen Z’ers said they’d written online reviews of a doctor or a hospital.
 

Factors in patient loyalty

The Press Ganey survey asked which of several factors, besides excellent care, patients weighed when giving a five-star review to a health care provider.

Quality of customer service was rated first by 70.8% of respondents, followed by cleanliness of facilities (67.5%), communication (63.4%), the provider’s bedside manner (63%), ease of appointment booking (58.8%), ease of patient intake/registration (52.3%), quality and accuracy of information (40.1%), availability of telehealth services (21.7%), and waiting room amenities (21.8%).

The report explained that “quality of customer service” means “demeanor, attentiveness, and helpfulness of staff and practitioners.” “Communication” refers to things like follow-up appointment reminders and annual checkup reminders.

According to Mr. Jeffrey, these factors were considered more important than a doctor’s bedside manner because of the team care approach in most physician offices. “We see a lot more folks derive their notion of quality from continuity of care. And if they feel the physician they love is being supported by a less than competent team, that can impact significantly their sense of the quality of care,” he said.
 

Online appointment booking is a must

To win over the online consumer, Press Ganey emphasized, practices should ensure that provider listings are accurate and complete. In addition, offering online appointment booking can avoid the top challenge in making a new appointment, which is getting through to the office.

Mr. Jeffrey concurred, although he notes that practices have to be careful about how they enable patients to select appointment slots online. He suggests that an appointment request form on a patient portal first ask what the purpose of the visit is and that it offer five or so options. If the request fits into a routine visit category, the provider’s calendar pops up and the patient can select a convenient time slot. If it’s something else, an appointment scheduler calls the patient back.

“There needs to be greater access to standard appointments online,” he said. “While privacy is an issue, you can use the patient portal that most EHRs have to provide online booking. If you want to succeed going forward, that’s going to be a major plus.”

Of course, to do any of this, including reading provider reviews, a consumer needs a good internet connection and a mobile or desktop device. While broadband internet access is still not available in some communities, the breakdown of the survey respondents by demographics shows that low-income people were included.

Mr. Jeffrey doesn’t believe that a lack of internet access or digital devices prevents many Americans from going online today. “Even in poor communities, most people have internet access through their smartphones. Even baby boomers are familiar with smartphones. I haven’t seen internet access be a big barrier for low-income households, because they all have access to phones.”

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

Key toxicities related to treating acute lymphoblastic leukemia (ALL) with asparaginase, specifically pancreatitis and osteonecrosis, are associated with increases in asparaginase enzyme activity, suggesting that patients at risk for those toxicities would benefit from therapeutic drug monitoring, according to new research.

In the study, published Oct. 8 in Blood Advances, increased asparaginase enzyme activity was not significantly associated with overall asparaginase toxicity. However,“ a significant association between increasing asparaginase enzyme activity levels and pancreatitis and osteonecrosis was found, which should be taken into consideration when future treatment protocols are designed,” the authors concluded.

“The [findings are] new, and we have included patients from a quite big cohort, which is unique,” coauthor Birgitte Klug Albertsen, MD, PhD, associate clinical professor with Aarhus (Denmark) University Hospital, told this news organization.

Therapeutic drug monitoring already is widely used during treatment with asparaginase, the standard of care treatment for ALL; however, the focus of this monitoring has typically been on clinical effectiveness, as levels of asparaginase enzyme activity can indicate hypersensitivity reactions, while the absence of such activity can suggest inferior outcomes.

Meanwhile, drug monitoring is not normally used to assess the risk of treatment-related toxicities. This has been due to a lack of evidence regarding asparaginase enzyme activity and toxicity risk, which, if severe enough, can prevent further treatment.

To investigate the relationship with toxicities, Dr. Albertsen and colleagues evaluated data from seven countries in Europe on 1,155 children between the ages of 1 and 17.9 who were diagnosed with ALL and treated with asparaginase, according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol between July 2008 and March 2016.

Blood samples drawn approximately 14 days after asparaginase administration showed that some level of asparaginase enzyme activity was measurable in 955 patients (82.7%), while 200 patients (17.3%) had asparaginase inactivation. Overall, there were 159 asparaginase-associated toxicities of pancreatitis, thromboembolism, or osteonecrosis among the 955 patients with measurable asparaginase enzyme activity.

There were no significant differences in median asparaginase enzyme activity levels between those who did and did not experience toxicities (224 IU/L vs. 221 IU/L, respectively; P = .1), and the results did not change after adjustment for age and sex. However, the risk of pancreatitis was found to increase with a hazard ratio (HR) of 1.40 for each 100 IU/L increase in the median asparaginase enzyme activity level (P = .002).

Likewise, an increase in risk was observed for osteonecrosis (HR 1.36; P = .02) per 100 IU/L increase in median asparaginase enzyme activity. However, the HR for the risk of thromboembolism, the most common of asparaginase-related toxicities, was not significant (HR 0.99; P = .96).

Dr. Albertsen said the etiology behind the occurrence of osteonecrosis is not well understood.

“We know that steroids, especially dexamethasone, are a risk factor,” she said. “We believe that asparaginase may play a role too, but a clear association has not been demonstrated.”

In the NOPHO ALL2008 protocol used in the study, dexamethasone is used in the same time periods as PEG-asparaginase treatment for patients receiving 15 doses.

The finding of only a nonsignificant trend between asparaginase enzyme activity with overall toxicities may have reflected the low dose that was used, Dr. Albertsen added.

“In the NOPHO ALL2008 protocol, we used quite a low dose of PEG-asparaginase, and the risk may be higher in protocols using higher doses,” she said.
 

Relapse reduction

Notably, the study showed that asparaginase enzyme elevations were, in fact, not significantly associated with a reduction in the risk of leukemic relapse (HR .88 per 100 IU/L increase; P = .35).

Those findings suggest that measurable asparaginase enzyme activity levels, and thus asparaginase depletion, “may be sufficient to ensure an antileukemic effect,” the authors noted.

“Therapeutic drug monitoring of asparaginase enzyme activity is indicated mainly to detect inactivation, but [it] may be further explored for dose reduction to reduce some specific toxicities,” they concluded.

Dr. Albertsen disclosed being sponsor of the investigator-initiatied NOR-GRASPALL 2016 trial.

Key toxicities related to treating acute lymphoblastic leukemia (ALL) with asparaginase, specifically pancreatitis and osteonecrosis, are associated with increases in asparaginase enzyme activity, suggesting that patients at risk for those toxicities would benefit from therapeutic drug monitoring, according to new research.

In the study, published Oct. 8 in Blood Advances, increased asparaginase enzyme activity was not significantly associated with overall asparaginase toxicity. However,“ a significant association between increasing asparaginase enzyme activity levels and pancreatitis and osteonecrosis was found, which should be taken into consideration when future treatment protocols are designed,” the authors concluded.

“The [findings are] new, and we have included patients from a quite big cohort, which is unique,” coauthor Birgitte Klug Albertsen, MD, PhD, associate clinical professor with Aarhus (Denmark) University Hospital, told this news organization.

Therapeutic drug monitoring already is widely used during treatment with asparaginase, the standard of care treatment for ALL; however, the focus of this monitoring has typically been on clinical effectiveness, as levels of asparaginase enzyme activity can indicate hypersensitivity reactions, while the absence of such activity can suggest inferior outcomes.

Meanwhile, drug monitoring is not normally used to assess the risk of treatment-related toxicities. This has been due to a lack of evidence regarding asparaginase enzyme activity and toxicity risk, which, if severe enough, can prevent further treatment.

To investigate the relationship with toxicities, Dr. Albertsen and colleagues evaluated data from seven countries in Europe on 1,155 children between the ages of 1 and 17.9 who were diagnosed with ALL and treated with asparaginase, according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol between July 2008 and March 2016.

Blood samples drawn approximately 14 days after asparaginase administration showed that some level of asparaginase enzyme activity was measurable in 955 patients (82.7%), while 200 patients (17.3%) had asparaginase inactivation. Overall, there were 159 asparaginase-associated toxicities of pancreatitis, thromboembolism, or osteonecrosis among the 955 patients with measurable asparaginase enzyme activity.

There were no significant differences in median asparaginase enzyme activity levels between those who did and did not experience toxicities (224 IU/L vs. 221 IU/L, respectively; P = .1), and the results did not change after adjustment for age and sex. However, the risk of pancreatitis was found to increase with a hazard ratio (HR) of 1.40 for each 100 IU/L increase in the median asparaginase enzyme activity level (P = .002).

Likewise, an increase in risk was observed for osteonecrosis (HR 1.36; P = .02) per 100 IU/L increase in median asparaginase enzyme activity. However, the HR for the risk of thromboembolism, the most common of asparaginase-related toxicities, was not significant (HR 0.99; P = .96).

Dr. Albertsen said the etiology behind the occurrence of osteonecrosis is not well understood.

“We know that steroids, especially dexamethasone, are a risk factor,” she said. “We believe that asparaginase may play a role too, but a clear association has not been demonstrated.”

In the NOPHO ALL2008 protocol used in the study, dexamethasone is used in the same time periods as PEG-asparaginase treatment for patients receiving 15 doses.

The finding of only a nonsignificant trend between asparaginase enzyme activity with overall toxicities may have reflected the low dose that was used, Dr. Albertsen added.

“In the NOPHO ALL2008 protocol, we used quite a low dose of PEG-asparaginase, and the risk may be higher in protocols using higher doses,” she said.
 

Relapse reduction

Notably, the study showed that asparaginase enzyme elevations were, in fact, not significantly associated with a reduction in the risk of leukemic relapse (HR .88 per 100 IU/L increase; P = .35).

Those findings suggest that measurable asparaginase enzyme activity levels, and thus asparaginase depletion, “may be sufficient to ensure an antileukemic effect,” the authors noted.

“Therapeutic drug monitoring of asparaginase enzyme activity is indicated mainly to detect inactivation, but [it] may be further explored for dose reduction to reduce some specific toxicities,” they concluded.

Dr. Albertsen disclosed being sponsor of the investigator-initiatied NOR-GRASPALL 2016 trial.

Key toxicities related to treating acute lymphoblastic leukemia (ALL) with asparaginase, specifically pancreatitis and osteonecrosis, are associated with increases in asparaginase enzyme activity, suggesting that patients at risk for those toxicities would benefit from therapeutic drug monitoring, according to new research.

In the study, published Oct. 8 in Blood Advances, increased asparaginase enzyme activity was not significantly associated with overall asparaginase toxicity. However,“ a significant association between increasing asparaginase enzyme activity levels and pancreatitis and osteonecrosis was found, which should be taken into consideration when future treatment protocols are designed,” the authors concluded.

“The [findings are] new, and we have included patients from a quite big cohort, which is unique,” coauthor Birgitte Klug Albertsen, MD, PhD, associate clinical professor with Aarhus (Denmark) University Hospital, told this news organization.

Therapeutic drug monitoring already is widely used during treatment with asparaginase, the standard of care treatment for ALL; however, the focus of this monitoring has typically been on clinical effectiveness, as levels of asparaginase enzyme activity can indicate hypersensitivity reactions, while the absence of such activity can suggest inferior outcomes.

Meanwhile, drug monitoring is not normally used to assess the risk of treatment-related toxicities. This has been due to a lack of evidence regarding asparaginase enzyme activity and toxicity risk, which, if severe enough, can prevent further treatment.

To investigate the relationship with toxicities, Dr. Albertsen and colleagues evaluated data from seven countries in Europe on 1,155 children between the ages of 1 and 17.9 who were diagnosed with ALL and treated with asparaginase, according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol between July 2008 and March 2016.

Blood samples drawn approximately 14 days after asparaginase administration showed that some level of asparaginase enzyme activity was measurable in 955 patients (82.7%), while 200 patients (17.3%) had asparaginase inactivation. Overall, there were 159 asparaginase-associated toxicities of pancreatitis, thromboembolism, or osteonecrosis among the 955 patients with measurable asparaginase enzyme activity.

There were no significant differences in median asparaginase enzyme activity levels between those who did and did not experience toxicities (224 IU/L vs. 221 IU/L, respectively; P = .1), and the results did not change after adjustment for age and sex. However, the risk of pancreatitis was found to increase with a hazard ratio (HR) of 1.40 for each 100 IU/L increase in the median asparaginase enzyme activity level (P = .002).

Likewise, an increase in risk was observed for osteonecrosis (HR 1.36; P = .02) per 100 IU/L increase in median asparaginase enzyme activity. However, the HR for the risk of thromboembolism, the most common of asparaginase-related toxicities, was not significant (HR 0.99; P = .96).

Dr. Albertsen said the etiology behind the occurrence of osteonecrosis is not well understood.

“We know that steroids, especially dexamethasone, are a risk factor,” she said. “We believe that asparaginase may play a role too, but a clear association has not been demonstrated.”

In the NOPHO ALL2008 protocol used in the study, dexamethasone is used in the same time periods as PEG-asparaginase treatment for patients receiving 15 doses.

The finding of only a nonsignificant trend between asparaginase enzyme activity with overall toxicities may have reflected the low dose that was used, Dr. Albertsen added.

“In the NOPHO ALL2008 protocol, we used quite a low dose of PEG-asparaginase, and the risk may be higher in protocols using higher doses,” she said.
 

Relapse reduction

Notably, the study showed that asparaginase enzyme elevations were, in fact, not significantly associated with a reduction in the risk of leukemic relapse (HR .88 per 100 IU/L increase; P = .35).

Those findings suggest that measurable asparaginase enzyme activity levels, and thus asparaginase depletion, “may be sufficient to ensure an antileukemic effect,” the authors noted.

“Therapeutic drug monitoring of asparaginase enzyme activity is indicated mainly to detect inactivation, but [it] may be further explored for dose reduction to reduce some specific toxicities,” they concluded.

Dr. Albertsen disclosed being sponsor of the investigator-initiatied NOR-GRASPALL 2016 trial.

Apixaban appears to be safer and more effective than rivaroxaban for reducing risk of venous thromboembolism and bleeding, based on new research.

Recurrent venous thromboembolism (VTE) – a composite of pulmonary embolism and deep vein thrombosis – was the primary effectiveness outcome in the retrospective analysis of new-user data from almost 40,000 patients, which was published in Annals of Internal Medicine. Safety was evaluated through a composite of intracranial and gastrointestinal bleeding.

After a median follow-up of 102 days in the apixaban group and 105 days in the rivaroxaban group, apixaban demonstrated superiority for both primary outcomes.

These real-world findings may guide selection of initial anticoagulant therapy, reported lead author Ghadeer K. Dawwas, PhD, MSc, MBA, of the University of Pennsylvania, Philadelphia, and colleagues.

“Randomized clinical trials comparing apixaban with rivaroxaban in patients with VTE are under way (for example, COBRRA (NCT03266783),” the investigators wrote. “Until the results from these trials become available (The estimated completion date for COBRRA is December 2023.), observational studies that use existing data can provide evidence on the effectiveness and safety of these alternatives to inform clinical practice.”

In the new research, apixaban was associated with a 23% lower rate of recurrent VTE (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87), including a 15% lower rate of deep vein thrombosis and a 41% lower rate of pulmonary embolism. Apixaban was associated with 40% fewer bleeding events (HR, 0.60; 95% CI, 0.53-0.69]), including a 40% lower rate of GI bleeding and a 46% lower rate of intracranial bleeding.

The study involved 37,236 patients with VTE, all of whom were diagnosed in at least one inpatient encounter and initiated direct oral anticoagulant (DOAC) therapy within 30 days, according to Optum’s deidentified Clinformatics Data Mart Database. Patients were evenly split into apixaban and rivaroxaban groups, with 18,618 individuals in each. Propensity score matching was used to minimize differences in baseline characteristics.

Apixaban was associated with an absolute reduction in recurrent VTE of 0.6% and 1.1% over 2 and 6 months, respectively, as well as reductions in bleeding of 1.1% and 1.5% over the same respective time periods.

The investigators noted that these findings were maintained in various sensitivity and subgroup analyses, including a model in which patients with VTE who had transient risk factors were compared with VTE patients exhibiting chronic risk factors.

“These findings suggest that apixaban has superior effectiveness and safety, compared with rivaroxaban and may provide guidance to clinicians and patients regarding selection of an anticoagulant for treatment of VTE,” Dr. Dawwas and colleagues concluded.

Study may have missed some nuance in possible outcomes, according to vascular surgeon

Thomas Wakefield, MD, a vascular surgeon and a professor of surgery at the University of Michigan Health Frankel Cardiovascular Center, Ann Arbor, generally agreed with the investigators’ conclusion, although he noted that DOAC selection may also be influenced by other considerations.

“The results of this study suggest that, when choosing an agent for an individual patient, apixaban does appear to have an advantage over rivaroxaban related to recurrent VTE and bleeding,” Dr. Wakefield said in an interview. “One must keep in mind that these are not the only factors that are considered when choosing an agent and these are not the only two DOACs available. For example, rivaroxaban is given once per day while apixaban is given twice per day, and rivaroxaban has been shown to be successful in the treatment of other thrombotic disorders.”

Dr. Wakefield also pointed out that the study may have missed some nuance in possible outcomes.

“The current study looked at severe outcomes that resulted in inpatient hospitalization, so the generalization to strictly outpatient treatment and less severe outcomes cannot be inferred,” he said.

Damon E. Houghton, MD, of the department of medicine and a consultant in the department of vascular medicine and hematology at Mayo Clinic, Rochester, Minn., called the study a “very nice analysis,” highlighting the large sample size.

“The results are not a reason to abandon rivaroxaban altogether, but do suggest that, when otherwise appropriate for a patient, apixaban should be the first choice,” Dr. Houghton said in a written comment. “Hopefully this analysis will encourage more payers to create financial incentives that facilitate the use of apixaban in more patients.”

Randomized trial needed, says hematologist

Colleen Edwards, MD, of the departments of medicine, hematology, and medical oncology, at the Icahn School of Medicine at Mount Sinai, New York, had a more guarded view of the findings than Dr. Wakefield and Dr. Houghton.

“[The investigators] certainly seem to be doing a lot of statistical gymnastics in this paper,” Dr. Edwards said in an interview. “They used all kinds of surrogates in place of real data that you would get from a randomized trial.”

For example, Dr. Edwards noted the use of prescription refills as a surrogate for medication adherence, and emphasized that inpatient observational data may not reflect outpatient therapy.

“Inpatients are constantly missing their medicines all the time,” she said. “They’re holding it for procedures, they’re NPO, they’re off the floor, so they missed their medicine. So it’s just a very different patient population than the outpatient population, which is where venous thromboembolism is treated now, by and large.”

Although Dr. Edwards suggested that the findings might guide treatment selection “a little bit,” she noted that insurance constraints and costs play a greater role, and ultimately concluded that a randomized trial is needed to materially alter clinical decision-making.

“I think we really have to wait for randomized trial before we abandon our other choices,” she said.

The investigators disclosed relationships with Merck, Celgene, UCB, and others. Dr. Wakefield reported awaiting disclosures. Dr. Houghton and Dr. Edwards reported no relevant conflicts of interest.

Apixaban appears to be safer and more effective than rivaroxaban for reducing risk of venous thromboembolism and bleeding, based on new research.

Recurrent venous thromboembolism (VTE) – a composite of pulmonary embolism and deep vein thrombosis – was the primary effectiveness outcome in the retrospective analysis of new-user data from almost 40,000 patients, which was published in Annals of Internal Medicine. Safety was evaluated through a composite of intracranial and gastrointestinal bleeding.

After a median follow-up of 102 days in the apixaban group and 105 days in the rivaroxaban group, apixaban demonstrated superiority for both primary outcomes.

These real-world findings may guide selection of initial anticoagulant therapy, reported lead author Ghadeer K. Dawwas, PhD, MSc, MBA, of the University of Pennsylvania, Philadelphia, and colleagues.

“Randomized clinical trials comparing apixaban with rivaroxaban in patients with VTE are under way (for example, COBRRA (NCT03266783),” the investigators wrote. “Until the results from these trials become available (The estimated completion date for COBRRA is December 2023.), observational studies that use existing data can provide evidence on the effectiveness and safety of these alternatives to inform clinical practice.”

In the new research, apixaban was associated with a 23% lower rate of recurrent VTE (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87), including a 15% lower rate of deep vein thrombosis and a 41% lower rate of pulmonary embolism. Apixaban was associated with 40% fewer bleeding events (HR, 0.60; 95% CI, 0.53-0.69]), including a 40% lower rate of GI bleeding and a 46% lower rate of intracranial bleeding.

The study involved 37,236 patients with VTE, all of whom were diagnosed in at least one inpatient encounter and initiated direct oral anticoagulant (DOAC) therapy within 30 days, according to Optum’s deidentified Clinformatics Data Mart Database. Patients were evenly split into apixaban and rivaroxaban groups, with 18,618 individuals in each. Propensity score matching was used to minimize differences in baseline characteristics.

Apixaban was associated with an absolute reduction in recurrent VTE of 0.6% and 1.1% over 2 and 6 months, respectively, as well as reductions in bleeding of 1.1% and 1.5% over the same respective time periods.

The investigators noted that these findings were maintained in various sensitivity and subgroup analyses, including a model in which patients with VTE who had transient risk factors were compared with VTE patients exhibiting chronic risk factors.

“These findings suggest that apixaban has superior effectiveness and safety, compared with rivaroxaban and may provide guidance to clinicians and patients regarding selection of an anticoagulant for treatment of VTE,” Dr. Dawwas and colleagues concluded.

Study may have missed some nuance in possible outcomes, according to vascular surgeon

Thomas Wakefield, MD, a vascular surgeon and a professor of surgery at the University of Michigan Health Frankel Cardiovascular Center, Ann Arbor, generally agreed with the investigators’ conclusion, although he noted that DOAC selection may also be influenced by other considerations.

“The results of this study suggest that, when choosing an agent for an individual patient, apixaban does appear to have an advantage over rivaroxaban related to recurrent VTE and bleeding,” Dr. Wakefield said in an interview. “One must keep in mind that these are not the only factors that are considered when choosing an agent and these are not the only two DOACs available. For example, rivaroxaban is given once per day while apixaban is given twice per day, and rivaroxaban has been shown to be successful in the treatment of other thrombotic disorders.”

Dr. Wakefield also pointed out that the study may have missed some nuance in possible outcomes.

“The current study looked at severe outcomes that resulted in inpatient hospitalization, so the generalization to strictly outpatient treatment and less severe outcomes cannot be inferred,” he said.

Damon E. Houghton, MD, of the department of medicine and a consultant in the department of vascular medicine and hematology at Mayo Clinic, Rochester, Minn., called the study a “very nice analysis,” highlighting the large sample size.

“The results are not a reason to abandon rivaroxaban altogether, but do suggest that, when otherwise appropriate for a patient, apixaban should be the first choice,” Dr. Houghton said in a written comment. “Hopefully this analysis will encourage more payers to create financial incentives that facilitate the use of apixaban in more patients.”

Randomized trial needed, says hematologist

Colleen Edwards, MD, of the departments of medicine, hematology, and medical oncology, at the Icahn School of Medicine at Mount Sinai, New York, had a more guarded view of the findings than Dr. Wakefield and Dr. Houghton.

“[The investigators] certainly seem to be doing a lot of statistical gymnastics in this paper,” Dr. Edwards said in an interview. “They used all kinds of surrogates in place of real data that you would get from a randomized trial.”

For example, Dr. Edwards noted the use of prescription refills as a surrogate for medication adherence, and emphasized that inpatient observational data may not reflect outpatient therapy.

“Inpatients are constantly missing their medicines all the time,” she said. “They’re holding it for procedures, they’re NPO, they’re off the floor, so they missed their medicine. So it’s just a very different patient population than the outpatient population, which is where venous thromboembolism is treated now, by and large.”

Although Dr. Edwards suggested that the findings might guide treatment selection “a little bit,” she noted that insurance constraints and costs play a greater role, and ultimately concluded that a randomized trial is needed to materially alter clinical decision-making.

“I think we really have to wait for randomized trial before we abandon our other choices,” she said.

The investigators disclosed relationships with Merck, Celgene, UCB, and others. Dr. Wakefield reported awaiting disclosures. Dr. Houghton and Dr. Edwards reported no relevant conflicts of interest.

Apixaban appears to be safer and more effective than rivaroxaban for reducing risk of venous thromboembolism and bleeding, based on new research.

Recurrent venous thromboembolism (VTE) – a composite of pulmonary embolism and deep vein thrombosis – was the primary effectiveness outcome in the retrospective analysis of new-user data from almost 40,000 patients, which was published in Annals of Internal Medicine. Safety was evaluated through a composite of intracranial and gastrointestinal bleeding.

After a median follow-up of 102 days in the apixaban group and 105 days in the rivaroxaban group, apixaban demonstrated superiority for both primary outcomes.

These real-world findings may guide selection of initial anticoagulant therapy, reported lead author Ghadeer K. Dawwas, PhD, MSc, MBA, of the University of Pennsylvania, Philadelphia, and colleagues.

“Randomized clinical trials comparing apixaban with rivaroxaban in patients with VTE are under way (for example, COBRRA (NCT03266783),” the investigators wrote. “Until the results from these trials become available (The estimated completion date for COBRRA is December 2023.), observational studies that use existing data can provide evidence on the effectiveness and safety of these alternatives to inform clinical practice.”

In the new research, apixaban was associated with a 23% lower rate of recurrent VTE (hazard ratio, 0.77; 95% confidence interval, 0.69-0.87), including a 15% lower rate of deep vein thrombosis and a 41% lower rate of pulmonary embolism. Apixaban was associated with 40% fewer bleeding events (HR, 0.60; 95% CI, 0.53-0.69]), including a 40% lower rate of GI bleeding and a 46% lower rate of intracranial bleeding.

The study involved 37,236 patients with VTE, all of whom were diagnosed in at least one inpatient encounter and initiated direct oral anticoagulant (DOAC) therapy within 30 days, according to Optum’s deidentified Clinformatics Data Mart Database. Patients were evenly split into apixaban and rivaroxaban groups, with 18,618 individuals in each. Propensity score matching was used to minimize differences in baseline characteristics.

Apixaban was associated with an absolute reduction in recurrent VTE of 0.6% and 1.1% over 2 and 6 months, respectively, as well as reductions in bleeding of 1.1% and 1.5% over the same respective time periods.

The investigators noted that these findings were maintained in various sensitivity and subgroup analyses, including a model in which patients with VTE who had transient risk factors were compared with VTE patients exhibiting chronic risk factors.

“These findings suggest that apixaban has superior effectiveness and safety, compared with rivaroxaban and may provide guidance to clinicians and patients regarding selection of an anticoagulant for treatment of VTE,” Dr. Dawwas and colleagues concluded.

Study may have missed some nuance in possible outcomes, according to vascular surgeon

Thomas Wakefield, MD, a vascular surgeon and a professor of surgery at the University of Michigan Health Frankel Cardiovascular Center, Ann Arbor, generally agreed with the investigators’ conclusion, although he noted that DOAC selection may also be influenced by other considerations.

“The results of this study suggest that, when choosing an agent for an individual patient, apixaban does appear to have an advantage over rivaroxaban related to recurrent VTE and bleeding,” Dr. Wakefield said in an interview. “One must keep in mind that these are not the only factors that are considered when choosing an agent and these are not the only two DOACs available. For example, rivaroxaban is given once per day while apixaban is given twice per day, and rivaroxaban has been shown to be successful in the treatment of other thrombotic disorders.”

Dr. Wakefield also pointed out that the study may have missed some nuance in possible outcomes.

“The current study looked at severe outcomes that resulted in inpatient hospitalization, so the generalization to strictly outpatient treatment and less severe outcomes cannot be inferred,” he said.

Damon E. Houghton, MD, of the department of medicine and a consultant in the department of vascular medicine and hematology at Mayo Clinic, Rochester, Minn., called the study a “very nice analysis,” highlighting the large sample size.

“The results are not a reason to abandon rivaroxaban altogether, but do suggest that, when otherwise appropriate for a patient, apixaban should be the first choice,” Dr. Houghton said in a written comment. “Hopefully this analysis will encourage more payers to create financial incentives that facilitate the use of apixaban in more patients.”

Randomized trial needed, says hematologist

Colleen Edwards, MD, of the departments of medicine, hematology, and medical oncology, at the Icahn School of Medicine at Mount Sinai, New York, had a more guarded view of the findings than Dr. Wakefield and Dr. Houghton.

“[The investigators] certainly seem to be doing a lot of statistical gymnastics in this paper,” Dr. Edwards said in an interview. “They used all kinds of surrogates in place of real data that you would get from a randomized trial.”

For example, Dr. Edwards noted the use of prescription refills as a surrogate for medication adherence, and emphasized that inpatient observational data may not reflect outpatient therapy.

“Inpatients are constantly missing their medicines all the time,” she said. “They’re holding it for procedures, they’re NPO, they’re off the floor, so they missed their medicine. So it’s just a very different patient population than the outpatient population, which is where venous thromboembolism is treated now, by and large.”

Although Dr. Edwards suggested that the findings might guide treatment selection “a little bit,” she noted that insurance constraints and costs play a greater role, and ultimately concluded that a randomized trial is needed to materially alter clinical decision-making.

“I think we really have to wait for randomized trial before we abandon our other choices,” she said.

The investigators disclosed relationships with Merck, Celgene, UCB, and others. Dr. Wakefield reported awaiting disclosures. Dr. Houghton and Dr. Edwards reported no relevant conflicts of interest.