MDedge Endocrinology

Radiofrequency ablation (RFA) shows efficacy as a potential noninvasive option for the treatment of low-risk microcarcinomas in papillary thyroid cancer (PTC) when measures beyond active surveillance are warranted, results from a new review show.

“The results in the current study suggest that RFA could function as a useful alternative treatment strategy in which patients are treated minimally invasively with curative intentions,” reported the authors of the meta-analysis published online in JAMA Otolaryngology – Head and Neck Surgery.

Commenting on the research, Joanna Klubo-Gwiezdzinska, MD, PhD, said the work offers useful evidence on the potential role for RFA in low-risk micro-PTC – with some notable caveats.

“I agree that RFA might be a good option for patients unwilling or unable to accept active surveillance and for patients who are at high surgical risk because of comorbid conditions,” she told this news organization.

However, “RFA for patients with an evidence of nodule growth requires more data to be analyzed and a longer follow-up period in lieu of the fact that 21% of nodules subjected to RFA did not disappear, based on the data the authors provide,” noted Dr. Klubo-Gwiezdzinska, who is acting chief of thyroid tumors and functional thyroid disorders at the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, in Bethesda, Md.  
 

When active surveillance isn’t enough

Microcarcinoma PTC, defined as measuring 10 mm or less, is highly common, making up approximately half of papillary thyroid cancers diagnosed in some countries, and the outcomes of those cancers are excellent, with disease-specific survival of more than 99% after 10 years.

Guidelines in the United States and Europe typically recommend surgery (lobectomy) as a standard treatment for thyroid cancer, however, with many of the low-risk microcarcinomas remaining indolent and never progressing to the point of requiring treatment over a person’s lifetime, some also recommend considering active surveillance, or watchful waiting, for those lower-risk cancers.

In situations such as evidence of tumor growth during active surveillance, some countries, particularly Asian countries, also suggest considering thermal ablation techniques, including RFA, as an alternative to surgery, with key benefits including lower costs and potentially a lower risk of complications, compared with surgical lobectomy.

Otherwise, RFA is more typically reserved for benign nodules, recurrent PTC, or inoperable disease.
 

New meta-analysis

To investigate reported outcomes with RFA specifically in the treatment of microcarcinoma PTC, the authors, led by Sam P.J. van Dijk, BSc, of University Medical Center Rotterdam (the Netherlands), identified 15 studies published after 2016 involving 1,770 adult patients and 1,822 tumors who received RFA for the treatment of low-risk PTC microcarcinomas, defined as measuring 10 mm or less.

The studies were conducted in China and South Korea, where RFA is more commonly used in low-risk microcarcinoma PTC.

Patients were 77.9% women and a mean age of 45.4 years. The analysis excluded patients with pre-ablation lymph node or distant metastases, recurrence of disease, or extrathyroidal extension.

Of the 1,822 tumors treated with RFA, 49 required an additional RFA treatment and 1 tumor had two additional treatments.

With a mean follow-up of 33 months (range, 6-131 months), the primary outcome of the pooled rate of complete disappearance of microcarcinoma PTC on ultrasonography was 79%.

The overall rate of tumor progression was 1.5% (26 patients), and local residual microcarcinoma PTC occurred in 0.4% (7 tumors).

New microcarcinoma PTC occurred in 0.9% (15) of patients; 0.2% (4) developed lymph node metastases during follow-up, and no distant metastases were observed.

Minor complications occurred in 45 patients, and there were three major complications, including two voice changes that lasted more than 2 months and one cardiac arrhythmia.

“This study suggests that radiofrequency ablation is a safe and efficient method to treat selected low-risk papillary microcarcinoma of the thyroid,” the researchers said.
 

Questions surrounding the 20% of patients who still had residual nodules

While the analysis did not include direct comparisons between RFA and lobectomy, Dr. Klubo-Gwiezdzinska noted that, in general, “RFA appears to be associated with a lower complication rate compared with surgery, but also lower efficacy, with 21% of patients with residual nodules.”

The results raise the question of whether “all of the residual lesions are associated with persistent disease, and, if so, do they warrant further intervention?” she added.

To that point, the authors noted that only seven (0.4%) of the 21% of patients with persistent nodules showed residual microcarcinoma PTC cells after RFA, a fact that underscores that “the assessment of tumor response in patients with mPTC after RFA is complicated,” they wrote.

A key concern with assessing responses in RFA is that fine needle aspiration has been shown to have reduced diagnostic accuracy following treatment due to insufficient cellularity in the ablation area, the authors noted.

They add that core needle biopsy is believed to have higher accuracy.

While commenting that the analysis used the “best standards,” Dr. Klubo-Gwiezdzinska noted the caveat that it provides “low- to moderate-quality evidence as it included either case series or retrospective cohort studies, characterized by an inherent bias associated with these study designs.”

And as the authors also acknowledge, possible overlap in the included cohorts “could mean that sample sizes might be smaller than reported,” Dr. Klubo-Gwiezdzinska commented.

To further evaluate the pros and cons of RFA, the authors suggested that “future studies may focus on improving complete disappearance rates of the tumor volume, possibly with more advanced or longer RFA procedures.”
 

RFA an option for some patients

In the meantime, senior author Tessa M. van Ginhoven, MD, PhD, of the department of surgical oncology and gastrointestinal surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, suggests that, in addition to cases of local tumor growth, possible uses of RFA for micro-PTC could include situations of patient anxiety due to active surveillance.

“If active surveillance is appropriate for your population, but the patient is anxious and prefers lobectomy, one could envision RFA as a possible adjunct to active surveillance,” she told this news organization.

The authors and Dr. Klubo-Gwiezdzinska reported no relevant financial relationships.

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

Radiofrequency ablation (RFA) shows efficacy as a potential noninvasive option for the treatment of low-risk microcarcinomas in papillary thyroid cancer (PTC) when measures beyond active surveillance are warranted, results from a new review show.

“The results in the current study suggest that RFA could function as a useful alternative treatment strategy in which patients are treated minimally invasively with curative intentions,” reported the authors of the meta-analysis published online in JAMA Otolaryngology – Head and Neck Surgery.

Commenting on the research, Joanna Klubo-Gwiezdzinska, MD, PhD, said the work offers useful evidence on the potential role for RFA in low-risk micro-PTC – with some notable caveats.

“I agree that RFA might be a good option for patients unwilling or unable to accept active surveillance and for patients who are at high surgical risk because of comorbid conditions,” she told this news organization.

However, “RFA for patients with an evidence of nodule growth requires more data to be analyzed and a longer follow-up period in lieu of the fact that 21% of nodules subjected to RFA did not disappear, based on the data the authors provide,” noted Dr. Klubo-Gwiezdzinska, who is acting chief of thyroid tumors and functional thyroid disorders at the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, in Bethesda, Md.  
 

When active surveillance isn’t enough

Microcarcinoma PTC, defined as measuring 10 mm or less, is highly common, making up approximately half of papillary thyroid cancers diagnosed in some countries, and the outcomes of those cancers are excellent, with disease-specific survival of more than 99% after 10 years.

Guidelines in the United States and Europe typically recommend surgery (lobectomy) as a standard treatment for thyroid cancer, however, with many of the low-risk microcarcinomas remaining indolent and never progressing to the point of requiring treatment over a person’s lifetime, some also recommend considering active surveillance, or watchful waiting, for those lower-risk cancers.

In situations such as evidence of tumor growth during active surveillance, some countries, particularly Asian countries, also suggest considering thermal ablation techniques, including RFA, as an alternative to surgery, with key benefits including lower costs and potentially a lower risk of complications, compared with surgical lobectomy.

Otherwise, RFA is more typically reserved for benign nodules, recurrent PTC, or inoperable disease.
 

New meta-analysis

To investigate reported outcomes with RFA specifically in the treatment of microcarcinoma PTC, the authors, led by Sam P.J. van Dijk, BSc, of University Medical Center Rotterdam (the Netherlands), identified 15 studies published after 2016 involving 1,770 adult patients and 1,822 tumors who received RFA for the treatment of low-risk PTC microcarcinomas, defined as measuring 10 mm or less.

The studies were conducted in China and South Korea, where RFA is more commonly used in low-risk microcarcinoma PTC.

Patients were 77.9% women and a mean age of 45.4 years. The analysis excluded patients with pre-ablation lymph node or distant metastases, recurrence of disease, or extrathyroidal extension.

Of the 1,822 tumors treated with RFA, 49 required an additional RFA treatment and 1 tumor had two additional treatments.

With a mean follow-up of 33 months (range, 6-131 months), the primary outcome of the pooled rate of complete disappearance of microcarcinoma PTC on ultrasonography was 79%.

The overall rate of tumor progression was 1.5% (26 patients), and local residual microcarcinoma PTC occurred in 0.4% (7 tumors).

New microcarcinoma PTC occurred in 0.9% (15) of patients; 0.2% (4) developed lymph node metastases during follow-up, and no distant metastases were observed.

Minor complications occurred in 45 patients, and there were three major complications, including two voice changes that lasted more than 2 months and one cardiac arrhythmia.

“This study suggests that radiofrequency ablation is a safe and efficient method to treat selected low-risk papillary microcarcinoma of the thyroid,” the researchers said.
 

Questions surrounding the 20% of patients who still had residual nodules

While the analysis did not include direct comparisons between RFA and lobectomy, Dr. Klubo-Gwiezdzinska noted that, in general, “RFA appears to be associated with a lower complication rate compared with surgery, but also lower efficacy, with 21% of patients with residual nodules.”

The results raise the question of whether “all of the residual lesions are associated with persistent disease, and, if so, do they warrant further intervention?” she added.

To that point, the authors noted that only seven (0.4%) of the 21% of patients with persistent nodules showed residual microcarcinoma PTC cells after RFA, a fact that underscores that “the assessment of tumor response in patients with mPTC after RFA is complicated,” they wrote.

A key concern with assessing responses in RFA is that fine needle aspiration has been shown to have reduced diagnostic accuracy following treatment due to insufficient cellularity in the ablation area, the authors noted.

They add that core needle biopsy is believed to have higher accuracy.

While commenting that the analysis used the “best standards,” Dr. Klubo-Gwiezdzinska noted the caveat that it provides “low- to moderate-quality evidence as it included either case series or retrospective cohort studies, characterized by an inherent bias associated with these study designs.”

And as the authors also acknowledge, possible overlap in the included cohorts “could mean that sample sizes might be smaller than reported,” Dr. Klubo-Gwiezdzinska commented.

To further evaluate the pros and cons of RFA, the authors suggested that “future studies may focus on improving complete disappearance rates of the tumor volume, possibly with more advanced or longer RFA procedures.”
 

RFA an option for some patients

In the meantime, senior author Tessa M. van Ginhoven, MD, PhD, of the department of surgical oncology and gastrointestinal surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, suggests that, in addition to cases of local tumor growth, possible uses of RFA for micro-PTC could include situations of patient anxiety due to active surveillance.

“If active surveillance is appropriate for your population, but the patient is anxious and prefers lobectomy, one could envision RFA as a possible adjunct to active surveillance,” she told this news organization.

The authors and Dr. Klubo-Gwiezdzinska reported no relevant financial relationships.

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

Radiofrequency ablation (RFA) shows efficacy as a potential noninvasive option for the treatment of low-risk microcarcinomas in papillary thyroid cancer (PTC) when measures beyond active surveillance are warranted, results from a new review show.

“The results in the current study suggest that RFA could function as a useful alternative treatment strategy in which patients are treated minimally invasively with curative intentions,” reported the authors of the meta-analysis published online in JAMA Otolaryngology – Head and Neck Surgery.

Commenting on the research, Joanna Klubo-Gwiezdzinska, MD, PhD, said the work offers useful evidence on the potential role for RFA in low-risk micro-PTC – with some notable caveats.

“I agree that RFA might be a good option for patients unwilling or unable to accept active surveillance and for patients who are at high surgical risk because of comorbid conditions,” she told this news organization.

However, “RFA for patients with an evidence of nodule growth requires more data to be analyzed and a longer follow-up period in lieu of the fact that 21% of nodules subjected to RFA did not disappear, based on the data the authors provide,” noted Dr. Klubo-Gwiezdzinska, who is acting chief of thyroid tumors and functional thyroid disorders at the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, in Bethesda, Md.  
 

When active surveillance isn’t enough

Microcarcinoma PTC, defined as measuring 10 mm or less, is highly common, making up approximately half of papillary thyroid cancers diagnosed in some countries, and the outcomes of those cancers are excellent, with disease-specific survival of more than 99% after 10 years.

Guidelines in the United States and Europe typically recommend surgery (lobectomy) as a standard treatment for thyroid cancer, however, with many of the low-risk microcarcinomas remaining indolent and never progressing to the point of requiring treatment over a person’s lifetime, some also recommend considering active surveillance, or watchful waiting, for those lower-risk cancers.

In situations such as evidence of tumor growth during active surveillance, some countries, particularly Asian countries, also suggest considering thermal ablation techniques, including RFA, as an alternative to surgery, with key benefits including lower costs and potentially a lower risk of complications, compared with surgical lobectomy.

Otherwise, RFA is more typically reserved for benign nodules, recurrent PTC, or inoperable disease.
 

New meta-analysis

To investigate reported outcomes with RFA specifically in the treatment of microcarcinoma PTC, the authors, led by Sam P.J. van Dijk, BSc, of University Medical Center Rotterdam (the Netherlands), identified 15 studies published after 2016 involving 1,770 adult patients and 1,822 tumors who received RFA for the treatment of low-risk PTC microcarcinomas, defined as measuring 10 mm or less.

The studies were conducted in China and South Korea, where RFA is more commonly used in low-risk microcarcinoma PTC.

Patients were 77.9% women and a mean age of 45.4 years. The analysis excluded patients with pre-ablation lymph node or distant metastases, recurrence of disease, or extrathyroidal extension.

Of the 1,822 tumors treated with RFA, 49 required an additional RFA treatment and 1 tumor had two additional treatments.

With a mean follow-up of 33 months (range, 6-131 months), the primary outcome of the pooled rate of complete disappearance of microcarcinoma PTC on ultrasonography was 79%.

The overall rate of tumor progression was 1.5% (26 patients), and local residual microcarcinoma PTC occurred in 0.4% (7 tumors).

New microcarcinoma PTC occurred in 0.9% (15) of patients; 0.2% (4) developed lymph node metastases during follow-up, and no distant metastases were observed.

Minor complications occurred in 45 patients, and there were three major complications, including two voice changes that lasted more than 2 months and one cardiac arrhythmia.

“This study suggests that radiofrequency ablation is a safe and efficient method to treat selected low-risk papillary microcarcinoma of the thyroid,” the researchers said.
 

Questions surrounding the 20% of patients who still had residual nodules

While the analysis did not include direct comparisons between RFA and lobectomy, Dr. Klubo-Gwiezdzinska noted that, in general, “RFA appears to be associated with a lower complication rate compared with surgery, but also lower efficacy, with 21% of patients with residual nodules.”

The results raise the question of whether “all of the residual lesions are associated with persistent disease, and, if so, do they warrant further intervention?” she added.

To that point, the authors noted that only seven (0.4%) of the 21% of patients with persistent nodules showed residual microcarcinoma PTC cells after RFA, a fact that underscores that “the assessment of tumor response in patients with mPTC after RFA is complicated,” they wrote.

A key concern with assessing responses in RFA is that fine needle aspiration has been shown to have reduced diagnostic accuracy following treatment due to insufficient cellularity in the ablation area, the authors noted.

They add that core needle biopsy is believed to have higher accuracy.

While commenting that the analysis used the “best standards,” Dr. Klubo-Gwiezdzinska noted the caveat that it provides “low- to moderate-quality evidence as it included either case series or retrospective cohort studies, characterized by an inherent bias associated with these study designs.”

And as the authors also acknowledge, possible overlap in the included cohorts “could mean that sample sizes might be smaller than reported,” Dr. Klubo-Gwiezdzinska commented.

To further evaluate the pros and cons of RFA, the authors suggested that “future studies may focus on improving complete disappearance rates of the tumor volume, possibly with more advanced or longer RFA procedures.”
 

RFA an option for some patients

In the meantime, senior author Tessa M. van Ginhoven, MD, PhD, of the department of surgical oncology and gastrointestinal surgery, Erasmus MC Cancer Institute, University Medical Centre Rotterdam, suggests that, in addition to cases of local tumor growth, possible uses of RFA for micro-PTC could include situations of patient anxiety due to active surveillance.

“If active surveillance is appropriate for your population, but the patient is anxious and prefers lobectomy, one could envision RFA as a possible adjunct to active surveillance,” she told this news organization.

The authors and Dr. Klubo-Gwiezdzinska reported no relevant financial relationships.

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

As COVID-19 cases and hospitalizations continue to decline across the United States, all states but one -- Hawaii -- have dropped their mask mandates or have announced plans to do so in coming weeks.

Retailers and cruises are following along, with Apple and Target stores lifting their own mask mandates this week. Cruise lines such as Norwegian and Royal Caribbean International have said mask requirements will be relaxed for vaccinated passengers, according to the Washington Post.

But guidance from the Centers for Disease Control and Prevention hasn’t changed even as the Omicron variant recedes across the country. Vaccinated people should wear masks when indoors in areas of “substantial or high transmission,” which still covers more than 95% of the country, according to a CDC map.

As daily cases continue to fall, the CDC is reviewing its recommendations, Rochelle Walensky, MD, the CDC director, said during a briefing last week.

“We want to give people a break from things like mask-wearing, when these metrics are better, and then have the ability to reach for them again should things worsen,” she said.

As states relax mask rules, county and city officials are now deciding what to do in their jurisdictions. Vaccinated residents in Los Angeles County may soon be able to go maskless in indoor settings that check for proof of vaccination, according to the Los Angeles Times.

Chicago will also end its mask and COVID-19 vaccine mandates for public places such as restaurants Feb. 28, according to the Chicago Tribune. Illinois will end a statewide indoor mask mandate on the same day. Masks will still be required in health care settings and public transmit.

State and local school boards are debating their mask policies as well. The Maryland State Board of Education voted Feb. 22 to allow local school districts to decide whether students must wear face coverings in school, according to the Associated Press. The update will take effect on March 1 if approved by a Maryland General Assembly committee that oversees the rule.

In New York, state officials have begun lifting mask rules. At the same time, 58% of New York voters want to see early March data before school mask mandates are ended, according to a new poll, released Feb. 22 by the Siena College Research Institute. About 45% of those polled said the state’s indoor public mask mandate should also still be in place.

The debate about wearing masks in schools will likely continue, especially as districts get caught between health authorities and parents, according to the Wall Street Journal. District officials in several states are receiving hundreds of emails daily from both sides, with parents calling for mask rules to end or saying that requirements should remain in place for now to keep kids safe.

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

As COVID-19 cases and hospitalizations continue to decline across the United States, all states but one -- Hawaii -- have dropped their mask mandates or have announced plans to do so in coming weeks.

Retailers and cruises are following along, with Apple and Target stores lifting their own mask mandates this week. Cruise lines such as Norwegian and Royal Caribbean International have said mask requirements will be relaxed for vaccinated passengers, according to the Washington Post.

But guidance from the Centers for Disease Control and Prevention hasn’t changed even as the Omicron variant recedes across the country. Vaccinated people should wear masks when indoors in areas of “substantial or high transmission,” which still covers more than 95% of the country, according to a CDC map.

As daily cases continue to fall, the CDC is reviewing its recommendations, Rochelle Walensky, MD, the CDC director, said during a briefing last week.

“We want to give people a break from things like mask-wearing, when these metrics are better, and then have the ability to reach for them again should things worsen,” she said.

As states relax mask rules, county and city officials are now deciding what to do in their jurisdictions. Vaccinated residents in Los Angeles County may soon be able to go maskless in indoor settings that check for proof of vaccination, according to the Los Angeles Times.

Chicago will also end its mask and COVID-19 vaccine mandates for public places such as restaurants Feb. 28, according to the Chicago Tribune. Illinois will end a statewide indoor mask mandate on the same day. Masks will still be required in health care settings and public transmit.

State and local school boards are debating their mask policies as well. The Maryland State Board of Education voted Feb. 22 to allow local school districts to decide whether students must wear face coverings in school, according to the Associated Press. The update will take effect on March 1 if approved by a Maryland General Assembly committee that oversees the rule.

In New York, state officials have begun lifting mask rules. At the same time, 58% of New York voters want to see early March data before school mask mandates are ended, according to a new poll, released Feb. 22 by the Siena College Research Institute. About 45% of those polled said the state’s indoor public mask mandate should also still be in place.

The debate about wearing masks in schools will likely continue, especially as districts get caught between health authorities and parents, according to the Wall Street Journal. District officials in several states are receiving hundreds of emails daily from both sides, with parents calling for mask rules to end or saying that requirements should remain in place for now to keep kids safe.

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

As COVID-19 cases and hospitalizations continue to decline across the United States, all states but one -- Hawaii -- have dropped their mask mandates or have announced plans to do so in coming weeks.

Retailers and cruises are following along, with Apple and Target stores lifting their own mask mandates this week. Cruise lines such as Norwegian and Royal Caribbean International have said mask requirements will be relaxed for vaccinated passengers, according to the Washington Post.

But guidance from the Centers for Disease Control and Prevention hasn’t changed even as the Omicron variant recedes across the country. Vaccinated people should wear masks when indoors in areas of “substantial or high transmission,” which still covers more than 95% of the country, according to a CDC map.

As daily cases continue to fall, the CDC is reviewing its recommendations, Rochelle Walensky, MD, the CDC director, said during a briefing last week.

“We want to give people a break from things like mask-wearing, when these metrics are better, and then have the ability to reach for them again should things worsen,” she said.

As states relax mask rules, county and city officials are now deciding what to do in their jurisdictions. Vaccinated residents in Los Angeles County may soon be able to go maskless in indoor settings that check for proof of vaccination, according to the Los Angeles Times.

Chicago will also end its mask and COVID-19 vaccine mandates for public places such as restaurants Feb. 28, according to the Chicago Tribune. Illinois will end a statewide indoor mask mandate on the same day. Masks will still be required in health care settings and public transmit.

State and local school boards are debating their mask policies as well. The Maryland State Board of Education voted Feb. 22 to allow local school districts to decide whether students must wear face coverings in school, according to the Associated Press. The update will take effect on March 1 if approved by a Maryland General Assembly committee that oversees the rule.

In New York, state officials have begun lifting mask rules. At the same time, 58% of New York voters want to see early March data before school mask mandates are ended, according to a new poll, released Feb. 22 by the Siena College Research Institute. About 45% of those polled said the state’s indoor public mask mandate should also still be in place.

The debate about wearing masks in schools will likely continue, especially as districts get caught between health authorities and parents, according to the Wall Street Journal. District officials in several states are receiving hundreds of emails daily from both sides, with parents calling for mask rules to end or saying that requirements should remain in place for now to keep kids safe.

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

American health care workers have remained resilient during the pandemic but are feeling the ongoing strain, with 23% saying they are likely to leave the field in the near future, according to a new poll.

About half of the respondents to the poll from USA Today/Ipsos reported feeling “burned out,” 43% said they were “anxious,” and 21% said they were “angry” about politics and abuse from patients and families.

“We’re trying to help people here, and we are getting verbally and physically abused for it,” Sarah Fried, a nurse in California who responded to the survey, told USA Today in a follow-up interview.

“Early in this pandemic, people were clapping for us and calling us heroes,” she said. “And what happened to that? What happened to them appreciating what nurses are doing?”

The poll was done Feb. 9-16 among 1,170 adults in the U.S. health care industry, including doctors, nurses, paramedics, therapists, home health aides, dentists, and other medical professionals.

A large majority of workers still reported being satisfied with their jobs, although that optimism has declined somewhat since early 2021 when the COVID-19 vaccine rollout was underway. About 80% of those in the recent poll said they were somewhat or very satisfied with their current job, which is down from 89% in an April 2021 poll from Kaiser Family Foundation/the Washington Post.

Most health care workers reported feeling “hopeful” (59%), “motivated” (59%), or “optimistic” (56%) about going to work. But “hopeful” is down from 76% and “optimistic” is down from 67%, compared with last year.

If they could pick a career over again, about 16% disagreed with the statement, “I would still decide to go into health care,” and 18% said they didn’t know how they felt about it.

“The pandemic has actually made me realize how important this career is and how I really do make a difference. I still love it,” Christina Rosa, a mental health counselor in Massachusetts, told USA Today.

During the pandemic, about 66% of those polled said they had treated a COVID-19 patient, which increased to 84% among nurses and 86% among hospital workers. Among those, 47% reported having a patient who died from COVID-19, including 53% of nurses and 55% of hospital workers.

What’s more, 81% of those who treated COVID-19 patients have cared for unvaccinated patients. Among those, 67% said their patients continued to express skepticism toward COVID-19 vaccines, and 38% said some patients expressed regret for not getting a vaccine. Beyond that, 26% said unvaccinated patients asked for unproven treatments, and 30% said the patient or family criticized the care they received.

Regarding coronavirus-related policy, most Americans working in health care expressed skepticism or criticism of the nation’s handling of the pandemic. About 39% agreed that the American health care system is “on the verge of collapse.”

Only 21% said the pandemic is mostly or completely under control. About 61% don’t think Americans are taking enough precautions to prevent the spread of the coronavirus.

Health care workers were slightly positive when it comes to the Centers for Disease Control and Prevention (54% approve, 34% disapprove), divided on the Biden administration (41% approve, 40% disapprove), and critical of the news media (20% approve, 61% disapprove) and the American public (18% approve, 68% disapprove).

Broadly, though, health care workers support public health efforts. About 85% back measures that provide N95 masks, and 83% back measures that provide COVID-19 tests.

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

American health care workers have remained resilient during the pandemic but are feeling the ongoing strain, with 23% saying they are likely to leave the field in the near future, according to a new poll.

About half of the respondents to the poll from USA Today/Ipsos reported feeling “burned out,” 43% said they were “anxious,” and 21% said they were “angry” about politics and abuse from patients and families.

“We’re trying to help people here, and we are getting verbally and physically abused for it,” Sarah Fried, a nurse in California who responded to the survey, told USA Today in a follow-up interview.

“Early in this pandemic, people were clapping for us and calling us heroes,” she said. “And what happened to that? What happened to them appreciating what nurses are doing?”

The poll was done Feb. 9-16 among 1,170 adults in the U.S. health care industry, including doctors, nurses, paramedics, therapists, home health aides, dentists, and other medical professionals.

A large majority of workers still reported being satisfied with their jobs, although that optimism has declined somewhat since early 2021 when the COVID-19 vaccine rollout was underway. About 80% of those in the recent poll said they were somewhat or very satisfied with their current job, which is down from 89% in an April 2021 poll from Kaiser Family Foundation/the Washington Post.

Most health care workers reported feeling “hopeful” (59%), “motivated” (59%), or “optimistic” (56%) about going to work. But “hopeful” is down from 76% and “optimistic” is down from 67%, compared with last year.

If they could pick a career over again, about 16% disagreed with the statement, “I would still decide to go into health care,” and 18% said they didn’t know how they felt about it.

“The pandemic has actually made me realize how important this career is and how I really do make a difference. I still love it,” Christina Rosa, a mental health counselor in Massachusetts, told USA Today.

During the pandemic, about 66% of those polled said they had treated a COVID-19 patient, which increased to 84% among nurses and 86% among hospital workers. Among those, 47% reported having a patient who died from COVID-19, including 53% of nurses and 55% of hospital workers.

What’s more, 81% of those who treated COVID-19 patients have cared for unvaccinated patients. Among those, 67% said their patients continued to express skepticism toward COVID-19 vaccines, and 38% said some patients expressed regret for not getting a vaccine. Beyond that, 26% said unvaccinated patients asked for unproven treatments, and 30% said the patient or family criticized the care they received.

Regarding coronavirus-related policy, most Americans working in health care expressed skepticism or criticism of the nation’s handling of the pandemic. About 39% agreed that the American health care system is “on the verge of collapse.”

Only 21% said the pandemic is mostly or completely under control. About 61% don’t think Americans are taking enough precautions to prevent the spread of the coronavirus.

Health care workers were slightly positive when it comes to the Centers for Disease Control and Prevention (54% approve, 34% disapprove), divided on the Biden administration (41% approve, 40% disapprove), and critical of the news media (20% approve, 61% disapprove) and the American public (18% approve, 68% disapprove).

Broadly, though, health care workers support public health efforts. About 85% back measures that provide N95 masks, and 83% back measures that provide COVID-19 tests.

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

American health care workers have remained resilient during the pandemic but are feeling the ongoing strain, with 23% saying they are likely to leave the field in the near future, according to a new poll.

About half of the respondents to the poll from USA Today/Ipsos reported feeling “burned out,” 43% said they were “anxious,” and 21% said they were “angry” about politics and abuse from patients and families.

“We’re trying to help people here, and we are getting verbally and physically abused for it,” Sarah Fried, a nurse in California who responded to the survey, told USA Today in a follow-up interview.

“Early in this pandemic, people were clapping for us and calling us heroes,” she said. “And what happened to that? What happened to them appreciating what nurses are doing?”

The poll was done Feb. 9-16 among 1,170 adults in the U.S. health care industry, including doctors, nurses, paramedics, therapists, home health aides, dentists, and other medical professionals.

A large majority of workers still reported being satisfied with their jobs, although that optimism has declined somewhat since early 2021 when the COVID-19 vaccine rollout was underway. About 80% of those in the recent poll said they were somewhat or very satisfied with their current job, which is down from 89% in an April 2021 poll from Kaiser Family Foundation/the Washington Post.

Most health care workers reported feeling “hopeful” (59%), “motivated” (59%), or “optimistic” (56%) about going to work. But “hopeful” is down from 76% and “optimistic” is down from 67%, compared with last year.

If they could pick a career over again, about 16% disagreed with the statement, “I would still decide to go into health care,” and 18% said they didn’t know how they felt about it.

“The pandemic has actually made me realize how important this career is and how I really do make a difference. I still love it,” Christina Rosa, a mental health counselor in Massachusetts, told USA Today.

During the pandemic, about 66% of those polled said they had treated a COVID-19 patient, which increased to 84% among nurses and 86% among hospital workers. Among those, 47% reported having a patient who died from COVID-19, including 53% of nurses and 55% of hospital workers.

What’s more, 81% of those who treated COVID-19 patients have cared for unvaccinated patients. Among those, 67% said their patients continued to express skepticism toward COVID-19 vaccines, and 38% said some patients expressed regret for not getting a vaccine. Beyond that, 26% said unvaccinated patients asked for unproven treatments, and 30% said the patient or family criticized the care they received.

Regarding coronavirus-related policy, most Americans working in health care expressed skepticism or criticism of the nation’s handling of the pandemic. About 39% agreed that the American health care system is “on the verge of collapse.”

Only 21% said the pandemic is mostly or completely under control. About 61% don’t think Americans are taking enough precautions to prevent the spread of the coronavirus.

Health care workers were slightly positive when it comes to the Centers for Disease Control and Prevention (54% approve, 34% disapprove), divided on the Biden administration (41% approve, 40% disapprove), and critical of the news media (20% approve, 61% disapprove) and the American public (18% approve, 68% disapprove).

Broadly, though, health care workers support public health efforts. About 85% back measures that provide N95 masks, and 83% back measures that provide COVID-19 tests.

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

Big Vegetable has lied to us all

Hear this, children of the world: Your parents have betrayed you. They tell you day in and day out that vegetables are necessary, that they’re healthy, that you need them, but it is not the truth. Behind their foul taste is nothing but empty lies.

Okay, before we get a full-blown child rebellion on our hands, let’s reel things in. Eating vegetables has many benefits, and will help prevent many nasty medical conditions, such as diabetes or cancer. However, cardiovascular disease is not among them.

nneem/Pixabay

For their study published in Frontiers in Nutrition, researchers analyzed the diet, lifestyle, and medical history of nearly 400,000 U.K. adults over a 5-year period, finding that 4.5% developed heart disease and that the average adult consumed about 5 tablespoons of vegetables per day. Those who consumed the most vegetables had a reduction in heart disease incidence of about 15%, compared with those who ate the least.

Hang on, you’re thinking, we just said that vegetables didn’t prevent cardiovascular disease. But the data show otherwise! Ah, but the data are unadjusted. Once the researchers took socioeconomic status, information level, and general lifestyle into account, that benefit disappeared almost completely. The benefit seems to come not from the vegetables themselves, but from being able to afford better food and medical care in general.

The researchers were quick to note the other benefits of eating vegetables, and that people should probably keep eating those five servings a day. But we’re onto you, scientists. You can’t fool us with your vegetable-based lies. Unless we’re talking about pizza. Pizza is the best vegetable.
 

The good old days of surgery?

Modern surgical instruments, techniques, and technological innovations are amazing. It’s hard to imagine what surgery was like before laparoscopes came along, or x-ray machines, or even anesthesia. But those days weren’t really that long ago. Modern anesthesia, after all, dates back to just 1846. We’ve got socks almost that old.

Petar Ubiparip/Pixabay

But suppose we go back even further … say 5,300 years. Older than the oldest sock. Scientists studying a funerary chamber in Burgos, Spain, which was built in the 4th millennium B.C., have come across what looks like “the first known radical mastoidectomy in the history of humankind,” Sonia Díaz-Navarro of the University of Valladolid (Spain) and associates wrote in Scientific Reports.

One of the skulls they uncovered shows signs of trepanation. “Despite the [evidence] of cut marks, it is difficult to conclude the type of tool used to remove the bone tissue, most likely a sharp instrument with a circular movement,” they investigators said.

What is clear, though, is that the patient survived the surgery, because there is evidence of bone regeneration at the surgical sites. Sites? “Based on the differences in bone remodelling between the two temporals, it appears that the procedure was first conducted on the right ear, due to an ear pathology sufficiently alarming to require an intervention, which this prehistoric woman survived,” they explained.

The same procedure was then performed on the left ear, “but whether this was performed shortly after the right ear, or several months or even years later can’t be concluded from the existing evidence,” IFL Science reported.

Located nearby was a small section of tree bark with some scratches on it. That, ladies and gentlemen, was the first prior authorization form.
 

I hate that song, with reason

Do you have a favorite song? You may have a million reasons for loving that song. And past research can tell you why. But it’s only in a recent study that researchers were able to tell you why you dislike a song. And you know the song we’re talking about.

MPI for Empirical Aesthetics

Dislike breaks down into three major categories of rationale: subject-related reasons (how the song makes you feel emotionally and/or physically), object-related reasons (the lyrics or composition), and social reasons (do you relate to this?). Researchers at the Max Planck Institute for Empirical Aesthetics in Frankfurt, Germany, interviewed 21 participants and asked them to come up with a prepared list of music that they disliked and why they didn’t like it. And there was a lot that they didn’t like: 277 dislikes worth, to be exact.

“The most often mentioned type of dislike was musical style, followed by artist and genre,” senior author Julia Merrill explained on Eurekalert. Just over 40% of those rationales for not liking the music just had to do with the music itself, but 85% involved the music combined with one of the other categories.

Social reasoning played a big part in dislike. If the listener didn’t feel like a part of the target in-group for the music or the music didn’t have the same social values as those of the listener, it had an impact on dislike, they said.

But our dislike of certain types of music doesn’t just separate us from people in a negative way. Looking at the dislike of certain types of music helps us define our terms of having good taste, the researchers explained. Saying that one type of music is better than another can bring us closer with like-minded people and becomes a piece of how we identify ourselves. Cue the music snobs.

So if you can blast Barry Manilow but can’t bring yourself to play the Rolling Stones, there’s a reason for that. And if you love Aretha Franklin but not Frank Sinatra, there’s a reason for that, too. It’s all very personal. Just as music is meant to be.

Big Vegetable has lied to us all

Hear this, children of the world: Your parents have betrayed you. They tell you day in and day out that vegetables are necessary, that they’re healthy, that you need them, but it is not the truth. Behind their foul taste is nothing but empty lies.

Okay, before we get a full-blown child rebellion on our hands, let’s reel things in. Eating vegetables has many benefits, and will help prevent many nasty medical conditions, such as diabetes or cancer. However, cardiovascular disease is not among them.

nneem/Pixabay

For their study published in Frontiers in Nutrition, researchers analyzed the diet, lifestyle, and medical history of nearly 400,000 U.K. adults over a 5-year period, finding that 4.5% developed heart disease and that the average adult consumed about 5 tablespoons of vegetables per day. Those who consumed the most vegetables had a reduction in heart disease incidence of about 15%, compared with those who ate the least.

Hang on, you’re thinking, we just said that vegetables didn’t prevent cardiovascular disease. But the data show otherwise! Ah, but the data are unadjusted. Once the researchers took socioeconomic status, information level, and general lifestyle into account, that benefit disappeared almost completely. The benefit seems to come not from the vegetables themselves, but from being able to afford better food and medical care in general.

The researchers were quick to note the other benefits of eating vegetables, and that people should probably keep eating those five servings a day. But we’re onto you, scientists. You can’t fool us with your vegetable-based lies. Unless we’re talking about pizza. Pizza is the best vegetable.
 

The good old days of surgery?

Modern surgical instruments, techniques, and technological innovations are amazing. It’s hard to imagine what surgery was like before laparoscopes came along, or x-ray machines, or even anesthesia. But those days weren’t really that long ago. Modern anesthesia, after all, dates back to just 1846. We’ve got socks almost that old.

Petar Ubiparip/Pixabay

But suppose we go back even further … say 5,300 years. Older than the oldest sock. Scientists studying a funerary chamber in Burgos, Spain, which was built in the 4th millennium B.C., have come across what looks like “the first known radical mastoidectomy in the history of humankind,” Sonia Díaz-Navarro of the University of Valladolid (Spain) and associates wrote in Scientific Reports.

One of the skulls they uncovered shows signs of trepanation. “Despite the [evidence] of cut marks, it is difficult to conclude the type of tool used to remove the bone tissue, most likely a sharp instrument with a circular movement,” they investigators said.

What is clear, though, is that the patient survived the surgery, because there is evidence of bone regeneration at the surgical sites. Sites? “Based on the differences in bone remodelling between the two temporals, it appears that the procedure was first conducted on the right ear, due to an ear pathology sufficiently alarming to require an intervention, which this prehistoric woman survived,” they explained.

The same procedure was then performed on the left ear, “but whether this was performed shortly after the right ear, or several months or even years later can’t be concluded from the existing evidence,” IFL Science reported.

Located nearby was a small section of tree bark with some scratches on it. That, ladies and gentlemen, was the first prior authorization form.
 

I hate that song, with reason

Do you have a favorite song? You may have a million reasons for loving that song. And past research can tell you why. But it’s only in a recent study that researchers were able to tell you why you dislike a song. And you know the song we’re talking about.

MPI for Empirical Aesthetics

Dislike breaks down into three major categories of rationale: subject-related reasons (how the song makes you feel emotionally and/or physically), object-related reasons (the lyrics or composition), and social reasons (do you relate to this?). Researchers at the Max Planck Institute for Empirical Aesthetics in Frankfurt, Germany, interviewed 21 participants and asked them to come up with a prepared list of music that they disliked and why they didn’t like it. And there was a lot that they didn’t like: 277 dislikes worth, to be exact.

“The most often mentioned type of dislike was musical style, followed by artist and genre,” senior author Julia Merrill explained on Eurekalert. Just over 40% of those rationales for not liking the music just had to do with the music itself, but 85% involved the music combined with one of the other categories.

Social reasoning played a big part in dislike. If the listener didn’t feel like a part of the target in-group for the music or the music didn’t have the same social values as those of the listener, it had an impact on dislike, they said.

But our dislike of certain types of music doesn’t just separate us from people in a negative way. Looking at the dislike of certain types of music helps us define our terms of having good taste, the researchers explained. Saying that one type of music is better than another can bring us closer with like-minded people and becomes a piece of how we identify ourselves. Cue the music snobs.

So if you can blast Barry Manilow but can’t bring yourself to play the Rolling Stones, there’s a reason for that. And if you love Aretha Franklin but not Frank Sinatra, there’s a reason for that, too. It’s all very personal. Just as music is meant to be.

Big Vegetable has lied to us all

Hear this, children of the world: Your parents have betrayed you. They tell you day in and day out that vegetables are necessary, that they’re healthy, that you need them, but it is not the truth. Behind their foul taste is nothing but empty lies.

Okay, before we get a full-blown child rebellion on our hands, let’s reel things in. Eating vegetables has many benefits, and will help prevent many nasty medical conditions, such as diabetes or cancer. However, cardiovascular disease is not among them.

nneem/Pixabay

For their study published in Frontiers in Nutrition, researchers analyzed the diet, lifestyle, and medical history of nearly 400,000 U.K. adults over a 5-year period, finding that 4.5% developed heart disease and that the average adult consumed about 5 tablespoons of vegetables per day. Those who consumed the most vegetables had a reduction in heart disease incidence of about 15%, compared with those who ate the least.

Hang on, you’re thinking, we just said that vegetables didn’t prevent cardiovascular disease. But the data show otherwise! Ah, but the data are unadjusted. Once the researchers took socioeconomic status, information level, and general lifestyle into account, that benefit disappeared almost completely. The benefit seems to come not from the vegetables themselves, but from being able to afford better food and medical care in general.

The researchers were quick to note the other benefits of eating vegetables, and that people should probably keep eating those five servings a day. But we’re onto you, scientists. You can’t fool us with your vegetable-based lies. Unless we’re talking about pizza. Pizza is the best vegetable.
 

The good old days of surgery?

Modern surgical instruments, techniques, and technological innovations are amazing. It’s hard to imagine what surgery was like before laparoscopes came along, or x-ray machines, or even anesthesia. But those days weren’t really that long ago. Modern anesthesia, after all, dates back to just 1846. We’ve got socks almost that old.

Petar Ubiparip/Pixabay

But suppose we go back even further … say 5,300 years. Older than the oldest sock. Scientists studying a funerary chamber in Burgos, Spain, which was built in the 4th millennium B.C., have come across what looks like “the first known radical mastoidectomy in the history of humankind,” Sonia Díaz-Navarro of the University of Valladolid (Spain) and associates wrote in Scientific Reports.

One of the skulls they uncovered shows signs of trepanation. “Despite the [evidence] of cut marks, it is difficult to conclude the type of tool used to remove the bone tissue, most likely a sharp instrument with a circular movement,” they investigators said.

What is clear, though, is that the patient survived the surgery, because there is evidence of bone regeneration at the surgical sites. Sites? “Based on the differences in bone remodelling between the two temporals, it appears that the procedure was first conducted on the right ear, due to an ear pathology sufficiently alarming to require an intervention, which this prehistoric woman survived,” they explained.

The same procedure was then performed on the left ear, “but whether this was performed shortly after the right ear, or several months or even years later can’t be concluded from the existing evidence,” IFL Science reported.

Located nearby was a small section of tree bark with some scratches on it. That, ladies and gentlemen, was the first prior authorization form.
 

I hate that song, with reason

Do you have a favorite song? You may have a million reasons for loving that song. And past research can tell you why. But it’s only in a recent study that researchers were able to tell you why you dislike a song. And you know the song we’re talking about.

MPI for Empirical Aesthetics

Dislike breaks down into three major categories of rationale: subject-related reasons (how the song makes you feel emotionally and/or physically), object-related reasons (the lyrics or composition), and social reasons (do you relate to this?). Researchers at the Max Planck Institute for Empirical Aesthetics in Frankfurt, Germany, interviewed 21 participants and asked them to come up with a prepared list of music that they disliked and why they didn’t like it. And there was a lot that they didn’t like: 277 dislikes worth, to be exact.

“The most often mentioned type of dislike was musical style, followed by artist and genre,” senior author Julia Merrill explained on Eurekalert. Just over 40% of those rationales for not liking the music just had to do with the music itself, but 85% involved the music combined with one of the other categories.

Social reasoning played a big part in dislike. If the listener didn’t feel like a part of the target in-group for the music or the music didn’t have the same social values as those of the listener, it had an impact on dislike, they said.

But our dislike of certain types of music doesn’t just separate us from people in a negative way. Looking at the dislike of certain types of music helps us define our terms of having good taste, the researchers explained. Saying that one type of music is better than another can bring us closer with like-minded people and becomes a piece of how we identify ourselves. Cue the music snobs.

So if you can blast Barry Manilow but can’t bring yourself to play the Rolling Stones, there’s a reason for that. And if you love Aretha Franklin but not Frank Sinatra, there’s a reason for that, too. It’s all very personal. Just as music is meant to be.

Ronald Goldenberg, MD, completed his residency in Internal Medicine in 1987 at the University of Toronto, and his fellowship in Endocrinology & Metabolism in 1989 at the University of Toronto.  Dr. Goldenberg is a past chair of the Ontario Medical Association Section on Endocrinology & Metabolism and a previous President of the Toronto Diabetes Association. Dr. Goldenberg has been an investigator in a wide array of clinical trials in the areas of diabetes, hypertension, obesity, and dyslipidemia. His major areas of interest include clinical care of diabetes, obesity, dyslipidemia and thyroid disorders. He has been actively involved in Continuing Medical Education for the last 3 decades, with a strong focus on translating evidence-based medicine into practical patient care.

As a consultant endocrinologist with an area of interest that includes clinical care of diabetes, can you briefly tell us what the top 5 studies of 2021 were that are most likely to influence diabetes or obesity practice?

Dr. Goldenberg: 2021 was a banner year for clinicians managing diabetes and or obesity. There were many key trials that were published and or presented. In my mind, the most important ones that will really influence practice include the STEP program of semaglutide 2.4 mg once weekly in the management of overweight or obesity. There is the FIGARO-DKD and FIDELITY analysis of finerenone in patients with type 2 diabetes and chronic kidney disease. Other top studies include the SURPASS trials of a novel dual incretin agonist called tirzepatide, the EMPEROR-Preserved trial with empagliflozin and a pooled analysis of empagliflozin in both HFrEF and HFpEF trials, and the AMPLITUDE-O trial, which is a cardiovascular outcome trial with an exendin-based GLP-1 receptor agonist known as efpeglenatide.

2021 was definitely a landmark year in diabetes. Let's start with the STEP program with semaglutide 2.4. What were the important findings in these studies?

Dr. Goldenberg: STEP is the Phase III program for 2.4 milligrams once weekly in the management of overweight or obesity. The STEP program studies that have been published and/or presented in 2021 include four Phase IIIa trials STEP 1 through STEP 4, as well as three Phase IIIb trials, STEP 5, 6, and 8. They're all rather similar, as they each enrolled patients with overweight and/or obesity. Patients were up-titrated to semaglutide 2.4 milligrams once weekly, and the top-line summary across all of these trials is that patients randomized to semaglutide 2.4 mg once weekly lost 15% to 17% of their body weight amongst those that did not have diabetes, which is really a tremendous amount of weight loss for an anti-obesity drug. And even those with type 2 diabetes lost almost 10% of their body weight, which is pretty impressive given that patients with type 2 diabetes are often somewhat refractory to weight loss.

There was a high percentage of body weight loss across these trials, as roughly 86 to 90% of patients without diabetes achieved at least a 5% body weight loss and even in those with diabetes, almost 70% achieved a 5% loss in their body weight. As far as overall safety, the safety profile of semaglutide 2.4 mg once weekly was generally similar to the GLP-1 receptor agonist class. The most common side effects were gastrointestinal. Nausea occurred anywhere from 20% to 58% of patients, but it was generally transient. Very few people withdrew because of gastrointestinal side effects.

 I think the key thing for clinicians to know about the STEP program is that it's the results of these trials that led to the FDA approving semaglutide 2.4 mg once weekly as a new agent for the management of overweight and/or obesity.

You mentioned FIGARO-DKD and FIDELITY with Finerenone. Can you talk more about the relevance of this data and summarize the key findings?

Dr. Goldenberg: Finerenone is a new selective non-steroidal mineralocorticoid receptor antagonist that interacts with the mineralocorticoid receptor in a different way compared to traditional steroidal mineralocorticoid receptor agonists.  We know from pre-clinical data that this agent targets inflammation and fibrosis in both the kidney and the heart. The finerenone Phase III program focused on patients with type 2 diabetes and chronic kidney disease. In 2021, they published the FIGARO-DKD trial. This enrolled almost 7,500 patients with type 2 diabetes and an eGFR of 25 ml/min or more along with albuminuria.

The key result of this trial is the primary outcome of CV death non-fatal MI, non-fatal stroke, or hospitalization for heart failure was reduced by 13%. The number needed to treat after 3 ½ years was 47. The primary outcome was mainly driven by a reduction for hospitalization for heart failure. Key secondary outcomes included composite kidney outcomes, one of which was defined by a sustained eGFR reduction of 40% or more along with end-stage kidney disease or renal death. This did not quite reach statistical significance, but a more stringent outcome that included a reduction in eGFR of at least 57% or more was in fact reduced by 23%.

End-stage kidney disease was reduced by 36% in the FIGARO-DKD trial. Finerenone was well tolerated. Hyperkalemia occurred in 10.8% of patients on finerenone and 5.3% on placebo but it was quite unusual to have to stop finerenone because of hyperkalemia. Building on FIGARO-DKD in 2021 was a prespecified meta-analysis of two large Phase III trials, the FIGARO-DKD trial and also the previously published FIDELIO-DKD trial and in this pooled analysis the composite cardiovascular outcome was reduced by 14%. The benefit on cardiovascular events was independent of the baseline eGFR or urine albumin to creatinine ratio, as well as independent of the use of SGLT2 inhibitors or GLP-1 receptor agonists.

There was also a 23% reduction in a composite kidney outcome that used a sustained 57% reduction in eGFR as part of that outcome and essentially each component of the composite kidney outcome was reduced,  including kidney failure, end-stage kidney disease, eGFR of less than 15 ml/min in addition to a  ≥57% decrease in eGFR. And this kidney outcome showed a benefit irrespective of the use of SGLT2 inhibitor at baseline although the number of patients taking an SGLT2 inhibitor in this analysis was relatively small. So overall, the results of finerenone in 2021 support the use of this agent in patients with type 2 diabetes and chronic kidney disease to improve both cardiovascular and kidney outcomes.

Thank you for this insight. Regarding the SURPASS trials with tirzepatide, what is tirzepatide and what was its impact on glycemia and weight?

Dr. Goldenberg. My pleasure. Tirzepatide is a unique dual GIP/GLP-1 receptor agonist that has been formulated to be given as a once weekly injection. In 2021, we heard the first results from the Phase III program including SURPASS-1 through SURPASS-5. In these trials, patients were randomized to tirzepatide 5 mg, 10 mg, or 15 mg, and often compared to placebo or an active comparator. Across the SURPASS trials, the A1C reduction from baseline was between 1.9% to 2.6%. Up to 97% of patients on tirzepatide achieved a HbA1c of less than 7%, and up to 62% achieve a normal HbA1c of less than 5.7%.

In addition to these rather robust glycemic outcomes, there was excellent weight loss in the SURPASS program with the weight reduction ranging from 6 to 13 kg from baseline. Interestingly, in the SURPASS studies, tirzepatide showed superiority to semaglutide 1 mg and also superiority to titrated basal insulin. As far as safety, the side effect profile was similar to all GLP-1 receptor agonists with transient nausea being the most common side effect. Overall, tirzepatide will definitely add to our ability to treat our patients with type 2 diabetes with an incretin agent, and when this agent gets approved, hopefully, it will provide robust glycemic lowering and weight loss.

The fourth key study you mentioned is the EMPEROR-Preserved along with the EMPEROR-Pooled with the empagliflozin. What did they find in this analysis?

Dr. Goldenberg: The EMPEROR-Preserved was the first completed large randomized clinical trial of an SGLT2 inhibitor in patients with heart failure with preserved ejection fraction. They enrolled almost 6,000 patients with HFpEF with or without type 2 diabetes and they were randomized to empagliflozin 10 mg or placebo. The primary outcome of cardiovascular death or hospitalization for heart failure was reduced by 21% with empagliflozin and the number needed to treat was 31. This primary outcome was largely driven by a reduction in hospitalization for heart failure. The primary outcome showed consistent benefit across 15 prespecified subgroups, including those with or without type 2 diabetes, and including a spectrum of baseline left ventricular ejection fractions from 40% to 50% to greater than 60%.

There were also some key secondary endpoints:  total hospitalization for heart failure was reduced by 27% and empagliflozin also slowed the decline of eGFR over time in the EMPEROR-Preserved trial. The agent was well tolerated. There was a slight signal for more hypotension and genital mycotic infections, but otherwise really no concerning adverse effects.

Building on the EMPEROR-Preserved trial was a prespecified pooled analysis of EMPEROR-Reduced and EMPEROR-Preserved,  the two large outcome trials with empagliflozin in heart failure patients. The prespecified primary outcome of this analysis was a major renal outcome which included a GFR reduction of ≥40%, renal replacement therapy or sustained eGFR <10-15 ml/min. While in EMPEROR-Reduced there was a significant 49% reduction in this composite renal outcome, in EMPEROR-Preserved there was no significant reduction. Because of the heterogeneity across these two trials, it was not statistically valid to pool these two results for the composite renal outcome. However, what they found in EMPEROR-Pooled is that if you use a more robust renal outcome including at least a 50% decline in eGFR, then there seems to be a trend that varies depending on baseline left ventricular ejection fraction, suggesting a benefit on the renal outcome if your baseline left ventricular function ranges from 40% to 60%, but lack of benefit with a baseline left ventricular ejection fraction of over 60%. The top line summary of this data is that for the first time we have robust evidence that an SGLT2 inhibitor, in this case empagliflozin 10 mg, can provide a cardiovascular benefit in patients with HFpEF, in addition to the known benefit in HFrEF patients.

Finally, there's the AMPLITUDE-O with efpeglenatide, an international randomized controlled trial conducted at approximately 344 sites in 28 countries. What are the key learnings and messages for this specific study?

Dr. Goldenberg: Efpeglenatide is an exendin-4-based GLP-1 receptor agonist that is given once weekly and the AMPLITUDE-O trial is the cardiovascular outcome trial with efpeglenatide done in patients with type 2 diabetes and either cardiovascular disease or chronic kidney disease plus at least one cardiovascular risk factor. It was an important trial because prior to this cardiovascular outcome trial studies of exendin-4-based GLP-1 receptor agonist have been neutral. However, the AMPLITUDE-O study showed for the first-time superiority with an exendin-4-based GLP-1 receptor agonist. In this case, efpeglenatide 4 or 6 milligrams versus placebo was associated with a 27% reduction in the primary outcome of CV death, non-fatal MI or non-fatal stroke.

Importantly, there was a consistent benefit with efpeglenatide across a spectrum of prespecified subgroups,  the most important one being those that entered the trial on a background SGLT2 inhibitor, which represented about 15% of the patients. They derived the same overall benefit as those not taking an SGLT2 inhibitor. It is important to appreciate that this is probably the most robust data we have for showing a cardiovascular benefit of adding a GLP-1 receptor agonist to an SGLT2 inhibitor in high risk patients with type 2 diabetes. AMPLITUDE-O also adds to the already appreciated knowledge of the cardiovascular benefit of GLP-1 receptor agonists and builds on this story by showing that you can get a cardiovascular benefit with an exendin-4-based GLP-1 receptor agonist and you can get a benefit as an add on to SGLT2 inhibitors.

Ronald Goldenberg, MD, completed his residency in Internal Medicine in 1987 at the University of Toronto, and his fellowship in Endocrinology & Metabolism in 1989 at the University of Toronto.  Dr. Goldenberg is a past chair of the Ontario Medical Association Section on Endocrinology & Metabolism and a previous President of the Toronto Diabetes Association. Dr. Goldenberg has been an investigator in a wide array of clinical trials in the areas of diabetes, hypertension, obesity, and dyslipidemia. His major areas of interest include clinical care of diabetes, obesity, dyslipidemia and thyroid disorders. He has been actively involved in Continuing Medical Education for the last 3 decades, with a strong focus on translating evidence-based medicine into practical patient care.

As a consultant endocrinologist with an area of interest that includes clinical care of diabetes, can you briefly tell us what the top 5 studies of 2021 were that are most likely to influence diabetes or obesity practice?

Dr. Goldenberg: 2021 was a banner year for clinicians managing diabetes and or obesity. There were many key trials that were published and or presented. In my mind, the most important ones that will really influence practice include the STEP program of semaglutide 2.4 mg once weekly in the management of overweight or obesity. There is the FIGARO-DKD and FIDELITY analysis of finerenone in patients with type 2 diabetes and chronic kidney disease. Other top studies include the SURPASS trials of a novel dual incretin agonist called tirzepatide, the EMPEROR-Preserved trial with empagliflozin and a pooled analysis of empagliflozin in both HFrEF and HFpEF trials, and the AMPLITUDE-O trial, which is a cardiovascular outcome trial with an exendin-based GLP-1 receptor agonist known as efpeglenatide.

2021 was definitely a landmark year in diabetes. Let's start with the STEP program with semaglutide 2.4. What were the important findings in these studies?

Dr. Goldenberg: STEP is the Phase III program for 2.4 milligrams once weekly in the management of overweight or obesity. The STEP program studies that have been published and/or presented in 2021 include four Phase IIIa trials STEP 1 through STEP 4, as well as three Phase IIIb trials, STEP 5, 6, and 8. They're all rather similar, as they each enrolled patients with overweight and/or obesity. Patients were up-titrated to semaglutide 2.4 milligrams once weekly, and the top-line summary across all of these trials is that patients randomized to semaglutide 2.4 mg once weekly lost 15% to 17% of their body weight amongst those that did not have diabetes, which is really a tremendous amount of weight loss for an anti-obesity drug. And even those with type 2 diabetes lost almost 10% of their body weight, which is pretty impressive given that patients with type 2 diabetes are often somewhat refractory to weight loss.

There was a high percentage of body weight loss across these trials, as roughly 86 to 90% of patients without diabetes achieved at least a 5% body weight loss and even in those with diabetes, almost 70% achieved a 5% loss in their body weight. As far as overall safety, the safety profile of semaglutide 2.4 mg once weekly was generally similar to the GLP-1 receptor agonist class. The most common side effects were gastrointestinal. Nausea occurred anywhere from 20% to 58% of patients, but it was generally transient. Very few people withdrew because of gastrointestinal side effects.

 I think the key thing for clinicians to know about the STEP program is that it's the results of these trials that led to the FDA approving semaglutide 2.4 mg once weekly as a new agent for the management of overweight and/or obesity.

You mentioned FIGARO-DKD and FIDELITY with Finerenone. Can you talk more about the relevance of this data and summarize the key findings?

Dr. Goldenberg: Finerenone is a new selective non-steroidal mineralocorticoid receptor antagonist that interacts with the mineralocorticoid receptor in a different way compared to traditional steroidal mineralocorticoid receptor agonists.  We know from pre-clinical data that this agent targets inflammation and fibrosis in both the kidney and the heart. The finerenone Phase III program focused on patients with type 2 diabetes and chronic kidney disease. In 2021, they published the FIGARO-DKD trial. This enrolled almost 7,500 patients with type 2 diabetes and an eGFR of 25 ml/min or more along with albuminuria.

The key result of this trial is the primary outcome of CV death non-fatal MI, non-fatal stroke, or hospitalization for heart failure was reduced by 13%. The number needed to treat after 3 ½ years was 47. The primary outcome was mainly driven by a reduction for hospitalization for heart failure. Key secondary outcomes included composite kidney outcomes, one of which was defined by a sustained eGFR reduction of 40% or more along with end-stage kidney disease or renal death. This did not quite reach statistical significance, but a more stringent outcome that included a reduction in eGFR of at least 57% or more was in fact reduced by 23%.

End-stage kidney disease was reduced by 36% in the FIGARO-DKD trial. Finerenone was well tolerated. Hyperkalemia occurred in 10.8% of patients on finerenone and 5.3% on placebo but it was quite unusual to have to stop finerenone because of hyperkalemia. Building on FIGARO-DKD in 2021 was a prespecified meta-analysis of two large Phase III trials, the FIGARO-DKD trial and also the previously published FIDELIO-DKD trial and in this pooled analysis the composite cardiovascular outcome was reduced by 14%. The benefit on cardiovascular events was independent of the baseline eGFR or urine albumin to creatinine ratio, as well as independent of the use of SGLT2 inhibitors or GLP-1 receptor agonists.

There was also a 23% reduction in a composite kidney outcome that used a sustained 57% reduction in eGFR as part of that outcome and essentially each component of the composite kidney outcome was reduced,  including kidney failure, end-stage kidney disease, eGFR of less than 15 ml/min in addition to a  ≥57% decrease in eGFR. And this kidney outcome showed a benefit irrespective of the use of SGLT2 inhibitor at baseline although the number of patients taking an SGLT2 inhibitor in this analysis was relatively small. So overall, the results of finerenone in 2021 support the use of this agent in patients with type 2 diabetes and chronic kidney disease to improve both cardiovascular and kidney outcomes.

Thank you for this insight. Regarding the SURPASS trials with tirzepatide, what is tirzepatide and what was its impact on glycemia and weight?

Dr. Goldenberg. My pleasure. Tirzepatide is a unique dual GIP/GLP-1 receptor agonist that has been formulated to be given as a once weekly injection. In 2021, we heard the first results from the Phase III program including SURPASS-1 through SURPASS-5. In these trials, patients were randomized to tirzepatide 5 mg, 10 mg, or 15 mg, and often compared to placebo or an active comparator. Across the SURPASS trials, the A1C reduction from baseline was between 1.9% to 2.6%. Up to 97% of patients on tirzepatide achieved a HbA1c of less than 7%, and up to 62% achieve a normal HbA1c of less than 5.7%.

In addition to these rather robust glycemic outcomes, there was excellent weight loss in the SURPASS program with the weight reduction ranging from 6 to 13 kg from baseline. Interestingly, in the SURPASS studies, tirzepatide showed superiority to semaglutide 1 mg and also superiority to titrated basal insulin. As far as safety, the side effect profile was similar to all GLP-1 receptor agonists with transient nausea being the most common side effect. Overall, tirzepatide will definitely add to our ability to treat our patients with type 2 diabetes with an incretin agent, and when this agent gets approved, hopefully, it will provide robust glycemic lowering and weight loss.

The fourth key study you mentioned is the EMPEROR-Preserved along with the EMPEROR-Pooled with the empagliflozin. What did they find in this analysis?

Dr. Goldenberg: The EMPEROR-Preserved was the first completed large randomized clinical trial of an SGLT2 inhibitor in patients with heart failure with preserved ejection fraction. They enrolled almost 6,000 patients with HFpEF with or without type 2 diabetes and they were randomized to empagliflozin 10 mg or placebo. The primary outcome of cardiovascular death or hospitalization for heart failure was reduced by 21% with empagliflozin and the number needed to treat was 31. This primary outcome was largely driven by a reduction in hospitalization for heart failure. The primary outcome showed consistent benefit across 15 prespecified subgroups, including those with or without type 2 diabetes, and including a spectrum of baseline left ventricular ejection fractions from 40% to 50% to greater than 60%.

There were also some key secondary endpoints:  total hospitalization for heart failure was reduced by 27% and empagliflozin also slowed the decline of eGFR over time in the EMPEROR-Preserved trial. The agent was well tolerated. There was a slight signal for more hypotension and genital mycotic infections, but otherwise really no concerning adverse effects.

Building on the EMPEROR-Preserved trial was a prespecified pooled analysis of EMPEROR-Reduced and EMPEROR-Preserved,  the two large outcome trials with empagliflozin in heart failure patients. The prespecified primary outcome of this analysis was a major renal outcome which included a GFR reduction of ≥40%, renal replacement therapy or sustained eGFR <10-15 ml/min. While in EMPEROR-Reduced there was a significant 49% reduction in this composite renal outcome, in EMPEROR-Preserved there was no significant reduction. Because of the heterogeneity across these two trials, it was not statistically valid to pool these two results for the composite renal outcome. However, what they found in EMPEROR-Pooled is that if you use a more robust renal outcome including at least a 50% decline in eGFR, then there seems to be a trend that varies depending on baseline left ventricular ejection fraction, suggesting a benefit on the renal outcome if your baseline left ventricular function ranges from 40% to 60%, but lack of benefit with a baseline left ventricular ejection fraction of over 60%. The top line summary of this data is that for the first time we have robust evidence that an SGLT2 inhibitor, in this case empagliflozin 10 mg, can provide a cardiovascular benefit in patients with HFpEF, in addition to the known benefit in HFrEF patients.

Finally, there's the AMPLITUDE-O with efpeglenatide, an international randomized controlled trial conducted at approximately 344 sites in 28 countries. What are the key learnings and messages for this specific study?

Dr. Goldenberg: Efpeglenatide is an exendin-4-based GLP-1 receptor agonist that is given once weekly and the AMPLITUDE-O trial is the cardiovascular outcome trial with efpeglenatide done in patients with type 2 diabetes and either cardiovascular disease or chronic kidney disease plus at least one cardiovascular risk factor. It was an important trial because prior to this cardiovascular outcome trial studies of exendin-4-based GLP-1 receptor agonist have been neutral. However, the AMPLITUDE-O study showed for the first-time superiority with an exendin-4-based GLP-1 receptor agonist. In this case, efpeglenatide 4 or 6 milligrams versus placebo was associated with a 27% reduction in the primary outcome of CV death, non-fatal MI or non-fatal stroke.

Importantly, there was a consistent benefit with efpeglenatide across a spectrum of prespecified subgroups,  the most important one being those that entered the trial on a background SGLT2 inhibitor, which represented about 15% of the patients. They derived the same overall benefit as those not taking an SGLT2 inhibitor. It is important to appreciate that this is probably the most robust data we have for showing a cardiovascular benefit of adding a GLP-1 receptor agonist to an SGLT2 inhibitor in high risk patients with type 2 diabetes. AMPLITUDE-O also adds to the already appreciated knowledge of the cardiovascular benefit of GLP-1 receptor agonists and builds on this story by showing that you can get a cardiovascular benefit with an exendin-4-based GLP-1 receptor agonist and you can get a benefit as an add on to SGLT2 inhibitors.

Ronald Goldenberg, MD, completed his residency in Internal Medicine in 1987 at the University of Toronto, and his fellowship in Endocrinology & Metabolism in 1989 at the University of Toronto.  Dr. Goldenberg is a past chair of the Ontario Medical Association Section on Endocrinology & Metabolism and a previous President of the Toronto Diabetes Association. Dr. Goldenberg has been an investigator in a wide array of clinical trials in the areas of diabetes, hypertension, obesity, and dyslipidemia. His major areas of interest include clinical care of diabetes, obesity, dyslipidemia and thyroid disorders. He has been actively involved in Continuing Medical Education for the last 3 decades, with a strong focus on translating evidence-based medicine into practical patient care.

As a consultant endocrinologist with an area of interest that includes clinical care of diabetes, can you briefly tell us what the top 5 studies of 2021 were that are most likely to influence diabetes or obesity practice?

Dr. Goldenberg: 2021 was a banner year for clinicians managing diabetes and or obesity. There were many key trials that were published and or presented. In my mind, the most important ones that will really influence practice include the STEP program of semaglutide 2.4 mg once weekly in the management of overweight or obesity. There is the FIGARO-DKD and FIDELITY analysis of finerenone in patients with type 2 diabetes and chronic kidney disease. Other top studies include the SURPASS trials of a novel dual incretin agonist called tirzepatide, the EMPEROR-Preserved trial with empagliflozin and a pooled analysis of empagliflozin in both HFrEF and HFpEF trials, and the AMPLITUDE-O trial, which is a cardiovascular outcome trial with an exendin-based GLP-1 receptor agonist known as efpeglenatide.

2021 was definitely a landmark year in diabetes. Let's start with the STEP program with semaglutide 2.4. What were the important findings in these studies?

Dr. Goldenberg: STEP is the Phase III program for 2.4 milligrams once weekly in the management of overweight or obesity. The STEP program studies that have been published and/or presented in 2021 include four Phase IIIa trials STEP 1 through STEP 4, as well as three Phase IIIb trials, STEP 5, 6, and 8. They're all rather similar, as they each enrolled patients with overweight and/or obesity. Patients were up-titrated to semaglutide 2.4 milligrams once weekly, and the top-line summary across all of these trials is that patients randomized to semaglutide 2.4 mg once weekly lost 15% to 17% of their body weight amongst those that did not have diabetes, which is really a tremendous amount of weight loss for an anti-obesity drug. And even those with type 2 diabetes lost almost 10% of their body weight, which is pretty impressive given that patients with type 2 diabetes are often somewhat refractory to weight loss.

There was a high percentage of body weight loss across these trials, as roughly 86 to 90% of patients without diabetes achieved at least a 5% body weight loss and even in those with diabetes, almost 70% achieved a 5% loss in their body weight. As far as overall safety, the safety profile of semaglutide 2.4 mg once weekly was generally similar to the GLP-1 receptor agonist class. The most common side effects were gastrointestinal. Nausea occurred anywhere from 20% to 58% of patients, but it was generally transient. Very few people withdrew because of gastrointestinal side effects.

 I think the key thing for clinicians to know about the STEP program is that it's the results of these trials that led to the FDA approving semaglutide 2.4 mg once weekly as a new agent for the management of overweight and/or obesity.

You mentioned FIGARO-DKD and FIDELITY with Finerenone. Can you talk more about the relevance of this data and summarize the key findings?

Dr. Goldenberg: Finerenone is a new selective non-steroidal mineralocorticoid receptor antagonist that interacts with the mineralocorticoid receptor in a different way compared to traditional steroidal mineralocorticoid receptor agonists.  We know from pre-clinical data that this agent targets inflammation and fibrosis in both the kidney and the heart. The finerenone Phase III program focused on patients with type 2 diabetes and chronic kidney disease. In 2021, they published the FIGARO-DKD trial. This enrolled almost 7,500 patients with type 2 diabetes and an eGFR of 25 ml/min or more along with albuminuria.

The key result of this trial is the primary outcome of CV death non-fatal MI, non-fatal stroke, or hospitalization for heart failure was reduced by 13%. The number needed to treat after 3 ½ years was 47. The primary outcome was mainly driven by a reduction for hospitalization for heart failure. Key secondary outcomes included composite kidney outcomes, one of which was defined by a sustained eGFR reduction of 40% or more along with end-stage kidney disease or renal death. This did not quite reach statistical significance, but a more stringent outcome that included a reduction in eGFR of at least 57% or more was in fact reduced by 23%.

End-stage kidney disease was reduced by 36% in the FIGARO-DKD trial. Finerenone was well tolerated. Hyperkalemia occurred in 10.8% of patients on finerenone and 5.3% on placebo but it was quite unusual to have to stop finerenone because of hyperkalemia. Building on FIGARO-DKD in 2021 was a prespecified meta-analysis of two large Phase III trials, the FIGARO-DKD trial and also the previously published FIDELIO-DKD trial and in this pooled analysis the composite cardiovascular outcome was reduced by 14%. The benefit on cardiovascular events was independent of the baseline eGFR or urine albumin to creatinine ratio, as well as independent of the use of SGLT2 inhibitors or GLP-1 receptor agonists.

There was also a 23% reduction in a composite kidney outcome that used a sustained 57% reduction in eGFR as part of that outcome and essentially each component of the composite kidney outcome was reduced,  including kidney failure, end-stage kidney disease, eGFR of less than 15 ml/min in addition to a  ≥57% decrease in eGFR. And this kidney outcome showed a benefit irrespective of the use of SGLT2 inhibitor at baseline although the number of patients taking an SGLT2 inhibitor in this analysis was relatively small. So overall, the results of finerenone in 2021 support the use of this agent in patients with type 2 diabetes and chronic kidney disease to improve both cardiovascular and kidney outcomes.

Thank you for this insight. Regarding the SURPASS trials with tirzepatide, what is tirzepatide and what was its impact on glycemia and weight?

Dr. Goldenberg. My pleasure. Tirzepatide is a unique dual GIP/GLP-1 receptor agonist that has been formulated to be given as a once weekly injection. In 2021, we heard the first results from the Phase III program including SURPASS-1 through SURPASS-5. In these trials, patients were randomized to tirzepatide 5 mg, 10 mg, or 15 mg, and often compared to placebo or an active comparator. Across the SURPASS trials, the A1C reduction from baseline was between 1.9% to 2.6%. Up to 97% of patients on tirzepatide achieved a HbA1c of less than 7%, and up to 62% achieve a normal HbA1c of less than 5.7%.

In addition to these rather robust glycemic outcomes, there was excellent weight loss in the SURPASS program with the weight reduction ranging from 6 to 13 kg from baseline. Interestingly, in the SURPASS studies, tirzepatide showed superiority to semaglutide 1 mg and also superiority to titrated basal insulin. As far as safety, the side effect profile was similar to all GLP-1 receptor agonists with transient nausea being the most common side effect. Overall, tirzepatide will definitely add to our ability to treat our patients with type 2 diabetes with an incretin agent, and when this agent gets approved, hopefully, it will provide robust glycemic lowering and weight loss.

The fourth key study you mentioned is the EMPEROR-Preserved along with the EMPEROR-Pooled with the empagliflozin. What did they find in this analysis?

Dr. Goldenberg: The EMPEROR-Preserved was the first completed large randomized clinical trial of an SGLT2 inhibitor in patients with heart failure with preserved ejection fraction. They enrolled almost 6,000 patients with HFpEF with or without type 2 diabetes and they were randomized to empagliflozin 10 mg or placebo. The primary outcome of cardiovascular death or hospitalization for heart failure was reduced by 21% with empagliflozin and the number needed to treat was 31. This primary outcome was largely driven by a reduction in hospitalization for heart failure. The primary outcome showed consistent benefit across 15 prespecified subgroups, including those with or without type 2 diabetes, and including a spectrum of baseline left ventricular ejection fractions from 40% to 50% to greater than 60%.

There were also some key secondary endpoints:  total hospitalization for heart failure was reduced by 27% and empagliflozin also slowed the decline of eGFR over time in the EMPEROR-Preserved trial. The agent was well tolerated. There was a slight signal for more hypotension and genital mycotic infections, but otherwise really no concerning adverse effects.

Building on the EMPEROR-Preserved trial was a prespecified pooled analysis of EMPEROR-Reduced and EMPEROR-Preserved,  the two large outcome trials with empagliflozin in heart failure patients. The prespecified primary outcome of this analysis was a major renal outcome which included a GFR reduction of ≥40%, renal replacement therapy or sustained eGFR <10-15 ml/min. While in EMPEROR-Reduced there was a significant 49% reduction in this composite renal outcome, in EMPEROR-Preserved there was no significant reduction. Because of the heterogeneity across these two trials, it was not statistically valid to pool these two results for the composite renal outcome. However, what they found in EMPEROR-Pooled is that if you use a more robust renal outcome including at least a 50% decline in eGFR, then there seems to be a trend that varies depending on baseline left ventricular ejection fraction, suggesting a benefit on the renal outcome if your baseline left ventricular function ranges from 40% to 60%, but lack of benefit with a baseline left ventricular ejection fraction of over 60%. The top line summary of this data is that for the first time we have robust evidence that an SGLT2 inhibitor, in this case empagliflozin 10 mg, can provide a cardiovascular benefit in patients with HFpEF, in addition to the known benefit in HFrEF patients.

Finally, there's the AMPLITUDE-O with efpeglenatide, an international randomized controlled trial conducted at approximately 344 sites in 28 countries. What are the key learnings and messages for this specific study?

Dr. Goldenberg: Efpeglenatide is an exendin-4-based GLP-1 receptor agonist that is given once weekly and the AMPLITUDE-O trial is the cardiovascular outcome trial with efpeglenatide done in patients with type 2 diabetes and either cardiovascular disease or chronic kidney disease plus at least one cardiovascular risk factor. It was an important trial because prior to this cardiovascular outcome trial studies of exendin-4-based GLP-1 receptor agonist have been neutral. However, the AMPLITUDE-O study showed for the first-time superiority with an exendin-4-based GLP-1 receptor agonist. In this case, efpeglenatide 4 or 6 milligrams versus placebo was associated with a 27% reduction in the primary outcome of CV death, non-fatal MI or non-fatal stroke.

Importantly, there was a consistent benefit with efpeglenatide across a spectrum of prespecified subgroups,  the most important one being those that entered the trial on a background SGLT2 inhibitor, which represented about 15% of the patients. They derived the same overall benefit as those not taking an SGLT2 inhibitor. It is important to appreciate that this is probably the most robust data we have for showing a cardiovascular benefit of adding a GLP-1 receptor agonist to an SGLT2 inhibitor in high risk patients with type 2 diabetes. AMPLITUDE-O also adds to the already appreciated knowledge of the cardiovascular benefit of GLP-1 receptor agonists and builds on this story by showing that you can get a cardiovascular benefit with an exendin-4-based GLP-1 receptor agonist and you can get a benefit as an add on to SGLT2 inhibitors.

Given the expansive contemporary role of statins for primary cardiovascular disease (CVD) prevention, the language in the new U.S. Preventive Services Task Force draft guidance on their use in that setting may seem conservative. Even so, the proposed recommendations, open to public comment until March 21, take more recent data into account but don’t substantially vary from the 2016 USPSTF document they are intended to replace.

The task force concluded “with moderate certainty” that a statin prescription will clinically benefit adults aged 40-75 years without CVD but with at least one of several risk factors, such as dyslipidemia or diabetes, who have a 10-year CVD risk of at least 7.5%.

AndrewSoundarajan/Thinkstock

The net benefit of statin therapy is “at least small” for individuals in whom the 10-year CVD risk is 7.5% up to 10.0%, the new report states. That, says an accompanying USPSTF press release, means such people “may benefit from statin use and should decide with their clinician if taking a statin is right for them.”

Also, notes the report, the net benefit of statin therapy is “at least moderate” for individuals with a 10% or greater CVD risk over the next decade who, the press release states, “should take a statin to prevent a first heart attack or stroke.”

The evidence review on which the task force based the guidance, the report says, lacked sufficient basis for determining statin benefit versus risk in adults older than 75 years without a history of CVD. “In the absence of this evidence, clinicians should use their judgment as to whether to offer a statin to a patient in this age group,” according to the press release.

The review focused on 22 clinical trials for data on the statin benefits and saw significantly decreased associated risks for death from any cause, fatal or nonfatal stroke, and fatal or nonfatal myocardial infarction with treatment. The combined trial populations exceeded 85,000 for assessing all-cause mortality and 76,000 for each of the other two endpoints.

To assess any potential statin therapy harms, the evidence review covered 19 clinical trials with a combined enrollment of about 75,000 – two more trials than considered in the 2016 document – plus three observational studies with more than 400,000 participants. Statins were found not to be associated with an increased risk for study withdrawal because of adverse events, nor were there signs of greater risk for myalgia or new-onset diabetes, compared with placebo.

“A majority of the trials reviewed by the USPSTF used moderate-intensity statin therapy,” the report states. “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CVD in most persons.”

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

Given the expansive contemporary role of statins for primary cardiovascular disease (CVD) prevention, the language in the new U.S. Preventive Services Task Force draft guidance on their use in that setting may seem conservative. Even so, the proposed recommendations, open to public comment until March 21, take more recent data into account but don’t substantially vary from the 2016 USPSTF document they are intended to replace.

The task force concluded “with moderate certainty” that a statin prescription will clinically benefit adults aged 40-75 years without CVD but with at least one of several risk factors, such as dyslipidemia or diabetes, who have a 10-year CVD risk of at least 7.5%.

AndrewSoundarajan/Thinkstock

The net benefit of statin therapy is “at least small” for individuals in whom the 10-year CVD risk is 7.5% up to 10.0%, the new report states. That, says an accompanying USPSTF press release, means such people “may benefit from statin use and should decide with their clinician if taking a statin is right for them.”

Also, notes the report, the net benefit of statin therapy is “at least moderate” for individuals with a 10% or greater CVD risk over the next decade who, the press release states, “should take a statin to prevent a first heart attack or stroke.”

The evidence review on which the task force based the guidance, the report says, lacked sufficient basis for determining statin benefit versus risk in adults older than 75 years without a history of CVD. “In the absence of this evidence, clinicians should use their judgment as to whether to offer a statin to a patient in this age group,” according to the press release.

The review focused on 22 clinical trials for data on the statin benefits and saw significantly decreased associated risks for death from any cause, fatal or nonfatal stroke, and fatal or nonfatal myocardial infarction with treatment. The combined trial populations exceeded 85,000 for assessing all-cause mortality and 76,000 for each of the other two endpoints.

To assess any potential statin therapy harms, the evidence review covered 19 clinical trials with a combined enrollment of about 75,000 – two more trials than considered in the 2016 document – plus three observational studies with more than 400,000 participants. Statins were found not to be associated with an increased risk for study withdrawal because of adverse events, nor were there signs of greater risk for myalgia or new-onset diabetes, compared with placebo.

“A majority of the trials reviewed by the USPSTF used moderate-intensity statin therapy,” the report states. “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CVD in most persons.”

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

Given the expansive contemporary role of statins for primary cardiovascular disease (CVD) prevention, the language in the new U.S. Preventive Services Task Force draft guidance on their use in that setting may seem conservative. Even so, the proposed recommendations, open to public comment until March 21, take more recent data into account but don’t substantially vary from the 2016 USPSTF document they are intended to replace.

The task force concluded “with moderate certainty” that a statin prescription will clinically benefit adults aged 40-75 years without CVD but with at least one of several risk factors, such as dyslipidemia or diabetes, who have a 10-year CVD risk of at least 7.5%.

AndrewSoundarajan/Thinkstock

The net benefit of statin therapy is “at least small” for individuals in whom the 10-year CVD risk is 7.5% up to 10.0%, the new report states. That, says an accompanying USPSTF press release, means such people “may benefit from statin use and should decide with their clinician if taking a statin is right for them.”

Also, notes the report, the net benefit of statin therapy is “at least moderate” for individuals with a 10% or greater CVD risk over the next decade who, the press release states, “should take a statin to prevent a first heart attack or stroke.”

The evidence review on which the task force based the guidance, the report says, lacked sufficient basis for determining statin benefit versus risk in adults older than 75 years without a history of CVD. “In the absence of this evidence, clinicians should use their judgment as to whether to offer a statin to a patient in this age group,” according to the press release.

The review focused on 22 clinical trials for data on the statin benefits and saw significantly decreased associated risks for death from any cause, fatal or nonfatal stroke, and fatal or nonfatal myocardial infarction with treatment. The combined trial populations exceeded 85,000 for assessing all-cause mortality and 76,000 for each of the other two endpoints.

To assess any potential statin therapy harms, the evidence review covered 19 clinical trials with a combined enrollment of about 75,000 – two more trials than considered in the 2016 document – plus three observational studies with more than 400,000 participants. Statins were found not to be associated with an increased risk for study withdrawal because of adverse events, nor were there signs of greater risk for myalgia or new-onset diabetes, compared with placebo.

“A majority of the trials reviewed by the USPSTF used moderate-intensity statin therapy,” the report states. “Based on available evidence, use of moderate-intensity statin therapy seems reasonable for the primary prevention of CVD in most persons.”

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

The Omicron subvariant, BA.2, is not only more transmissible than the original Omicron strain, BA.1, but may cause more severe disease, a lab study from Japan says.

“Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1,” the researchers said in the study published on the preprint server bioRxiv. The study has not been peer-reviewed.

The researchers infected hamsters with BA.1 and BA.2. The hamsters infected with BA.2 got sicker, with more lung damage and loss of body weight. Results were similar when mice were infected with BA.1 and BA.2.

“Infection experiments using hamsters show that BA.2 is more pathogenic than BA.1,” the study said.

BA.1 and BA.2 both appear to evade immunity created by COVID-19 vaccines, the study said. But a booster shot makes illness after infection 74% less likely, CNN said.

What’s more, therapeutic monoclonal antibodies used to treat people infected with COVID didn’t have much effect on BA.2. 

BA.2 was “almost completely resistant” to casirivimab and imdevimab and was 35 times more resistant to sotrovimab, compared to the original B.1.1 virus, the researchers wrote. 

“In summary, our data suggest the possibility that BA.2 would be the most concerned variant to global health,” the researchers wrote. “Currently, both BA.2 and BA.1 are recognised together as Omicron and these are almost undistinguishable. Based on our findings, we propose that BA.2 should be recognised as a unique variant of concern, and this SARS-CoV-2 variant should be monitored in depth.”

If the World Health Organization recognized BA.2 as a “unique variant of concern,” it would be given its own Greek letter.

But some scientists noted that findings in the lab don’t always reflect what’s happening in the real world of people.

“I think it’s always hard to translate differences in animal and cell culture models to what’s going on with regards to human disease,” Jeremy Kamil, PhD, an associate professor of microbiology and immunology at Louisiana State University Health Shreveport, told Newsweek. “That said, the differences do look real.”

“It might be, from a human’s perspective, a worse virus than BA.1 and might be able to transmit better and cause worse disease,” Daniel Rhoads, MD, section head of microbiology at the Cleveland Clinic in Ohio, told CNN. He reviewed the Japanese study but was not involved in it.

Another scientist who reviewed the study but was not involved in the research noted that human immune systems are evolving along with the COVID variants. 

“One of the caveats that we have to think about, as we get new variants that might seem more dangerous, is the fact that there’s two sides to the story,” Deborah Fuller, PhD, a virologist at the University of Washington School of Medicine, told CNN. “Our immune system is evolving as well. And so that’s pushing back on things.”

Scientists have already established that BA.2 is more transmissible than BA.1. The Omicron subvariant has been detected in 74 countries and 47 U.S. states, according to CNN. About 4% of Americans with COVID were infected with BA.2, the outlet reported, citing the CDC, but it’s now the dominant strain in other nations.

It’s not clear yet if BA.2 causes more severe illness in people. While BA.2 spreads faster than BA.1, there’s no evidence the subvariant makes people any sicker, an official with the World Health Organization said, according to CNBC.

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

The Omicron subvariant, BA.2, is not only more transmissible than the original Omicron strain, BA.1, but may cause more severe disease, a lab study from Japan says.

“Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1,” the researchers said in the study published on the preprint server bioRxiv. The study has not been peer-reviewed.

The researchers infected hamsters with BA.1 and BA.2. The hamsters infected with BA.2 got sicker, with more lung damage and loss of body weight. Results were similar when mice were infected with BA.1 and BA.2.

“Infection experiments using hamsters show that BA.2 is more pathogenic than BA.1,” the study said.

BA.1 and BA.2 both appear to evade immunity created by COVID-19 vaccines, the study said. But a booster shot makes illness after infection 74% less likely, CNN said.

What’s more, therapeutic monoclonal antibodies used to treat people infected with COVID didn’t have much effect on BA.2. 

BA.2 was “almost completely resistant” to casirivimab and imdevimab and was 35 times more resistant to sotrovimab, compared to the original B.1.1 virus, the researchers wrote. 

“In summary, our data suggest the possibility that BA.2 would be the most concerned variant to global health,” the researchers wrote. “Currently, both BA.2 and BA.1 are recognised together as Omicron and these are almost undistinguishable. Based on our findings, we propose that BA.2 should be recognised as a unique variant of concern, and this SARS-CoV-2 variant should be monitored in depth.”

If the World Health Organization recognized BA.2 as a “unique variant of concern,” it would be given its own Greek letter.

But some scientists noted that findings in the lab don’t always reflect what’s happening in the real world of people.

“I think it’s always hard to translate differences in animal and cell culture models to what’s going on with regards to human disease,” Jeremy Kamil, PhD, an associate professor of microbiology and immunology at Louisiana State University Health Shreveport, told Newsweek. “That said, the differences do look real.”

“It might be, from a human’s perspective, a worse virus than BA.1 and might be able to transmit better and cause worse disease,” Daniel Rhoads, MD, section head of microbiology at the Cleveland Clinic in Ohio, told CNN. He reviewed the Japanese study but was not involved in it.

Another scientist who reviewed the study but was not involved in the research noted that human immune systems are evolving along with the COVID variants. 

“One of the caveats that we have to think about, as we get new variants that might seem more dangerous, is the fact that there’s two sides to the story,” Deborah Fuller, PhD, a virologist at the University of Washington School of Medicine, told CNN. “Our immune system is evolving as well. And so that’s pushing back on things.”

Scientists have already established that BA.2 is more transmissible than BA.1. The Omicron subvariant has been detected in 74 countries and 47 U.S. states, according to CNN. About 4% of Americans with COVID were infected with BA.2, the outlet reported, citing the CDC, but it’s now the dominant strain in other nations.

It’s not clear yet if BA.2 causes more severe illness in people. While BA.2 spreads faster than BA.1, there’s no evidence the subvariant makes people any sicker, an official with the World Health Organization said, according to CNBC.

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

The Omicron subvariant, BA.2, is not only more transmissible than the original Omicron strain, BA.1, but may cause more severe disease, a lab study from Japan says.

“Our multiscale investigations suggest that the risk of BA.2 for global health is potentially higher than that of BA.1,” the researchers said in the study published on the preprint server bioRxiv. The study has not been peer-reviewed.

The researchers infected hamsters with BA.1 and BA.2. The hamsters infected with BA.2 got sicker, with more lung damage and loss of body weight. Results were similar when mice were infected with BA.1 and BA.2.

“Infection experiments using hamsters show that BA.2 is more pathogenic than BA.1,” the study said.

BA.1 and BA.2 both appear to evade immunity created by COVID-19 vaccines, the study said. But a booster shot makes illness after infection 74% less likely, CNN said.

What’s more, therapeutic monoclonal antibodies used to treat people infected with COVID didn’t have much effect on BA.2. 

BA.2 was “almost completely resistant” to casirivimab and imdevimab and was 35 times more resistant to sotrovimab, compared to the original B.1.1 virus, the researchers wrote. 

“In summary, our data suggest the possibility that BA.2 would be the most concerned variant to global health,” the researchers wrote. “Currently, both BA.2 and BA.1 are recognised together as Omicron and these are almost undistinguishable. Based on our findings, we propose that BA.2 should be recognised as a unique variant of concern, and this SARS-CoV-2 variant should be monitored in depth.”

If the World Health Organization recognized BA.2 as a “unique variant of concern,” it would be given its own Greek letter.

But some scientists noted that findings in the lab don’t always reflect what’s happening in the real world of people.

“I think it’s always hard to translate differences in animal and cell culture models to what’s going on with regards to human disease,” Jeremy Kamil, PhD, an associate professor of microbiology and immunology at Louisiana State University Health Shreveport, told Newsweek. “That said, the differences do look real.”

“It might be, from a human’s perspective, a worse virus than BA.1 and might be able to transmit better and cause worse disease,” Daniel Rhoads, MD, section head of microbiology at the Cleveland Clinic in Ohio, told CNN. He reviewed the Japanese study but was not involved in it.

Another scientist who reviewed the study but was not involved in the research noted that human immune systems are evolving along with the COVID variants. 

“One of the caveats that we have to think about, as we get new variants that might seem more dangerous, is the fact that there’s two sides to the story,” Deborah Fuller, PhD, a virologist at the University of Washington School of Medicine, told CNN. “Our immune system is evolving as well. And so that’s pushing back on things.”

Scientists have already established that BA.2 is more transmissible than BA.1. The Omicron subvariant has been detected in 74 countries and 47 U.S. states, according to CNN. About 4% of Americans with COVID were infected with BA.2, the outlet reported, citing the CDC, but it’s now the dominant strain in other nations.

It’s not clear yet if BA.2 causes more severe illness in people. While BA.2 spreads faster than BA.1, there’s no evidence the subvariant makes people any sicker, an official with the World Health Organization said, according to CNBC.

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

Spironolactone was not associated with any meaningful increase in the risk of breast cancer or other solid organ cancers in a systematic review and meta-analysis covering seven observational studies and a total population of over 4.5 million people.

The data, published in JAMA Dermatology, are “reassuring,” the authors reported, considering that the spironolactone label carries a Food and Drug Administration warning regarding possible tumorigenicity, which is based on animal studies of doses up to 150-fold greater than doses used for humans. The drug’s antiandrogenic properties have driven its off-label use as a treatment for acne, hidradenitis, androgenetic alopecia, and hirsutism.

Spironolactone, a synthetic 17-lactone steroid, is approved for the treatment of heart failure, edema and ascites, hypertension, and primary hyperaldosteronism. Off label, it is also frequently used in gender-affirming care and is included in Endocrine Society guidelines as part of hormonal regimens for transgender women, the authors noted.

The seven eligible studies looked at the occurrence of cancer in men and women who had any exposure to the drug, regardless of the primary indication. Sample sizes ranged from 18,035 to 2.3 million, and the mean age across all studies was 62.6-72 years.

The researchers synthesized the studies, mostly of European individuals, using random effects meta-analysis and found no statistically significant association between spironolactone use and risk of breast cancer (risk ratio, 1.04; 95% confidence interval, 0.86-1.22). Three of the seven studies investigated breast cancer.

There was also no significant association between spironolactone use and risk of ovarian cancer (two studies), bladder cancer (three studies), kidney cancer (two studies), gastric cancer (two studies), or esophageal cancer (two studies).

For prostate cancer, investigated in four studies, use of the drug was associated with decreased risk (RR, 0.79, 95% CI, 0.68-0.90).

Kanthi Bommareddy, MD, of the University of Miami and coauthors concluded that all studies were at low risk of bias after appraising each one using a scale that looks at selection bias, confounding bias, and detection and outcome bias.

In dermatology, the results should “help us to take a collective sigh of relief,” said Julie C. Harper, MD, of the Dermatology and Skin Care Center of Birmingham, Ala., who was asked to comment on the study. The drug has been “safe and effective in our clinics and it is affordable and accessible to our patients,” she said, but with the FDA’s warning and the drug’s antiandrogen capacity, “there has been concern that we might be putting our patients at increased risk of breast cancer [in particular].”

The pooling of seven large studies together and the finding of no substantive increased risk of cancer “gives us evidence and comfort that spironolactone does not increase the risk of cancer in our dermatology patients,” said Dr. Harper, a past president of the American Acne & Rosacea Society.

“With every passing year,” she noted, “dermatologists are prescribing more and more spironolactone for acne, hidradenitis, androgenetic alopecia, and hirsutism.”

Four of the seven studies stratified analyses by sex, and in those without stratification by sex, women accounted for 17.2%-54.4% of the samples.

The studies had long follow-up periods of 5-20 years, but certainty of the evidence was low and since many of the studies included mostly older individuals, “they may not generalize to younger populations, such as those treated with spironolactone for acne,” the investigators wrote.

The authors also noted they were unable to look for dose-dependent associations between spironolactone and cancer risk, and that confidence intervals for rarer cancers like ovarian cancer were wide. “We cannot entirely exclude the potential for a meaningful increase in cancer risk,” and future studies are needed, in populations that include younger patients and those with acne or hirsutism.

Dr. Bommareddy reported no disclosures. Other coauthors reported grants from the National Cancer Institute outside the submitted work, and personal fees as a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research. There was no funding reported for the study. Dr. Harper said she had no disclosures.

Spironolactone was not associated with any meaningful increase in the risk of breast cancer or other solid organ cancers in a systematic review and meta-analysis covering seven observational studies and a total population of over 4.5 million people.

The data, published in JAMA Dermatology, are “reassuring,” the authors reported, considering that the spironolactone label carries a Food and Drug Administration warning regarding possible tumorigenicity, which is based on animal studies of doses up to 150-fold greater than doses used for humans. The drug’s antiandrogenic properties have driven its off-label use as a treatment for acne, hidradenitis, androgenetic alopecia, and hirsutism.

Spironolactone, a synthetic 17-lactone steroid, is approved for the treatment of heart failure, edema and ascites, hypertension, and primary hyperaldosteronism. Off label, it is also frequently used in gender-affirming care and is included in Endocrine Society guidelines as part of hormonal regimens for transgender women, the authors noted.

The seven eligible studies looked at the occurrence of cancer in men and women who had any exposure to the drug, regardless of the primary indication. Sample sizes ranged from 18,035 to 2.3 million, and the mean age across all studies was 62.6-72 years.

The researchers synthesized the studies, mostly of European individuals, using random effects meta-analysis and found no statistically significant association between spironolactone use and risk of breast cancer (risk ratio, 1.04; 95% confidence interval, 0.86-1.22). Three of the seven studies investigated breast cancer.

There was also no significant association between spironolactone use and risk of ovarian cancer (two studies), bladder cancer (three studies), kidney cancer (two studies), gastric cancer (two studies), or esophageal cancer (two studies).

For prostate cancer, investigated in four studies, use of the drug was associated with decreased risk (RR, 0.79, 95% CI, 0.68-0.90).

Kanthi Bommareddy, MD, of the University of Miami and coauthors concluded that all studies were at low risk of bias after appraising each one using a scale that looks at selection bias, confounding bias, and detection and outcome bias.

In dermatology, the results should “help us to take a collective sigh of relief,” said Julie C. Harper, MD, of the Dermatology and Skin Care Center of Birmingham, Ala., who was asked to comment on the study. The drug has been “safe and effective in our clinics and it is affordable and accessible to our patients,” she said, but with the FDA’s warning and the drug’s antiandrogen capacity, “there has been concern that we might be putting our patients at increased risk of breast cancer [in particular].”

The pooling of seven large studies together and the finding of no substantive increased risk of cancer “gives us evidence and comfort that spironolactone does not increase the risk of cancer in our dermatology patients,” said Dr. Harper, a past president of the American Acne & Rosacea Society.

“With every passing year,” she noted, “dermatologists are prescribing more and more spironolactone for acne, hidradenitis, androgenetic alopecia, and hirsutism.”

Four of the seven studies stratified analyses by sex, and in those without stratification by sex, women accounted for 17.2%-54.4% of the samples.

The studies had long follow-up periods of 5-20 years, but certainty of the evidence was low and since many of the studies included mostly older individuals, “they may not generalize to younger populations, such as those treated with spironolactone for acne,” the investigators wrote.

The authors also noted they were unable to look for dose-dependent associations between spironolactone and cancer risk, and that confidence intervals for rarer cancers like ovarian cancer were wide. “We cannot entirely exclude the potential for a meaningful increase in cancer risk,” and future studies are needed, in populations that include younger patients and those with acne or hirsutism.

Dr. Bommareddy reported no disclosures. Other coauthors reported grants from the National Cancer Institute outside the submitted work, and personal fees as a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research. There was no funding reported for the study. Dr. Harper said she had no disclosures.

Spironolactone was not associated with any meaningful increase in the risk of breast cancer or other solid organ cancers in a systematic review and meta-analysis covering seven observational studies and a total population of over 4.5 million people.

The data, published in JAMA Dermatology, are “reassuring,” the authors reported, considering that the spironolactone label carries a Food and Drug Administration warning regarding possible tumorigenicity, which is based on animal studies of doses up to 150-fold greater than doses used for humans. The drug’s antiandrogenic properties have driven its off-label use as a treatment for acne, hidradenitis, androgenetic alopecia, and hirsutism.

Spironolactone, a synthetic 17-lactone steroid, is approved for the treatment of heart failure, edema and ascites, hypertension, and primary hyperaldosteronism. Off label, it is also frequently used in gender-affirming care and is included in Endocrine Society guidelines as part of hormonal regimens for transgender women, the authors noted.

The seven eligible studies looked at the occurrence of cancer in men and women who had any exposure to the drug, regardless of the primary indication. Sample sizes ranged from 18,035 to 2.3 million, and the mean age across all studies was 62.6-72 years.

The researchers synthesized the studies, mostly of European individuals, using random effects meta-analysis and found no statistically significant association between spironolactone use and risk of breast cancer (risk ratio, 1.04; 95% confidence interval, 0.86-1.22). Three of the seven studies investigated breast cancer.

There was also no significant association between spironolactone use and risk of ovarian cancer (two studies), bladder cancer (three studies), kidney cancer (two studies), gastric cancer (two studies), or esophageal cancer (two studies).

For prostate cancer, investigated in four studies, use of the drug was associated with decreased risk (RR, 0.79, 95% CI, 0.68-0.90).

Kanthi Bommareddy, MD, of the University of Miami and coauthors concluded that all studies were at low risk of bias after appraising each one using a scale that looks at selection bias, confounding bias, and detection and outcome bias.

In dermatology, the results should “help us to take a collective sigh of relief,” said Julie C. Harper, MD, of the Dermatology and Skin Care Center of Birmingham, Ala., who was asked to comment on the study. The drug has been “safe and effective in our clinics and it is affordable and accessible to our patients,” she said, but with the FDA’s warning and the drug’s antiandrogen capacity, “there has been concern that we might be putting our patients at increased risk of breast cancer [in particular].”

The pooling of seven large studies together and the finding of no substantive increased risk of cancer “gives us evidence and comfort that spironolactone does not increase the risk of cancer in our dermatology patients,” said Dr. Harper, a past president of the American Acne & Rosacea Society.

“With every passing year,” she noted, “dermatologists are prescribing more and more spironolactone for acne, hidradenitis, androgenetic alopecia, and hirsutism.”

Four of the seven studies stratified analyses by sex, and in those without stratification by sex, women accounted for 17.2%-54.4% of the samples.

The studies had long follow-up periods of 5-20 years, but certainty of the evidence was low and since many of the studies included mostly older individuals, “they may not generalize to younger populations, such as those treated with spironolactone for acne,” the investigators wrote.

The authors also noted they were unable to look for dose-dependent associations between spironolactone and cancer risk, and that confidence intervals for rarer cancers like ovarian cancer were wide. “We cannot entirely exclude the potential for a meaningful increase in cancer risk,” and future studies are needed, in populations that include younger patients and those with acne or hirsutism.

Dr. Bommareddy reported no disclosures. Other coauthors reported grants from the National Cancer Institute outside the submitted work, and personal fees as a Cancer Prevention and Research Institute of Texas Scholar in Cancer Research. There was no funding reported for the study. Dr. Harper said she had no disclosures.

Ivermectin treatment given to high-risk patients with mild-to-moderate COVID-19 during the first week of illness did not prevent progression to severe disease, according to results from a randomized clinical trial.

“The study findings do not support the use of ivermectin for patients with COVID-19,” researchers conclude in the paper published online in JAMA Internal Medicine.

The open-label trial was conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and Oct. 25, 2021. It was led by Steven Chee Loon Lim, MRCP, department of medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia.

Among 490 patients in the primary analysis, 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk, 1.25; 95% confidence interval, 0.87-1.80; P = .25). All major ethnic groups in Malaysia were well represented, the researchers write.

Participants (average age 62.5 and 54.5% women) were randomly assigned 1:1 to receive either a 5-day course of oral ivermectin (0.4 mg/kg body weight daily for 5 days) plus standard of care (n = 241) or standard of care alone (n = 249). Standard of care included symptomatic therapy and monitoring for early deterioration based on clinical findings, laboratory tests, and chest imaging.
 

Secondary outcomes

Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, 28-day in-hospital mortality, and side effects.

In all the secondary outcomes, there were no significant differences between groups.

Mechanical ventilation occurred in four patients on the ivermectin protocol (1.7%) versus 10 patients in the control group (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17); ICU admission occurred in six (2.4%) versus eight (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79); and 28-day in-hospital death occurred in three (1.2%) versus 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09).

The most common adverse event was diarrhea, reported by 5.8% in the ivermectin group and 1.6% in the control group.
 

No difference by vaccine status

The researchers conducted a subgroup analysis to evaluate any differences in whether participants were vaccinated. They said that analysis was “unremarkable.”

Just more than half of participants (51.8%) were fully vaccinated, with two doses of COVID-19 vaccines. Among the fully vaccinated patients, 17.7% in the ivermectin group and 9.2% in the control group developed severe disease (RR, 1.92; 95% CI, 0.99-3.71; P = .06).

Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19 but has not been approved by the U.S. Food and Drug Administration for that purpose. Evidence-based data for or against use has been sparse.

The authors write that “although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses.”

Dr. Lim and colleagues point out that their findings are consistent with those of the IVERCOR-COVID19 trial, which found ivermectin ineffective in reducing hospitalization risk.

Previous randomized trials of ivermectin for COVID-19 patients that have included at least 400 patients have focused on outpatients.

In the current study, the authors note, patients were hospitalized, which allowed investigators to observe administration of ivermectin with a high adherence rate. Additionally, the researchers used clearly defined criteria for determining progression to severe disease.

Limitations of the current study include that the open-label design might lead to under-reporting of adverse events in the control group while overestimating the drug effects of ivermectin. The study was also not designed to assess the effects of ivermectin on mortality from COVID-19.

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

Ivermectin treatment given to high-risk patients with mild-to-moderate COVID-19 during the first week of illness did not prevent progression to severe disease, according to results from a randomized clinical trial.

“The study findings do not support the use of ivermectin for patients with COVID-19,” researchers conclude in the paper published online in JAMA Internal Medicine.

The open-label trial was conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and Oct. 25, 2021. It was led by Steven Chee Loon Lim, MRCP, department of medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia.

Among 490 patients in the primary analysis, 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk, 1.25; 95% confidence interval, 0.87-1.80; P = .25). All major ethnic groups in Malaysia were well represented, the researchers write.

Participants (average age 62.5 and 54.5% women) were randomly assigned 1:1 to receive either a 5-day course of oral ivermectin (0.4 mg/kg body weight daily for 5 days) plus standard of care (n = 241) or standard of care alone (n = 249). Standard of care included symptomatic therapy and monitoring for early deterioration based on clinical findings, laboratory tests, and chest imaging.
 

Secondary outcomes

Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, 28-day in-hospital mortality, and side effects.

In all the secondary outcomes, there were no significant differences between groups.

Mechanical ventilation occurred in four patients on the ivermectin protocol (1.7%) versus 10 patients in the control group (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17); ICU admission occurred in six (2.4%) versus eight (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79); and 28-day in-hospital death occurred in three (1.2%) versus 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09).

The most common adverse event was diarrhea, reported by 5.8% in the ivermectin group and 1.6% in the control group.
 

No difference by vaccine status

The researchers conducted a subgroup analysis to evaluate any differences in whether participants were vaccinated. They said that analysis was “unremarkable.”

Just more than half of participants (51.8%) were fully vaccinated, with two doses of COVID-19 vaccines. Among the fully vaccinated patients, 17.7% in the ivermectin group and 9.2% in the control group developed severe disease (RR, 1.92; 95% CI, 0.99-3.71; P = .06).

Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19 but has not been approved by the U.S. Food and Drug Administration for that purpose. Evidence-based data for or against use has been sparse.

The authors write that “although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses.”

Dr. Lim and colleagues point out that their findings are consistent with those of the IVERCOR-COVID19 trial, which found ivermectin ineffective in reducing hospitalization risk.

Previous randomized trials of ivermectin for COVID-19 patients that have included at least 400 patients have focused on outpatients.

In the current study, the authors note, patients were hospitalized, which allowed investigators to observe administration of ivermectin with a high adherence rate. Additionally, the researchers used clearly defined criteria for determining progression to severe disease.

Limitations of the current study include that the open-label design might lead to under-reporting of adverse events in the control group while overestimating the drug effects of ivermectin. The study was also not designed to assess the effects of ivermectin on mortality from COVID-19.

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

Ivermectin treatment given to high-risk patients with mild-to-moderate COVID-19 during the first week of illness did not prevent progression to severe disease, according to results from a randomized clinical trial.

“The study findings do not support the use of ivermectin for patients with COVID-19,” researchers conclude in the paper published online in JAMA Internal Medicine.

The open-label trial was conducted at 20 public hospitals and a COVID-19 quarantine center in Malaysia between May 31 and Oct. 25, 2021. It was led by Steven Chee Loon Lim, MRCP, department of medicine, Raja Permaisuri Bainun Hospital, Perak, Malaysia.

Among 490 patients in the primary analysis, 52 of 241 patients (21.6%) in the ivermectin group and 43 of 249 patients (17.3%) in the control group progressed to severe disease (relative risk, 1.25; 95% confidence interval, 0.87-1.80; P = .25). All major ethnic groups in Malaysia were well represented, the researchers write.

Participants (average age 62.5 and 54.5% women) were randomly assigned 1:1 to receive either a 5-day course of oral ivermectin (0.4 mg/kg body weight daily for 5 days) plus standard of care (n = 241) or standard of care alone (n = 249). Standard of care included symptomatic therapy and monitoring for early deterioration based on clinical findings, laboratory tests, and chest imaging.
 

Secondary outcomes

Secondary outcomes included rates of mechanical ventilation, intensive care unit (ICU) admission, 28-day in-hospital mortality, and side effects.

In all the secondary outcomes, there were no significant differences between groups.

Mechanical ventilation occurred in four patients on the ivermectin protocol (1.7%) versus 10 patients in the control group (4.0%) (RR, 0.41; 95% CI, 0.13-1.30; P = .17); ICU admission occurred in six (2.4%) versus eight (3.2%) (RR, 0.78; 95% CI, 0.27-2.20; P = .79); and 28-day in-hospital death occurred in three (1.2%) versus 10 (4.0%) (RR, 0.31; 95% CI, 0.09-1.11; P = .09).

The most common adverse event was diarrhea, reported by 5.8% in the ivermectin group and 1.6% in the control group.
 

No difference by vaccine status

The researchers conducted a subgroup analysis to evaluate any differences in whether participants were vaccinated. They said that analysis was “unremarkable.”

Just more than half of participants (51.8%) were fully vaccinated, with two doses of COVID-19 vaccines. Among the fully vaccinated patients, 17.7% in the ivermectin group and 9.2% in the control group developed severe disease (RR, 1.92; 95% CI, 0.99-3.71; P = .06).

Ivermectin, an inexpensive and widely available antiparasitic drug, is prescribed to treat COVID-19 but has not been approved by the U.S. Food and Drug Administration for that purpose. Evidence-based data for or against use has been sparse.

The authors write that “although some early clinical studies suggested the potential efficacy of ivermectin in the treatment and prevention of COVID-19, these studies had methodologic weaknesses.”

Dr. Lim and colleagues point out that their findings are consistent with those of the IVERCOR-COVID19 trial, which found ivermectin ineffective in reducing hospitalization risk.

Previous randomized trials of ivermectin for COVID-19 patients that have included at least 400 patients have focused on outpatients.

In the current study, the authors note, patients were hospitalized, which allowed investigators to observe administration of ivermectin with a high adherence rate. Additionally, the researchers used clearly defined criteria for determining progression to severe disease.

Limitations of the current study include that the open-label design might lead to under-reporting of adverse events in the control group while overestimating the drug effects of ivermectin. The study was also not designed to assess the effects of ivermectin on mortality from COVID-19.

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

Researchers point the finger squarely at starting salaries for physicians as the reason women earn less than their male peers in academic medicine, according to a new study. Worse still, the earning potential of women in most specialties is $214,440 (or 10%) less than their male colleagues over the course of the first 10 years of their careers in academic medicine.

Among the vast majority of subspecialties, women’s starting salaries and their salaries 10 years into their careers were lower than their male colleagues in academic medicine, per the study in JAMA Network Open.

Eva Catenaccio, MD, an epilepsy fellow at Children’s Hospital of Philadelphia and the lead author of the study, told this news organization that the gender disparities in earning potential are “pervasive in academic medicine.” These earnings disparities, which occur in nearly all subspecialties and can reach hundreds of thousands of dollars in the first 10 years of an academic physician’s career, “are largely the result of gender differences in annual salary that start immediately after training,” she said.

Changing the timing of academic promotion and equalizing starting salary and salary growth can help close the salary gap, said Dr. Catenaccio.

The study also reveals that women could face a 1-year delay in promotion from assistant to associate professor, compared with men. This delay could reduce female physicians’ earning potential by a 10-year median of $26,042 (or 2%), whereas failure to be promoted at all could decrease the 10-year earning potential by a median of $218,724 (or 13%).

Across medicine more broadly, male physicians continue to earn 35% more than their female colleagues, according to the 2021 Medscape Physician Compensation Report. The biggest differences in take-home pay exist between male and female specialists, per the report. On average, male physicians earn $376,000, while women’s take-home pay is $283,000.
 

Medical schools and hospital leaders have a role to play

The earning potential during the first 10 years of post-training employment by gender was the most dramatic in neurosurgery, orthopedic surgery, and cardiology, per the study. Three subspecialties where women and men have similar earning potential include pediatric nephrology, pediatric neurology, and pediatric rheumatology.

The coauthors note that it’s commonly understood that women don’t negotiate as often or as successfully as their male colleagues. A 2019 study in JAMA Surgery of 606 male and female surgery residents revealed that while residents of both genders shared similar career goals, women had lower future salary expectations and a significantly more negative view of the salary negotiation process.

Dr. Catenaccio and her coauthors acknowledge that negotiation skills and financial literacy should be taught during medical school and postgraduate training. “However, the onus for ensuring salary equity should not fall on the individual candidate alone; rather, departmental and hospital leadership should take responsibility to ensure uniform starting salaries and prevent gender-based inequalities,” they wrote in the study.

“We hope that this study encourages academic medical institutions to increase transparency and equity around compensation, particularly for junior faculty,” Dr. Catenaccio said in an interview. “This will require both ensuring equal starting salaries and providing periodic adjustments throughout individuals’ careers to prevent divergence in earning potential by gender or any other individual characteristics.”

Harold Simon, MD, MBA, vice chair for faculty for the department of pediatrics and professor of pediatrics and emergency medicine at Emory University, Atlanta, told this news organization that “[i]ncreased transparency around compensation can enable women to advocate for equitable pay. However, the burden for ensuring equity should not fall on individuals but instead must be the primary responsibility of academic institutions.”

Specifically, Dr. Simon advocates for hospital leaders to “ensure equity among providers including compensation [as] a crucial part of maintaining a diverse workforce and, ultimately, providing balanced access to health care for patients.”

In addition, the authors call for periodic compensation evaluations and adjustments to help prevent gender-based salary differences among female and male physicians in academia. “This is absolutely necessary, both to develop future compensation plans and to address any pre-existing gender-based salary inequities for those women currently well into their careers,” they wrote in the study.

Data analysis was conducted from March to May 2021. Researchers used models to estimate the impacts of promotion timing and potential interventions, which include equalizing starting salaries and annual salary rates.

The study included compensation data for 24,593 female and 29,886 male academic physicians across 45 subspecialties. It relied on publicly available data from the Association of American Medical Colleges’ annual Medical School Faculty Salary Survey report.

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

Researchers point the finger squarely at starting salaries for physicians as the reason women earn less than their male peers in academic medicine, according to a new study. Worse still, the earning potential of women in most specialties is $214,440 (or 10%) less than their male colleagues over the course of the first 10 years of their careers in academic medicine.

Among the vast majority of subspecialties, women’s starting salaries and their salaries 10 years into their careers were lower than their male colleagues in academic medicine, per the study in JAMA Network Open.

Eva Catenaccio, MD, an epilepsy fellow at Children’s Hospital of Philadelphia and the lead author of the study, told this news organization that the gender disparities in earning potential are “pervasive in academic medicine.” These earnings disparities, which occur in nearly all subspecialties and can reach hundreds of thousands of dollars in the first 10 years of an academic physician’s career, “are largely the result of gender differences in annual salary that start immediately after training,” she said.

Changing the timing of academic promotion and equalizing starting salary and salary growth can help close the salary gap, said Dr. Catenaccio.

The study also reveals that women could face a 1-year delay in promotion from assistant to associate professor, compared with men. This delay could reduce female physicians’ earning potential by a 10-year median of $26,042 (or 2%), whereas failure to be promoted at all could decrease the 10-year earning potential by a median of $218,724 (or 13%).

Across medicine more broadly, male physicians continue to earn 35% more than their female colleagues, according to the 2021 Medscape Physician Compensation Report. The biggest differences in take-home pay exist between male and female specialists, per the report. On average, male physicians earn $376,000, while women’s take-home pay is $283,000.
 

Medical schools and hospital leaders have a role to play

The earning potential during the first 10 years of post-training employment by gender was the most dramatic in neurosurgery, orthopedic surgery, and cardiology, per the study. Three subspecialties where women and men have similar earning potential include pediatric nephrology, pediatric neurology, and pediatric rheumatology.

The coauthors note that it’s commonly understood that women don’t negotiate as often or as successfully as their male colleagues. A 2019 study in JAMA Surgery of 606 male and female surgery residents revealed that while residents of both genders shared similar career goals, women had lower future salary expectations and a significantly more negative view of the salary negotiation process.

Dr. Catenaccio and her coauthors acknowledge that negotiation skills and financial literacy should be taught during medical school and postgraduate training. “However, the onus for ensuring salary equity should not fall on the individual candidate alone; rather, departmental and hospital leadership should take responsibility to ensure uniform starting salaries and prevent gender-based inequalities,” they wrote in the study.

“We hope that this study encourages academic medical institutions to increase transparency and equity around compensation, particularly for junior faculty,” Dr. Catenaccio said in an interview. “This will require both ensuring equal starting salaries and providing periodic adjustments throughout individuals’ careers to prevent divergence in earning potential by gender or any other individual characteristics.”

Harold Simon, MD, MBA, vice chair for faculty for the department of pediatrics and professor of pediatrics and emergency medicine at Emory University, Atlanta, told this news organization that “[i]ncreased transparency around compensation can enable women to advocate for equitable pay. However, the burden for ensuring equity should not fall on individuals but instead must be the primary responsibility of academic institutions.”

Specifically, Dr. Simon advocates for hospital leaders to “ensure equity among providers including compensation [as] a crucial part of maintaining a diverse workforce and, ultimately, providing balanced access to health care for patients.”

In addition, the authors call for periodic compensation evaluations and adjustments to help prevent gender-based salary differences among female and male physicians in academia. “This is absolutely necessary, both to develop future compensation plans and to address any pre-existing gender-based salary inequities for those women currently well into their careers,” they wrote in the study.

Data analysis was conducted from March to May 2021. Researchers used models to estimate the impacts of promotion timing and potential interventions, which include equalizing starting salaries and annual salary rates.

The study included compensation data for 24,593 female and 29,886 male academic physicians across 45 subspecialties. It relied on publicly available data from the Association of American Medical Colleges’ annual Medical School Faculty Salary Survey report.

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

Researchers point the finger squarely at starting salaries for physicians as the reason women earn less than their male peers in academic medicine, according to a new study. Worse still, the earning potential of women in most specialties is $214,440 (or 10%) less than their male colleagues over the course of the first 10 years of their careers in academic medicine.

Among the vast majority of subspecialties, women’s starting salaries and their salaries 10 years into their careers were lower than their male colleagues in academic medicine, per the study in JAMA Network Open.

Eva Catenaccio, MD, an epilepsy fellow at Children’s Hospital of Philadelphia and the lead author of the study, told this news organization that the gender disparities in earning potential are “pervasive in academic medicine.” These earnings disparities, which occur in nearly all subspecialties and can reach hundreds of thousands of dollars in the first 10 years of an academic physician’s career, “are largely the result of gender differences in annual salary that start immediately after training,” she said.

Changing the timing of academic promotion and equalizing starting salary and salary growth can help close the salary gap, said Dr. Catenaccio.

The study also reveals that women could face a 1-year delay in promotion from assistant to associate professor, compared with men. This delay could reduce female physicians’ earning potential by a 10-year median of $26,042 (or 2%), whereas failure to be promoted at all could decrease the 10-year earning potential by a median of $218,724 (or 13%).

Across medicine more broadly, male physicians continue to earn 35% more than their female colleagues, according to the 2021 Medscape Physician Compensation Report. The biggest differences in take-home pay exist between male and female specialists, per the report. On average, male physicians earn $376,000, while women’s take-home pay is $283,000.
 

Medical schools and hospital leaders have a role to play

The earning potential during the first 10 years of post-training employment by gender was the most dramatic in neurosurgery, orthopedic surgery, and cardiology, per the study. Three subspecialties where women and men have similar earning potential include pediatric nephrology, pediatric neurology, and pediatric rheumatology.

The coauthors note that it’s commonly understood that women don’t negotiate as often or as successfully as their male colleagues. A 2019 study in JAMA Surgery of 606 male and female surgery residents revealed that while residents of both genders shared similar career goals, women had lower future salary expectations and a significantly more negative view of the salary negotiation process.

Dr. Catenaccio and her coauthors acknowledge that negotiation skills and financial literacy should be taught during medical school and postgraduate training. “However, the onus for ensuring salary equity should not fall on the individual candidate alone; rather, departmental and hospital leadership should take responsibility to ensure uniform starting salaries and prevent gender-based inequalities,” they wrote in the study.

“We hope that this study encourages academic medical institutions to increase transparency and equity around compensation, particularly for junior faculty,” Dr. Catenaccio said in an interview. “This will require both ensuring equal starting salaries and providing periodic adjustments throughout individuals’ careers to prevent divergence in earning potential by gender or any other individual characteristics.”

Harold Simon, MD, MBA, vice chair for faculty for the department of pediatrics and professor of pediatrics and emergency medicine at Emory University, Atlanta, told this news organization that “[i]ncreased transparency around compensation can enable women to advocate for equitable pay. However, the burden for ensuring equity should not fall on individuals but instead must be the primary responsibility of academic institutions.”

Specifically, Dr. Simon advocates for hospital leaders to “ensure equity among providers including compensation [as] a crucial part of maintaining a diverse workforce and, ultimately, providing balanced access to health care for patients.”

In addition, the authors call for periodic compensation evaluations and adjustments to help prevent gender-based salary differences among female and male physicians in academia. “This is absolutely necessary, both to develop future compensation plans and to address any pre-existing gender-based salary inequities for those women currently well into their careers,” they wrote in the study.

Data analysis was conducted from March to May 2021. Researchers used models to estimate the impacts of promotion timing and potential interventions, which include equalizing starting salaries and annual salary rates.

The study included compensation data for 24,593 female and 29,886 male academic physicians across 45 subspecialties. It relied on publicly available data from the Association of American Medical Colleges’ annual Medical School Faculty Salary Survey report.

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