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Physician groups saw staff-to-physician ratios decline even as their workforce expenses rose between 2019 and 2021, according to recent reports from the American Medical Group Association (AMGA) and the Medical Group Management Association (MGMA).

As patients started to return to doctors’ offices as the pandemic eased in 2021, physician groups found it increasingly difficult to recruit and retain lower-level clinicians, including medical assistants and LPNs, officials from both associations told this news organization. Many clinics had to raise their pay scales to be competitive with employers in other fields, and some had to hire higher-priced RNs to keep their practices running.

The AMGA report was based largely on data from groups of over 500 physicians, mostly affiliated with health systems. According to a news release accompanying the report, the ratio between full-time equivalent (FTE) clinic staff and health care professionals in direct patient care dropped by 11.3% between 2019 and 2021. The ratio of medical assistants (MAs) to clinicians declined by a greater percentage.

In the MGMA report, which represented about 4,000 practices ranging from very small (two doctors) to very large groups, total support staff per FTE primary-care physician dropped by 18% from 2019 to 2021 in independent groups and by 13% in hospital-affiliated groups. The ratios decreased by smaller amounts in surgical practices.

In contrast, nonsurgical specialty groups under both types of ownership saw their staffing ratios rise slightly.

Although it’s unclear why medical specialties increased their staff while other types of specialties lost employees, Ron Holder, MHA, chief operating officer of MGMA, said that some specialists may have opened more ancillary facilities and hired new employees to recoup revenue lost during the pandemic.
 

Expenses rise sharply

The AMGA report found that staffing expenses for the surveyed groups increased by 15% between 2019 and 2021.

“We saw a decrease in staff and an increase in expenses during that time period, and there are a few reasons for that,” Rose Wagner, RN, chief operating officer of AMGA, said. “Groups increased salaries to maintain staff. We also saw lower-paid staff find other jobs outside of health care. For example, medical assistants and receptionists could find jobs outside of health care that paid more. [Open positions] got back-filled with other higher paid staff, such as RNs, doing lower skilled jobs.”

Mr. Holder added that rising wages in other sectors made leaving physician groups more attractive for employees.

“Three years ago, there weren’t many positions in a medical practice where you were competing with Chick-fil-A or Taco Bell,” he said. In Denver, where Mr. Holder is based, “every restaurant in town is now advertising $17-$19 [hourly] starting pay just to do fast food. That causes practices to either lose employees or pay more for the employees they have. So that raises per-employee expense significantly,” he said.

Mr. Holder noted that inflation also has driven up wages as employees demand higher pay to keep up with the cost of living.
 

Unusual exodus of employees

Fred Horton, MHA, president of AMGA Consulting, said he has never seen so many people leaving health care for other occupations.

Some exits resulted from practices laying people off early in the pandemic, but most staff members who left practices were seeking higher pay, he said. In addition, Ms. Wagner noted, some staff members didn’t want to be exposed to COVID at work.

“There was an exodus from health care that was different from what we’d experienced in the past,” Mr. Horton added. “It’s still extremely challenging to get up to the staffing levels that are appropriate.”

Mr. Holder, however, said that the situation is slowly improving. “Health care is fairly recession-proof, because people need it. So when you see companies in other industries closing shop or reducing their head count, that actually helps health care recruiting in some jobs. And people are coming back to the workplace who previously were worried about COVID or didn’t want to get the vaccine.”
 

Paying more for nurses

In 2021, groups adopted a variety of tactics to adapt to the pandemic and respond to patient demand, the AMGA survey shows. Forty percent of system-affiliated groups and 18% of independent practices changed registered nurses’ responsibilities, in many cases having them do the work of medical assistants who were in short supply.

Some practices hired RNs, who have historically been utilized less by primary care than by surgical specialties, Mr. Holder noted. Other clinics paid temp agencies to supply nurses at a steep cost.

“When you’re short staffed, you end up paying more overtime, you end up paying temporary agencies at higher dollars, and you hire higher skilled people to do lower-skilled work,” Ms. Wagner said.

Meanwhile, many physician groups tried to cope with the physician shortage by bringing on more advanced practice clinicians (APCs), including nurse practitioners (NPs) and physician assistants (PAs). Seventy percent of the AMGA groups used this strategy, the report revealed.

“The use of APCs has been steadily increasing as groups try to adopt a lower-cost care model in the midst of a nationwide physician shortage,” Ms. Wagner said in the press release.
 

Changes in patient care

About half of the groups in the AMGA survey said they changed their staff structure to allow APCs to carry their own patient panels. Although most of these clinicians were probably under physician supervision, nearly half of the states now allow NPs to practice autonomously.

Mr. Horton cautioned that APCs can’t fully substitute for physicians and require the same support staff that doctors do if they have their own panels. In primary care groups, Mr. Holder noted, the average salary of an APC “is continuing to rise, and there isn’t a huge difference between what they and doctors make.”

Nevertheless, he added, “there are more NPs and PAs being added to the marketplace all the time, whereas [physician] residency programs aren’t really growing. There are caps on the number of residency positions, and some physicians are retiring. So the clock is ticking to the point where someday doctors will be grossly outnumbered by NPs.”

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

Physician groups saw staff-to-physician ratios decline even as their workforce expenses rose between 2019 and 2021, according to recent reports from the American Medical Group Association (AMGA) and the Medical Group Management Association (MGMA).

As patients started to return to doctors’ offices as the pandemic eased in 2021, physician groups found it increasingly difficult to recruit and retain lower-level clinicians, including medical assistants and LPNs, officials from both associations told this news organization. Many clinics had to raise their pay scales to be competitive with employers in other fields, and some had to hire higher-priced RNs to keep their practices running.

The AMGA report was based largely on data from groups of over 500 physicians, mostly affiliated with health systems. According to a news release accompanying the report, the ratio between full-time equivalent (FTE) clinic staff and health care professionals in direct patient care dropped by 11.3% between 2019 and 2021. The ratio of medical assistants (MAs) to clinicians declined by a greater percentage.

In the MGMA report, which represented about 4,000 practices ranging from very small (two doctors) to very large groups, total support staff per FTE primary-care physician dropped by 18% from 2019 to 2021 in independent groups and by 13% in hospital-affiliated groups. The ratios decreased by smaller amounts in surgical practices.

In contrast, nonsurgical specialty groups under both types of ownership saw their staffing ratios rise slightly.

Although it’s unclear why medical specialties increased their staff while other types of specialties lost employees, Ron Holder, MHA, chief operating officer of MGMA, said that some specialists may have opened more ancillary facilities and hired new employees to recoup revenue lost during the pandemic.
 

Expenses rise sharply

The AMGA report found that staffing expenses for the surveyed groups increased by 15% between 2019 and 2021.

“We saw a decrease in staff and an increase in expenses during that time period, and there are a few reasons for that,” Rose Wagner, RN, chief operating officer of AMGA, said. “Groups increased salaries to maintain staff. We also saw lower-paid staff find other jobs outside of health care. For example, medical assistants and receptionists could find jobs outside of health care that paid more. [Open positions] got back-filled with other higher paid staff, such as RNs, doing lower skilled jobs.”

Mr. Holder added that rising wages in other sectors made leaving physician groups more attractive for employees.

“Three years ago, there weren’t many positions in a medical practice where you were competing with Chick-fil-A or Taco Bell,” he said. In Denver, where Mr. Holder is based, “every restaurant in town is now advertising $17-$19 [hourly] starting pay just to do fast food. That causes practices to either lose employees or pay more for the employees they have. So that raises per-employee expense significantly,” he said.

Mr. Holder noted that inflation also has driven up wages as employees demand higher pay to keep up with the cost of living.
 

Unusual exodus of employees

Fred Horton, MHA, president of AMGA Consulting, said he has never seen so many people leaving health care for other occupations.

Some exits resulted from practices laying people off early in the pandemic, but most staff members who left practices were seeking higher pay, he said. In addition, Ms. Wagner noted, some staff members didn’t want to be exposed to COVID at work.

“There was an exodus from health care that was different from what we’d experienced in the past,” Mr. Horton added. “It’s still extremely challenging to get up to the staffing levels that are appropriate.”

Mr. Holder, however, said that the situation is slowly improving. “Health care is fairly recession-proof, because people need it. So when you see companies in other industries closing shop or reducing their head count, that actually helps health care recruiting in some jobs. And people are coming back to the workplace who previously were worried about COVID or didn’t want to get the vaccine.”
 

Paying more for nurses

In 2021, groups adopted a variety of tactics to adapt to the pandemic and respond to patient demand, the AMGA survey shows. Forty percent of system-affiliated groups and 18% of independent practices changed registered nurses’ responsibilities, in many cases having them do the work of medical assistants who were in short supply.

Some practices hired RNs, who have historically been utilized less by primary care than by surgical specialties, Mr. Holder noted. Other clinics paid temp agencies to supply nurses at a steep cost.

“When you’re short staffed, you end up paying more overtime, you end up paying temporary agencies at higher dollars, and you hire higher skilled people to do lower-skilled work,” Ms. Wagner said.

Meanwhile, many physician groups tried to cope with the physician shortage by bringing on more advanced practice clinicians (APCs), including nurse practitioners (NPs) and physician assistants (PAs). Seventy percent of the AMGA groups used this strategy, the report revealed.

“The use of APCs has been steadily increasing as groups try to adopt a lower-cost care model in the midst of a nationwide physician shortage,” Ms. Wagner said in the press release.
 

Changes in patient care

About half of the groups in the AMGA survey said they changed their staff structure to allow APCs to carry their own patient panels. Although most of these clinicians were probably under physician supervision, nearly half of the states now allow NPs to practice autonomously.

Mr. Horton cautioned that APCs can’t fully substitute for physicians and require the same support staff that doctors do if they have their own panels. In primary care groups, Mr. Holder noted, the average salary of an APC “is continuing to rise, and there isn’t a huge difference between what they and doctors make.”

Nevertheless, he added, “there are more NPs and PAs being added to the marketplace all the time, whereas [physician] residency programs aren’t really growing. There are caps on the number of residency positions, and some physicians are retiring. So the clock is ticking to the point where someday doctors will be grossly outnumbered by NPs.”

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

Physician groups saw staff-to-physician ratios decline even as their workforce expenses rose between 2019 and 2021, according to recent reports from the American Medical Group Association (AMGA) and the Medical Group Management Association (MGMA).

As patients started to return to doctors’ offices as the pandemic eased in 2021, physician groups found it increasingly difficult to recruit and retain lower-level clinicians, including medical assistants and LPNs, officials from both associations told this news organization. Many clinics had to raise their pay scales to be competitive with employers in other fields, and some had to hire higher-priced RNs to keep their practices running.

The AMGA report was based largely on data from groups of over 500 physicians, mostly affiliated with health systems. According to a news release accompanying the report, the ratio between full-time equivalent (FTE) clinic staff and health care professionals in direct patient care dropped by 11.3% between 2019 and 2021. The ratio of medical assistants (MAs) to clinicians declined by a greater percentage.

In the MGMA report, which represented about 4,000 practices ranging from very small (two doctors) to very large groups, total support staff per FTE primary-care physician dropped by 18% from 2019 to 2021 in independent groups and by 13% in hospital-affiliated groups. The ratios decreased by smaller amounts in surgical practices.

In contrast, nonsurgical specialty groups under both types of ownership saw their staffing ratios rise slightly.

Although it’s unclear why medical specialties increased their staff while other types of specialties lost employees, Ron Holder, MHA, chief operating officer of MGMA, said that some specialists may have opened more ancillary facilities and hired new employees to recoup revenue lost during the pandemic.
 

Expenses rise sharply

The AMGA report found that staffing expenses for the surveyed groups increased by 15% between 2019 and 2021.

“We saw a decrease in staff and an increase in expenses during that time period, and there are a few reasons for that,” Rose Wagner, RN, chief operating officer of AMGA, said. “Groups increased salaries to maintain staff. We also saw lower-paid staff find other jobs outside of health care. For example, medical assistants and receptionists could find jobs outside of health care that paid more. [Open positions] got back-filled with other higher paid staff, such as RNs, doing lower skilled jobs.”

Mr. Holder added that rising wages in other sectors made leaving physician groups more attractive for employees.

“Three years ago, there weren’t many positions in a medical practice where you were competing with Chick-fil-A or Taco Bell,” he said. In Denver, where Mr. Holder is based, “every restaurant in town is now advertising $17-$19 [hourly] starting pay just to do fast food. That causes practices to either lose employees or pay more for the employees they have. So that raises per-employee expense significantly,” he said.

Mr. Holder noted that inflation also has driven up wages as employees demand higher pay to keep up with the cost of living.
 

Unusual exodus of employees

Fred Horton, MHA, president of AMGA Consulting, said he has never seen so many people leaving health care for other occupations.

Some exits resulted from practices laying people off early in the pandemic, but most staff members who left practices were seeking higher pay, he said. In addition, Ms. Wagner noted, some staff members didn’t want to be exposed to COVID at work.

“There was an exodus from health care that was different from what we’d experienced in the past,” Mr. Horton added. “It’s still extremely challenging to get up to the staffing levels that are appropriate.”

Mr. Holder, however, said that the situation is slowly improving. “Health care is fairly recession-proof, because people need it. So when you see companies in other industries closing shop or reducing their head count, that actually helps health care recruiting in some jobs. And people are coming back to the workplace who previously were worried about COVID or didn’t want to get the vaccine.”
 

Paying more for nurses

In 2021, groups adopted a variety of tactics to adapt to the pandemic and respond to patient demand, the AMGA survey shows. Forty percent of system-affiliated groups and 18% of independent practices changed registered nurses’ responsibilities, in many cases having them do the work of medical assistants who were in short supply.

Some practices hired RNs, who have historically been utilized less by primary care than by surgical specialties, Mr. Holder noted. Other clinics paid temp agencies to supply nurses at a steep cost.

“When you’re short staffed, you end up paying more overtime, you end up paying temporary agencies at higher dollars, and you hire higher skilled people to do lower-skilled work,” Ms. Wagner said.

Meanwhile, many physician groups tried to cope with the physician shortage by bringing on more advanced practice clinicians (APCs), including nurse practitioners (NPs) and physician assistants (PAs). Seventy percent of the AMGA groups used this strategy, the report revealed.

“The use of APCs has been steadily increasing as groups try to adopt a lower-cost care model in the midst of a nationwide physician shortage,” Ms. Wagner said in the press release.
 

Changes in patient care

About half of the groups in the AMGA survey said they changed their staff structure to allow APCs to carry their own patient panels. Although most of these clinicians were probably under physician supervision, nearly half of the states now allow NPs to practice autonomously.

Mr. Horton cautioned that APCs can’t fully substitute for physicians and require the same support staff that doctors do if they have their own panels. In primary care groups, Mr. Holder noted, the average salary of an APC “is continuing to rise, and there isn’t a huge difference between what they and doctors make.”

Nevertheless, he added, “there are more NPs and PAs being added to the marketplace all the time, whereas [physician] residency programs aren’t really growing. There are caps on the number of residency positions, and some physicians are retiring. So the clock is ticking to the point where someday doctors will be grossly outnumbered by NPs.”

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

Doctors and their family members are less likely than other people to follow guidelines for taking medication, according to a study by economic professors from the Massachusetts Institute of Technology, Cambridge; Stanford (Calif.) University; and the George Gund Professor of Economics and Business Administration at Harvard University, Boston.

What to know

• Doctors’ medical knowledge may influence them and their families to often ignore medical advice while the rest of the population adheres to general medication guidelines.
• Of the 63 guidelines used in the study, doctors and their families followed the standards less than a third of the time.
• The difference in adherence to guidelines between experts and nonexperts is largest with respect to antibiotics, in which doctors and their families are 5.2 percentage points less in compliance than everyone else.
• Doctors could be more likely to prescribe broader-spectrum antibiotics for themselves and their families, whereas most patients receive more narrow-spectrum antibiotics.
• Many members of the general public don’t understand medical guidelines, finding them too complex to follow, and many people don’t trust their doctors.

This is a summary of the article, “A Taste of Their Own Medicine: Guideline Adherence and Access to Expertise,” published in the American Economic Review: Insights on December 13, 2022. The full article can be found on aeaweb.org.

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

Doctors and their family members are less likely than other people to follow guidelines for taking medication, according to a study by economic professors from the Massachusetts Institute of Technology, Cambridge; Stanford (Calif.) University; and the George Gund Professor of Economics and Business Administration at Harvard University, Boston.

What to know

• Doctors’ medical knowledge may influence them and their families to often ignore medical advice while the rest of the population adheres to general medication guidelines.
• Of the 63 guidelines used in the study, doctors and their families followed the standards less than a third of the time.
• The difference in adherence to guidelines between experts and nonexperts is largest with respect to antibiotics, in which doctors and their families are 5.2 percentage points less in compliance than everyone else.
• Doctors could be more likely to prescribe broader-spectrum antibiotics for themselves and their families, whereas most patients receive more narrow-spectrum antibiotics.
• Many members of the general public don’t understand medical guidelines, finding them too complex to follow, and many people don’t trust their doctors.

This is a summary of the article, “A Taste of Their Own Medicine: Guideline Adherence and Access to Expertise,” published in the American Economic Review: Insights on December 13, 2022. The full article can be found on aeaweb.org.

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

Doctors and their family members are less likely than other people to follow guidelines for taking medication, according to a study by economic professors from the Massachusetts Institute of Technology, Cambridge; Stanford (Calif.) University; and the George Gund Professor of Economics and Business Administration at Harvard University, Boston.

What to know

• Doctors’ medical knowledge may influence them and their families to often ignore medical advice while the rest of the population adheres to general medication guidelines.
• Of the 63 guidelines used in the study, doctors and their families followed the standards less than a third of the time.
• The difference in adherence to guidelines between experts and nonexperts is largest with respect to antibiotics, in which doctors and their families are 5.2 percentage points less in compliance than everyone else.
• Doctors could be more likely to prescribe broader-spectrum antibiotics for themselves and their families, whereas most patients receive more narrow-spectrum antibiotics.
• Many members of the general public don’t understand medical guidelines, finding them too complex to follow, and many people don’t trust their doctors.

This is a summary of the article, “A Taste of Their Own Medicine: Guideline Adherence and Access to Expertise,” published in the American Economic Review: Insights on December 13, 2022. The full article can be found on aeaweb.org.

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

A new study published in JAMA suggests that doctors with one paid malpractice claim are almost four times more likely than their peers to have additional paid claims in the future, regardless of specialty or whether a state publicly discloses paid claims.

In this retrospective case-control study, law and public health researchers from Georgetown University, the National Opinion Research Center, the University of Colorado, and Northwestern University analyzed paid malpractice claims for all licensed U.S. physicians.

The findings suggest that a single malpractice claim may not be a random stroke of bad luck but instead holds some predictive power into the risk for future paid claims.

“A four times increase in risk is huge, particularly since we observe a similar increase in both high-risk and lower-risk specialties,” David Hyman, JD, MD, professor of health law and policy at Georgetown University, Washington, and lead researcher on the study, told this news organization. “There are surely some false positives, but there must be lots of actual negligence too, or we would not see these results.”

For the 881,876 physicians analyzed, researchers looked at malpractice claims paid during two 5-year periods: 2009-2013 and 2014-2018. Nearly 96% of physicians had no paid malpractice claims between 2009 and 2013; 3% had one, and less than 1% had multiple claims. The proportion of physicians with paid claims between 2014 and 2018 was similar.

Compared with physicians with no 2009-2013 claims, a physician with just one paid claim in that time period had a 3.7 times higher risk for a future paid claim. Physicians with two paid claims were nearly 7 times more likely to have a future paid claim, and those with three or more paid claims were more than 11 times more likely to have one.

Approximately 3% of physicians with no paid claims between 2009 and 2013 had a future paid claim, growing to 12.4% of those with one paid claim during that time.

The study’s findings may have implications for medical licensing boards and hospitals granting staff privileges.

“After some number of paid claims, there should be an official response” from these entities, such as a hands-on assessment of technical skills or assignment of a peer mentor, said Dr. Hyman, who is also coauthor of a book titled “Medical Malpractice Litigation: How It Works, Why Tort Reform Hasn’t Helped.” A graduated set of interventions, whether voluntary or mandatory, can reduce future claim risk and patient harm, Dr. Hyman added.

Interventions may include error avoidance and post-error communication training, counseling to improve bedside skills, and encouragement to move into nonclinical practice. Either way, Dr. Hyman says a nuanced intervention strategy would be a welcome shift away from the current “all or nothing approach” that too often ends in the revocation of a physician’s medical license.

Although there are strategies to proactively identify physicians with excess risk for malpractice claims and implement preventive measures – like Vanderbilt University’s Patient Advocacy Reporting System, for example – most hospitals and physician groups fail to initiate even informal interventions after a malpractice settlement or verdict, which is a missed opportunity, Dr. Hyman said.

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

A new study published in JAMA suggests that doctors with one paid malpractice claim are almost four times more likely than their peers to have additional paid claims in the future, regardless of specialty or whether a state publicly discloses paid claims.

In this retrospective case-control study, law and public health researchers from Georgetown University, the National Opinion Research Center, the University of Colorado, and Northwestern University analyzed paid malpractice claims for all licensed U.S. physicians.

The findings suggest that a single malpractice claim may not be a random stroke of bad luck but instead holds some predictive power into the risk for future paid claims.

“A four times increase in risk is huge, particularly since we observe a similar increase in both high-risk and lower-risk specialties,” David Hyman, JD, MD, professor of health law and policy at Georgetown University, Washington, and lead researcher on the study, told this news organization. “There are surely some false positives, but there must be lots of actual negligence too, or we would not see these results.”

For the 881,876 physicians analyzed, researchers looked at malpractice claims paid during two 5-year periods: 2009-2013 and 2014-2018. Nearly 96% of physicians had no paid malpractice claims between 2009 and 2013; 3% had one, and less than 1% had multiple claims. The proportion of physicians with paid claims between 2014 and 2018 was similar.

Compared with physicians with no 2009-2013 claims, a physician with just one paid claim in that time period had a 3.7 times higher risk for a future paid claim. Physicians with two paid claims were nearly 7 times more likely to have a future paid claim, and those with three or more paid claims were more than 11 times more likely to have one.

Approximately 3% of physicians with no paid claims between 2009 and 2013 had a future paid claim, growing to 12.4% of those with one paid claim during that time.

The study’s findings may have implications for medical licensing boards and hospitals granting staff privileges.

“After some number of paid claims, there should be an official response” from these entities, such as a hands-on assessment of technical skills or assignment of a peer mentor, said Dr. Hyman, who is also coauthor of a book titled “Medical Malpractice Litigation: How It Works, Why Tort Reform Hasn’t Helped.” A graduated set of interventions, whether voluntary or mandatory, can reduce future claim risk and patient harm, Dr. Hyman added.

Interventions may include error avoidance and post-error communication training, counseling to improve bedside skills, and encouragement to move into nonclinical practice. Either way, Dr. Hyman says a nuanced intervention strategy would be a welcome shift away from the current “all or nothing approach” that too often ends in the revocation of a physician’s medical license.

Although there are strategies to proactively identify physicians with excess risk for malpractice claims and implement preventive measures – like Vanderbilt University’s Patient Advocacy Reporting System, for example – most hospitals and physician groups fail to initiate even informal interventions after a malpractice settlement or verdict, which is a missed opportunity, Dr. Hyman said.

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

A new study published in JAMA suggests that doctors with one paid malpractice claim are almost four times more likely than their peers to have additional paid claims in the future, regardless of specialty or whether a state publicly discloses paid claims.

In this retrospective case-control study, law and public health researchers from Georgetown University, the National Opinion Research Center, the University of Colorado, and Northwestern University analyzed paid malpractice claims for all licensed U.S. physicians.

The findings suggest that a single malpractice claim may not be a random stroke of bad luck but instead holds some predictive power into the risk for future paid claims.

“A four times increase in risk is huge, particularly since we observe a similar increase in both high-risk and lower-risk specialties,” David Hyman, JD, MD, professor of health law and policy at Georgetown University, Washington, and lead researcher on the study, told this news organization. “There are surely some false positives, but there must be lots of actual negligence too, or we would not see these results.”

For the 881,876 physicians analyzed, researchers looked at malpractice claims paid during two 5-year periods: 2009-2013 and 2014-2018. Nearly 96% of physicians had no paid malpractice claims between 2009 and 2013; 3% had one, and less than 1% had multiple claims. The proportion of physicians with paid claims between 2014 and 2018 was similar.

Compared with physicians with no 2009-2013 claims, a physician with just one paid claim in that time period had a 3.7 times higher risk for a future paid claim. Physicians with two paid claims were nearly 7 times more likely to have a future paid claim, and those with three or more paid claims were more than 11 times more likely to have one.

Approximately 3% of physicians with no paid claims between 2009 and 2013 had a future paid claim, growing to 12.4% of those with one paid claim during that time.

The study’s findings may have implications for medical licensing boards and hospitals granting staff privileges.

“After some number of paid claims, there should be an official response” from these entities, such as a hands-on assessment of technical skills or assignment of a peer mentor, said Dr. Hyman, who is also coauthor of a book titled “Medical Malpractice Litigation: How It Works, Why Tort Reform Hasn’t Helped.” A graduated set of interventions, whether voluntary or mandatory, can reduce future claim risk and patient harm, Dr. Hyman added.

Interventions may include error avoidance and post-error communication training, counseling to improve bedside skills, and encouragement to move into nonclinical practice. Either way, Dr. Hyman says a nuanced intervention strategy would be a welcome shift away from the current “all or nothing approach” that too often ends in the revocation of a physician’s medical license.

Although there are strategies to proactively identify physicians with excess risk for malpractice claims and implement preventive measures – like Vanderbilt University’s Patient Advocacy Reporting System, for example – most hospitals and physician groups fail to initiate even informal interventions after a malpractice settlement or verdict, which is a missed opportunity, Dr. Hyman said.

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

COVID-19 remains deadlier than influenza in severe cases requiring hospitalization, a new study shows.

People who were hospitalized with Omicron COVID-19 infections were 54% more likely to die, compared with people who were hospitalized with the flu, Swiss researchers found.

The results of the study continue to debunk an earlier belief from the start of the pandemic that the flu was the more dangerous of the two respiratory viruses. The researchers noted that the deadliness of COVID-19, compared with flu, persisted “despite virus evolution and improved management strategies.”

The study was published in JAMA Network Open and included 5,212 patients in Switzerland hospitalized with COVID-19 or the flu. All the COVID patients were infected with the Omicron variant and hospitalized between Jan. 15, 2022, and March 15, 2022. Flu data included cases from January 2018 to March 15, 2022. 

Overall, 7% of COVID-19 patients died, compared with 4.4% of flu patients. Researchers noted that the death rate for hospitalized COVID patients had declined since their previous study, which was conducted during the first COVID wave in the first half of 2020. At that time, the death rate of hospitalized COVID patients was 12.8%. 

Since then, 98% of the Swiss population has been vaccinated. “Vaccination still plays a significant role regarding the main outcome,” the authors concluded, since a secondary analysis in this most recent study showed that unvaccinated COVID patients were twice as likely to die, compared with flu patients.

“Our results demonstrate that COVID-19 still cannot simply be compared with influenza,” they wrote.

While the death rate among COVID patients was significantly higher, there was no difference in the rate that COVID or flu patients were admitted to the ICU, which was around 8%.

A limitation of the study was that all the COVID cases did not have laboratory testing to confirm the Omicron variant. However, the study authors noted that Omicron accounted for at least 95% of cases during the time the patients were hospitalized. The authors were confident that their results were not biased by the potential for other variants being included in the data.

Four coauthors reported receiving grants and personal fees from various sources.

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

COVID-19 remains deadlier than influenza in severe cases requiring hospitalization, a new study shows.

People who were hospitalized with Omicron COVID-19 infections were 54% more likely to die, compared with people who were hospitalized with the flu, Swiss researchers found.

The results of the study continue to debunk an earlier belief from the start of the pandemic that the flu was the more dangerous of the two respiratory viruses. The researchers noted that the deadliness of COVID-19, compared with flu, persisted “despite virus evolution and improved management strategies.”

The study was published in JAMA Network Open and included 5,212 patients in Switzerland hospitalized with COVID-19 or the flu. All the COVID patients were infected with the Omicron variant and hospitalized between Jan. 15, 2022, and March 15, 2022. Flu data included cases from January 2018 to March 15, 2022. 

Overall, 7% of COVID-19 patients died, compared with 4.4% of flu patients. Researchers noted that the death rate for hospitalized COVID patients had declined since their previous study, which was conducted during the first COVID wave in the first half of 2020. At that time, the death rate of hospitalized COVID patients was 12.8%. 

Since then, 98% of the Swiss population has been vaccinated. “Vaccination still plays a significant role regarding the main outcome,” the authors concluded, since a secondary analysis in this most recent study showed that unvaccinated COVID patients were twice as likely to die, compared with flu patients.

“Our results demonstrate that COVID-19 still cannot simply be compared with influenza,” they wrote.

While the death rate among COVID patients was significantly higher, there was no difference in the rate that COVID or flu patients were admitted to the ICU, which was around 8%.

A limitation of the study was that all the COVID cases did not have laboratory testing to confirm the Omicron variant. However, the study authors noted that Omicron accounted for at least 95% of cases during the time the patients were hospitalized. The authors were confident that their results were not biased by the potential for other variants being included in the data.

Four coauthors reported receiving grants and personal fees from various sources.

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

COVID-19 remains deadlier than influenza in severe cases requiring hospitalization, a new study shows.

People who were hospitalized with Omicron COVID-19 infections were 54% more likely to die, compared with people who were hospitalized with the flu, Swiss researchers found.

The results of the study continue to debunk an earlier belief from the start of the pandemic that the flu was the more dangerous of the two respiratory viruses. The researchers noted that the deadliness of COVID-19, compared with flu, persisted “despite virus evolution and improved management strategies.”

The study was published in JAMA Network Open and included 5,212 patients in Switzerland hospitalized with COVID-19 or the flu. All the COVID patients were infected with the Omicron variant and hospitalized between Jan. 15, 2022, and March 15, 2022. Flu data included cases from January 2018 to March 15, 2022. 

Overall, 7% of COVID-19 patients died, compared with 4.4% of flu patients. Researchers noted that the death rate for hospitalized COVID patients had declined since their previous study, which was conducted during the first COVID wave in the first half of 2020. At that time, the death rate of hospitalized COVID patients was 12.8%. 

Since then, 98% of the Swiss population has been vaccinated. “Vaccination still plays a significant role regarding the main outcome,” the authors concluded, since a secondary analysis in this most recent study showed that unvaccinated COVID patients were twice as likely to die, compared with flu patients.

“Our results demonstrate that COVID-19 still cannot simply be compared with influenza,” they wrote.

While the death rate among COVID patients was significantly higher, there was no difference in the rate that COVID or flu patients were admitted to the ICU, which was around 8%.

A limitation of the study was that all the COVID cases did not have laboratory testing to confirm the Omicron variant. However, the study authors noted that Omicron accounted for at least 95% of cases during the time the patients were hospitalized. The authors were confident that their results were not biased by the potential for other variants being included in the data.

Four coauthors reported receiving grants and personal fees from various sources.

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

Treatment with the diabetes drug metformin shows a significant, dose-dependent effect in lowering SARS-CoV-2 viral load within days of administration, according to the latest analysis of the phase 3 COVID-OUT trial. These findings add to a multitude of benefits the drug has been shown to have in COVID infection.

COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.

“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
 

Study details

For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.

A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.

The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.

The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.

About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.

The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.

The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).

An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.

Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).

The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.

No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.

The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.

The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.

Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.

In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.

“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
 

‘Data from other studies are conflicting’

Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.

However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.

Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.

Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.

The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.

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

Treatment with the diabetes drug metformin shows a significant, dose-dependent effect in lowering SARS-CoV-2 viral load within days of administration, according to the latest analysis of the phase 3 COVID-OUT trial. These findings add to a multitude of benefits the drug has been shown to have in COVID infection.

COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.

“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
 

Study details

For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.

A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.

The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.

The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.

About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.

The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.

The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).

An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.

Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).

The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.

No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.

The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.

The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.

Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.

In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.

“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
 

‘Data from other studies are conflicting’

Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.

However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.

Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.

Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.

The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.

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

Treatment with the diabetes drug metformin shows a significant, dose-dependent effect in lowering SARS-CoV-2 viral load within days of administration, according to the latest analysis of the phase 3 COVID-OUT trial. These findings add to a multitude of benefits the drug has been shown to have in COVID infection.

COVID-OUT did not meet its primary endpoint, but it did show important secondary outcomes including a 42% reduction in ED visits and in hospitalizations and/or deaths by day 14, and a 58% reduction in hospitalizations/death by day 28. A further subanalysis has shown a 42% reduction in long COVID, compared with placebo.

“In this phase 3 randomized controlled trial, metformin showed prevention of severe COVID, prevention of long COVID, and an antiviral effect, and this is consistent with other data,” said coauthor Carolyn Bramante, MD, University of Minnesota, Minneapolis, in presenting the findings at the Conference on Retroviruses & Opportunistic Infections.
 

Study details

For the new subanalysis, the authors further evaluated the effects of metformin treatment on SARS-CoV-2 viral load.

A total of 1,323 patients in the study, enrolled at six centers, were randomized to treatment either with metformin 1,000 mg per day on days 2-5 and 1,500 mg per day on days 6 to 14 (n = 187), or to ivermectin 390-470 mcg/kg per day for 3 days (n = 187), fluvoxamine 50 mg twice daily for 14 days, and/or an exact-matching placebo in a 2 x 3 factorial trial design.

The subanalysis on viral load included 483 patients from the trial who were treated with metformin versus 462 who received placebo, who were all enrolled within 3 days of a documented SARS-CoV-2 infection and less than 7 days after symptom onset.

The patients had a median age of 46 years, and all had either overweight or obesity. Only about 2% had diabetes, and only patients considered low-risk were excluded from the trial, including those under age 30 and those with a body mass index under 25.

About half of patients had received a primary vaccine and about 5% had received a vaccine booster. SARS-CoV-2 variants that were prominent during the study included Alpha, Delta, and Omicron.

The viral samples available on days 1, 5, and 10 showed a mean change in viral load from baseline to follow-up; the viral load was significantly lower with metformin versus placebo (–0.64 log10 copies/mL), representing a 4.4-fold greater decrease in viral load with metformin.

The mean rate of undetectable SARS-CoV-2 viral load at day 5 was 49.9% in the metformin group versus 54.6% in the placebo group (odds ratio, 1.235), and the undetectable rate at day 10 was 14.3% in the metformin group and 22.6% in the placebo group (OR, 1.663; P = .003).

An increased antiviral effect corresponded with increases in metformin dosing on days 6 through 14. Furthermore, the antiviral effect became stronger when metformin was started earlier in the course of infection.

Of note, the antiviral effect was more pronounced among those who were not vaccinated (mean, –0.95 log copies/mL), compared with the vaccinated (mean, –0.39 log copies/mL).

The antiviral effect with metformin was similar to that seen with nirmatrelvir at day 5 and was greater than nirmatrelvir at day 10.

No similar relationships in SARS-CoV-2 viral load were observed between ivermectin or fluvoxamine and placebo.

The findings are consistent with results of other recent observational studies, including research showing metformin to be associated with reductions in COVID-19 severity in patients with prediabetes, Dr. Bramante noted.

The authors’ previous analysis looking at long COVID in the COVID-OUT study showed that metformin treatment during acute COVID significantly reduced the risk for a diagnosis of long COVID versus placebo at 300 days following randomization, with a hazard ratio of 0.59 after adjustment for the study drug and vaccination at baseline.

Dr. Bramante noted that metformin’s potential antiviral properties have long been speculated, with some of the earliest research on the drug suggesting less severe outcomes in influenza, and more recently, RNA assays suggesting effects against other RNA viruses, including the Zika virus.

In terms of COVID, Dr. Bramante noted that the drug has plenty of potentially favorable benefits.

“Metformin is very safe and is known to have very few contraindications, so the next steps could be to consider looking at this in terms of a combination therapy,” she said.
 

‘Data from other studies are conflicting’

Commenting on the study, Diane V. Havlir, MD, cautioned that “metformin is currently not recommended in treatment guidelines, [and] data from other studies are conflicting; side effects can be an issue, and the study presented here was in a select population,” she said in an interview.

However, “what is both new and interesting in this presentation is the reduction of viral load, which [was observed] in the samples collected not only on days 1-5, but also days 6-14,” said Dr. Havlir, who is professor and associate chair of clinical research, department of medicine, and chief of the division of HIV, infectious diseases and global medicine and director of the AIDS Research Institute at the University of California, San Francisco.

Key questions the findings raise include whether the results correlate with clinical outcomes or transmission, and whether the findings are generalizable to other populations and settings, Dr. Havlir said.

Ultimately, “we need to continue to pursue all aspects of outpatient treatments for COVID to address questions like these for new and existing agents,” she added.

The trial received funding from the Parsemus Foundation, the Rainwater Charitable Foundation, Fast Grants, and the United Health Group. The authors and Dr. Havlir disclosed no relevant financial relationships.

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

Warming U.S. temperatures, the resumption of travel, and new knowledge about Zika’s long-term effects on children signal that Zika prevention and vaccine development should be on public health officials’, doctors’, and communities’ radar, even when community infection is not occurring.

“Although we haven’t seen confirmed Zika virus circulation in the continental United States or its territories for several years, it’s still something that we are closely monitoring, particularly as we move into the summer months,” Erin Staples, MD, PhD, medical epidemiologist at the Arboviral Diseases Branch of the Centers for Disease Control and Prevention in Fort Collins, Colo., told this news organization.

“This is because cases are still being reported in other countries, particularly in South America. Travel to these places is increasing following the pandemic, leaving more potential for individuals who might have acquired the infection to come back and restart community transmission.”
 

How Zika might reemerge

The Aedes aegypti mosquito is the vector by which Zika spreads, and “during the COVID pandemic, these mosquitoes moved further north in the United States, into southern California, and were identified as far north as Washington, D.C.,” said Neil Silverman, MD, professor of clinical obstetrics and gynecology and director of the Infections in Pregnancy Program at UCLA Medical Center in Los Angeles.

“On a population level, Americans have essentially no immunity to Zika from prior infection, and there is no vaccine yet approved. If individuals infected with Zika came into a U.S. region where the Aedes aegypti mosquito was present, that population could be very susceptible to infection spread and even another outbreak. This would be a confluence of bad circumstances, but that’s exactly what infectious disease specialists continue to be watchful about, especially because Zika is so dangerous for fetuses,” said Dr. Silverman.
 

How the public can prepare

The CDC recommends that pregnant women or women who plan to become pregnant avoid traveling to regions where there are currently outbreaks of Zika, but this is not the only way that individuals can protect themselves.

“The message we want to deliver to people is that in the United States, people are at risk for several mosquito-borne diseases every summer beyond just Zika,” Dr. Staples said. “It’s really important that people are instructed to make a habit of wearing EPA [U.S. Environmental Protection Agency)–registered insect repellents when they go outside. Right now, that is the single best tool that we have to prevent mosquito-borne diseases in the U.S.

“From a community standpoint, there are several emerging mosquito control methods that are being evaluated right now, such as genetic modification and irradiation of mosquitoes. These methods are aimed at producing sterile mosquitoes that are released into the wild to mate with the local mosquito population, which will render them infertile. This leads, over time, to suppression of the overall Aedes aegypti mosquito population – the main vector of Zika transmission,” said Dr. Staples.

Monica Gandhi, MD, MPH, professor of medicine and associate chief of the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco, encourages her patients to wear mosquito repellent but cautioned that “there’s no antiviral that you can take for Zika. Until we have a vaccine, the key to controlling/preventing Zika is controlling the mosquitoes that spread the virus.”
 

Vaccines

The National Institute of Allergy and Infectious Diseases (NIAID) is currently investigating a variety of Zika vaccines, including a DNA-based vaccine, (phase 2), a purified inactivated virus vaccine (phase 1), live attenuated vaccines (phase 2), and mRNA vaccines (phase 2).

“I’m most excited about mRNA vaccines because they help patients produce a lot of proteins. The protein from a typical protein-adjuvant vaccine will break down, and patients can only raise an immune response to whatever proteins are left. On the other hand, mRNA vaccines provide the body [with] a recipe to make the protein from the pathogen in high amounts, so that a strong immune response can be raised for protection,” noted Dr. Gandhi.

Moderna’s mRNA-1893 vaccine was recently studied in a randomized, observer-blind, controlled, phase 1 trial among 120 adults in the United States and Puerto Rico, the results of which were published online in The Lancet. “The vaccine was found to be generally well tolerated with no serious adverse events considered related to vaccine. Furthermore, the vaccine was able to generate a potent immune response that was capable of neutralizing the virus in vitro,” said Brett Leav, MD, executive director of clinical development for public health vaccines at Moderna.

“Our mRNA platform technology ... can be very helpful against emerging pandemic threats, as we saw in response to COVID-19. What is unique in our approach is that if the genetic sequence of the virus is known, we can quickly generate vaccines to test for their capability to generate a functional immune response. In the case of the mRNA-1893 trial, the vaccine was developed with antigens that were present in the strain of virus circulating in 2016, but we could easily match whatever strain reemerges,” said Dr. Leav.

A phase 2 trial to confirm the dose of mRNA-1893 in a larger study population is underway.

Although it’s been demonstrated that Moderna’s mRNA vaccine is safe and effective, moving from a phase 2 to a phase 3 study presents a challenge, given the fact that currently, the disease burden from Zika is low. If an outbreak were to occur in the future, these mRNA vaccines could potentially be given emergency approval, as occurred during the COVID pandemic, according to Dr. Silverman.

If approved, provisionally or through a traditional route, the vaccine would “accelerate the ability to tamp down any further outbreaks, because vaccine-based immunity could be made available to a large portion of the population who were pregnant or planning a pregnancy, not just in the U.S. but also in these endemic areas,” said Dr. Silverman.


 

Takeaways from the last Zika outbreak

Practical steps such as mosquito eradication and development of vaccines are not the only takeaway from the recent Zika epidemics inside and outside the United States. A clearer picture of the short- and long-term stakes of the disease has emerged.

According to the CDC, most people who become infected with Zika experience only mild symptoms, such as fever, rash, headache, and muscle pain, but babies conceived by mothers infected with Zika are at risk for stillbirth, miscarriage, and microcephaly and other brain defects.

Although a pregnant woman who tests positive for Zika is in a very high-risk situation, “data show that only about 30% of mothers with Zika have a baby with birth defects. If a pregnant woman contracted Zika, what would happen is we would just do very close screening by ultrasound of the fetus. If microcephaly in utero or fetal brain defects were observed, then a mother would be counseled on her options,” said Dr. Gandhi.

Dr. Silverman noted that “new data on children who were exposed in utero and had normal exams, including head measurements when they were born, have raised concerns. In recently published long-term follow-up studies, even when children born to mothers infected with Zika during pregnancy had normal head growth at least 3 years after birth, they were still at risk for neurodevelopmental delay and behavioral disorders, including impact on coordination and executive function.

“This is another good reason to keep the potential risks of Zika active in the public’s consciousness and in public health planning.”

Dr. Silverman, Dr. Gandhi, and Dr. Staples have disclosed no relevant financial relationships. Dr. Leav is an employee of Moderna and owns stock in the company.

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

Warming U.S. temperatures, the resumption of travel, and new knowledge about Zika’s long-term effects on children signal that Zika prevention and vaccine development should be on public health officials’, doctors’, and communities’ radar, even when community infection is not occurring.

“Although we haven’t seen confirmed Zika virus circulation in the continental United States or its territories for several years, it’s still something that we are closely monitoring, particularly as we move into the summer months,” Erin Staples, MD, PhD, medical epidemiologist at the Arboviral Diseases Branch of the Centers for Disease Control and Prevention in Fort Collins, Colo., told this news organization.

“This is because cases are still being reported in other countries, particularly in South America. Travel to these places is increasing following the pandemic, leaving more potential for individuals who might have acquired the infection to come back and restart community transmission.”
 

How Zika might reemerge

The Aedes aegypti mosquito is the vector by which Zika spreads, and “during the COVID pandemic, these mosquitoes moved further north in the United States, into southern California, and were identified as far north as Washington, D.C.,” said Neil Silverman, MD, professor of clinical obstetrics and gynecology and director of the Infections in Pregnancy Program at UCLA Medical Center in Los Angeles.

“On a population level, Americans have essentially no immunity to Zika from prior infection, and there is no vaccine yet approved. If individuals infected with Zika came into a U.S. region where the Aedes aegypti mosquito was present, that population could be very susceptible to infection spread and even another outbreak. This would be a confluence of bad circumstances, but that’s exactly what infectious disease specialists continue to be watchful about, especially because Zika is so dangerous for fetuses,” said Dr. Silverman.
 

How the public can prepare

The CDC recommends that pregnant women or women who plan to become pregnant avoid traveling to regions where there are currently outbreaks of Zika, but this is not the only way that individuals can protect themselves.

“The message we want to deliver to people is that in the United States, people are at risk for several mosquito-borne diseases every summer beyond just Zika,” Dr. Staples said. “It’s really important that people are instructed to make a habit of wearing EPA [U.S. Environmental Protection Agency)–registered insect repellents when they go outside. Right now, that is the single best tool that we have to prevent mosquito-borne diseases in the U.S.

“From a community standpoint, there are several emerging mosquito control methods that are being evaluated right now, such as genetic modification and irradiation of mosquitoes. These methods are aimed at producing sterile mosquitoes that are released into the wild to mate with the local mosquito population, which will render them infertile. This leads, over time, to suppression of the overall Aedes aegypti mosquito population – the main vector of Zika transmission,” said Dr. Staples.

Monica Gandhi, MD, MPH, professor of medicine and associate chief of the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco, encourages her patients to wear mosquito repellent but cautioned that “there’s no antiviral that you can take for Zika. Until we have a vaccine, the key to controlling/preventing Zika is controlling the mosquitoes that spread the virus.”
 

Vaccines

The National Institute of Allergy and Infectious Diseases (NIAID) is currently investigating a variety of Zika vaccines, including a DNA-based vaccine, (phase 2), a purified inactivated virus vaccine (phase 1), live attenuated vaccines (phase 2), and mRNA vaccines (phase 2).

“I’m most excited about mRNA vaccines because they help patients produce a lot of proteins. The protein from a typical protein-adjuvant vaccine will break down, and patients can only raise an immune response to whatever proteins are left. On the other hand, mRNA vaccines provide the body [with] a recipe to make the protein from the pathogen in high amounts, so that a strong immune response can be raised for protection,” noted Dr. Gandhi.

Moderna’s mRNA-1893 vaccine was recently studied in a randomized, observer-blind, controlled, phase 1 trial among 120 adults in the United States and Puerto Rico, the results of which were published online in The Lancet. “The vaccine was found to be generally well tolerated with no serious adverse events considered related to vaccine. Furthermore, the vaccine was able to generate a potent immune response that was capable of neutralizing the virus in vitro,” said Brett Leav, MD, executive director of clinical development for public health vaccines at Moderna.

“Our mRNA platform technology ... can be very helpful against emerging pandemic threats, as we saw in response to COVID-19. What is unique in our approach is that if the genetic sequence of the virus is known, we can quickly generate vaccines to test for their capability to generate a functional immune response. In the case of the mRNA-1893 trial, the vaccine was developed with antigens that were present in the strain of virus circulating in 2016, but we could easily match whatever strain reemerges,” said Dr. Leav.

A phase 2 trial to confirm the dose of mRNA-1893 in a larger study population is underway.

Although it’s been demonstrated that Moderna’s mRNA vaccine is safe and effective, moving from a phase 2 to a phase 3 study presents a challenge, given the fact that currently, the disease burden from Zika is low. If an outbreak were to occur in the future, these mRNA vaccines could potentially be given emergency approval, as occurred during the COVID pandemic, according to Dr. Silverman.

If approved, provisionally or through a traditional route, the vaccine would “accelerate the ability to tamp down any further outbreaks, because vaccine-based immunity could be made available to a large portion of the population who were pregnant or planning a pregnancy, not just in the U.S. but also in these endemic areas,” said Dr. Silverman.


 

Takeaways from the last Zika outbreak

Practical steps such as mosquito eradication and development of vaccines are not the only takeaway from the recent Zika epidemics inside and outside the United States. A clearer picture of the short- and long-term stakes of the disease has emerged.

According to the CDC, most people who become infected with Zika experience only mild symptoms, such as fever, rash, headache, and muscle pain, but babies conceived by mothers infected with Zika are at risk for stillbirth, miscarriage, and microcephaly and other brain defects.

Although a pregnant woman who tests positive for Zika is in a very high-risk situation, “data show that only about 30% of mothers with Zika have a baby with birth defects. If a pregnant woman contracted Zika, what would happen is we would just do very close screening by ultrasound of the fetus. If microcephaly in utero or fetal brain defects were observed, then a mother would be counseled on her options,” said Dr. Gandhi.

Dr. Silverman noted that “new data on children who were exposed in utero and had normal exams, including head measurements when they were born, have raised concerns. In recently published long-term follow-up studies, even when children born to mothers infected with Zika during pregnancy had normal head growth at least 3 years after birth, they were still at risk for neurodevelopmental delay and behavioral disorders, including impact on coordination and executive function.

“This is another good reason to keep the potential risks of Zika active in the public’s consciousness and in public health planning.”

Dr. Silverman, Dr. Gandhi, and Dr. Staples have disclosed no relevant financial relationships. Dr. Leav is an employee of Moderna and owns stock in the company.

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

Warming U.S. temperatures, the resumption of travel, and new knowledge about Zika’s long-term effects on children signal that Zika prevention and vaccine development should be on public health officials’, doctors’, and communities’ radar, even when community infection is not occurring.

“Although we haven’t seen confirmed Zika virus circulation in the continental United States or its territories for several years, it’s still something that we are closely monitoring, particularly as we move into the summer months,” Erin Staples, MD, PhD, medical epidemiologist at the Arboviral Diseases Branch of the Centers for Disease Control and Prevention in Fort Collins, Colo., told this news organization.

“This is because cases are still being reported in other countries, particularly in South America. Travel to these places is increasing following the pandemic, leaving more potential for individuals who might have acquired the infection to come back and restart community transmission.”
 

How Zika might reemerge

The Aedes aegypti mosquito is the vector by which Zika spreads, and “during the COVID pandemic, these mosquitoes moved further north in the United States, into southern California, and were identified as far north as Washington, D.C.,” said Neil Silverman, MD, professor of clinical obstetrics and gynecology and director of the Infections in Pregnancy Program at UCLA Medical Center in Los Angeles.

“On a population level, Americans have essentially no immunity to Zika from prior infection, and there is no vaccine yet approved. If individuals infected with Zika came into a U.S. region where the Aedes aegypti mosquito was present, that population could be very susceptible to infection spread and even another outbreak. This would be a confluence of bad circumstances, but that’s exactly what infectious disease specialists continue to be watchful about, especially because Zika is so dangerous for fetuses,” said Dr. Silverman.
 

How the public can prepare

The CDC recommends that pregnant women or women who plan to become pregnant avoid traveling to regions where there are currently outbreaks of Zika, but this is not the only way that individuals can protect themselves.

“The message we want to deliver to people is that in the United States, people are at risk for several mosquito-borne diseases every summer beyond just Zika,” Dr. Staples said. “It’s really important that people are instructed to make a habit of wearing EPA [U.S. Environmental Protection Agency)–registered insect repellents when they go outside. Right now, that is the single best tool that we have to prevent mosquito-borne diseases in the U.S.

“From a community standpoint, there are several emerging mosquito control methods that are being evaluated right now, such as genetic modification and irradiation of mosquitoes. These methods are aimed at producing sterile mosquitoes that are released into the wild to mate with the local mosquito population, which will render them infertile. This leads, over time, to suppression of the overall Aedes aegypti mosquito population – the main vector of Zika transmission,” said Dr. Staples.

Monica Gandhi, MD, MPH, professor of medicine and associate chief of the division of HIV, infectious diseases, and global medicine at the University of California, San Francisco, encourages her patients to wear mosquito repellent but cautioned that “there’s no antiviral that you can take for Zika. Until we have a vaccine, the key to controlling/preventing Zika is controlling the mosquitoes that spread the virus.”
 

Vaccines

The National Institute of Allergy and Infectious Diseases (NIAID) is currently investigating a variety of Zika vaccines, including a DNA-based vaccine, (phase 2), a purified inactivated virus vaccine (phase 1), live attenuated vaccines (phase 2), and mRNA vaccines (phase 2).

“I’m most excited about mRNA vaccines because they help patients produce a lot of proteins. The protein from a typical protein-adjuvant vaccine will break down, and patients can only raise an immune response to whatever proteins are left. On the other hand, mRNA vaccines provide the body [with] a recipe to make the protein from the pathogen in high amounts, so that a strong immune response can be raised for protection,” noted Dr. Gandhi.

Moderna’s mRNA-1893 vaccine was recently studied in a randomized, observer-blind, controlled, phase 1 trial among 120 adults in the United States and Puerto Rico, the results of which were published online in The Lancet. “The vaccine was found to be generally well tolerated with no serious adverse events considered related to vaccine. Furthermore, the vaccine was able to generate a potent immune response that was capable of neutralizing the virus in vitro,” said Brett Leav, MD, executive director of clinical development for public health vaccines at Moderna.

“Our mRNA platform technology ... can be very helpful against emerging pandemic threats, as we saw in response to COVID-19. What is unique in our approach is that if the genetic sequence of the virus is known, we can quickly generate vaccines to test for their capability to generate a functional immune response. In the case of the mRNA-1893 trial, the vaccine was developed with antigens that were present in the strain of virus circulating in 2016, but we could easily match whatever strain reemerges,” said Dr. Leav.

A phase 2 trial to confirm the dose of mRNA-1893 in a larger study population is underway.

Although it’s been demonstrated that Moderna’s mRNA vaccine is safe and effective, moving from a phase 2 to a phase 3 study presents a challenge, given the fact that currently, the disease burden from Zika is low. If an outbreak were to occur in the future, these mRNA vaccines could potentially be given emergency approval, as occurred during the COVID pandemic, according to Dr. Silverman.

If approved, provisionally or through a traditional route, the vaccine would “accelerate the ability to tamp down any further outbreaks, because vaccine-based immunity could be made available to a large portion of the population who were pregnant or planning a pregnancy, not just in the U.S. but also in these endemic areas,” said Dr. Silverman.


 

Takeaways from the last Zika outbreak

Practical steps such as mosquito eradication and development of vaccines are not the only takeaway from the recent Zika epidemics inside and outside the United States. A clearer picture of the short- and long-term stakes of the disease has emerged.

According to the CDC, most people who become infected with Zika experience only mild symptoms, such as fever, rash, headache, and muscle pain, but babies conceived by mothers infected with Zika are at risk for stillbirth, miscarriage, and microcephaly and other brain defects.

Although a pregnant woman who tests positive for Zika is in a very high-risk situation, “data show that only about 30% of mothers with Zika have a baby with birth defects. If a pregnant woman contracted Zika, what would happen is we would just do very close screening by ultrasound of the fetus. If microcephaly in utero or fetal brain defects were observed, then a mother would be counseled on her options,” said Dr. Gandhi.

Dr. Silverman noted that “new data on children who were exposed in utero and had normal exams, including head measurements when they were born, have raised concerns. In recently published long-term follow-up studies, even when children born to mothers infected with Zika during pregnancy had normal head growth at least 3 years after birth, they were still at risk for neurodevelopmental delay and behavioral disorders, including impact on coordination and executive function.

“This is another good reason to keep the potential risks of Zika active in the public’s consciousness and in public health planning.”

Dr. Silverman, Dr. Gandhi, and Dr. Staples have disclosed no relevant financial relationships. Dr. Leav is an employee of Moderna and owns stock in the company.

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

A new study shows the Pfizer vaccine is safe and highly effective against COVID-19 in children as young as 6 months old.

A three-dose series of the Pfizer COVID-19 vaccine was 73% effective at preventing symptomatic COVID-19 in children aged 6 months to 4 years, the researchers found. They also found that an examination of reactions and safety results “did not suggest any concerns.”

The study, published in the New England Journal of Medicine, included 1,776 children aged 6 months to 2 years old, and 2,750 children aged 2-4 years. Children were randomly assigned to receive either the three-shot series of the Pfizer vaccine or placebo shots. Participants received the first dose of the vaccine by March 31, 2022, and lived in Brazil, Finland, Poland, Spain, or the United States.

The authors wrote that having safe and effective COVID vaccines for young children is important to protect them from hospitalization or death and because young children play a role in spreading highly transmissible variants of the virus. COVID hospitalizations for children under 5 years old peaked at a rate of 14.5 per 100,000 in January 2022, the authors wrote, noting that the Omicron virus variant appeared to affect young children more severely than the previous variant, Delta.

When the researchers evaluated vaccine effectiveness by age group, they found that it prevented symptomatic COVID in 75.8% of children aged 6 months to 2 years, and in 71.8% of children aged 2-4 years.

Less than 0.5% of participants reported severe reactions to the vaccine. The most common reactions reported were tenderness or pain. Reactions typically appeared within the first couple days following vaccine administration and resolved within 2 days. No cases of inflammation of the heart muscle or its lining were reported among participants.

Uptake of COVID vaccines for young children has been lower than other age groups in the United States. The Centers for Disease Control and Prevention says 10% of children younger than 5 have received at least one dose of a COVID-19 vaccine, and 5% have completed a primary vaccine series.

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

A new study shows the Pfizer vaccine is safe and highly effective against COVID-19 in children as young as 6 months old.

A three-dose series of the Pfizer COVID-19 vaccine was 73% effective at preventing symptomatic COVID-19 in children aged 6 months to 4 years, the researchers found. They also found that an examination of reactions and safety results “did not suggest any concerns.”

The study, published in the New England Journal of Medicine, included 1,776 children aged 6 months to 2 years old, and 2,750 children aged 2-4 years. Children were randomly assigned to receive either the three-shot series of the Pfizer vaccine or placebo shots. Participants received the first dose of the vaccine by March 31, 2022, and lived in Brazil, Finland, Poland, Spain, or the United States.

The authors wrote that having safe and effective COVID vaccines for young children is important to protect them from hospitalization or death and because young children play a role in spreading highly transmissible variants of the virus. COVID hospitalizations for children under 5 years old peaked at a rate of 14.5 per 100,000 in January 2022, the authors wrote, noting that the Omicron virus variant appeared to affect young children more severely than the previous variant, Delta.

When the researchers evaluated vaccine effectiveness by age group, they found that it prevented symptomatic COVID in 75.8% of children aged 6 months to 2 years, and in 71.8% of children aged 2-4 years.

Less than 0.5% of participants reported severe reactions to the vaccine. The most common reactions reported were tenderness or pain. Reactions typically appeared within the first couple days following vaccine administration and resolved within 2 days. No cases of inflammation of the heart muscle or its lining were reported among participants.

Uptake of COVID vaccines for young children has been lower than other age groups in the United States. The Centers for Disease Control and Prevention says 10% of children younger than 5 have received at least one dose of a COVID-19 vaccine, and 5% have completed a primary vaccine series.

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

A new study shows the Pfizer vaccine is safe and highly effective against COVID-19 in children as young as 6 months old.

A three-dose series of the Pfizer COVID-19 vaccine was 73% effective at preventing symptomatic COVID-19 in children aged 6 months to 4 years, the researchers found. They also found that an examination of reactions and safety results “did not suggest any concerns.”

The study, published in the New England Journal of Medicine, included 1,776 children aged 6 months to 2 years old, and 2,750 children aged 2-4 years. Children were randomly assigned to receive either the three-shot series of the Pfizer vaccine or placebo shots. Participants received the first dose of the vaccine by March 31, 2022, and lived in Brazil, Finland, Poland, Spain, or the United States.

The authors wrote that having safe and effective COVID vaccines for young children is important to protect them from hospitalization or death and because young children play a role in spreading highly transmissible variants of the virus. COVID hospitalizations for children under 5 years old peaked at a rate of 14.5 per 100,000 in January 2022, the authors wrote, noting that the Omicron virus variant appeared to affect young children more severely than the previous variant, Delta.

When the researchers evaluated vaccine effectiveness by age group, they found that it prevented symptomatic COVID in 75.8% of children aged 6 months to 2 years, and in 71.8% of children aged 2-4 years.

Less than 0.5% of participants reported severe reactions to the vaccine. The most common reactions reported were tenderness or pain. Reactions typically appeared within the first couple days following vaccine administration and resolved within 2 days. No cases of inflammation of the heart muscle or its lining were reported among participants.

Uptake of COVID vaccines for young children has been lower than other age groups in the United States. The Centers for Disease Control and Prevention says 10% of children younger than 5 have received at least one dose of a COVID-19 vaccine, and 5% have completed a primary vaccine series.

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

Children born to mothers who had urinary or genital tract infections during pregnancy appear to have an increased risk for childhood leukemia, said researchers reporting a Danish registry analysis that may point to preventive strategies for the disease.

The research was published online in JAMA Network Open.

The team studied more than 2.2 million children born in Denmark over more than 3 decades, linking their records across multiple national registries to examine both later cancer risk and maternal infection rates.

They found that, overall, at least one maternal infection during pregnancy was associated with a 35% increased risk for leukemia in the children, rising to 65% for urinary tract infections, and 142% for genital infections.

“The findings of this large population-based cohort study suggest that maternal urinary and genital tract infections during pregnancy are associated with a higher risk of childhood leukemia in offspring,” said lead author Jian-Rong He, DPhil, division of birth cohort study, Guangzhou (China) Women and Children’s Medical Center.

However, he added, “the associated absolute risk remained small given the rarity” of the disease. In absolute terms, the risk difference between exposed and unexposed children was 1.8 cases per 100,000 person-years for any infection, 3.4 cases per 100,000 person-years for urinary traction infection, and 7.1 cases per 100,000 person-years for genital tract infection.

Maternal infections during pregnancy may be associated with chromosomal and immunologic alterations in the fetus, the authors speculated.

“Given that little is known about the etiology of childhood leukemia,” these results “suggest an important direction for research on the etiology of childhood leukemia as well as development of potential preventive measures,” they wrote.

In many countries, pregnant women are tested for urinary tract infection and bacterial vaginosis, and treated with antibiotics in antenatal care, as these infections are linked to adverse perinatal outcomes, they pointed out.
 

Study details

The team conducted a large population-based study that included all live births in Denmark between 1978 and 2015.

After exclusions, they gathered information on 2,222,797 children, linking data from several national registries, including the Danish Medical Birth Register, the Danish National Patient Registry, and the Danish National Cancer Registry, to identify cases of childhood cancers and maternal infection during pregnancy.

The results were then validated by comparing them with those in 2.6 million live births in Sweden between 1988 and 2014, for whom similar data were available through linkage with several Swedish registries.

The Danish cohort was followed up for a mean of 12 years per person, yielding a total of 27 million person-years. Just over half (51.3%) were boys.

Cancer was diagnosed in 4,362 children before 15 years of age, of whom 1,307 had leukemia (1,050 had acute lymphocytic leukemia), 1,267 had a brain tumor, 224 had lymphoma, and 1,564 had other cancers.

At least one infection during pregnancy was diagnosed in 81,717 mothers (3.7%). Urinary tract infections were the most common (in 1.7% of women), followed by genital tract infection (in 0.7%), digestive system infection (in 0.5%), and respiratory tract infection (in 0.3%).

Women with any infection during pregnancy were more likely to be younger and primiparous than were women who did not have infections, and they were also more likely to have fewer years of education, higher prepregnancy BMI, diabetes, and to smoke during early pregnancy.

Preterm delivery and low-birth-weight infants were also more common in women with infections during pregnancy.

Cox proportional hazards regression models revealed that, after adjustment for confounders, any maternal infection was associated with a hazard ratio of childhood leukemia of 1.35.

Further analysis revealed that the association was driven by genital tract infection, at a hazard ratio for childhood leukemia of 2.42, and urinary tract infection, at a hazard ratio 1.65.

Moreover, children born to women who had a sexually transmitted infection during pregnancy had a hazard ratio for developing leukemia of 3.13 compared with unexposed children.

There were no associations between other maternal infections and childhood leukemia.

The patterns of association between maternal infections and childhood leukemia were similar when looking at disease subtypes, as well as in the Swedish validation cohort, they added.

When interpreting the results, the researchers caution that, as data on maternal infection were drawn from hospital data, “milder infections and those not diagnosed or treated in specialized health care facilities were not captured.”

“Also, some infections could be captured because the mother sought care for other, more serious conditions, which might bias the association of maternal infections and childhood leukemia.”

The study was supported by grants from the China Scholarship Council–University of Oxford; National Natural Science Foundation of China; Danish Council for Independent Research; Nordic Cancer Union; Novo Nordisk Fonden; and the Swedish Council for Working Life and Social Research. Dr He reported receiving a PhD scholarship from the China Scholarship Council during the conduct of the study. Several other coauthors have disclosures; the full list can be found with the original article.

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

Children born to mothers who had urinary or genital tract infections during pregnancy appear to have an increased risk for childhood leukemia, said researchers reporting a Danish registry analysis that may point to preventive strategies for the disease.

The research was published online in JAMA Network Open.

The team studied more than 2.2 million children born in Denmark over more than 3 decades, linking their records across multiple national registries to examine both later cancer risk and maternal infection rates.

They found that, overall, at least one maternal infection during pregnancy was associated with a 35% increased risk for leukemia in the children, rising to 65% for urinary tract infections, and 142% for genital infections.

“The findings of this large population-based cohort study suggest that maternal urinary and genital tract infections during pregnancy are associated with a higher risk of childhood leukemia in offspring,” said lead author Jian-Rong He, DPhil, division of birth cohort study, Guangzhou (China) Women and Children’s Medical Center.

However, he added, “the associated absolute risk remained small given the rarity” of the disease. In absolute terms, the risk difference between exposed and unexposed children was 1.8 cases per 100,000 person-years for any infection, 3.4 cases per 100,000 person-years for urinary traction infection, and 7.1 cases per 100,000 person-years for genital tract infection.

Maternal infections during pregnancy may be associated with chromosomal and immunologic alterations in the fetus, the authors speculated.

“Given that little is known about the etiology of childhood leukemia,” these results “suggest an important direction for research on the etiology of childhood leukemia as well as development of potential preventive measures,” they wrote.

In many countries, pregnant women are tested for urinary tract infection and bacterial vaginosis, and treated with antibiotics in antenatal care, as these infections are linked to adverse perinatal outcomes, they pointed out.
 

Study details

The team conducted a large population-based study that included all live births in Denmark between 1978 and 2015.

After exclusions, they gathered information on 2,222,797 children, linking data from several national registries, including the Danish Medical Birth Register, the Danish National Patient Registry, and the Danish National Cancer Registry, to identify cases of childhood cancers and maternal infection during pregnancy.

The results were then validated by comparing them with those in 2.6 million live births in Sweden between 1988 and 2014, for whom similar data were available through linkage with several Swedish registries.

The Danish cohort was followed up for a mean of 12 years per person, yielding a total of 27 million person-years. Just over half (51.3%) were boys.

Cancer was diagnosed in 4,362 children before 15 years of age, of whom 1,307 had leukemia (1,050 had acute lymphocytic leukemia), 1,267 had a brain tumor, 224 had lymphoma, and 1,564 had other cancers.

At least one infection during pregnancy was diagnosed in 81,717 mothers (3.7%). Urinary tract infections were the most common (in 1.7% of women), followed by genital tract infection (in 0.7%), digestive system infection (in 0.5%), and respiratory tract infection (in 0.3%).

Women with any infection during pregnancy were more likely to be younger and primiparous than were women who did not have infections, and they were also more likely to have fewer years of education, higher prepregnancy BMI, diabetes, and to smoke during early pregnancy.

Preterm delivery and low-birth-weight infants were also more common in women with infections during pregnancy.

Cox proportional hazards regression models revealed that, after adjustment for confounders, any maternal infection was associated with a hazard ratio of childhood leukemia of 1.35.

Further analysis revealed that the association was driven by genital tract infection, at a hazard ratio for childhood leukemia of 2.42, and urinary tract infection, at a hazard ratio 1.65.

Moreover, children born to women who had a sexually transmitted infection during pregnancy had a hazard ratio for developing leukemia of 3.13 compared with unexposed children.

There were no associations between other maternal infections and childhood leukemia.

The patterns of association between maternal infections and childhood leukemia were similar when looking at disease subtypes, as well as in the Swedish validation cohort, they added.

When interpreting the results, the researchers caution that, as data on maternal infection were drawn from hospital data, “milder infections and those not diagnosed or treated in specialized health care facilities were not captured.”

“Also, some infections could be captured because the mother sought care for other, more serious conditions, which might bias the association of maternal infections and childhood leukemia.”

The study was supported by grants from the China Scholarship Council–University of Oxford; National Natural Science Foundation of China; Danish Council for Independent Research; Nordic Cancer Union; Novo Nordisk Fonden; and the Swedish Council for Working Life and Social Research. Dr He reported receiving a PhD scholarship from the China Scholarship Council during the conduct of the study. Several other coauthors have disclosures; the full list can be found with the original article.

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

Children born to mothers who had urinary or genital tract infections during pregnancy appear to have an increased risk for childhood leukemia, said researchers reporting a Danish registry analysis that may point to preventive strategies for the disease.

The research was published online in JAMA Network Open.

The team studied more than 2.2 million children born in Denmark over more than 3 decades, linking their records across multiple national registries to examine both later cancer risk and maternal infection rates.

They found that, overall, at least one maternal infection during pregnancy was associated with a 35% increased risk for leukemia in the children, rising to 65% for urinary tract infections, and 142% for genital infections.

“The findings of this large population-based cohort study suggest that maternal urinary and genital tract infections during pregnancy are associated with a higher risk of childhood leukemia in offspring,” said lead author Jian-Rong He, DPhil, division of birth cohort study, Guangzhou (China) Women and Children’s Medical Center.

However, he added, “the associated absolute risk remained small given the rarity” of the disease. In absolute terms, the risk difference between exposed and unexposed children was 1.8 cases per 100,000 person-years for any infection, 3.4 cases per 100,000 person-years for urinary traction infection, and 7.1 cases per 100,000 person-years for genital tract infection.

Maternal infections during pregnancy may be associated with chromosomal and immunologic alterations in the fetus, the authors speculated.

“Given that little is known about the etiology of childhood leukemia,” these results “suggest an important direction for research on the etiology of childhood leukemia as well as development of potential preventive measures,” they wrote.

In many countries, pregnant women are tested for urinary tract infection and bacterial vaginosis, and treated with antibiotics in antenatal care, as these infections are linked to adverse perinatal outcomes, they pointed out.
 

Study details

The team conducted a large population-based study that included all live births in Denmark between 1978 and 2015.

After exclusions, they gathered information on 2,222,797 children, linking data from several national registries, including the Danish Medical Birth Register, the Danish National Patient Registry, and the Danish National Cancer Registry, to identify cases of childhood cancers and maternal infection during pregnancy.

The results were then validated by comparing them with those in 2.6 million live births in Sweden between 1988 and 2014, for whom similar data were available through linkage with several Swedish registries.

The Danish cohort was followed up for a mean of 12 years per person, yielding a total of 27 million person-years. Just over half (51.3%) were boys.

Cancer was diagnosed in 4,362 children before 15 years of age, of whom 1,307 had leukemia (1,050 had acute lymphocytic leukemia), 1,267 had a brain tumor, 224 had lymphoma, and 1,564 had other cancers.

At least one infection during pregnancy was diagnosed in 81,717 mothers (3.7%). Urinary tract infections were the most common (in 1.7% of women), followed by genital tract infection (in 0.7%), digestive system infection (in 0.5%), and respiratory tract infection (in 0.3%).

Women with any infection during pregnancy were more likely to be younger and primiparous than were women who did not have infections, and they were also more likely to have fewer years of education, higher prepregnancy BMI, diabetes, and to smoke during early pregnancy.

Preterm delivery and low-birth-weight infants were also more common in women with infections during pregnancy.

Cox proportional hazards regression models revealed that, after adjustment for confounders, any maternal infection was associated with a hazard ratio of childhood leukemia of 1.35.

Further analysis revealed that the association was driven by genital tract infection, at a hazard ratio for childhood leukemia of 2.42, and urinary tract infection, at a hazard ratio 1.65.

Moreover, children born to women who had a sexually transmitted infection during pregnancy had a hazard ratio for developing leukemia of 3.13 compared with unexposed children.

There were no associations between other maternal infections and childhood leukemia.

The patterns of association between maternal infections and childhood leukemia were similar when looking at disease subtypes, as well as in the Swedish validation cohort, they added.

When interpreting the results, the researchers caution that, as data on maternal infection were drawn from hospital data, “milder infections and those not diagnosed or treated in specialized health care facilities were not captured.”

“Also, some infections could be captured because the mother sought care for other, more serious conditions, which might bias the association of maternal infections and childhood leukemia.”

The study was supported by grants from the China Scholarship Council–University of Oxford; National Natural Science Foundation of China; Danish Council for Independent Research; Nordic Cancer Union; Novo Nordisk Fonden; and the Swedish Council for Working Life and Social Research. Dr He reported receiving a PhD scholarship from the China Scholarship Council during the conduct of the study. Several other coauthors have disclosures; the full list can be found with the original article.

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

A strategy for the treatment of tuberculosis involving just an 8-week treatment regimen – along with close posttreatment monitoring and treatment extension if needed – shows potential as an effective alternative to the standard 24-week regimen.

“We found that if we use the strategy of a bedaquiline-linezolid five-drug regimen for 8 weeks and then followed patients for 96 weeks, [the regimen] was noninferior, clinically, to the standard regimen in terms of the number of people alive, free of TB disease, and not on treatment,” said lead author Nicholas Paton, MD, of the National University of Singapore, in a press conference held during the Conference on Retroviruses & Opportunistic Infections.

“The total time on treatment was reduced by half – instead of 160 days, it was 85 days for the total duration.”

Commenting on the study, which was published concurrently in the New England Journal of Medicine, Richard E. Chaisson, MD, noted that, although more needs to be understood, the high number of responses is nevertheless encouraging.

“Clinicians will not feel comfortable with the short regimens at this point, but it is remarkable that so many patients did well with shorter treatments,” Dr. Chaisson, who is a professor of medicine, epidemiology, and international health and director of the Johns Hopkins University Center for Tuberculosis Research, Baltimore, said in an interview.

Importantly, the study should help push forward “future studies [that] will stratify patients according to their likelihood of responding to shorter treatments,” he said.

The current global standard for TB treatment, practiced for 4 decades, has been a 6-month rifampin-based regimen. Although the regimen performs well, curing more than 95% of cases in clinical trials, in real-world practice, the prolonged duration can be problematic, with issues of nonadherence and loss of patients to follow-up.

Previous research has shown that shorter regimens have potential, with some studies showing as many as 85% of patients cured with 3- and 4-month regimens, and some promising 2-month regimens showing efficacy specifically for those with smear-negative TB.

These efforts suggest that “the current 6-month regimen may lead to overtreatment in the majority of persons in order to prevent relapse in a minority of persons,” the authors asserted.
 

TRUNCATE-TB

To investigate a suitable shorter-term alternative, the authors conducted the phase 2-3, prospective, open-label TRUNCATE-TB trial, in which 674 patients with rifampin-susceptible pulmonary TB were enrolled at 18 sites in Asia and Africa.

The patients were randomly assigned to receive either the standard treatment regimen (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks; n = 181), or one of four novel five-drug regimens to be administered over 8 weeks, along with extended treatment for persistent clinical disease of up to 12 weeks, if needed, and a plan for retreatment in the case of relapse (n = 493).

Two of the regimens were dropped because of logistic criteria; the two remaining shorter-course groups included in the study involved either high-dose rifampin plus linezolid or bedaquiline plus linezolid, each combined with isoniazid, pyrazinamide, and ethambutol.

Of the patients, 62% were male, and four withdrew or were lost to follow-up by the end of the study at a final follow-up at week 96.

Among patients assigned to the 8-week regimens, 80% stopped at exactly 8 weeks, while 9% wound up having extended treatment to 10 weeks and 3% were extended to 12 weeks.

For the primary endpoint, a composite of death, ongoing treatment, or active disease at week 96, the rate was lowest in the standard 24-week therapy group, occurring in 7 of 181 patients (3.9%), compared with 21 of 184 patients (11.4%) in the rifampin plus linezolid group (adjusted difference, 7.4 percentage points, which did not meet noninferiority criterion), and 11 of 189 (5.8%) in the group in the bedaquiline plus linezolid group (adjusted difference, 0.8 percentage points, meeting noninferiority criterion).

The mean total duration of treatment through week 96 in the standard treatment group was 180 days versus 106 days in the rifampin–linezolid group, and 85 days in the bedaquiline-linezolid group.

The results were consistent across multiple subgroups defined according to baseline characteristics, including some that could be linked to severe disease and a high risk for relapse.

In terms of safety, there were no significant differences between the groups in terms of grade 3 or 4 adverse events.

Of note, only two patients (1.1%) in the bedaquiline plus linezolid group acquired a resistance, which Dr. Paton said was “encouraging,” because of concerns about resistance to that drug.
 

‘Unfavorable’ composite also evaluated

In an updated analysis of the study that Dr. Paton presented at the meeting, the authors looked at a revised “unfavorable” primary outcome – a composite including treatment failure, relapse, death, or nonattendance at week 96 without evidence of prior disease clearance.

The rate remained lowest in the standard 24-week therapy group (3.9%) versus 25% in the rifampin plus linezolid group, and 13.8% in the bedaquiline plus linezolid group.

Though the lower rate with the standard treatment was expected, Dr. Paton said the results nevertheless hold promise, at least for some patients, for successful treatment with the 8-week bedaquiline plus linezolid strategy.

“What the trial has told us is that even with that 13.8% relapse rate, we can manage patients within this strategy and people can do fine at the end, because with some simple clinical biomarkers, we can pick the people who may have a high chance of achieving a cure.”

Dr. Chaisson expressed concern over the higher unfavorable rates, but said the results help pave the way for refining a workable-shorter term strategy.

“TRUNCATE-TB did find that most patients could be successfully treated in 2 months with the novel regimen of bedaquiline plus linezolid, but the failure rate was still unacceptably high,” he said. 

“This regimen will not be widely adapted at this point, but additional analyses may identify subsets of patients who will do well with shorter regimens, and future studies will stratify patients according to their likelihood of responding to shorter treatments.”

The authors of an accompanying editorial further commented that the benefits of a shorter treatment strategy could very well outweigh possible shortcomings.

“Treatment algorithms such as that used in the TRUNCATE-TB trial are fundamental to tuberculosis control,” wrote Véronique Dartois, PhD, Center for Discovery and Innovation, Nutley, N.J., and Eric J. Rubin, MD, PhD, the editor-in-chief of NEJM. “Although implementing them could be a challenge, any added burden might be offset by reduced costs, better adherence, and increased patient satisfaction. Thus, for tuberculosis, a strategy might be more than just a regimen.”

The good news, as summed up by CROI vice-chair Landon Myer, MD, PhD, in the press conference, is that “we’re moving closer and closer to the holy grail of a short, efficacious regimen for TB treatment. We’re getting there slowly, but we’re getting there.”

The study received grant funding from the Singapore National Medical Research Council; a grant from the Department of Health and Social Care; the Foreign, Commonwealth, and Development Office; the Medical Research Council; and Wellcome Trust; as well as a grant from the UK Research and Innovation Medical Research Council. Dr. Dartois reported no relevant financial relationships. Dr. Chaisson had no disclosures to report.

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

A strategy for the treatment of tuberculosis involving just an 8-week treatment regimen – along with close posttreatment monitoring and treatment extension if needed – shows potential as an effective alternative to the standard 24-week regimen.

“We found that if we use the strategy of a bedaquiline-linezolid five-drug regimen for 8 weeks and then followed patients for 96 weeks, [the regimen] was noninferior, clinically, to the standard regimen in terms of the number of people alive, free of TB disease, and not on treatment,” said lead author Nicholas Paton, MD, of the National University of Singapore, in a press conference held during the Conference on Retroviruses & Opportunistic Infections.

“The total time on treatment was reduced by half – instead of 160 days, it was 85 days for the total duration.”

Commenting on the study, which was published concurrently in the New England Journal of Medicine, Richard E. Chaisson, MD, noted that, although more needs to be understood, the high number of responses is nevertheless encouraging.

“Clinicians will not feel comfortable with the short regimens at this point, but it is remarkable that so many patients did well with shorter treatments,” Dr. Chaisson, who is a professor of medicine, epidemiology, and international health and director of the Johns Hopkins University Center for Tuberculosis Research, Baltimore, said in an interview.

Importantly, the study should help push forward “future studies [that] will stratify patients according to their likelihood of responding to shorter treatments,” he said.

The current global standard for TB treatment, practiced for 4 decades, has been a 6-month rifampin-based regimen. Although the regimen performs well, curing more than 95% of cases in clinical trials, in real-world practice, the prolonged duration can be problematic, with issues of nonadherence and loss of patients to follow-up.

Previous research has shown that shorter regimens have potential, with some studies showing as many as 85% of patients cured with 3- and 4-month regimens, and some promising 2-month regimens showing efficacy specifically for those with smear-negative TB.

These efforts suggest that “the current 6-month regimen may lead to overtreatment in the majority of persons in order to prevent relapse in a minority of persons,” the authors asserted.
 

TRUNCATE-TB

To investigate a suitable shorter-term alternative, the authors conducted the phase 2-3, prospective, open-label TRUNCATE-TB trial, in which 674 patients with rifampin-susceptible pulmonary TB were enrolled at 18 sites in Asia and Africa.

The patients were randomly assigned to receive either the standard treatment regimen (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks; n = 181), or one of four novel five-drug regimens to be administered over 8 weeks, along with extended treatment for persistent clinical disease of up to 12 weeks, if needed, and a plan for retreatment in the case of relapse (n = 493).

Two of the regimens were dropped because of logistic criteria; the two remaining shorter-course groups included in the study involved either high-dose rifampin plus linezolid or bedaquiline plus linezolid, each combined with isoniazid, pyrazinamide, and ethambutol.

Of the patients, 62% were male, and four withdrew or were lost to follow-up by the end of the study at a final follow-up at week 96.

Among patients assigned to the 8-week regimens, 80% stopped at exactly 8 weeks, while 9% wound up having extended treatment to 10 weeks and 3% were extended to 12 weeks.

For the primary endpoint, a composite of death, ongoing treatment, or active disease at week 96, the rate was lowest in the standard 24-week therapy group, occurring in 7 of 181 patients (3.9%), compared with 21 of 184 patients (11.4%) in the rifampin plus linezolid group (adjusted difference, 7.4 percentage points, which did not meet noninferiority criterion), and 11 of 189 (5.8%) in the group in the bedaquiline plus linezolid group (adjusted difference, 0.8 percentage points, meeting noninferiority criterion).

The mean total duration of treatment through week 96 in the standard treatment group was 180 days versus 106 days in the rifampin–linezolid group, and 85 days in the bedaquiline-linezolid group.

The results were consistent across multiple subgroups defined according to baseline characteristics, including some that could be linked to severe disease and a high risk for relapse.

In terms of safety, there were no significant differences between the groups in terms of grade 3 or 4 adverse events.

Of note, only two patients (1.1%) in the bedaquiline plus linezolid group acquired a resistance, which Dr. Paton said was “encouraging,” because of concerns about resistance to that drug.
 

‘Unfavorable’ composite also evaluated

In an updated analysis of the study that Dr. Paton presented at the meeting, the authors looked at a revised “unfavorable” primary outcome – a composite including treatment failure, relapse, death, or nonattendance at week 96 without evidence of prior disease clearance.

The rate remained lowest in the standard 24-week therapy group (3.9%) versus 25% in the rifampin plus linezolid group, and 13.8% in the bedaquiline plus linezolid group.

Though the lower rate with the standard treatment was expected, Dr. Paton said the results nevertheless hold promise, at least for some patients, for successful treatment with the 8-week bedaquiline plus linezolid strategy.

“What the trial has told us is that even with that 13.8% relapse rate, we can manage patients within this strategy and people can do fine at the end, because with some simple clinical biomarkers, we can pick the people who may have a high chance of achieving a cure.”

Dr. Chaisson expressed concern over the higher unfavorable rates, but said the results help pave the way for refining a workable-shorter term strategy.

“TRUNCATE-TB did find that most patients could be successfully treated in 2 months with the novel regimen of bedaquiline plus linezolid, but the failure rate was still unacceptably high,” he said. 

“This regimen will not be widely adapted at this point, but additional analyses may identify subsets of patients who will do well with shorter regimens, and future studies will stratify patients according to their likelihood of responding to shorter treatments.”

The authors of an accompanying editorial further commented that the benefits of a shorter treatment strategy could very well outweigh possible shortcomings.

“Treatment algorithms such as that used in the TRUNCATE-TB trial are fundamental to tuberculosis control,” wrote Véronique Dartois, PhD, Center for Discovery and Innovation, Nutley, N.J., and Eric J. Rubin, MD, PhD, the editor-in-chief of NEJM. “Although implementing them could be a challenge, any added burden might be offset by reduced costs, better adherence, and increased patient satisfaction. Thus, for tuberculosis, a strategy might be more than just a regimen.”

The good news, as summed up by CROI vice-chair Landon Myer, MD, PhD, in the press conference, is that “we’re moving closer and closer to the holy grail of a short, efficacious regimen for TB treatment. We’re getting there slowly, but we’re getting there.”

The study received grant funding from the Singapore National Medical Research Council; a grant from the Department of Health and Social Care; the Foreign, Commonwealth, and Development Office; the Medical Research Council; and Wellcome Trust; as well as a grant from the UK Research and Innovation Medical Research Council. Dr. Dartois reported no relevant financial relationships. Dr. Chaisson had no disclosures to report.

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

A strategy for the treatment of tuberculosis involving just an 8-week treatment regimen – along with close posttreatment monitoring and treatment extension if needed – shows potential as an effective alternative to the standard 24-week regimen.

“We found that if we use the strategy of a bedaquiline-linezolid five-drug regimen for 8 weeks and then followed patients for 96 weeks, [the regimen] was noninferior, clinically, to the standard regimen in terms of the number of people alive, free of TB disease, and not on treatment,” said lead author Nicholas Paton, MD, of the National University of Singapore, in a press conference held during the Conference on Retroviruses & Opportunistic Infections.

“The total time on treatment was reduced by half – instead of 160 days, it was 85 days for the total duration.”

Commenting on the study, which was published concurrently in the New England Journal of Medicine, Richard E. Chaisson, MD, noted that, although more needs to be understood, the high number of responses is nevertheless encouraging.

“Clinicians will not feel comfortable with the short regimens at this point, but it is remarkable that so many patients did well with shorter treatments,” Dr. Chaisson, who is a professor of medicine, epidemiology, and international health and director of the Johns Hopkins University Center for Tuberculosis Research, Baltimore, said in an interview.

Importantly, the study should help push forward “future studies [that] will stratify patients according to their likelihood of responding to shorter treatments,” he said.

The current global standard for TB treatment, practiced for 4 decades, has been a 6-month rifampin-based regimen. Although the regimen performs well, curing more than 95% of cases in clinical trials, in real-world practice, the prolonged duration can be problematic, with issues of nonadherence and loss of patients to follow-up.

Previous research has shown that shorter regimens have potential, with some studies showing as many as 85% of patients cured with 3- and 4-month regimens, and some promising 2-month regimens showing efficacy specifically for those with smear-negative TB.

These efforts suggest that “the current 6-month regimen may lead to overtreatment in the majority of persons in order to prevent relapse in a minority of persons,” the authors asserted.
 

TRUNCATE-TB

To investigate a suitable shorter-term alternative, the authors conducted the phase 2-3, prospective, open-label TRUNCATE-TB trial, in which 674 patients with rifampin-susceptible pulmonary TB were enrolled at 18 sites in Asia and Africa.

The patients were randomly assigned to receive either the standard treatment regimen (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks; n = 181), or one of four novel five-drug regimens to be administered over 8 weeks, along with extended treatment for persistent clinical disease of up to 12 weeks, if needed, and a plan for retreatment in the case of relapse (n = 493).

Two of the regimens were dropped because of logistic criteria; the two remaining shorter-course groups included in the study involved either high-dose rifampin plus linezolid or bedaquiline plus linezolid, each combined with isoniazid, pyrazinamide, and ethambutol.

Of the patients, 62% were male, and four withdrew or were lost to follow-up by the end of the study at a final follow-up at week 96.

Among patients assigned to the 8-week regimens, 80% stopped at exactly 8 weeks, while 9% wound up having extended treatment to 10 weeks and 3% were extended to 12 weeks.

For the primary endpoint, a composite of death, ongoing treatment, or active disease at week 96, the rate was lowest in the standard 24-week therapy group, occurring in 7 of 181 patients (3.9%), compared with 21 of 184 patients (11.4%) in the rifampin plus linezolid group (adjusted difference, 7.4 percentage points, which did not meet noninferiority criterion), and 11 of 189 (5.8%) in the group in the bedaquiline plus linezolid group (adjusted difference, 0.8 percentage points, meeting noninferiority criterion).

The mean total duration of treatment through week 96 in the standard treatment group was 180 days versus 106 days in the rifampin–linezolid group, and 85 days in the bedaquiline-linezolid group.

The results were consistent across multiple subgroups defined according to baseline characteristics, including some that could be linked to severe disease and a high risk for relapse.

In terms of safety, there were no significant differences between the groups in terms of grade 3 or 4 adverse events.

Of note, only two patients (1.1%) in the bedaquiline plus linezolid group acquired a resistance, which Dr. Paton said was “encouraging,” because of concerns about resistance to that drug.
 

‘Unfavorable’ composite also evaluated

In an updated analysis of the study that Dr. Paton presented at the meeting, the authors looked at a revised “unfavorable” primary outcome – a composite including treatment failure, relapse, death, or nonattendance at week 96 without evidence of prior disease clearance.

The rate remained lowest in the standard 24-week therapy group (3.9%) versus 25% in the rifampin plus linezolid group, and 13.8% in the bedaquiline plus linezolid group.

Though the lower rate with the standard treatment was expected, Dr. Paton said the results nevertheless hold promise, at least for some patients, for successful treatment with the 8-week bedaquiline plus linezolid strategy.

“What the trial has told us is that even with that 13.8% relapse rate, we can manage patients within this strategy and people can do fine at the end, because with some simple clinical biomarkers, we can pick the people who may have a high chance of achieving a cure.”

Dr. Chaisson expressed concern over the higher unfavorable rates, but said the results help pave the way for refining a workable-shorter term strategy.

“TRUNCATE-TB did find that most patients could be successfully treated in 2 months with the novel regimen of bedaquiline plus linezolid, but the failure rate was still unacceptably high,” he said. 

“This regimen will not be widely adapted at this point, but additional analyses may identify subsets of patients who will do well with shorter regimens, and future studies will stratify patients according to their likelihood of responding to shorter treatments.”

The authors of an accompanying editorial further commented that the benefits of a shorter treatment strategy could very well outweigh possible shortcomings.

“Treatment algorithms such as that used in the TRUNCATE-TB trial are fundamental to tuberculosis control,” wrote Véronique Dartois, PhD, Center for Discovery and Innovation, Nutley, N.J., and Eric J. Rubin, MD, PhD, the editor-in-chief of NEJM. “Although implementing them could be a challenge, any added burden might be offset by reduced costs, better adherence, and increased patient satisfaction. Thus, for tuberculosis, a strategy might be more than just a regimen.”

The good news, as summed up by CROI vice-chair Landon Myer, MD, PhD, in the press conference, is that “we’re moving closer and closer to the holy grail of a short, efficacious regimen for TB treatment. We’re getting there slowly, but we’re getting there.”

The study received grant funding from the Singapore National Medical Research Council; a grant from the Department of Health and Social Care; the Foreign, Commonwealth, and Development Office; the Medical Research Council; and Wellcome Trust; as well as a grant from the UK Research and Innovation Medical Research Council. Dr. Dartois reported no relevant financial relationships. Dr. Chaisson had no disclosures to report.

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

The natural immunity provided by a COVID infection protects a person against severe illness on a par with two doses of mRNA vaccine, a new study says. 

People who’ve been infected with COVID reduced their chances of hospitalization and death by 88% over 10 months compared to somebody who hasn’t been infected, according to the study, published in The Lancet. 

The natural immunity provided by infection was “at least as high, if not higher” than the immunity provided by two doses of Moderna or Pfizer mRNA vaccines against the ancestral, Alpha, Delta, and Omicron BA.1 variants, the researchers reported. 

But protection against the BA.1 subvariant of Omicron was not as high – 36% at 10 months after infection, wrote the research team from the Institute for Health Metrics and Evaluation at the University of Washington.

They examined 65 studies from 19 countries through Sept. 31, 2022. They did not study data about infection from Omicron XBB and its sub-lineages. People who had immunity from both infection and vaccination, known as hybrid immunity, were not studied. 

The findings don’t mean people should skip the vaccines and get COVID on purpose, one of the researchers told NBC News. 

“The problem of saying ‘I’m gonna get infected to get immunity’ is you might be one of those people that end up in the hospital or die,” said Christopher Murray, MD, DPhil, director of the IHME. “Why would you take the risk when you can get immunity through vaccination quite safely?”

The findings could help people figure out the most effective time to get vaccinated or boosted and guide officials in setting policies on workplace vaccine mandates and rules for high-occupancy indoor settings, the researchers concluded.

This was the largest meta-analysis of immunity following infection to date, NBC News reports.

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

The natural immunity provided by a COVID infection protects a person against severe illness on a par with two doses of mRNA vaccine, a new study says. 

People who’ve been infected with COVID reduced their chances of hospitalization and death by 88% over 10 months compared to somebody who hasn’t been infected, according to the study, published in The Lancet. 

The natural immunity provided by infection was “at least as high, if not higher” than the immunity provided by two doses of Moderna or Pfizer mRNA vaccines against the ancestral, Alpha, Delta, and Omicron BA.1 variants, the researchers reported. 

But protection against the BA.1 subvariant of Omicron was not as high – 36% at 10 months after infection, wrote the research team from the Institute for Health Metrics and Evaluation at the University of Washington.

They examined 65 studies from 19 countries through Sept. 31, 2022. They did not study data about infection from Omicron XBB and its sub-lineages. People who had immunity from both infection and vaccination, known as hybrid immunity, were not studied. 

The findings don’t mean people should skip the vaccines and get COVID on purpose, one of the researchers told NBC News. 

“The problem of saying ‘I’m gonna get infected to get immunity’ is you might be one of those people that end up in the hospital or die,” said Christopher Murray, MD, DPhil, director of the IHME. “Why would you take the risk when you can get immunity through vaccination quite safely?”

The findings could help people figure out the most effective time to get vaccinated or boosted and guide officials in setting policies on workplace vaccine mandates and rules for high-occupancy indoor settings, the researchers concluded.

This was the largest meta-analysis of immunity following infection to date, NBC News reports.

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

The natural immunity provided by a COVID infection protects a person against severe illness on a par with two doses of mRNA vaccine, a new study says. 

People who’ve been infected with COVID reduced their chances of hospitalization and death by 88% over 10 months compared to somebody who hasn’t been infected, according to the study, published in The Lancet. 

The natural immunity provided by infection was “at least as high, if not higher” than the immunity provided by two doses of Moderna or Pfizer mRNA vaccines against the ancestral, Alpha, Delta, and Omicron BA.1 variants, the researchers reported. 

But protection against the BA.1 subvariant of Omicron was not as high – 36% at 10 months after infection, wrote the research team from the Institute for Health Metrics and Evaluation at the University of Washington.

They examined 65 studies from 19 countries through Sept. 31, 2022. They did not study data about infection from Omicron XBB and its sub-lineages. People who had immunity from both infection and vaccination, known as hybrid immunity, were not studied. 

The findings don’t mean people should skip the vaccines and get COVID on purpose, one of the researchers told NBC News. 

“The problem of saying ‘I’m gonna get infected to get immunity’ is you might be one of those people that end up in the hospital or die,” said Christopher Murray, MD, DPhil, director of the IHME. “Why would you take the risk when you can get immunity through vaccination quite safely?”

The findings could help people figure out the most effective time to get vaccinated or boosted and guide officials in setting policies on workplace vaccine mandates and rules for high-occupancy indoor settings, the researchers concluded.

This was the largest meta-analysis of immunity following infection to date, NBC News reports.

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