CHEST Physician

The federal government’s efforts to thwart information blocking are underway. As such, physicians would do well to be standing at the ready when the information-blocking regulations, designed to ensure that patients can access their electronic health information (EHI), shift into full gear.

Recently, the Office of the National Coordinator revealed that the Department of Health & Humans Services has received 299 reports of information blocking since inviting anyone who suspected that health care providers, IT developers, or health information networks/exchanges might have interfered with access, exchange, or use of EHI through the Report Information Blocking Portal on April 5, 2021.

The vast majority of these claims – 211 – were filed against providers, while 46 alleged incidents of information blocking were by health IT developers, and two claims point to health information networks/ exchanges. The other 25 claims did not appear to present a claim of information blocking.

Of the 274 possible claims of information blocking recently released by ONC, 176 were made by patients.

The ONC has sent all possible claims to the HHS’s Office of the Inspector General. The claims have not yet been investigated and substantiated.
 

Do the stats tell the story?

The numbers in the recent ONC report do not shed much light on how much impact the regulations are having on information sharing. Health care providers, including physicians, might not yet be complying with the rules because monetary penalties are not in place.

Indeed, HHS has yet to spell out exactly what the disincentives on providers will be, though the 21st Century Cures Act stipulates that regulators could fine up to $1 million per information-blocking incident.

“Some providers might be saying, ‘I’m not going to be penalized at this point … so I can take a little bit longer to think about how I come into compliance.’ That could be just one factor of a host of many that are affecting compliance. We also are still in the middle of a public health emergency. So it’s hard to say at this point” exactly how the regulations will affect information blocking, Lauren Riplinger, vice president of policy and public affairs at the American Health Information Management Association, Chicago, said in an interview.
 

A long time coming

The government first zeroed in on ensuring that patients have access to their information in 2016 when President Obama signed the Cures Act into law. The legislation directed ONC to implement a standardized process for the public to report claims of possible information blocking.

The initiative appears to be picking up steam. The ONC is expected to release monthly reports on the cumulative number of information-blocking claims. The announcement of associated penalties is expected sometime in the future.

Industry leaders are advising health care providers to brush up on compliance. Physicians can look to professional groups such as the American Medical Association, the Medical Group Management Association, and other specialty associations for guidance. In addition, the ONC is educating providers on the rule.

“The ONC has provided a lot of great content for the past couple months, not only in terms of putting out FAQs to help clarify some of the gray areas in the rule, but they also have produced a series of provider-specific webinars where they walk through a potential scenario and address the extent to the rules apply,” Ms. Riplinger said.
 

With education, more is better

These efforts, however, could be expanded, according to MGMA.

“There is a general awareness of the rules, but we encourage ONC to continue educating the provider community: More FAQs and educational webinars would be helpful,” Claire Ernst, director of government affairs for MGMA, said in an interview. “A June 2021 MGMA poll found that 51% of medical groups said they needed more government guidance on complying with the new information-blocking rules.”

Although ONC already has provided some “scenario-based” education, more of this type of guidance could prove valuable.

“This rule is that it is very circumstance based. … and so it’s those more nuanced cases that I think are more challenging for providers to know whether or not they are engaging in information blocking,” Ms. Riplinger noted.

For example, a physician might choose to not upload lab test results to a patient portal and prefer to wait to discuss the results directly with the patient, which could potentially be construed as information blocking under the regulations.

The MGMA is requesting that ONC take a second look at these situations – and possibly adjust the regulations.

“MGMA has heard concerns about the impact of providing immediate results to patients before medical groups have the time to thoroughly review test results and discuss them compassionately with their patients,” Ms. Ernst said. “To address this, ONC could expand the current definition of harm to account for other unintended consequences, such as emotional distress, or provide more flexibility in terms of the time frame.”

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

The federal government’s efforts to thwart information blocking are underway. As such, physicians would do well to be standing at the ready when the information-blocking regulations, designed to ensure that patients can access their electronic health information (EHI), shift into full gear.

Recently, the Office of the National Coordinator revealed that the Department of Health & Humans Services has received 299 reports of information blocking since inviting anyone who suspected that health care providers, IT developers, or health information networks/exchanges might have interfered with access, exchange, or use of EHI through the Report Information Blocking Portal on April 5, 2021.

The vast majority of these claims – 211 – were filed against providers, while 46 alleged incidents of information blocking were by health IT developers, and two claims point to health information networks/ exchanges. The other 25 claims did not appear to present a claim of information blocking.

Of the 274 possible claims of information blocking recently released by ONC, 176 were made by patients.

The ONC has sent all possible claims to the HHS’s Office of the Inspector General. The claims have not yet been investigated and substantiated.
 

Do the stats tell the story?

The numbers in the recent ONC report do not shed much light on how much impact the regulations are having on information sharing. Health care providers, including physicians, might not yet be complying with the rules because monetary penalties are not in place.

Indeed, HHS has yet to spell out exactly what the disincentives on providers will be, though the 21st Century Cures Act stipulates that regulators could fine up to $1 million per information-blocking incident.

“Some providers might be saying, ‘I’m not going to be penalized at this point … so I can take a little bit longer to think about how I come into compliance.’ That could be just one factor of a host of many that are affecting compliance. We also are still in the middle of a public health emergency. So it’s hard to say at this point” exactly how the regulations will affect information blocking, Lauren Riplinger, vice president of policy and public affairs at the American Health Information Management Association, Chicago, said in an interview.
 

A long time coming

The government first zeroed in on ensuring that patients have access to their information in 2016 when President Obama signed the Cures Act into law. The legislation directed ONC to implement a standardized process for the public to report claims of possible information blocking.

The initiative appears to be picking up steam. The ONC is expected to release monthly reports on the cumulative number of information-blocking claims. The announcement of associated penalties is expected sometime in the future.

Industry leaders are advising health care providers to brush up on compliance. Physicians can look to professional groups such as the American Medical Association, the Medical Group Management Association, and other specialty associations for guidance. In addition, the ONC is educating providers on the rule.

“The ONC has provided a lot of great content for the past couple months, not only in terms of putting out FAQs to help clarify some of the gray areas in the rule, but they also have produced a series of provider-specific webinars where they walk through a potential scenario and address the extent to the rules apply,” Ms. Riplinger said.
 

With education, more is better

These efforts, however, could be expanded, according to MGMA.

“There is a general awareness of the rules, but we encourage ONC to continue educating the provider community: More FAQs and educational webinars would be helpful,” Claire Ernst, director of government affairs for MGMA, said in an interview. “A June 2021 MGMA poll found that 51% of medical groups said they needed more government guidance on complying with the new information-blocking rules.”

Although ONC already has provided some “scenario-based” education, more of this type of guidance could prove valuable.

“This rule is that it is very circumstance based. … and so it’s those more nuanced cases that I think are more challenging for providers to know whether or not they are engaging in information blocking,” Ms. Riplinger noted.

For example, a physician might choose to not upload lab test results to a patient portal and prefer to wait to discuss the results directly with the patient, which could potentially be construed as information blocking under the regulations.

The MGMA is requesting that ONC take a second look at these situations – and possibly adjust the regulations.

“MGMA has heard concerns about the impact of providing immediate results to patients before medical groups have the time to thoroughly review test results and discuss them compassionately with their patients,” Ms. Ernst said. “To address this, ONC could expand the current definition of harm to account for other unintended consequences, such as emotional distress, or provide more flexibility in terms of the time frame.”

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

The federal government’s efforts to thwart information blocking are underway. As such, physicians would do well to be standing at the ready when the information-blocking regulations, designed to ensure that patients can access their electronic health information (EHI), shift into full gear.

Recently, the Office of the National Coordinator revealed that the Department of Health & Humans Services has received 299 reports of information blocking since inviting anyone who suspected that health care providers, IT developers, or health information networks/exchanges might have interfered with access, exchange, or use of EHI through the Report Information Blocking Portal on April 5, 2021.

The vast majority of these claims – 211 – were filed against providers, while 46 alleged incidents of information blocking were by health IT developers, and two claims point to health information networks/ exchanges. The other 25 claims did not appear to present a claim of information blocking.

Of the 274 possible claims of information blocking recently released by ONC, 176 were made by patients.

The ONC has sent all possible claims to the HHS’s Office of the Inspector General. The claims have not yet been investigated and substantiated.
 

Do the stats tell the story?

The numbers in the recent ONC report do not shed much light on how much impact the regulations are having on information sharing. Health care providers, including physicians, might not yet be complying with the rules because monetary penalties are not in place.

Indeed, HHS has yet to spell out exactly what the disincentives on providers will be, though the 21st Century Cures Act stipulates that regulators could fine up to $1 million per information-blocking incident.

“Some providers might be saying, ‘I’m not going to be penalized at this point … so I can take a little bit longer to think about how I come into compliance.’ That could be just one factor of a host of many that are affecting compliance. We also are still in the middle of a public health emergency. So it’s hard to say at this point” exactly how the regulations will affect information blocking, Lauren Riplinger, vice president of policy and public affairs at the American Health Information Management Association, Chicago, said in an interview.
 

A long time coming

The government first zeroed in on ensuring that patients have access to their information in 2016 when President Obama signed the Cures Act into law. The legislation directed ONC to implement a standardized process for the public to report claims of possible information blocking.

The initiative appears to be picking up steam. The ONC is expected to release monthly reports on the cumulative number of information-blocking claims. The announcement of associated penalties is expected sometime in the future.

Industry leaders are advising health care providers to brush up on compliance. Physicians can look to professional groups such as the American Medical Association, the Medical Group Management Association, and other specialty associations for guidance. In addition, the ONC is educating providers on the rule.

“The ONC has provided a lot of great content for the past couple months, not only in terms of putting out FAQs to help clarify some of the gray areas in the rule, but they also have produced a series of provider-specific webinars where they walk through a potential scenario and address the extent to the rules apply,” Ms. Riplinger said.
 

With education, more is better

These efforts, however, could be expanded, according to MGMA.

“There is a general awareness of the rules, but we encourage ONC to continue educating the provider community: More FAQs and educational webinars would be helpful,” Claire Ernst, director of government affairs for MGMA, said in an interview. “A June 2021 MGMA poll found that 51% of medical groups said they needed more government guidance on complying with the new information-blocking rules.”

Although ONC already has provided some “scenario-based” education, more of this type of guidance could prove valuable.

“This rule is that it is very circumstance based. … and so it’s those more nuanced cases that I think are more challenging for providers to know whether or not they are engaging in information blocking,” Ms. Riplinger noted.

For example, a physician might choose to not upload lab test results to a patient portal and prefer to wait to discuss the results directly with the patient, which could potentially be construed as information blocking under the regulations.

The MGMA is requesting that ONC take a second look at these situations – and possibly adjust the regulations.

“MGMA has heard concerns about the impact of providing immediate results to patients before medical groups have the time to thoroughly review test results and discuss them compassionately with their patients,” Ms. Ernst said. “To address this, ONC could expand the current definition of harm to account for other unintended consequences, such as emotional distress, or provide more flexibility in terms of the time frame.”

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

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee has chosen the influenza vaccine strains for the 2022-2023 season in the northern hemisphere, which begins in the fall of 2022.

On March 3, the committee unanimously voted to endorse the World Health Organization’s recommendations as to which influenza strains to include for coverage by vaccines for the upcoming flu season. Two of the four recommended strains are different from last season.

The committee also heard updates on flu activity this season. So far, data from the U.S. Flu Vaccine Effectiveness (VE) network, which consists of seven study sites, have not shown that the vaccine is protective against influenza A. “We can say that it is not highly effective,” Brendan Flannery, PhD, who leads the U.S. Flu VE network for the Centers for Disease Control and Prevention, said in an interview. He was not involved with the advisory committee meeting. Flu activity this season has been low, he explained, so there are fewer cases his team can use to estimate vaccine efficacy. “If there’s some benefit, it’s hard for us to show that now,” he said.
 

Vaccine strains

The panel voted to include a A/Darwin/9/2021-like strain for the H3N2 component of the vaccine; this is changed from A/Cambodia/e0826360/2020. For the influenza B Victoria lineage component, the committee voted to include a B/Austria/1359417/2021-like virus, a swap from this year’s B/Washington/02/2019-like virus. These changes apply to the egg-based, cell-culture, and recombinant vaccines. Both new strains were included in WHO’s 2022 influenza vaccine strain recommendations for the southern hemisphere.

For the influenza A H1N1 component, the group also agreed to include a A/Victoria/2570/2019 (H1N1) pdm09-like virus for the egg-based vaccine and the A/Wisconsin/588/2019 (H1N1) pdm09-like virus for cell culture or recombinant vaccines. These strains were included for the 2021-2022 season. The panel also voted for the inclusion of a B/Phuket/3073/2013-like virus (B/Yamagata lineage) as the second influenza B strain for the quadrivalent egg-based, cell culture, or recombinant vaccines, which is unchanged from this flu season.
 

‘Sporadic’ flu activity

While there was an uptick in influenza activity this year compared to the 2020-2021 season, hospitalization rates are lower than in the four seasons preceding the pandemic (from 2016-2017 to 2019-2020). As of Feb. 26, the cumulative hospitalization rate for this flu season was 5.2 hospitalizations per 100,000 individuals. There have been eight pediatric deaths due to influenza so far this season, compared to one pediatric death reported to the CDC during the 2020-2021 flu season.

About 4.1% of specimens tested at clinical laboratories were positive for flu. Since Oct. 30, 2.7% of specimens have been positive for influenza this season. Nearly all viruses detected (97.7%) have been influenza A.

Lisa Grohskopf, MD, MPH, a medical officer in the influenza division at the CDC who presented the data at the meeting, described flu activity this season as “sporadic” and noted that activity is increasing in some areas of the country. According to CDC’s weekly influenza surveillance report, most states had minimal influenza-like illness (ILI) activity, although Arkansas, Idaho, Iowa, Kansas, Minnesota, and Utah had slightly higher ILI activity as of Feb. 26. Champaign-Urbana, Illinois; St. Cloud, Minnesota; and Brownwood, Texas, had the highest levels of flu activity in the country.
 

Low vaccine effectiveness

As of Jan. 22, results from the U.S. Flu VE network do not show statistically significant evidence that the flu vaccine is effective. Currently, the vaccine is estimated to be 8% effective against preventing influenza A infection (95% confidence interval, –31% to 36%) and 14% effective against preventing A/H3N2 infection (95% CI, –28% to 43%) for people aged 6 months and older.

The network did not have enough data to provide age-specific VE estimates or estimates of effectiveness against influenza B. This could be due to low flu activity relative to prepandemic years, Dr. Flannery said. Of the 2,758 individuals enrolled in the VE flu network this season, just 147 (5%) tested positive for the flu this season. This is the lowest positivity rate observed in the Flu VE network participants with respiratory illness over the past 10 flu seasons, Dr. Grohskopf noted. In comparison, estimates from the 2019 to 2020 season included 4,112 individuals, and 1,060 tested positive for flu.

“We are really at the bare minimum of what we can use for a flu vaccine effectiveness estimate,” Dr. Flannery said about the more recent data. The network was not able to produce any estimates about flu vaccine effectiveness for the 2020-2021 season because of historically low flu activity.

The Department of Defense also presented vaccine efficacy estimates for the 2021–2022 season. The vaccine has been 36% effective (95% CI, 28%-44%) against all strains of the virus, 33% effective against influenza A (95% CI, 24%-41%), 32% effective against A/H3N2 (95% CI, 3%-53%), and 59% effective against influenza B (95% CI, 42%-71%). These results are from a young, healthy adult population, Lieutenant Commander Courtney Gustin, DrPH, MSN, told the panel, and they may not be reflective of efficacy rates across all age groups.

Though these findings suggest there is low to no measurable benefit against influenza A, Dr. Flannery said the CDC still recommends getting the flu vaccine, as it can be protective against other circulating flu strains. “We have been able to demonstrate protection against other H3 [viruses], B viruses, and H1 viruses in the past,” he said. And as these results only show protection against mild disease, “there is still possibility that there’s benefit against more severe disease,” he added. Studies measuring effectiveness against more severe outcomes are not yet available.

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

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee has chosen the influenza vaccine strains for the 2022-2023 season in the northern hemisphere, which begins in the fall of 2022.

On March 3, the committee unanimously voted to endorse the World Health Organization’s recommendations as to which influenza strains to include for coverage by vaccines for the upcoming flu season. Two of the four recommended strains are different from last season.

The committee also heard updates on flu activity this season. So far, data from the U.S. Flu Vaccine Effectiveness (VE) network, which consists of seven study sites, have not shown that the vaccine is protective against influenza A. “We can say that it is not highly effective,” Brendan Flannery, PhD, who leads the U.S. Flu VE network for the Centers for Disease Control and Prevention, said in an interview. He was not involved with the advisory committee meeting. Flu activity this season has been low, he explained, so there are fewer cases his team can use to estimate vaccine efficacy. “If there’s some benefit, it’s hard for us to show that now,” he said.
 

Vaccine strains

The panel voted to include a A/Darwin/9/2021-like strain for the H3N2 component of the vaccine; this is changed from A/Cambodia/e0826360/2020. For the influenza B Victoria lineage component, the committee voted to include a B/Austria/1359417/2021-like virus, a swap from this year’s B/Washington/02/2019-like virus. These changes apply to the egg-based, cell-culture, and recombinant vaccines. Both new strains were included in WHO’s 2022 influenza vaccine strain recommendations for the southern hemisphere.

For the influenza A H1N1 component, the group also agreed to include a A/Victoria/2570/2019 (H1N1) pdm09-like virus for the egg-based vaccine and the A/Wisconsin/588/2019 (H1N1) pdm09-like virus for cell culture or recombinant vaccines. These strains were included for the 2021-2022 season. The panel also voted for the inclusion of a B/Phuket/3073/2013-like virus (B/Yamagata lineage) as the second influenza B strain for the quadrivalent egg-based, cell culture, or recombinant vaccines, which is unchanged from this flu season.
 

‘Sporadic’ flu activity

While there was an uptick in influenza activity this year compared to the 2020-2021 season, hospitalization rates are lower than in the four seasons preceding the pandemic (from 2016-2017 to 2019-2020). As of Feb. 26, the cumulative hospitalization rate for this flu season was 5.2 hospitalizations per 100,000 individuals. There have been eight pediatric deaths due to influenza so far this season, compared to one pediatric death reported to the CDC during the 2020-2021 flu season.

About 4.1% of specimens tested at clinical laboratories were positive for flu. Since Oct. 30, 2.7% of specimens have been positive for influenza this season. Nearly all viruses detected (97.7%) have been influenza A.

Lisa Grohskopf, MD, MPH, a medical officer in the influenza division at the CDC who presented the data at the meeting, described flu activity this season as “sporadic” and noted that activity is increasing in some areas of the country. According to CDC’s weekly influenza surveillance report, most states had minimal influenza-like illness (ILI) activity, although Arkansas, Idaho, Iowa, Kansas, Minnesota, and Utah had slightly higher ILI activity as of Feb. 26. Champaign-Urbana, Illinois; St. Cloud, Minnesota; and Brownwood, Texas, had the highest levels of flu activity in the country.
 

Low vaccine effectiveness

As of Jan. 22, results from the U.S. Flu VE network do not show statistically significant evidence that the flu vaccine is effective. Currently, the vaccine is estimated to be 8% effective against preventing influenza A infection (95% confidence interval, –31% to 36%) and 14% effective against preventing A/H3N2 infection (95% CI, –28% to 43%) for people aged 6 months and older.

The network did not have enough data to provide age-specific VE estimates or estimates of effectiveness against influenza B. This could be due to low flu activity relative to prepandemic years, Dr. Flannery said. Of the 2,758 individuals enrolled in the VE flu network this season, just 147 (5%) tested positive for the flu this season. This is the lowest positivity rate observed in the Flu VE network participants with respiratory illness over the past 10 flu seasons, Dr. Grohskopf noted. In comparison, estimates from the 2019 to 2020 season included 4,112 individuals, and 1,060 tested positive for flu.

“We are really at the bare minimum of what we can use for a flu vaccine effectiveness estimate,” Dr. Flannery said about the more recent data. The network was not able to produce any estimates about flu vaccine effectiveness for the 2020-2021 season because of historically low flu activity.

The Department of Defense also presented vaccine efficacy estimates for the 2021–2022 season. The vaccine has been 36% effective (95% CI, 28%-44%) against all strains of the virus, 33% effective against influenza A (95% CI, 24%-41%), 32% effective against A/H3N2 (95% CI, 3%-53%), and 59% effective against influenza B (95% CI, 42%-71%). These results are from a young, healthy adult population, Lieutenant Commander Courtney Gustin, DrPH, MSN, told the panel, and they may not be reflective of efficacy rates across all age groups.

Though these findings suggest there is low to no measurable benefit against influenza A, Dr. Flannery said the CDC still recommends getting the flu vaccine, as it can be protective against other circulating flu strains. “We have been able to demonstrate protection against other H3 [viruses], B viruses, and H1 viruses in the past,” he said. And as these results only show protection against mild disease, “there is still possibility that there’s benefit against more severe disease,” he added. Studies measuring effectiveness against more severe outcomes are not yet available.

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

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee has chosen the influenza vaccine strains for the 2022-2023 season in the northern hemisphere, which begins in the fall of 2022.

On March 3, the committee unanimously voted to endorse the World Health Organization’s recommendations as to which influenza strains to include for coverage by vaccines for the upcoming flu season. Two of the four recommended strains are different from last season.

The committee also heard updates on flu activity this season. So far, data from the U.S. Flu Vaccine Effectiveness (VE) network, which consists of seven study sites, have not shown that the vaccine is protective against influenza A. “We can say that it is not highly effective,” Brendan Flannery, PhD, who leads the U.S. Flu VE network for the Centers for Disease Control and Prevention, said in an interview. He was not involved with the advisory committee meeting. Flu activity this season has been low, he explained, so there are fewer cases his team can use to estimate vaccine efficacy. “If there’s some benefit, it’s hard for us to show that now,” he said.
 

Vaccine strains

The panel voted to include a A/Darwin/9/2021-like strain for the H3N2 component of the vaccine; this is changed from A/Cambodia/e0826360/2020. For the influenza B Victoria lineage component, the committee voted to include a B/Austria/1359417/2021-like virus, a swap from this year’s B/Washington/02/2019-like virus. These changes apply to the egg-based, cell-culture, and recombinant vaccines. Both new strains were included in WHO’s 2022 influenza vaccine strain recommendations for the southern hemisphere.

For the influenza A H1N1 component, the group also agreed to include a A/Victoria/2570/2019 (H1N1) pdm09-like virus for the egg-based vaccine and the A/Wisconsin/588/2019 (H1N1) pdm09-like virus for cell culture or recombinant vaccines. These strains were included for the 2021-2022 season. The panel also voted for the inclusion of a B/Phuket/3073/2013-like virus (B/Yamagata lineage) as the second influenza B strain for the quadrivalent egg-based, cell culture, or recombinant vaccines, which is unchanged from this flu season.
 

‘Sporadic’ flu activity

While there was an uptick in influenza activity this year compared to the 2020-2021 season, hospitalization rates are lower than in the four seasons preceding the pandemic (from 2016-2017 to 2019-2020). As of Feb. 26, the cumulative hospitalization rate for this flu season was 5.2 hospitalizations per 100,000 individuals. There have been eight pediatric deaths due to influenza so far this season, compared to one pediatric death reported to the CDC during the 2020-2021 flu season.

About 4.1% of specimens tested at clinical laboratories were positive for flu. Since Oct. 30, 2.7% of specimens have been positive for influenza this season. Nearly all viruses detected (97.7%) have been influenza A.

Lisa Grohskopf, MD, MPH, a medical officer in the influenza division at the CDC who presented the data at the meeting, described flu activity this season as “sporadic” and noted that activity is increasing in some areas of the country. According to CDC’s weekly influenza surveillance report, most states had minimal influenza-like illness (ILI) activity, although Arkansas, Idaho, Iowa, Kansas, Minnesota, and Utah had slightly higher ILI activity as of Feb. 26. Champaign-Urbana, Illinois; St. Cloud, Minnesota; and Brownwood, Texas, had the highest levels of flu activity in the country.
 

Low vaccine effectiveness

As of Jan. 22, results from the U.S. Flu VE network do not show statistically significant evidence that the flu vaccine is effective. Currently, the vaccine is estimated to be 8% effective against preventing influenza A infection (95% confidence interval, –31% to 36%) and 14% effective against preventing A/H3N2 infection (95% CI, –28% to 43%) for people aged 6 months and older.

The network did not have enough data to provide age-specific VE estimates or estimates of effectiveness against influenza B. This could be due to low flu activity relative to prepandemic years, Dr. Flannery said. Of the 2,758 individuals enrolled in the VE flu network this season, just 147 (5%) tested positive for the flu this season. This is the lowest positivity rate observed in the Flu VE network participants with respiratory illness over the past 10 flu seasons, Dr. Grohskopf noted. In comparison, estimates from the 2019 to 2020 season included 4,112 individuals, and 1,060 tested positive for flu.

“We are really at the bare minimum of what we can use for a flu vaccine effectiveness estimate,” Dr. Flannery said about the more recent data. The network was not able to produce any estimates about flu vaccine effectiveness for the 2020-2021 season because of historically low flu activity.

The Department of Defense also presented vaccine efficacy estimates for the 2021–2022 season. The vaccine has been 36% effective (95% CI, 28%-44%) against all strains of the virus, 33% effective against influenza A (95% CI, 24%-41%), 32% effective against A/H3N2 (95% CI, 3%-53%), and 59% effective against influenza B (95% CI, 42%-71%). These results are from a young, healthy adult population, Lieutenant Commander Courtney Gustin, DrPH, MSN, told the panel, and they may not be reflective of efficacy rates across all age groups.

Though these findings suggest there is low to no measurable benefit against influenza A, Dr. Flannery said the CDC still recommends getting the flu vaccine, as it can be protective against other circulating flu strains. “We have been able to demonstrate protection against other H3 [viruses], B viruses, and H1 viruses in the past,” he said. And as these results only show protection against mild disease, “there is still possibility that there’s benefit against more severe disease,” he added. Studies measuring effectiveness against more severe outcomes are not yet available.

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

As the COVID-19 pandemic winds down – for the time being at least – efforts are ramping up to develop next-generation vaccines that can protect against future novel coronaviruses and variants. Several projects are presenting clever combinations of viral parts to the immune system that evoke a robust and hopefully lasting response.

The coming generation of “pan” vaccines aims to tamp down SARS-CoV-2, its closest relatives, and whatever may come into tamer respiratory viruses like the common cold. Whatever the eventual components of this new generation of vaccines, experts agree on the goal: preventing severe disease and death. And a broader approach is critical.

“All the vaccines have been amazing. But we’re playing a whack-a-mole game with the variants. We need to take a step back and ask if a pan-variant vaccine is possible. That’s important because Omicron isn’t the last variant,” said Jacob Lemieux, MD, PhD, instructor in medicine and infectious disease specialist at Massachusetts General Hospital, Boston.
 

A broad spectrum vaccine

The drive to create a vaccine that would deter multiple coronaviruses arose early, among many researchers. An article published in Nature in May 2020 by National Institute of Allergy and Infectious Diseases researcher Luca T. Giurgea, MD, and colleagues said it all in the title: “Universal coronavirus vaccines: the time to start is now.”

Their concerns? The diversity of bat coronaviruses poised to jump into humans; the high mutability of the spike gene that the immune response recognizes; and the persistence of mutations in an RNA virus, which can’t repair errors. 

Work on broader vaccines began in several labs as SARS-CoV-2 spawned variant after variant.

On Sept. 28, NIAID announced funding for developing ‘pan-coronavirus’ vaccines – the quotation marks theirs to indicate that a magic bullet against any new coronavirus is unrealistic. “These new awards are designed to look ahead and prepare for the next generation of coronaviruses with pandemic potential,” said NIAID director Anthony S. Fauci, MD. An initial three awards went to groups at the University of Wisconsin, Brigham and Women’s Hospital, and Duke University.

President Biden mentioned the NIAID funding in his State of the Union Address. He also talked about how the Biomedical Advanced Research and Development Authority, founded in 2006 to prepare for public health emergencies, is spearheading development of new vaccine platforms and vaccines that target a broader swath of pathogen parts.

Meanwhile, individual researchers from eclectic fields are finding new ways to prevent future pandemics.

Artem Babaian, PhD, a computational biologist at the University of Cambridge (England), had the idea to probe National Institutes of Health genome databases, going back more than a decade, for overlooked novel coronaviruses. He started the project while he was between jobs as the pandemic was unfurling, using a telltale enzyme unique to the RNA viruses to fish out COVID cousins. The work is published in Nature and the data freely available at serratus.io.

Among the nearly 132,000 novel RNA viruses Dr. Babaian’s team found, 9 were from previously unrecognized coronaviruses. The novel nine came from “ecologically diverse sources”: a seahorse, an axolotl, an eel, and several fishes. Deciphering the topographies of these coronaviruses may provide clues to developing vaccines that stay ahead of future pandemics.

But optics are important in keeping expectations reasonable. “‘Universal vaccine’ is a misnomer. I think about it as ‘broad spectrum vaccines.’ It’s critical to be up front that these vaccines can never guarantee immunity against all coronaviruses. There are no absolutes in biology, but they hopefully will work against the dangers that we do know exist. A vaccine that mimics exposure to many coronaviruses could protect against a currently unknown coronavirus, especially if slower-evolving antigens are included,” Dr. Babaian said in an interview.

Nikolai Petrovsky, MD, PhD, of Flinders University, Adelaide, and the biotechnology company Vaccine Pty, agrees, calling a literal pan-coronavirus vaccine a “pipe dream. What I do think is achievable is a broadly protective, pan–CoV-19 vaccine – I can say that because we have already developed and tested it, combining antigens rather than trying just one that can do everything.”
 

Immunity lures

The broader vaccines in development display viral antigens, such as spike proteins, to the immune system on diverse frameworks. Here are a few approaches.

Ferritin nanoparticles: A candidate vaccine from the emerging infectious diseases branch of Water Reed National Military Medical Center began phase 1 human trials in April 2021. Called SpFN, the vaccine consists of arrays of ferritin nanoparticles linked to spike proteins from various variants and species. Ferritin is a protein that binds and stores iron in the body.

“The repetitive and ordered display of the coronavirus spike protein on a multifaced nanoparticle may stimulate immunity in such a way as to translate into significantly broader protection,” said Walter Reed’s branch director and vaccine coinventor Kayvon Modjarrad, MD, PhD.

A second vaccine targets only the “bullseye” part of the spike that the virus uses to attach and gain access to human cells, called the receptor-binding domain (RBD), of SARS-CoV-2 variants and of the virus behind the original SARS. The preclinical data appeared in Science Translational Medicine.

Barton Haynes, MD and colleagues at the Duke Human Vaccine Institute are also using ferritin to design and develop a “pan-betacoronavirus vaccine,” referring to the genus to which SARS-CoV-2 belongs. They say their results in macaques, published in Nature, “demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses.”

Mosaic nanoparticles: Graduate student Alexander Cohen is leading an effort at CalTech, in the lab of Pamela Bjorkman, PhD, that uses nanoparticles consisting of proteins from a bacterium (Strep pyogenes) to which RBDs from spike proteins of four or eight different betacoronaviruses are attached. The strategy demonstrates that the whole is greater than the sum of the parts.

“Alex’s results show that it is possible to raise diverse neutralizing antibody responses, even against coronavirus strains that were not represented on the injected nanoparticle. We are hopeful that this technology could be used to protect against future animal coronaviruses that cross into humans,” said Dr. Björkman. The work appeared in Science.

Candidate vaccines from Inovio Pharmaceuticals also use a mosaic spike strategy, but with DNA rings (plasmids) rather than nanoparticles. One version works against pre-Omicron variants and is being tested against Omicron, and another with “pan–COVID-19” coverage has tested well in animal models. Inovio’s vaccines are delivered into the skin using a special device that applies an electric pulse that increases the cells’ permeability.

Chimeric spikes: Yet another approach is to fashion vaccines from various parts of the betacoronaviruses that are most closely related to SARS-CoV-2 – the pathogens behind Middle East respiratory syndrome and severe acute respiratory syndrome as well as several bat viruses and a few pangolin ones. The abundance and ubiquity of these viruses provide a toolbox of sorts, with instructions written in the language of RNA, from which to select, dissect, recombine, and customize vaccines.

“SARS-like viruses can recombine and exhibit great genetic diversity in several parts of the genome. We designed chimeric spikes to improve coverage of a multiplexed vaccine,” said David Martinez, PhD.

His team at the University of North Carolina at Chapel Hill has developed mRNA vaccines that deliver “scrambled coronavirus spikes” representing various parts, not just the RBD, as described in Science.

In mice, the chimeric vaccines elicit robust T- and B-cell immune responses, which stimulate antibody production and control other facets of building immunity.
 

Beyond the spike bullseye

The challenge of developing pan-coronavirus vaccines is dual. “The very best vaccines are highly specific to each strain, and the universal vaccines have to sacrifice effectiveness to get broad coverage. Life is a trade-off.” Dr. Petrovsky told this news organization. 

Efforts to broaden vaccine efficacy venture beyond targeting the RBD bullseyes of the spike triplets that festoon the virus. Some projects are focusing on less changeable spike parts that are more alike among less closely related coronaviruses than is the mutation-prone RBD. For example, the peptides that twist into the “stem-helix” portion of the part of the spike that adheres to host cells are the basis of some candidate vaccines now in preclinical studies.

Still other vaccines aren’t spike based at all. French company Osivax, for example, is working on a vaccine that targets the nucleocapsid protein that shields the viral RNA. The hope is that presenting various faces of the pathogen may spark immunity beyond an initial antibody rush and evoke more diverse and lasting T-cell responses.

With the myriad efforts to back up the first generation of COVID-19 vaccines with new ones offering broader protection, it appears that science may have finally learned from history.

“After the SARS outbreak, we lost interest and failed to complete development of a vaccine for use in case of a recurrent outbreak. We must not make the same mistake again,” Dr. Giurgea and colleagues wrote in their Nature article about universal coronavirus vaccines.

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

As the COVID-19 pandemic winds down – for the time being at least – efforts are ramping up to develop next-generation vaccines that can protect against future novel coronaviruses and variants. Several projects are presenting clever combinations of viral parts to the immune system that evoke a robust and hopefully lasting response.

The coming generation of “pan” vaccines aims to tamp down SARS-CoV-2, its closest relatives, and whatever may come into tamer respiratory viruses like the common cold. Whatever the eventual components of this new generation of vaccines, experts agree on the goal: preventing severe disease and death. And a broader approach is critical.

“All the vaccines have been amazing. But we’re playing a whack-a-mole game with the variants. We need to take a step back and ask if a pan-variant vaccine is possible. That’s important because Omicron isn’t the last variant,” said Jacob Lemieux, MD, PhD, instructor in medicine and infectious disease specialist at Massachusetts General Hospital, Boston.
 

A broad spectrum vaccine

The drive to create a vaccine that would deter multiple coronaviruses arose early, among many researchers. An article published in Nature in May 2020 by National Institute of Allergy and Infectious Diseases researcher Luca T. Giurgea, MD, and colleagues said it all in the title: “Universal coronavirus vaccines: the time to start is now.”

Their concerns? The diversity of bat coronaviruses poised to jump into humans; the high mutability of the spike gene that the immune response recognizes; and the persistence of mutations in an RNA virus, which can’t repair errors. 

Work on broader vaccines began in several labs as SARS-CoV-2 spawned variant after variant.

On Sept. 28, NIAID announced funding for developing ‘pan-coronavirus’ vaccines – the quotation marks theirs to indicate that a magic bullet against any new coronavirus is unrealistic. “These new awards are designed to look ahead and prepare for the next generation of coronaviruses with pandemic potential,” said NIAID director Anthony S. Fauci, MD. An initial three awards went to groups at the University of Wisconsin, Brigham and Women’s Hospital, and Duke University.

President Biden mentioned the NIAID funding in his State of the Union Address. He also talked about how the Biomedical Advanced Research and Development Authority, founded in 2006 to prepare for public health emergencies, is spearheading development of new vaccine platforms and vaccines that target a broader swath of pathogen parts.

Meanwhile, individual researchers from eclectic fields are finding new ways to prevent future pandemics.

Artem Babaian, PhD, a computational biologist at the University of Cambridge (England), had the idea to probe National Institutes of Health genome databases, going back more than a decade, for overlooked novel coronaviruses. He started the project while he was between jobs as the pandemic was unfurling, using a telltale enzyme unique to the RNA viruses to fish out COVID cousins. The work is published in Nature and the data freely available at serratus.io.

Among the nearly 132,000 novel RNA viruses Dr. Babaian’s team found, 9 were from previously unrecognized coronaviruses. The novel nine came from “ecologically diverse sources”: a seahorse, an axolotl, an eel, and several fishes. Deciphering the topographies of these coronaviruses may provide clues to developing vaccines that stay ahead of future pandemics.

But optics are important in keeping expectations reasonable. “‘Universal vaccine’ is a misnomer. I think about it as ‘broad spectrum vaccines.’ It’s critical to be up front that these vaccines can never guarantee immunity against all coronaviruses. There are no absolutes in biology, but they hopefully will work against the dangers that we do know exist. A vaccine that mimics exposure to many coronaviruses could protect against a currently unknown coronavirus, especially if slower-evolving antigens are included,” Dr. Babaian said in an interview.

Nikolai Petrovsky, MD, PhD, of Flinders University, Adelaide, and the biotechnology company Vaccine Pty, agrees, calling a literal pan-coronavirus vaccine a “pipe dream. What I do think is achievable is a broadly protective, pan–CoV-19 vaccine – I can say that because we have already developed and tested it, combining antigens rather than trying just one that can do everything.”
 

Immunity lures

The broader vaccines in development display viral antigens, such as spike proteins, to the immune system on diverse frameworks. Here are a few approaches.

Ferritin nanoparticles: A candidate vaccine from the emerging infectious diseases branch of Water Reed National Military Medical Center began phase 1 human trials in April 2021. Called SpFN, the vaccine consists of arrays of ferritin nanoparticles linked to spike proteins from various variants and species. Ferritin is a protein that binds and stores iron in the body.

“The repetitive and ordered display of the coronavirus spike protein on a multifaced nanoparticle may stimulate immunity in such a way as to translate into significantly broader protection,” said Walter Reed’s branch director and vaccine coinventor Kayvon Modjarrad, MD, PhD.

A second vaccine targets only the “bullseye” part of the spike that the virus uses to attach and gain access to human cells, called the receptor-binding domain (RBD), of SARS-CoV-2 variants and of the virus behind the original SARS. The preclinical data appeared in Science Translational Medicine.

Barton Haynes, MD and colleagues at the Duke Human Vaccine Institute are also using ferritin to design and develop a “pan-betacoronavirus vaccine,” referring to the genus to which SARS-CoV-2 belongs. They say their results in macaques, published in Nature, “demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses.”

Mosaic nanoparticles: Graduate student Alexander Cohen is leading an effort at CalTech, in the lab of Pamela Bjorkman, PhD, that uses nanoparticles consisting of proteins from a bacterium (Strep pyogenes) to which RBDs from spike proteins of four or eight different betacoronaviruses are attached. The strategy demonstrates that the whole is greater than the sum of the parts.

“Alex’s results show that it is possible to raise diverse neutralizing antibody responses, even against coronavirus strains that were not represented on the injected nanoparticle. We are hopeful that this technology could be used to protect against future animal coronaviruses that cross into humans,” said Dr. Björkman. The work appeared in Science.

Candidate vaccines from Inovio Pharmaceuticals also use a mosaic spike strategy, but with DNA rings (plasmids) rather than nanoparticles. One version works against pre-Omicron variants and is being tested against Omicron, and another with “pan–COVID-19” coverage has tested well in animal models. Inovio’s vaccines are delivered into the skin using a special device that applies an electric pulse that increases the cells’ permeability.

Chimeric spikes: Yet another approach is to fashion vaccines from various parts of the betacoronaviruses that are most closely related to SARS-CoV-2 – the pathogens behind Middle East respiratory syndrome and severe acute respiratory syndrome as well as several bat viruses and a few pangolin ones. The abundance and ubiquity of these viruses provide a toolbox of sorts, with instructions written in the language of RNA, from which to select, dissect, recombine, and customize vaccines.

“SARS-like viruses can recombine and exhibit great genetic diversity in several parts of the genome. We designed chimeric spikes to improve coverage of a multiplexed vaccine,” said David Martinez, PhD.

His team at the University of North Carolina at Chapel Hill has developed mRNA vaccines that deliver “scrambled coronavirus spikes” representing various parts, not just the RBD, as described in Science.

In mice, the chimeric vaccines elicit robust T- and B-cell immune responses, which stimulate antibody production and control other facets of building immunity.
 

Beyond the spike bullseye

The challenge of developing pan-coronavirus vaccines is dual. “The very best vaccines are highly specific to each strain, and the universal vaccines have to sacrifice effectiveness to get broad coverage. Life is a trade-off.” Dr. Petrovsky told this news organization. 

Efforts to broaden vaccine efficacy venture beyond targeting the RBD bullseyes of the spike triplets that festoon the virus. Some projects are focusing on less changeable spike parts that are more alike among less closely related coronaviruses than is the mutation-prone RBD. For example, the peptides that twist into the “stem-helix” portion of the part of the spike that adheres to host cells are the basis of some candidate vaccines now in preclinical studies.

Still other vaccines aren’t spike based at all. French company Osivax, for example, is working on a vaccine that targets the nucleocapsid protein that shields the viral RNA. The hope is that presenting various faces of the pathogen may spark immunity beyond an initial antibody rush and evoke more diverse and lasting T-cell responses.

With the myriad efforts to back up the first generation of COVID-19 vaccines with new ones offering broader protection, it appears that science may have finally learned from history.

“After the SARS outbreak, we lost interest and failed to complete development of a vaccine for use in case of a recurrent outbreak. We must not make the same mistake again,” Dr. Giurgea and colleagues wrote in their Nature article about universal coronavirus vaccines.

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

As the COVID-19 pandemic winds down – for the time being at least – efforts are ramping up to develop next-generation vaccines that can protect against future novel coronaviruses and variants. Several projects are presenting clever combinations of viral parts to the immune system that evoke a robust and hopefully lasting response.

The coming generation of “pan” vaccines aims to tamp down SARS-CoV-2, its closest relatives, and whatever may come into tamer respiratory viruses like the common cold. Whatever the eventual components of this new generation of vaccines, experts agree on the goal: preventing severe disease and death. And a broader approach is critical.

“All the vaccines have been amazing. But we’re playing a whack-a-mole game with the variants. We need to take a step back and ask if a pan-variant vaccine is possible. That’s important because Omicron isn’t the last variant,” said Jacob Lemieux, MD, PhD, instructor in medicine and infectious disease specialist at Massachusetts General Hospital, Boston.
 

A broad spectrum vaccine

The drive to create a vaccine that would deter multiple coronaviruses arose early, among many researchers. An article published in Nature in May 2020 by National Institute of Allergy and Infectious Diseases researcher Luca T. Giurgea, MD, and colleagues said it all in the title: “Universal coronavirus vaccines: the time to start is now.”

Their concerns? The diversity of bat coronaviruses poised to jump into humans; the high mutability of the spike gene that the immune response recognizes; and the persistence of mutations in an RNA virus, which can’t repair errors. 

Work on broader vaccines began in several labs as SARS-CoV-2 spawned variant after variant.

On Sept. 28, NIAID announced funding for developing ‘pan-coronavirus’ vaccines – the quotation marks theirs to indicate that a magic bullet against any new coronavirus is unrealistic. “These new awards are designed to look ahead and prepare for the next generation of coronaviruses with pandemic potential,” said NIAID director Anthony S. Fauci, MD. An initial three awards went to groups at the University of Wisconsin, Brigham and Women’s Hospital, and Duke University.

President Biden mentioned the NIAID funding in his State of the Union Address. He also talked about how the Biomedical Advanced Research and Development Authority, founded in 2006 to prepare for public health emergencies, is spearheading development of new vaccine platforms and vaccines that target a broader swath of pathogen parts.

Meanwhile, individual researchers from eclectic fields are finding new ways to prevent future pandemics.

Artem Babaian, PhD, a computational biologist at the University of Cambridge (England), had the idea to probe National Institutes of Health genome databases, going back more than a decade, for overlooked novel coronaviruses. He started the project while he was between jobs as the pandemic was unfurling, using a telltale enzyme unique to the RNA viruses to fish out COVID cousins. The work is published in Nature and the data freely available at serratus.io.

Among the nearly 132,000 novel RNA viruses Dr. Babaian’s team found, 9 were from previously unrecognized coronaviruses. The novel nine came from “ecologically diverse sources”: a seahorse, an axolotl, an eel, and several fishes. Deciphering the topographies of these coronaviruses may provide clues to developing vaccines that stay ahead of future pandemics.

But optics are important in keeping expectations reasonable. “‘Universal vaccine’ is a misnomer. I think about it as ‘broad spectrum vaccines.’ It’s critical to be up front that these vaccines can never guarantee immunity against all coronaviruses. There are no absolutes in biology, but they hopefully will work against the dangers that we do know exist. A vaccine that mimics exposure to many coronaviruses could protect against a currently unknown coronavirus, especially if slower-evolving antigens are included,” Dr. Babaian said in an interview.

Nikolai Petrovsky, MD, PhD, of Flinders University, Adelaide, and the biotechnology company Vaccine Pty, agrees, calling a literal pan-coronavirus vaccine a “pipe dream. What I do think is achievable is a broadly protective, pan–CoV-19 vaccine – I can say that because we have already developed and tested it, combining antigens rather than trying just one that can do everything.”
 

Immunity lures

The broader vaccines in development display viral antigens, such as spike proteins, to the immune system on diverse frameworks. Here are a few approaches.

Ferritin nanoparticles: A candidate vaccine from the emerging infectious diseases branch of Water Reed National Military Medical Center began phase 1 human trials in April 2021. Called SpFN, the vaccine consists of arrays of ferritin nanoparticles linked to spike proteins from various variants and species. Ferritin is a protein that binds and stores iron in the body.

“The repetitive and ordered display of the coronavirus spike protein on a multifaced nanoparticle may stimulate immunity in such a way as to translate into significantly broader protection,” said Walter Reed’s branch director and vaccine coinventor Kayvon Modjarrad, MD, PhD.

A second vaccine targets only the “bullseye” part of the spike that the virus uses to attach and gain access to human cells, called the receptor-binding domain (RBD), of SARS-CoV-2 variants and of the virus behind the original SARS. The preclinical data appeared in Science Translational Medicine.

Barton Haynes, MD and colleagues at the Duke Human Vaccine Institute are also using ferritin to design and develop a “pan-betacoronavirus vaccine,” referring to the genus to which SARS-CoV-2 belongs. They say their results in macaques, published in Nature, “demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses.”

Mosaic nanoparticles: Graduate student Alexander Cohen is leading an effort at CalTech, in the lab of Pamela Bjorkman, PhD, that uses nanoparticles consisting of proteins from a bacterium (Strep pyogenes) to which RBDs from spike proteins of four or eight different betacoronaviruses are attached. The strategy demonstrates that the whole is greater than the sum of the parts.

“Alex’s results show that it is possible to raise diverse neutralizing antibody responses, even against coronavirus strains that were not represented on the injected nanoparticle. We are hopeful that this technology could be used to protect against future animal coronaviruses that cross into humans,” said Dr. Björkman. The work appeared in Science.

Candidate vaccines from Inovio Pharmaceuticals also use a mosaic spike strategy, but with DNA rings (plasmids) rather than nanoparticles. One version works against pre-Omicron variants and is being tested against Omicron, and another with “pan–COVID-19” coverage has tested well in animal models. Inovio’s vaccines are delivered into the skin using a special device that applies an electric pulse that increases the cells’ permeability.

Chimeric spikes: Yet another approach is to fashion vaccines from various parts of the betacoronaviruses that are most closely related to SARS-CoV-2 – the pathogens behind Middle East respiratory syndrome and severe acute respiratory syndrome as well as several bat viruses and a few pangolin ones. The abundance and ubiquity of these viruses provide a toolbox of sorts, with instructions written in the language of RNA, from which to select, dissect, recombine, and customize vaccines.

“SARS-like viruses can recombine and exhibit great genetic diversity in several parts of the genome. We designed chimeric spikes to improve coverage of a multiplexed vaccine,” said David Martinez, PhD.

His team at the University of North Carolina at Chapel Hill has developed mRNA vaccines that deliver “scrambled coronavirus spikes” representing various parts, not just the RBD, as described in Science.

In mice, the chimeric vaccines elicit robust T- and B-cell immune responses, which stimulate antibody production and control other facets of building immunity.
 

Beyond the spike bullseye

The challenge of developing pan-coronavirus vaccines is dual. “The very best vaccines are highly specific to each strain, and the universal vaccines have to sacrifice effectiveness to get broad coverage. Life is a trade-off.” Dr. Petrovsky told this news organization. 

Efforts to broaden vaccine efficacy venture beyond targeting the RBD bullseyes of the spike triplets that festoon the virus. Some projects are focusing on less changeable spike parts that are more alike among less closely related coronaviruses than is the mutation-prone RBD. For example, the peptides that twist into the “stem-helix” portion of the part of the spike that adheres to host cells are the basis of some candidate vaccines now in preclinical studies.

Still other vaccines aren’t spike based at all. French company Osivax, for example, is working on a vaccine that targets the nucleocapsid protein that shields the viral RNA. The hope is that presenting various faces of the pathogen may spark immunity beyond an initial antibody rush and evoke more diverse and lasting T-cell responses.

With the myriad efforts to back up the first generation of COVID-19 vaccines with new ones offering broader protection, it appears that science may have finally learned from history.

“After the SARS outbreak, we lost interest and failed to complete development of a vaccine for use in case of a recurrent outbreak. We must not make the same mistake again,” Dr. Giurgea and colleagues wrote in their Nature article about universal coronavirus vaccines.

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

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

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

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

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

Data from the first 6 months after the rollout of mRNA COVID-19 vaccines in the United States released today show that adverse effects from shots are typically mild and short-lived.

Findings of the large study, compiled after nearly 300 million doses were administered, were published online March 7 in The Lancet Infectious Diseases.

Researchers, led by Hannah G. Rosenblum, MD, with the Centers for Disease Control and Prevention COVID Response Team, used passive U.S. surveillance data collected through the Vaccine Adverse Event Reporting System (VAERS), and the active system, v-safe, starting in December 2020 through the first 6 months of the U.S. COVID-19 vaccination program. V-safe is a voluntary, smartphone-based system set up in 2020 specifically for monitoring reactions to COVID-19 and health effects after vaccination. The health effects information from v-safe is presented in this study for the first time.

Of the 298.7 million doses of mRNA vaccines administered in the U.S. during the study period, VAERS processed 340,522 reports. Of those, 313,499 (92.1%) were nonserious; 22,527 (6.6%) were serious (nondeath); and 4,496 (1.3%) were deaths.

From v-safe reporting, researchers learned that about 71% of the 7.9 million participants reported local or systemic reactions, more frequently after dose 2 than after dose 1. Of those reporting reactions after dose 1, about two-thirds (68.6%) reported a local reaction and 52.7% reported a systemic reaction.

Among other findings:

• Injection-site pain occurred after dose 1 in 66.2% of participants and 68.6% after dose 2.
• One-third of participants (33.9%) reported fatigue after dose 1 and 55.7% after dose 2.
• Headache was reported among 27% of participants after dose 1 and 46.2% after dose 2.
• When injection site pain, fatigue, or headaches were reported, the reports were usually in the first week after vaccination.
• Reports of being unable to work or do normal daily activities, or instances of seeking medical care, occurred more commonly after dose 2 (32.1%) than after dose 1 (11.9%). Fewer than 1% of participants reported seeking medical care after dose 1 or 2 of the vaccine.
• Reactions and health effects were reported more often in female than in male recipients, and in people younger than 65 years, compared with older people.
• Serious adverse events, including myocarditis, have been identified following mRNA vaccinations, but the events are rare.

The authors wrote that these results are consistent with preauthorization clinical trials and early postauthorization reports.

“On the basis of our findings, mild to moderate transient reactogenicity should be anticipated,” they said, “particularly among younger and female vaccine recipients.”
 

‘Robust and reassuring data’

“The safety monitoring of the mRNA COVID-19 vaccines stands out as the most comprehensive of any vaccine in U.S. history. The use of these complementary monitoring systems has provided robust and reassuring data,” Matthew S. Krantz, MD, with the division of allergy, pulmonary, and critical care medicine at Vanderbilt University, Nashville, Tenn., and Elizabeth J. Phillips, MD, with the department of pathology, microbiology, and immunology at Vanderbilt, wrote in a related commentary in The Lancet Infectious Diseases.

They point out that the v-safe reports of reactions are consistent with those reported from clinical trials and a large population study in the United Kingdom.

Dr. Phillips said in a press release, “[A]lthough approximately one in 1,000 individuals vaccinated may have an adverse effect, most of these are nonserious. No unusual patterns emerged in the cause of death or serious adverse effects among VAERS reports. For adverse events of special interest, it is reassuring that there were no unexpected signals other than myopericarditis and anaphylaxis, already known to be associated with mRNA vaccines.”

The study authors and editorialists have disclosed no relevant financial relationships.

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

The U.S. Food and Drug Administration has approved nivolumab for neoadjuvant treatment of non–small cell lung cancer (NSCLC) in combination with platinum-doublet chemotherapy, regardless of PDL-1 status.

Nivolumab is the first immune checkpoint inhibitor to be approved for resectable NSCLC; its three prior NSCLC indications are for metastatic disease, the agency said in its announcement. 

Approval was based on the CheckMate 816 trial, which randomized 358 patients evenly to either nivolumab plus platinum doublets or to platinum doublets alone every 3 weeks for up to 3 cycles.

Trial participants had histologically confirmed stage IB, II, or IIIA disease, which was measurable by RECIST criteria. They were enrolled regardless of tumor PD-L1 status.

At surgery, the pathologic complete response rate was 24% in the nivolumab arm versus 2.2% in the chemotherapy-alone group.

Median event-free survival was 31.6 months with nivolumab but 20.8 months without it, which translated to a 37% reduction in the risk for progression, recurrence, or death following surgery. A trend toward better overall survival was not statistically significant, Bristol Myers Squibb said in its own announcement.

Nivolumab’s new neoadjuvant indication is for adult patients with resectable NSCLC (tumors greater than or equal to 4 cm or node positive). The recommended dosage is 360 mg in combination with platinum-doublet chemotherapy on the same day every 3 weeks for three cycles.

In a press release from Bristol Myers Squibb, CheckMate 816 investigator and Dana-Farber Cancer Institute thoracic oncologist Mark Awad, MD, PhD, called the approval “a turning point in how we treat resectable NSCLC.”

Patients with known EGFR mutations or ALK translocations, grade 2 or higher peripheral neuropathy, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded.

There were no fatal adverse events in the nivolumab arm, but 30% of participants had serious adverse events, most commonly pneumonia and vomiting.

The most common side effects across all grades were nausea (38%), constipation (34%), fatigue (26%), decreased appetite (20%), and rash (20%). Surgical complications and hospital lengths were similar between the two study groups.

Rival checkpoint inhibitor pembrolizumab is also being investigated for neoadjuvant NSCLC.

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

The U.S. Food and Drug Administration has approved nivolumab for neoadjuvant treatment of non–small cell lung cancer (NSCLC) in combination with platinum-doublet chemotherapy, regardless of PDL-1 status.

Nivolumab is the first immune checkpoint inhibitor to be approved for resectable NSCLC; its three prior NSCLC indications are for metastatic disease, the agency said in its announcement. 

Approval was based on the CheckMate 816 trial, which randomized 358 patients evenly to either nivolumab plus platinum doublets or to platinum doublets alone every 3 weeks for up to 3 cycles.

Trial participants had histologically confirmed stage IB, II, or IIIA disease, which was measurable by RECIST criteria. They were enrolled regardless of tumor PD-L1 status.

At surgery, the pathologic complete response rate was 24% in the nivolumab arm versus 2.2% in the chemotherapy-alone group.

Median event-free survival was 31.6 months with nivolumab but 20.8 months without it, which translated to a 37% reduction in the risk for progression, recurrence, or death following surgery. A trend toward better overall survival was not statistically significant, Bristol Myers Squibb said in its own announcement.

Nivolumab’s new neoadjuvant indication is for adult patients with resectable NSCLC (tumors greater than or equal to 4 cm or node positive). The recommended dosage is 360 mg in combination with platinum-doublet chemotherapy on the same day every 3 weeks for three cycles.

In a press release from Bristol Myers Squibb, CheckMate 816 investigator and Dana-Farber Cancer Institute thoracic oncologist Mark Awad, MD, PhD, called the approval “a turning point in how we treat resectable NSCLC.”

Patients with known EGFR mutations or ALK translocations, grade 2 or higher peripheral neuropathy, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded.

There were no fatal adverse events in the nivolumab arm, but 30% of participants had serious adverse events, most commonly pneumonia and vomiting.

The most common side effects across all grades were nausea (38%), constipation (34%), fatigue (26%), decreased appetite (20%), and rash (20%). Surgical complications and hospital lengths were similar between the two study groups.

Rival checkpoint inhibitor pembrolizumab is also being investigated for neoadjuvant NSCLC.

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

The U.S. Food and Drug Administration has approved nivolumab for neoadjuvant treatment of non–small cell lung cancer (NSCLC) in combination with platinum-doublet chemotherapy, regardless of PDL-1 status.

Nivolumab is the first immune checkpoint inhibitor to be approved for resectable NSCLC; its three prior NSCLC indications are for metastatic disease, the agency said in its announcement. 

Approval was based on the CheckMate 816 trial, which randomized 358 patients evenly to either nivolumab plus platinum doublets or to platinum doublets alone every 3 weeks for up to 3 cycles.

Trial participants had histologically confirmed stage IB, II, or IIIA disease, which was measurable by RECIST criteria. They were enrolled regardless of tumor PD-L1 status.

At surgery, the pathologic complete response rate was 24% in the nivolumab arm versus 2.2% in the chemotherapy-alone group.

Median event-free survival was 31.6 months with nivolumab but 20.8 months without it, which translated to a 37% reduction in the risk for progression, recurrence, or death following surgery. A trend toward better overall survival was not statistically significant, Bristol Myers Squibb said in its own announcement.

Nivolumab’s new neoadjuvant indication is for adult patients with resectable NSCLC (tumors greater than or equal to 4 cm or node positive). The recommended dosage is 360 mg in combination with platinum-doublet chemotherapy on the same day every 3 weeks for three cycles.

In a press release from Bristol Myers Squibb, CheckMate 816 investigator and Dana-Farber Cancer Institute thoracic oncologist Mark Awad, MD, PhD, called the approval “a turning point in how we treat resectable NSCLC.”

Patients with known EGFR mutations or ALK translocations, grade 2 or higher peripheral neuropathy, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded.

There were no fatal adverse events in the nivolumab arm, but 30% of participants had serious adverse events, most commonly pneumonia and vomiting.

The most common side effects across all grades were nausea (38%), constipation (34%), fatigue (26%), decreased appetite (20%), and rash (20%). Surgical complications and hospital lengths were similar between the two study groups.

Rival checkpoint inhibitor pembrolizumab is also being investigated for neoadjuvant NSCLC.

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

Compared with control treatment among critically ill adults, low-molecular-weight heparin (LMWH) reduces the incidence of deep vein thrombosis (DVT), according to a systematic review and network meta-analysis of randomized clinical trials (RCTs) published in CHEST. The analysis showed also that risk of DVT may be reduced by unfractionated heparin (UFH) and by mechanical compressive devices, although LMWH should be considered the primary pharmacologic agent for thromboprophylaxis.

Risk of venous thromboembolism (VTE), including DVT and pulmonary embolism (PE), is heightened in critically ill patients. VTE incidence is highest in major surgery and trauma patients, and mortality estimates from PE among intensive care unit patients are as high as 12%. Clinical practice guidelines recommend prophylaxis with pharmacologic agents over no prophylaxis in critically ill adults. Shannon M. Fernando, MD, of the University of Ottawa and colleagues examined the comparative efficacy and safety of various agents for VTE prophylaxis in critically ill patients through a review of 13 RCTs (9,619 patients) in six databases (Medline, PubMed, EMBASE, Scopus, Webof Science, and the Cochrane Database of Systematic Reviews). The ICU patients received a variety of therapies including pharmacologic, mechanical, or their combination for thromboprophylaxis. The control population consisted of a composite of no prophylaxis, placebo, or compression stockings only.
 

Indicative results

Analysis showed LMWH to reduce the incidence of DVT (odds ratio, 0.59; high certainty), while UFH may reduce the incidence of DVT (OR, 0.82; low certainty). Compared with UFH, LMWH probably reduces DVT (OR, 0.72; moderate certainty). Compressive devices, based on low-certainty evidence, may reduce risk of DVT, compared with control treatments (OR, 0.85).

The effect of combination therapy on DVT, compared with either therapy alone was unclear (very low certainty). The large-scale (2,000 patients) PREVENT trial in 2019, Dr. Fernando noted in an interview, found that adding compression therapy to pharmacologic therapy produced no reduction in proximal lower limb DVT.

“Ultimately, I think that, even if multiple RCTs and subsequent meta-analyses were performed, at best we would find that the incremental benefit of combination therapy is very minimal,” Dr. Fernando stated.

The findings provide evidence supporting LMWH and UFH use as compared with no pharmacologic prophylaxis for prevention of DVT, according to the researchers. While a similar certainty of effect in reducing PE was not found, evidence with moderate certainty suggested that LMWH and UFH probably reduce the incidence of any VTE, compared with no pharmacologic prophylaxis. Cost-effectiveness modeling that takes into account VTE incidence supports the practice. “If you’re reducing the incidence of DVT, it’s likely you’re similarly reducing incidence of PE, though I will agree that currently the data do not support this,” he said in an interview.

Noting that, while support in existing literature for any specific agent is controversial, the authors cite that American Society of Hematology guidelines suggest considering LMWH over UFH in critically ill patients, and that their findings lend support to that position. Regarding safety, pair-wise meta-analysis did not reveal clear major bleeding incidence differences between UFH and LMWH.
 

In and out of the ICU

Concordant with studies outside the ICU finding that heparin-induced thrombocytopenia (HIT) incidence is lower among patients receiving LMWH rather than UFH for VTE prophylaxis, the meta-analysis revealed a lower incidence of HIT among the critically ill receiving LMWH, but with evidence that was of low certainty.

Uncertainty around the optimal approach to VTE prophylaxis in the ICU along with wide variations in clinical practice persist despite recognition of the issue’s importance, note Major Michael J. McMahon, MD, of Honolulu and Colonel Aaron B. Holley, MD, of Bethesda, Md., authors of an accompanying editorial, “To generalize or not to generalize? The approach to VTE prophylaxis”. They acknowledge also that the Fernando et al. analysis yields important insights into VTE prevention in the ICU. Rhetorically raising the question, “Can we now say without doubt that LMWH is the preferred agent for all patients in the ICU?” – they responded, “probably.” Not entirely eliminated, they observe, is the possibility that a specific patient subgroup may benefit from one agent compared with another. They add, “We came away more confident that LMWH should be the default choice for VTE prevention in the ICU.”

Dr. Fernando and coauthors listed multiple disclosures, but declared that they received no financial support. Dr. McMahon and Dr. Holley declared that they have no disclosures.

Compared with control treatment among critically ill adults, low-molecular-weight heparin (LMWH) reduces the incidence of deep vein thrombosis (DVT), according to a systematic review and network meta-analysis of randomized clinical trials (RCTs) published in CHEST. The analysis showed also that risk of DVT may be reduced by unfractionated heparin (UFH) and by mechanical compressive devices, although LMWH should be considered the primary pharmacologic agent for thromboprophylaxis.

Risk of venous thromboembolism (VTE), including DVT and pulmonary embolism (PE), is heightened in critically ill patients. VTE incidence is highest in major surgery and trauma patients, and mortality estimates from PE among intensive care unit patients are as high as 12%. Clinical practice guidelines recommend prophylaxis with pharmacologic agents over no prophylaxis in critically ill adults. Shannon M. Fernando, MD, of the University of Ottawa and colleagues examined the comparative efficacy and safety of various agents for VTE prophylaxis in critically ill patients through a review of 13 RCTs (9,619 patients) in six databases (Medline, PubMed, EMBASE, Scopus, Webof Science, and the Cochrane Database of Systematic Reviews). The ICU patients received a variety of therapies including pharmacologic, mechanical, or their combination for thromboprophylaxis. The control population consisted of a composite of no prophylaxis, placebo, or compression stockings only.
 

Indicative results

Analysis showed LMWH to reduce the incidence of DVT (odds ratio, 0.59; high certainty), while UFH may reduce the incidence of DVT (OR, 0.82; low certainty). Compared with UFH, LMWH probably reduces DVT (OR, 0.72; moderate certainty). Compressive devices, based on low-certainty evidence, may reduce risk of DVT, compared with control treatments (OR, 0.85).

The effect of combination therapy on DVT, compared with either therapy alone was unclear (very low certainty). The large-scale (2,000 patients) PREVENT trial in 2019, Dr. Fernando noted in an interview, found that adding compression therapy to pharmacologic therapy produced no reduction in proximal lower limb DVT.

“Ultimately, I think that, even if multiple RCTs and subsequent meta-analyses were performed, at best we would find that the incremental benefit of combination therapy is very minimal,” Dr. Fernando stated.

The findings provide evidence supporting LMWH and UFH use as compared with no pharmacologic prophylaxis for prevention of DVT, according to the researchers. While a similar certainty of effect in reducing PE was not found, evidence with moderate certainty suggested that LMWH and UFH probably reduce the incidence of any VTE, compared with no pharmacologic prophylaxis. Cost-effectiveness modeling that takes into account VTE incidence supports the practice. “If you’re reducing the incidence of DVT, it’s likely you’re similarly reducing incidence of PE, though I will agree that currently the data do not support this,” he said in an interview.

Noting that, while support in existing literature for any specific agent is controversial, the authors cite that American Society of Hematology guidelines suggest considering LMWH over UFH in critically ill patients, and that their findings lend support to that position. Regarding safety, pair-wise meta-analysis did not reveal clear major bleeding incidence differences between UFH and LMWH.
 

In and out of the ICU

Concordant with studies outside the ICU finding that heparin-induced thrombocytopenia (HIT) incidence is lower among patients receiving LMWH rather than UFH for VTE prophylaxis, the meta-analysis revealed a lower incidence of HIT among the critically ill receiving LMWH, but with evidence that was of low certainty.

Uncertainty around the optimal approach to VTE prophylaxis in the ICU along with wide variations in clinical practice persist despite recognition of the issue’s importance, note Major Michael J. McMahon, MD, of Honolulu and Colonel Aaron B. Holley, MD, of Bethesda, Md., authors of an accompanying editorial, “To generalize or not to generalize? The approach to VTE prophylaxis”. They acknowledge also that the Fernando et al. analysis yields important insights into VTE prevention in the ICU. Rhetorically raising the question, “Can we now say without doubt that LMWH is the preferred agent for all patients in the ICU?” – they responded, “probably.” Not entirely eliminated, they observe, is the possibility that a specific patient subgroup may benefit from one agent compared with another. They add, “We came away more confident that LMWH should be the default choice for VTE prevention in the ICU.”

Dr. Fernando and coauthors listed multiple disclosures, but declared that they received no financial support. Dr. McMahon and Dr. Holley declared that they have no disclosures.

Compared with control treatment among critically ill adults, low-molecular-weight heparin (LMWH) reduces the incidence of deep vein thrombosis (DVT), according to a systematic review and network meta-analysis of randomized clinical trials (RCTs) published in CHEST. The analysis showed also that risk of DVT may be reduced by unfractionated heparin (UFH) and by mechanical compressive devices, although LMWH should be considered the primary pharmacologic agent for thromboprophylaxis.

Risk of venous thromboembolism (VTE), including DVT and pulmonary embolism (PE), is heightened in critically ill patients. VTE incidence is highest in major surgery and trauma patients, and mortality estimates from PE among intensive care unit patients are as high as 12%. Clinical practice guidelines recommend prophylaxis with pharmacologic agents over no prophylaxis in critically ill adults. Shannon M. Fernando, MD, of the University of Ottawa and colleagues examined the comparative efficacy and safety of various agents for VTE prophylaxis in critically ill patients through a review of 13 RCTs (9,619 patients) in six databases (Medline, PubMed, EMBASE, Scopus, Webof Science, and the Cochrane Database of Systematic Reviews). The ICU patients received a variety of therapies including pharmacologic, mechanical, or their combination for thromboprophylaxis. The control population consisted of a composite of no prophylaxis, placebo, or compression stockings only.
 

Indicative results

Analysis showed LMWH to reduce the incidence of DVT (odds ratio, 0.59; high certainty), while UFH may reduce the incidence of DVT (OR, 0.82; low certainty). Compared with UFH, LMWH probably reduces DVT (OR, 0.72; moderate certainty). Compressive devices, based on low-certainty evidence, may reduce risk of DVT, compared with control treatments (OR, 0.85).

The effect of combination therapy on DVT, compared with either therapy alone was unclear (very low certainty). The large-scale (2,000 patients) PREVENT trial in 2019, Dr. Fernando noted in an interview, found that adding compression therapy to pharmacologic therapy produced no reduction in proximal lower limb DVT.

“Ultimately, I think that, even if multiple RCTs and subsequent meta-analyses were performed, at best we would find that the incremental benefit of combination therapy is very minimal,” Dr. Fernando stated.

The findings provide evidence supporting LMWH and UFH use as compared with no pharmacologic prophylaxis for prevention of DVT, according to the researchers. While a similar certainty of effect in reducing PE was not found, evidence with moderate certainty suggested that LMWH and UFH probably reduce the incidence of any VTE, compared with no pharmacologic prophylaxis. Cost-effectiveness modeling that takes into account VTE incidence supports the practice. “If you’re reducing the incidence of DVT, it’s likely you’re similarly reducing incidence of PE, though I will agree that currently the data do not support this,” he said in an interview.

Noting that, while support in existing literature for any specific agent is controversial, the authors cite that American Society of Hematology guidelines suggest considering LMWH over UFH in critically ill patients, and that their findings lend support to that position. Regarding safety, pair-wise meta-analysis did not reveal clear major bleeding incidence differences between UFH and LMWH.
 

In and out of the ICU

Concordant with studies outside the ICU finding that heparin-induced thrombocytopenia (HIT) incidence is lower among patients receiving LMWH rather than UFH for VTE prophylaxis, the meta-analysis revealed a lower incidence of HIT among the critically ill receiving LMWH, but with evidence that was of low certainty.

Uncertainty around the optimal approach to VTE prophylaxis in the ICU along with wide variations in clinical practice persist despite recognition of the issue’s importance, note Major Michael J. McMahon, MD, of Honolulu and Colonel Aaron B. Holley, MD, of Bethesda, Md., authors of an accompanying editorial, “To generalize or not to generalize? The approach to VTE prophylaxis”. They acknowledge also that the Fernando et al. analysis yields important insights into VTE prevention in the ICU. Rhetorically raising the question, “Can we now say without doubt that LMWH is the preferred agent for all patients in the ICU?” – they responded, “probably.” Not entirely eliminated, they observe, is the possibility that a specific patient subgroup may benefit from one agent compared with another. They add, “We came away more confident that LMWH should be the default choice for VTE prevention in the ICU.”

Dr. Fernando and coauthors listed multiple disclosures, but declared that they received no financial support. Dr. McMahon and Dr. Holley declared that they have no disclosures.

A former pain medicine physician received a sentence of 20 years in prison for selling opioids and writing prescriptions for patients who were abusing or diverting the medications.

Patrick Titus, 58, operated Lighthouse Internal Medicine in Milford, Delaware, from 2005-2014.

Federal prosecutors said Mr. Titus unlawfully distributed or dispensed opioids including fentanyl, morphine, methadone, OxyContin, and oxycodone outside the scope of practice and often prescribed them in combination with each other or in other dangerous combinations. Mr. Titus distributed over 1 million pills, said the government.

In a 2018 indictment, the government said that Mr. Titus would, “at the first and nearly every follow-up visit” prescribe opioids in high dosages, often without conducting an exam or reviewing any urine test results. He would also write prescriptions for opioids without getting patients’s prior medical records or reviewing test results and rarely referred patients to alternative pain treatments such as physical therapy, psychotherapy, or massage.

According to the indictment, he ignored “red flags,” including that patients would come from long distances, sometimes from out of state, and would pay cash, despite having Medicaid coverage.

“Today’s sentencing makes clear that medical professionals who recklessly prescribe opioids and endanger the safety and health of patients will be held accountable,” said Anne Milgram, a Drug Enforcement Administration administrator.

“This sentence is a reminder that the Department of Justice will hold accountable those doctors who are illegitimately prescribing opioids and fueling the country’s opioid crisis,” said Assistant Attorney General Kenneth A. Polite Jr., of the Justice Department’s Criminal Division, in the same statement. “Doctors who commit these unlawful acts exploit their roles as stewards of their patients’s care for their own profit,” he added.

The sentence follows Mr. Titus’s 2-week jury trial in 2021, when he was convicted of 13 counts of unlawful distribution and dispensing of controlled substances and one count of maintaining his practice primarily as a location to sell drugs. Mr. Titus faced a maximum of 20 years per count.

At the time of his conviction, Mr. Titus’s attorney said he planned to appeal, according to Delaware Online.

Delaware suspended Mr. Titus’s registration to prescribe controlled substances for 1 year in 2011. At the time, the state said it had determined that his continued prescribing “poses [an] imminent danger to the public health or safety.”

The state found that from January to November 2011, Mr. Titus issued 3,941 prescriptions for almost 750,000 pills for 17 different controlled substances, all sent to a single pharmacy.

The state also alleged that he wrote prescriptions for controlled substances to patients with felony convictions for drug trafficking and to at least one patient who his staff told him was selling the opioid that Mr. Titus had prescribed. It later determined that Mr. Titus continued prescribing even after it had suspended his DEA registration.

According to a 2014 consent agreement, the state subsequently ordered another 1-year suspension of his DEA registration, to be followed by a 3-year probation period.

Meanwhile, the same year, the state Board of Medical Licensure put Mr. Titus’s medical license on probation for 2 years and ordered him to complete 15 continuing medical education credits in medical recordkeeping, ethics, how to detect diversion and abuse, and in some other areas, and to pay a $7,500 fine.

In 2016, the medical board revoked Mr. Titus’s license, after finding that he continued to prescribe pain medications to patients he did not screen or monitor and for a multitude of other infractions.

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

A former pain medicine physician received a sentence of 20 years in prison for selling opioids and writing prescriptions for patients who were abusing or diverting the medications.

Patrick Titus, 58, operated Lighthouse Internal Medicine in Milford, Delaware, from 2005-2014.

Federal prosecutors said Mr. Titus unlawfully distributed or dispensed opioids including fentanyl, morphine, methadone, OxyContin, and oxycodone outside the scope of practice and often prescribed them in combination with each other or in other dangerous combinations. Mr. Titus distributed over 1 million pills, said the government.

In a 2018 indictment, the government said that Mr. Titus would, “at the first and nearly every follow-up visit” prescribe opioids in high dosages, often without conducting an exam or reviewing any urine test results. He would also write prescriptions for opioids without getting patients’s prior medical records or reviewing test results and rarely referred patients to alternative pain treatments such as physical therapy, psychotherapy, or massage.

According to the indictment, he ignored “red flags,” including that patients would come from long distances, sometimes from out of state, and would pay cash, despite having Medicaid coverage.

“Today’s sentencing makes clear that medical professionals who recklessly prescribe opioids and endanger the safety and health of patients will be held accountable,” said Anne Milgram, a Drug Enforcement Administration administrator.

“This sentence is a reminder that the Department of Justice will hold accountable those doctors who are illegitimately prescribing opioids and fueling the country’s opioid crisis,” said Assistant Attorney General Kenneth A. Polite Jr., of the Justice Department’s Criminal Division, in the same statement. “Doctors who commit these unlawful acts exploit their roles as stewards of their patients’s care for their own profit,” he added.

The sentence follows Mr. Titus’s 2-week jury trial in 2021, when he was convicted of 13 counts of unlawful distribution and dispensing of controlled substances and one count of maintaining his practice primarily as a location to sell drugs. Mr. Titus faced a maximum of 20 years per count.

At the time of his conviction, Mr. Titus’s attorney said he planned to appeal, according to Delaware Online.

Delaware suspended Mr. Titus’s registration to prescribe controlled substances for 1 year in 2011. At the time, the state said it had determined that his continued prescribing “poses [an] imminent danger to the public health or safety.”

The state found that from January to November 2011, Mr. Titus issued 3,941 prescriptions for almost 750,000 pills for 17 different controlled substances, all sent to a single pharmacy.

The state also alleged that he wrote prescriptions for controlled substances to patients with felony convictions for drug trafficking and to at least one patient who his staff told him was selling the opioid that Mr. Titus had prescribed. It later determined that Mr. Titus continued prescribing even after it had suspended his DEA registration.

According to a 2014 consent agreement, the state subsequently ordered another 1-year suspension of his DEA registration, to be followed by a 3-year probation period.

Meanwhile, the same year, the state Board of Medical Licensure put Mr. Titus’s medical license on probation for 2 years and ordered him to complete 15 continuing medical education credits in medical recordkeeping, ethics, how to detect diversion and abuse, and in some other areas, and to pay a $7,500 fine.

In 2016, the medical board revoked Mr. Titus’s license, after finding that he continued to prescribe pain medications to patients he did not screen or monitor and for a multitude of other infractions.

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

A former pain medicine physician received a sentence of 20 years in prison for selling opioids and writing prescriptions for patients who were abusing or diverting the medications.

Patrick Titus, 58, operated Lighthouse Internal Medicine in Milford, Delaware, from 2005-2014.

Federal prosecutors said Mr. Titus unlawfully distributed or dispensed opioids including fentanyl, morphine, methadone, OxyContin, and oxycodone outside the scope of practice and often prescribed them in combination with each other or in other dangerous combinations. Mr. Titus distributed over 1 million pills, said the government.

In a 2018 indictment, the government said that Mr. Titus would, “at the first and nearly every follow-up visit” prescribe opioids in high dosages, often without conducting an exam or reviewing any urine test results. He would also write prescriptions for opioids without getting patients’s prior medical records or reviewing test results and rarely referred patients to alternative pain treatments such as physical therapy, psychotherapy, or massage.

According to the indictment, he ignored “red flags,” including that patients would come from long distances, sometimes from out of state, and would pay cash, despite having Medicaid coverage.

“Today’s sentencing makes clear that medical professionals who recklessly prescribe opioids and endanger the safety and health of patients will be held accountable,” said Anne Milgram, a Drug Enforcement Administration administrator.

“This sentence is a reminder that the Department of Justice will hold accountable those doctors who are illegitimately prescribing opioids and fueling the country’s opioid crisis,” said Assistant Attorney General Kenneth A. Polite Jr., of the Justice Department’s Criminal Division, in the same statement. “Doctors who commit these unlawful acts exploit their roles as stewards of their patients’s care for their own profit,” he added.

The sentence follows Mr. Titus’s 2-week jury trial in 2021, when he was convicted of 13 counts of unlawful distribution and dispensing of controlled substances and one count of maintaining his practice primarily as a location to sell drugs. Mr. Titus faced a maximum of 20 years per count.

At the time of his conviction, Mr. Titus’s attorney said he planned to appeal, according to Delaware Online.

Delaware suspended Mr. Titus’s registration to prescribe controlled substances for 1 year in 2011. At the time, the state said it had determined that his continued prescribing “poses [an] imminent danger to the public health or safety.”

The state found that from January to November 2011, Mr. Titus issued 3,941 prescriptions for almost 750,000 pills for 17 different controlled substances, all sent to a single pharmacy.

The state also alleged that he wrote prescriptions for controlled substances to patients with felony convictions for drug trafficking and to at least one patient who his staff told him was selling the opioid that Mr. Titus had prescribed. It later determined that Mr. Titus continued prescribing even after it had suspended his DEA registration.

According to a 2014 consent agreement, the state subsequently ordered another 1-year suspension of his DEA registration, to be followed by a 3-year probation period.

Meanwhile, the same year, the state Board of Medical Licensure put Mr. Titus’s medical license on probation for 2 years and ordered him to complete 15 continuing medical education credits in medical recordkeeping, ethics, how to detect diversion and abuse, and in some other areas, and to pay a $7,500 fine.

In 2016, the medical board revoked Mr. Titus’s license, after finding that he continued to prescribe pain medications to patients he did not screen or monitor and for a multitude of other infractions.

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

Unless air pollution and smoking patterns are reversed, lung cancer cases and deaths will grow unabated in some countries, according to estimates of lung cancer incident cases, deaths, and their age-standardized rates.

The findings, based on recently released data from GLOBOCAN 2020 projected to the year 2050, suggest that the lung cancer epidemic will continue to unfold, according to Rajesh Sharma, PhD, et al., in a study published in the International Journal of Clinical Oncology. GLOBOCAN 2020 is an online database produced by the International Agency for Research on Cancer. It provides global cancer statistics from 185 countries for 36 cancer types.

The increase in lung cancer, the leading cancer worldwide in terms of deaths, is generally attributed to increases in cigarette smoking, Sharma et al. wrote. They point out that, while cigarette smoking is expected to have peaked in industrialized countries in the latter half of the twentieth century, the tobacco smoking epidemic is unfolding in regions of Asia and Africa with concomitant increases in lung cancer burden in several countries. Smoking is the most significant lung cancer risk factor, followed by air pollution (especially particulate matter, passive smoking, and occupational exposure to radon and asbestos).

The authors investigated bivariate associations between smoking prevalence and age-standardized rates of lung cancer, and projected lung cancer incident cases and deaths to 2050. They also looked at mortality-to-incidence, considered to be a proxy indicator of 5-year survival, and at human development index, a measure including life expectancy at birth, years of schooling, and standard of living. The results, they state, are expected to aid in policy formulation to combat the lung cancer burden at global, regional, and national levels.

Tobacco smoking prevalence was 21.9% worldwide in 2016, with tobacco smoking prevalence exceeding 25% in 57/149 countries. It was high in European countries with 5 of the top-10 countries among the 149 countries within Europe. Prevalence was greater than 10% in all European countries. Notably, 11/33 countries in Africa had a smoking prevalence less than 10%.

Analysis showed 2.21 million new lung cancer cases and 1.8 million deaths attributed to lung cancer worldwide in 2020, with males accounting for about two-thirds of the burden. The analysis projection for 2050 was for 3.8 million incident cases of lung cancer and 3.2 million lung cancer deaths globally. In 2050, lung cancer cases and deaths are projected to be more than 100,000 in 10/21 regions, led by Eastern Asia, projected to record 1.7 million incident cases and 1.5 million deaths.

The burden of lung cancer in regions of Asia and Africa is expected to increase at least twofold from 2020 to 2050, surpassing European regions that are expected to have the smallest increases. Also, while incident cases will remain much higher in Northern America than in Southeastern Asia and South-Central Asia, the number of lives lost is projected to be similar. The age-specific incidence and death rates rose with age such that the oldest age groups had the highest age-specific rates. With the human development index, mortality-to-incidence showed a negative correlation.

The authors wrote that worsening smoking and pollution levels in developing countries may push the future lung cancer burden much higher than these projections. Unless reversed, cases and death will grow unabated.

“Countering the burden of lung cancer also requires curtailment of other risk factors such as air pollution and exposure to carcinogens,” the authors wrote.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors stated that they have no conflicts of interest.

Unless air pollution and smoking patterns are reversed, lung cancer cases and deaths will grow unabated in some countries, according to estimates of lung cancer incident cases, deaths, and their age-standardized rates.

The findings, based on recently released data from GLOBOCAN 2020 projected to the year 2050, suggest that the lung cancer epidemic will continue to unfold, according to Rajesh Sharma, PhD, et al., in a study published in the International Journal of Clinical Oncology. GLOBOCAN 2020 is an online database produced by the International Agency for Research on Cancer. It provides global cancer statistics from 185 countries for 36 cancer types.

The increase in lung cancer, the leading cancer worldwide in terms of deaths, is generally attributed to increases in cigarette smoking, Sharma et al. wrote. They point out that, while cigarette smoking is expected to have peaked in industrialized countries in the latter half of the twentieth century, the tobacco smoking epidemic is unfolding in regions of Asia and Africa with concomitant increases in lung cancer burden in several countries. Smoking is the most significant lung cancer risk factor, followed by air pollution (especially particulate matter, passive smoking, and occupational exposure to radon and asbestos).

The authors investigated bivariate associations between smoking prevalence and age-standardized rates of lung cancer, and projected lung cancer incident cases and deaths to 2050. They also looked at mortality-to-incidence, considered to be a proxy indicator of 5-year survival, and at human development index, a measure including life expectancy at birth, years of schooling, and standard of living. The results, they state, are expected to aid in policy formulation to combat the lung cancer burden at global, regional, and national levels.

Tobacco smoking prevalence was 21.9% worldwide in 2016, with tobacco smoking prevalence exceeding 25% in 57/149 countries. It was high in European countries with 5 of the top-10 countries among the 149 countries within Europe. Prevalence was greater than 10% in all European countries. Notably, 11/33 countries in Africa had a smoking prevalence less than 10%.

Analysis showed 2.21 million new lung cancer cases and 1.8 million deaths attributed to lung cancer worldwide in 2020, with males accounting for about two-thirds of the burden. The analysis projection for 2050 was for 3.8 million incident cases of lung cancer and 3.2 million lung cancer deaths globally. In 2050, lung cancer cases and deaths are projected to be more than 100,000 in 10/21 regions, led by Eastern Asia, projected to record 1.7 million incident cases and 1.5 million deaths.

The burden of lung cancer in regions of Asia and Africa is expected to increase at least twofold from 2020 to 2050, surpassing European regions that are expected to have the smallest increases. Also, while incident cases will remain much higher in Northern America than in Southeastern Asia and South-Central Asia, the number of lives lost is projected to be similar. The age-specific incidence and death rates rose with age such that the oldest age groups had the highest age-specific rates. With the human development index, mortality-to-incidence showed a negative correlation.

The authors wrote that worsening smoking and pollution levels in developing countries may push the future lung cancer burden much higher than these projections. Unless reversed, cases and death will grow unabated.

“Countering the burden of lung cancer also requires curtailment of other risk factors such as air pollution and exposure to carcinogens,” the authors wrote.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors stated that they have no conflicts of interest.

Unless air pollution and smoking patterns are reversed, lung cancer cases and deaths will grow unabated in some countries, according to estimates of lung cancer incident cases, deaths, and their age-standardized rates.

The findings, based on recently released data from GLOBOCAN 2020 projected to the year 2050, suggest that the lung cancer epidemic will continue to unfold, according to Rajesh Sharma, PhD, et al., in a study published in the International Journal of Clinical Oncology. GLOBOCAN 2020 is an online database produced by the International Agency for Research on Cancer. It provides global cancer statistics from 185 countries for 36 cancer types.

The increase in lung cancer, the leading cancer worldwide in terms of deaths, is generally attributed to increases in cigarette smoking, Sharma et al. wrote. They point out that, while cigarette smoking is expected to have peaked in industrialized countries in the latter half of the twentieth century, the tobacco smoking epidemic is unfolding in regions of Asia and Africa with concomitant increases in lung cancer burden in several countries. Smoking is the most significant lung cancer risk factor, followed by air pollution (especially particulate matter, passive smoking, and occupational exposure to radon and asbestos).

The authors investigated bivariate associations between smoking prevalence and age-standardized rates of lung cancer, and projected lung cancer incident cases and deaths to 2050. They also looked at mortality-to-incidence, considered to be a proxy indicator of 5-year survival, and at human development index, a measure including life expectancy at birth, years of schooling, and standard of living. The results, they state, are expected to aid in policy formulation to combat the lung cancer burden at global, regional, and national levels.

Tobacco smoking prevalence was 21.9% worldwide in 2016, with tobacco smoking prevalence exceeding 25% in 57/149 countries. It was high in European countries with 5 of the top-10 countries among the 149 countries within Europe. Prevalence was greater than 10% in all European countries. Notably, 11/33 countries in Africa had a smoking prevalence less than 10%.

Analysis showed 2.21 million new lung cancer cases and 1.8 million deaths attributed to lung cancer worldwide in 2020, with males accounting for about two-thirds of the burden. The analysis projection for 2050 was for 3.8 million incident cases of lung cancer and 3.2 million lung cancer deaths globally. In 2050, lung cancer cases and deaths are projected to be more than 100,000 in 10/21 regions, led by Eastern Asia, projected to record 1.7 million incident cases and 1.5 million deaths.

The burden of lung cancer in regions of Asia and Africa is expected to increase at least twofold from 2020 to 2050, surpassing European regions that are expected to have the smallest increases. Also, while incident cases will remain much higher in Northern America than in Southeastern Asia and South-Central Asia, the number of lives lost is projected to be similar. The age-specific incidence and death rates rose with age such that the oldest age groups had the highest age-specific rates. With the human development index, mortality-to-incidence showed a negative correlation.

The authors wrote that worsening smoking and pollution levels in developing countries may push the future lung cancer burden much higher than these projections. Unless reversed, cases and death will grow unabated.

“Countering the burden of lung cancer also requires curtailment of other risk factors such as air pollution and exposure to carcinogens,” the authors wrote.

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors stated that they have no conflicts of interest.

Research suggests that physicians have suicidal thoughts at about twice the rate of the general population (7.2% vs. 4%). Now, as they bear the weight of a multiyear pandemic alongside the perpetual struggle to maintain some semblance of work-life balance, their resiliency has been stretched to the brink.

In 2022, the Medscape Physician Suicide Report surveyed more than 13,000 physicians in 29 specialties who were candid about their experiences with suicidal thoughts, how they support their besieged colleagues, and their go-to coping strategies.

Overall, 21% of physicians reported having feelings of depression. Of those, 24% had clinical depression and 64% had colloquial depression. Physicians who felt sad or blue decreased slightly, compared with the 2021 report, but the number of physicians experiencing severe depression rose 4%.

One in 10 physicians said they have thought about or attempted suicide. However, the number of physicians with suicidal thoughts dropped to 9%, down substantially from the 22% who reported similar feelings in 2020.

Still, there was a slight uptick in women physicians contemplating suicide, likely linked to their larger share of childcare and family responsibilities.

Washington University School of Medicine

“They have needed to pull double duty even more than usual, and that may have increased their sense of burnout and vulnerability to suicidal thoughts,” said Andrea Giedinghagen, MD, assistant professor in the department of psychiatry at Washington University in St. Louis, and coauthor of “Physician Suicide: A Call to Action
 

Fighting the stigma of seeking mental health help

Although the number of physicians attempting, but not completing suicide, has remained steady at 1% for several years, the recent passage of the Dr. Lorna Breen Health Care Provider Protection Act by Congress aims to drive that figure even lower. Dr. Breen, an ED physician at New York–Presbyterian Hospital, died by suicide in April 2020. Overwhelmed by the onslaught of COVID patients, Dr. Breen was reluctant to seek mental health services for fear of being ostracized.

“Many physicians don’t seek mental health care due to fear of negative consequences in the workplace, including retribution, exclusion, loss of license, or even their job,” Gary Price, MD, president of The Physicians Foundation, told this news organization. “This was the experience of Dr. Lorna Breen. She was convinced that if she talked to a professional, she would lose her medical license. Perhaps if Dr. Breen was equipped with the accurate information – there is no mental health reporting requirement in her state’s medical license application – it might have saved her life.”

This same stigma was reflected in the survey, with one physician saying: “I’m afraid that if I spoke to a therapist, I’d have to report receiving psychiatric treatment to credentialing or licensing boards.” Roughly 40% of survey respondents, regardless of age, chose not to disclose their suicidal thoughts to anyone, not even a family member or suicide hotline. And just a tiny portion of physicians (10% of men and 13% of women) said that a colleague had discussed their suicidal thoughts with them.

“There is a longstanding culture of silence around physician mental health in the medical community,” said Dr. Price. “The strategies within the Act are critical to fixing this culture and making it acceptable and normalized for physicians to seek mental health care,” and for it to “become a fundamental and ongoing element of being a practicing physician.”

As part of the legislation, the Department of Health & Human Services must award grants to hospitals, medical associations, and other entities to facilitate mental health programs for providers. They must also establish policy recommendations and conduct campaigns to improve providers’ mental and behavioral health, encourage providers to seek mental health support and assistance, remove barriers to such treatment, and identify best practices to prevent suicide and promote resiliency
 

Addressing barriers to mental health

The new bill is a step in the right direction, but Dr. Price said health organizations must do more to address the six key structural barriers that are “discouraging physicians from seeking [mental health] help,” such as the inclusion of “intrusive mental health questions on medical board, hospital credentialing, and malpractice insurance applications.”

In addition, employers should allow physicians to seek out-of-network mental health services, if necessary, and not cause further humiliation by requiring them to be treated by colleagues within their hospital system. A similar proposal has recently been introduced and is gaining traction in Utah, following the suicide of ED physician Scott Jolley, MD, in 2021 after he was admitted for psychiatric care where he worked.

Diminishing the stigma surrounding physicians’ mental health encourages a more open dialogue, so if a colleague reaches out – listen. “Start by thanking the colleague for sharing the information: ‘I’m sure that wasn’t easy but I appreciate that you respect me enough to share this. Let’s talk more,’ ” said Michael F. Myers, MD, professor of clinical psychiatry at State University of New York, Brooklyn . “Then ask what you can do to help, which cuts down on the sense of isolation that colleague may feel.”

According to the survey, many physicians have developed strategies to support their happiness and mental health. Although fewer than 10% said reducing work hours or transitioning to a part-time schedule was most effective, the majority of physicians relied on spending time with family and friends (68%) – a choice that has considerable benefits.

“Close and intimate relationships are the single most protective factor for our mental health,” said Peter Yellowlees, MBBS, MD, chief wellness officer for UC Davis Health and professor of psychiatry at the University of California, Davis. “Isolation and loneliness are very important stressors, and we know that about 25% of the population reports being lonely.”

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

Research suggests that physicians have suicidal thoughts at about twice the rate of the general population (7.2% vs. 4%). Now, as they bear the weight of a multiyear pandemic alongside the perpetual struggle to maintain some semblance of work-life balance, their resiliency has been stretched to the brink.

In 2022, the Medscape Physician Suicide Report surveyed more than 13,000 physicians in 29 specialties who were candid about their experiences with suicidal thoughts, how they support their besieged colleagues, and their go-to coping strategies.

Overall, 21% of physicians reported having feelings of depression. Of those, 24% had clinical depression and 64% had colloquial depression. Physicians who felt sad or blue decreased slightly, compared with the 2021 report, but the number of physicians experiencing severe depression rose 4%.

One in 10 physicians said they have thought about or attempted suicide. However, the number of physicians with suicidal thoughts dropped to 9%, down substantially from the 22% who reported similar feelings in 2020.

Still, there was a slight uptick in women physicians contemplating suicide, likely linked to their larger share of childcare and family responsibilities.

Washington University School of Medicine

“They have needed to pull double duty even more than usual, and that may have increased their sense of burnout and vulnerability to suicidal thoughts,” said Andrea Giedinghagen, MD, assistant professor in the department of psychiatry at Washington University in St. Louis, and coauthor of “Physician Suicide: A Call to Action
 

Fighting the stigma of seeking mental health help

Although the number of physicians attempting, but not completing suicide, has remained steady at 1% for several years, the recent passage of the Dr. Lorna Breen Health Care Provider Protection Act by Congress aims to drive that figure even lower. Dr. Breen, an ED physician at New York–Presbyterian Hospital, died by suicide in April 2020. Overwhelmed by the onslaught of COVID patients, Dr. Breen was reluctant to seek mental health services for fear of being ostracized.

“Many physicians don’t seek mental health care due to fear of negative consequences in the workplace, including retribution, exclusion, loss of license, or even their job,” Gary Price, MD, president of The Physicians Foundation, told this news organization. “This was the experience of Dr. Lorna Breen. She was convinced that if she talked to a professional, she would lose her medical license. Perhaps if Dr. Breen was equipped with the accurate information – there is no mental health reporting requirement in her state’s medical license application – it might have saved her life.”

This same stigma was reflected in the survey, with one physician saying: “I’m afraid that if I spoke to a therapist, I’d have to report receiving psychiatric treatment to credentialing or licensing boards.” Roughly 40% of survey respondents, regardless of age, chose not to disclose their suicidal thoughts to anyone, not even a family member or suicide hotline. And just a tiny portion of physicians (10% of men and 13% of women) said that a colleague had discussed their suicidal thoughts with them.

“There is a longstanding culture of silence around physician mental health in the medical community,” said Dr. Price. “The strategies within the Act are critical to fixing this culture and making it acceptable and normalized for physicians to seek mental health care,” and for it to “become a fundamental and ongoing element of being a practicing physician.”

As part of the legislation, the Department of Health & Human Services must award grants to hospitals, medical associations, and other entities to facilitate mental health programs for providers. They must also establish policy recommendations and conduct campaigns to improve providers’ mental and behavioral health, encourage providers to seek mental health support and assistance, remove barriers to such treatment, and identify best practices to prevent suicide and promote resiliency
 

Addressing barriers to mental health

The new bill is a step in the right direction, but Dr. Price said health organizations must do more to address the six key structural barriers that are “discouraging physicians from seeking [mental health] help,” such as the inclusion of “intrusive mental health questions on medical board, hospital credentialing, and malpractice insurance applications.”

In addition, employers should allow physicians to seek out-of-network mental health services, if necessary, and not cause further humiliation by requiring them to be treated by colleagues within their hospital system. A similar proposal has recently been introduced and is gaining traction in Utah, following the suicide of ED physician Scott Jolley, MD, in 2021 after he was admitted for psychiatric care where he worked.

Diminishing the stigma surrounding physicians’ mental health encourages a more open dialogue, so if a colleague reaches out – listen. “Start by thanking the colleague for sharing the information: ‘I’m sure that wasn’t easy but I appreciate that you respect me enough to share this. Let’s talk more,’ ” said Michael F. Myers, MD, professor of clinical psychiatry at State University of New York, Brooklyn . “Then ask what you can do to help, which cuts down on the sense of isolation that colleague may feel.”

According to the survey, many physicians have developed strategies to support their happiness and mental health. Although fewer than 10% said reducing work hours or transitioning to a part-time schedule was most effective, the majority of physicians relied on spending time with family and friends (68%) – a choice that has considerable benefits.

“Close and intimate relationships are the single most protective factor for our mental health,” said Peter Yellowlees, MBBS, MD, chief wellness officer for UC Davis Health and professor of psychiatry at the University of California, Davis. “Isolation and loneliness are very important stressors, and we know that about 25% of the population reports being lonely.”

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

Research suggests that physicians have suicidal thoughts at about twice the rate of the general population (7.2% vs. 4%). Now, as they bear the weight of a multiyear pandemic alongside the perpetual struggle to maintain some semblance of work-life balance, their resiliency has been stretched to the brink.

In 2022, the Medscape Physician Suicide Report surveyed more than 13,000 physicians in 29 specialties who were candid about their experiences with suicidal thoughts, how they support their besieged colleagues, and their go-to coping strategies.

Overall, 21% of physicians reported having feelings of depression. Of those, 24% had clinical depression and 64% had colloquial depression. Physicians who felt sad or blue decreased slightly, compared with the 2021 report, but the number of physicians experiencing severe depression rose 4%.

One in 10 physicians said they have thought about or attempted suicide. However, the number of physicians with suicidal thoughts dropped to 9%, down substantially from the 22% who reported similar feelings in 2020.

Still, there was a slight uptick in women physicians contemplating suicide, likely linked to their larger share of childcare and family responsibilities.

Washington University School of Medicine

“They have needed to pull double duty even more than usual, and that may have increased their sense of burnout and vulnerability to suicidal thoughts,” said Andrea Giedinghagen, MD, assistant professor in the department of psychiatry at Washington University in St. Louis, and coauthor of “Physician Suicide: A Call to Action
 

Fighting the stigma of seeking mental health help

Although the number of physicians attempting, but not completing suicide, has remained steady at 1% for several years, the recent passage of the Dr. Lorna Breen Health Care Provider Protection Act by Congress aims to drive that figure even lower. Dr. Breen, an ED physician at New York–Presbyterian Hospital, died by suicide in April 2020. Overwhelmed by the onslaught of COVID patients, Dr. Breen was reluctant to seek mental health services for fear of being ostracized.

“Many physicians don’t seek mental health care due to fear of negative consequences in the workplace, including retribution, exclusion, loss of license, or even their job,” Gary Price, MD, president of The Physicians Foundation, told this news organization. “This was the experience of Dr. Lorna Breen. She was convinced that if she talked to a professional, she would lose her medical license. Perhaps if Dr. Breen was equipped with the accurate information – there is no mental health reporting requirement in her state’s medical license application – it might have saved her life.”

This same stigma was reflected in the survey, with one physician saying: “I’m afraid that if I spoke to a therapist, I’d have to report receiving psychiatric treatment to credentialing or licensing boards.” Roughly 40% of survey respondents, regardless of age, chose not to disclose their suicidal thoughts to anyone, not even a family member or suicide hotline. And just a tiny portion of physicians (10% of men and 13% of women) said that a colleague had discussed their suicidal thoughts with them.

“There is a longstanding culture of silence around physician mental health in the medical community,” said Dr. Price. “The strategies within the Act are critical to fixing this culture and making it acceptable and normalized for physicians to seek mental health care,” and for it to “become a fundamental and ongoing element of being a practicing physician.”

As part of the legislation, the Department of Health & Human Services must award grants to hospitals, medical associations, and other entities to facilitate mental health programs for providers. They must also establish policy recommendations and conduct campaigns to improve providers’ mental and behavioral health, encourage providers to seek mental health support and assistance, remove barriers to such treatment, and identify best practices to prevent suicide and promote resiliency
 

Addressing barriers to mental health

The new bill is a step in the right direction, but Dr. Price said health organizations must do more to address the six key structural barriers that are “discouraging physicians from seeking [mental health] help,” such as the inclusion of “intrusive mental health questions on medical board, hospital credentialing, and malpractice insurance applications.”

In addition, employers should allow physicians to seek out-of-network mental health services, if necessary, and not cause further humiliation by requiring them to be treated by colleagues within their hospital system. A similar proposal has recently been introduced and is gaining traction in Utah, following the suicide of ED physician Scott Jolley, MD, in 2021 after he was admitted for psychiatric care where he worked.

Diminishing the stigma surrounding physicians’ mental health encourages a more open dialogue, so if a colleague reaches out – listen. “Start by thanking the colleague for sharing the information: ‘I’m sure that wasn’t easy but I appreciate that you respect me enough to share this. Let’s talk more,’ ” said Michael F. Myers, MD, professor of clinical psychiatry at State University of New York, Brooklyn . “Then ask what you can do to help, which cuts down on the sense of isolation that colleague may feel.”

According to the survey, many physicians have developed strategies to support their happiness and mental health. Although fewer than 10% said reducing work hours or transitioning to a part-time schedule was most effective, the majority of physicians relied on spending time with family and friends (68%) – a choice that has considerable benefits.

“Close and intimate relationships are the single most protective factor for our mental health,” said Peter Yellowlees, MBBS, MD, chief wellness officer for UC Davis Health and professor of psychiatry at the University of California, Davis. “Isolation and loneliness are very important stressors, and we know that about 25% of the population reports being lonely.”

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

Children who survive an episode of acute respiratory failure that requires invasive mechanical ventilation may be at risk for slightly lower long-term neurocognitive function, new research suggests.

Investigators found lower IQs in children without previous neurocognitive problems who survived pediatric intensive care unit admission for acute respiratory failure, compared with their biological siblings.

Although this magnitude of difference was small on average, more than twice as many patients as siblings had an IQ of ≤85, and children hospitalized at the youngest ages did worse than their siblings.

“Children surviving acute respiratory failure may benefit from routine evaluation of neurocognitive function after hospital discharge and may require serial evaluation to identify deficits that emerge over the course of child’s continued development to facilitate early intervention to prevent disability and optimize school performance,” study investigator R. Scott Watson, MD, MPH, professor of pediatrics, University of Washington, Seattle, told this news organization.

The study was published online March 1 in JAMA.
 

Unknown long-term effects

“Approximately 23,700 U.S. children undergo invasive mechanical ventilation for acute respiratory failure annually, with unknown long-term effects on neurocognitive function,” the authors write.

“With improvements in pediatric critical care over the past several decades, critical illness–associated mortality has improved dramatically [but] as survivorship has increased, we are starting to learn that many patients and their families suffer from long-term morbidity associated with the illness and its treatment,” said Dr. Watson, who is the associate division chief, pediatric critical care medicine, Seattle Children’s Hospital, Center for Child Health, Behavior, and Development.

Animal studies “have found that some sedative medications commonly used to keep children safe during mechanical ventilation may have detrimental neurologic effects, particularly in the developing brain,” Dr. Watson added.

To gain a better understanding of this potential association, the researchers turned to a subset of participants in the previously conducted Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) trial of pediatric patients receiving mechanical ventilation for acute respiratory failure.

For the current study (RESTORE-Cognition), multiple domains of neurocognitive function were assessed 3-8 years after hospital discharge in trial patients who did not have a history of neurocognitive dysfunction, as well as matched, healthy siblings.

To be included in the study, the children had to be ≤8 years old at trial enrollment, have a Pediatric Cerebral Performance Category (PCPC) score of 1 (normal) prior to PICU admission, and have no worse than moderate neurocognitive dysfunction at PICU discharge.

Siblings of enrolled patients were required to be between 4 and 16 years old at the time of neurocognitive testing, have a PCPC score of 1, have the same biological parents as the patient, and live with the patient.

The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Secondary outcomes included attention, processing speed, learning and memory, visuospatial skills, motor skills, language, and executive function. Enough time was allowed after hospitalization “for transient deficits to resolve and longer-lasting neurocognitive sequelae to manifest.”
 

‘Uncertain’ clinical importance

Of the 121 sibling pairs (67% non-Hispanic White, 47% from families in which one or both parents worked full-time), 116 were included in the primary outcome analysis, and 66-19 were included in analyses of secondary outcomes.

Patients had been in the PICU at a median (interquartile range [IQR]) age of 1.0 (0.2-3.2) years and had received a median of 5.5 (3.1-7.7) days of invasive mechanical ventilation.

The median age at testing for patients and matched siblings was 6.6 (5.4-9.1) and 8.4 (7.0-10.2) years, respectively. Interviews with parents and testing of patients were conducted a median (IQR) of 3.8 (3.2-5.2) and 5.2 (4.3-6.1) years, respectively, after hospitalization.

The most common etiologies of respiratory failure were bronchiolitis and asthma and pneumonia (44% and 37%, respectively). Beyond respiratory failure, most patients (72%) also had experienced multiple organ dysfunction syndrome.

Patients had a lower mean estimated IQ, compared with the matched siblings (101.5 vs. 104.3; mean difference, –2.8 [95% confidence interval, –5.4 to –0.2]), and more patients than siblings had an estimated IQ of ≤5 but not of ≤70.

Patients also had significantly lower scores on nonverbal memory, visuospatial skills, and fine motor control (mean differences, –0.9 [–1.6 to –0.3]; –0.9 [–1.8 to –.1]; and –-3.1 [–4.9 to –1.4], respectively), compared with matched siblings. They also had significantly higher scores on processing speed (mean difference, 4.4 [0.2-8.5]). There were no significant differences in the other secondary outcomes.

Differences in scores between patients and siblings varied significantly by age at hospitalization in several tests – for example, Block Design scores in patients were lower than those of siblings for patients hospitalized at <1 year old, versus those hospitalized between ages 4 and 8 years.

“When adjusting for patient age at PICU admission, patient age at testing, sibling age at testing, and duration between hospital discharge and testing, the difference in estimated IQ between patients and siblings remained statistically significantly different,” the authors note.

The investigators point out several limitations, including the fact that “little is known about sibling outcomes after critical illness, nor about whether parenting of siblings or child development differs based on birth order or on relationship between patient critical illness and the birth of siblings. ... If siblings also incur negative effects related to the critical illness, differences between critically ill children and the control siblings would be blunted.”

Despite the statistical significance of the difference between the patients and the matched controls, ultimately, the magnitude of the difference was “small and of uncertain clinical importance,” the authors conclude.
 

Filling a research gap

Commenting on the findings, Alexandre T. Rotta, MD, professor of pediatrics and chief of the division of pediatric critical care medicine, Duke University Medical Center, Durham, N.C., said the study “addresses an important yet vastly understudied gap: long-term neurocognitive morbidity in children exposed to critical care.”

Dr. Rotta, who is also a coauthor of an accompanying editorial, noted that the fact that the “vast majority of children with an IQ significantly lower than their siblings were under the age of 4 years suggests that the developing immature brain may be particularly susceptible to the effects of critical illness and therapies required to treat it.”

The study “underscores the need to include assessments of long-term morbidity as part of any future trial evaluating interventions in pediatric critical care,” he added.

The study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development for RESTORE-Cognition and by grants for the RESTORE trial from the National Heart, Lung, and Blood Institute and the National Institute of Nursing Research, National Institutes of Health. Dr. Watson and coauthors report no relevant financial relationships. Dr. Rotta has received personal fees from Vapotherm for lecturing and development of educational materials and from Breas US for participation in a scientific advisory board, as well as royalties from Elsevier for editorial work outside the submitted work. His coauthor reports no relevant financial relationships.

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

Children who survive an episode of acute respiratory failure that requires invasive mechanical ventilation may be at risk for slightly lower long-term neurocognitive function, new research suggests.

Investigators found lower IQs in children without previous neurocognitive problems who survived pediatric intensive care unit admission for acute respiratory failure, compared with their biological siblings.

Although this magnitude of difference was small on average, more than twice as many patients as siblings had an IQ of ≤85, and children hospitalized at the youngest ages did worse than their siblings.

“Children surviving acute respiratory failure may benefit from routine evaluation of neurocognitive function after hospital discharge and may require serial evaluation to identify deficits that emerge over the course of child’s continued development to facilitate early intervention to prevent disability and optimize school performance,” study investigator R. Scott Watson, MD, MPH, professor of pediatrics, University of Washington, Seattle, told this news organization.

The study was published online March 1 in JAMA.
 

Unknown long-term effects

“Approximately 23,700 U.S. children undergo invasive mechanical ventilation for acute respiratory failure annually, with unknown long-term effects on neurocognitive function,” the authors write.

“With improvements in pediatric critical care over the past several decades, critical illness–associated mortality has improved dramatically [but] as survivorship has increased, we are starting to learn that many patients and their families suffer from long-term morbidity associated with the illness and its treatment,” said Dr. Watson, who is the associate division chief, pediatric critical care medicine, Seattle Children’s Hospital, Center for Child Health, Behavior, and Development.

Animal studies “have found that some sedative medications commonly used to keep children safe during mechanical ventilation may have detrimental neurologic effects, particularly in the developing brain,” Dr. Watson added.

To gain a better understanding of this potential association, the researchers turned to a subset of participants in the previously conducted Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) trial of pediatric patients receiving mechanical ventilation for acute respiratory failure.

For the current study (RESTORE-Cognition), multiple domains of neurocognitive function were assessed 3-8 years after hospital discharge in trial patients who did not have a history of neurocognitive dysfunction, as well as matched, healthy siblings.

To be included in the study, the children had to be ≤8 years old at trial enrollment, have a Pediatric Cerebral Performance Category (PCPC) score of 1 (normal) prior to PICU admission, and have no worse than moderate neurocognitive dysfunction at PICU discharge.

Siblings of enrolled patients were required to be between 4 and 16 years old at the time of neurocognitive testing, have a PCPC score of 1, have the same biological parents as the patient, and live with the patient.

The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Secondary outcomes included attention, processing speed, learning and memory, visuospatial skills, motor skills, language, and executive function. Enough time was allowed after hospitalization “for transient deficits to resolve and longer-lasting neurocognitive sequelae to manifest.”
 

‘Uncertain’ clinical importance

Of the 121 sibling pairs (67% non-Hispanic White, 47% from families in which one or both parents worked full-time), 116 were included in the primary outcome analysis, and 66-19 were included in analyses of secondary outcomes.

Patients had been in the PICU at a median (interquartile range [IQR]) age of 1.0 (0.2-3.2) years and had received a median of 5.5 (3.1-7.7) days of invasive mechanical ventilation.

The median age at testing for patients and matched siblings was 6.6 (5.4-9.1) and 8.4 (7.0-10.2) years, respectively. Interviews with parents and testing of patients were conducted a median (IQR) of 3.8 (3.2-5.2) and 5.2 (4.3-6.1) years, respectively, after hospitalization.

The most common etiologies of respiratory failure were bronchiolitis and asthma and pneumonia (44% and 37%, respectively). Beyond respiratory failure, most patients (72%) also had experienced multiple organ dysfunction syndrome.

Patients had a lower mean estimated IQ, compared with the matched siblings (101.5 vs. 104.3; mean difference, –2.8 [95% confidence interval, –5.4 to –0.2]), and more patients than siblings had an estimated IQ of ≤5 but not of ≤70.

Patients also had significantly lower scores on nonverbal memory, visuospatial skills, and fine motor control (mean differences, –0.9 [–1.6 to –0.3]; –0.9 [–1.8 to –.1]; and –-3.1 [–4.9 to –1.4], respectively), compared with matched siblings. They also had significantly higher scores on processing speed (mean difference, 4.4 [0.2-8.5]). There were no significant differences in the other secondary outcomes.

Differences in scores between patients and siblings varied significantly by age at hospitalization in several tests – for example, Block Design scores in patients were lower than those of siblings for patients hospitalized at <1 year old, versus those hospitalized between ages 4 and 8 years.

“When adjusting for patient age at PICU admission, patient age at testing, sibling age at testing, and duration between hospital discharge and testing, the difference in estimated IQ between patients and siblings remained statistically significantly different,” the authors note.

The investigators point out several limitations, including the fact that “little is known about sibling outcomes after critical illness, nor about whether parenting of siblings or child development differs based on birth order or on relationship between patient critical illness and the birth of siblings. ... If siblings also incur negative effects related to the critical illness, differences between critically ill children and the control siblings would be blunted.”

Despite the statistical significance of the difference between the patients and the matched controls, ultimately, the magnitude of the difference was “small and of uncertain clinical importance,” the authors conclude.
 

Filling a research gap

Commenting on the findings, Alexandre T. Rotta, MD, professor of pediatrics and chief of the division of pediatric critical care medicine, Duke University Medical Center, Durham, N.C., said the study “addresses an important yet vastly understudied gap: long-term neurocognitive morbidity in children exposed to critical care.”

Dr. Rotta, who is also a coauthor of an accompanying editorial, noted that the fact that the “vast majority of children with an IQ significantly lower than their siblings were under the age of 4 years suggests that the developing immature brain may be particularly susceptible to the effects of critical illness and therapies required to treat it.”

The study “underscores the need to include assessments of long-term morbidity as part of any future trial evaluating interventions in pediatric critical care,” he added.

The study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development for RESTORE-Cognition and by grants for the RESTORE trial from the National Heart, Lung, and Blood Institute and the National Institute of Nursing Research, National Institutes of Health. Dr. Watson and coauthors report no relevant financial relationships. Dr. Rotta has received personal fees from Vapotherm for lecturing and development of educational materials and from Breas US for participation in a scientific advisory board, as well as royalties from Elsevier for editorial work outside the submitted work. His coauthor reports no relevant financial relationships.

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

Children who survive an episode of acute respiratory failure that requires invasive mechanical ventilation may be at risk for slightly lower long-term neurocognitive function, new research suggests.

Investigators found lower IQs in children without previous neurocognitive problems who survived pediatric intensive care unit admission for acute respiratory failure, compared with their biological siblings.

Although this magnitude of difference was small on average, more than twice as many patients as siblings had an IQ of ≤85, and children hospitalized at the youngest ages did worse than their siblings.

“Children surviving acute respiratory failure may benefit from routine evaluation of neurocognitive function after hospital discharge and may require serial evaluation to identify deficits that emerge over the course of child’s continued development to facilitate early intervention to prevent disability and optimize school performance,” study investigator R. Scott Watson, MD, MPH, professor of pediatrics, University of Washington, Seattle, told this news organization.

The study was published online March 1 in JAMA.
 

Unknown long-term effects

“Approximately 23,700 U.S. children undergo invasive mechanical ventilation for acute respiratory failure annually, with unknown long-term effects on neurocognitive function,” the authors write.

“With improvements in pediatric critical care over the past several decades, critical illness–associated mortality has improved dramatically [but] as survivorship has increased, we are starting to learn that many patients and their families suffer from long-term morbidity associated with the illness and its treatment,” said Dr. Watson, who is the associate division chief, pediatric critical care medicine, Seattle Children’s Hospital, Center for Child Health, Behavior, and Development.

Animal studies “have found that some sedative medications commonly used to keep children safe during mechanical ventilation may have detrimental neurologic effects, particularly in the developing brain,” Dr. Watson added.

To gain a better understanding of this potential association, the researchers turned to a subset of participants in the previously conducted Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) trial of pediatric patients receiving mechanical ventilation for acute respiratory failure.

For the current study (RESTORE-Cognition), multiple domains of neurocognitive function were assessed 3-8 years after hospital discharge in trial patients who did not have a history of neurocognitive dysfunction, as well as matched, healthy siblings.

To be included in the study, the children had to be ≤8 years old at trial enrollment, have a Pediatric Cerebral Performance Category (PCPC) score of 1 (normal) prior to PICU admission, and have no worse than moderate neurocognitive dysfunction at PICU discharge.

Siblings of enrolled patients were required to be between 4 and 16 years old at the time of neurocognitive testing, have a PCPC score of 1, have the same biological parents as the patient, and live with the patient.

The primary outcome was IQ, estimated by the age-appropriate Vocabulary and Block Design subtests of the Wechsler Intelligence Scale. Secondary outcomes included attention, processing speed, learning and memory, visuospatial skills, motor skills, language, and executive function. Enough time was allowed after hospitalization “for transient deficits to resolve and longer-lasting neurocognitive sequelae to manifest.”
 

‘Uncertain’ clinical importance

Of the 121 sibling pairs (67% non-Hispanic White, 47% from families in which one or both parents worked full-time), 116 were included in the primary outcome analysis, and 66-19 were included in analyses of secondary outcomes.

Patients had been in the PICU at a median (interquartile range [IQR]) age of 1.0 (0.2-3.2) years and had received a median of 5.5 (3.1-7.7) days of invasive mechanical ventilation.

The median age at testing for patients and matched siblings was 6.6 (5.4-9.1) and 8.4 (7.0-10.2) years, respectively. Interviews with parents and testing of patients were conducted a median (IQR) of 3.8 (3.2-5.2) and 5.2 (4.3-6.1) years, respectively, after hospitalization.

The most common etiologies of respiratory failure were bronchiolitis and asthma and pneumonia (44% and 37%, respectively). Beyond respiratory failure, most patients (72%) also had experienced multiple organ dysfunction syndrome.

Patients had a lower mean estimated IQ, compared with the matched siblings (101.5 vs. 104.3; mean difference, –2.8 [95% confidence interval, –5.4 to –0.2]), and more patients than siblings had an estimated IQ of ≤5 but not of ≤70.

Patients also had significantly lower scores on nonverbal memory, visuospatial skills, and fine motor control (mean differences, –0.9 [–1.6 to –0.3]; –0.9 [–1.8 to –.1]; and –-3.1 [–4.9 to –1.4], respectively), compared with matched siblings. They also had significantly higher scores on processing speed (mean difference, 4.4 [0.2-8.5]). There were no significant differences in the other secondary outcomes.

Differences in scores between patients and siblings varied significantly by age at hospitalization in several tests – for example, Block Design scores in patients were lower than those of siblings for patients hospitalized at <1 year old, versus those hospitalized between ages 4 and 8 years.

“When adjusting for patient age at PICU admission, patient age at testing, sibling age at testing, and duration between hospital discharge and testing, the difference in estimated IQ between patients and siblings remained statistically significantly different,” the authors note.

The investigators point out several limitations, including the fact that “little is known about sibling outcomes after critical illness, nor about whether parenting of siblings or child development differs based on birth order or on relationship between patient critical illness and the birth of siblings. ... If siblings also incur negative effects related to the critical illness, differences between critically ill children and the control siblings would be blunted.”

Despite the statistical significance of the difference between the patients and the matched controls, ultimately, the magnitude of the difference was “small and of uncertain clinical importance,” the authors conclude.
 

Filling a research gap

Commenting on the findings, Alexandre T. Rotta, MD, professor of pediatrics and chief of the division of pediatric critical care medicine, Duke University Medical Center, Durham, N.C., said the study “addresses an important yet vastly understudied gap: long-term neurocognitive morbidity in children exposed to critical care.”

Dr. Rotta, who is also a coauthor of an accompanying editorial, noted that the fact that the “vast majority of children with an IQ significantly lower than their siblings were under the age of 4 years suggests that the developing immature brain may be particularly susceptible to the effects of critical illness and therapies required to treat it.”

The study “underscores the need to include assessments of long-term morbidity as part of any future trial evaluating interventions in pediatric critical care,” he added.

The study was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development for RESTORE-Cognition and by grants for the RESTORE trial from the National Heart, Lung, and Blood Institute and the National Institute of Nursing Research, National Institutes of Health. Dr. Watson and coauthors report no relevant financial relationships. Dr. Rotta has received personal fees from Vapotherm for lecturing and development of educational materials and from Breas US for participation in a scientific advisory board, as well as royalties from Elsevier for editorial work outside the submitted work. His coauthor reports no relevant financial relationships.

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