Clinical

Federal advisers on Thursday told US regulators that the benefits of Pfizer's COVID vaccine outweigh its risks for people aged 16 years and older, moving this product closer to a special emergency clearance. 

The US Food and Drug Administration (FDA) put Pfizer's application before its Vaccines and Related Biological Products Advisory Committee (VRBPAC), seeking expert feedback on what is likely to be the first COVID-19 vaccine cleared for use in the United States.

New York-based Pfizer is seeking an emergency use authorization (EUA) for its vaccine, known as BNT162b2, which it developed with Germany's BioNTech. The FDA asked its advisers to vote on a single question regarding this product: "Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?"

The members of VRBPAC voted 17-4 in favor of the Pfizer vaccine, with one panelist abstaining. The FDA considers the recommendations of its panels, but is not bound by them. The agency is expected to quickly grant the special clearance to Pfizer's vaccine, with the company then expected to complete work needed for a more complete biologics license application (BLA).

The FDA often allows members of its advisory committees to explain the reasons for their decisions to vote for or against an application after the tallies are publicly counted.

But the FDA did not give VRBPAC members this opportunity on Thursday, leaving the public without detailed insight into their support or objections.

Before the vote, several panelists had asked if the FDA could rephrase the voting question, raising the age for the approved group to perhaps 18 years of age. During the day, panelists also had questioned whether Pfizer's studies give enough information to judge whether the vaccine works against severe cases of COVID. And there was a discussion about how Pfizer could address concerns about the potential for allergic reactions to the vaccine, given the news of two healthcare workers who experienced allergic reactions after having the vaccine but who have since recovered.

In closing the meeting, VRBPAC chairman, Arnold Monto, MD, noted that the panel will on Dec. 17 meet again to offer recommendations on Moderna Inc.'s COVID vaccine.

"I believe most of us are going to be revisiting some of these issues in about a week," he said.

The panelist who abstained was H. Cody Meissner, MD, an expert in pediatric infectious disease from Tufts University. He earlier was among the several panelists who raised questions about the limited data available about the benefit to those ages 16 and 17. Those voting against the application were Michael Kurilla, MD, PhD; Archana Chatterjee, MD, PhD; A. Oveta Fuller, PhD, and David Kim, MD, MA, according to a tally read by the FDA staff after the vote.

Meanwhile, Sheldon Toubman, JD, voted in favor of the application according to the FDA staff's tally. Toubman had been a chief critic among VRBPAC members in reviewing Pfizer's application at the meeting. He'd suggested limiting the EUA to healthcare workers and residents of nursing homes. Members of these two groups are expected to be the first in the US to get Pfizer's vaccine, for which there will be only a limited initial supply. That idea gained no traction.

Toubman also pressed for more evidence that Pfizer's vaccine will work against severe cases of COVID.

The FDA staff on December 8 released a largely positive agency review of Pfizer vaccine. The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, with eight COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group. The FDA staff said that the 95% credible interval for the vaccine efficacy was 90.3% to 97.6%.

In that review, the FDA staff said there may be a hint from the results observed to date that the Pfizer vaccine may help ward off severe cases of COVID-19. There were 10 study participants that had severe COVID-19 disease after the first dose: one who received the vaccine and nine who received placebo.

"The total number of severe cases is small, which limits the overall conclusions that can be drawn; however, the case split does suggest protection from severe COVID-19 disease," the FDA staff said.

At the meeting today, Doron Fink, MD, PhD, a lead FDA official on the COVID vaccine review, responded directly to Toubman's concerns. There are many examples of vaccines that protect as well if not better against severe disease as they do against mild to moderate disease, Fink said.

"Protecting against disease of any severity is actually a pretty good predictor of protection against severe disease," Fink said, adding that there's already been a "strong result" shown in terms of the efficacy of Pfizer's vaccine.

Rolling out

Canadian health regulators on December 9 announced their nation's conditional approval of Pfizer's vaccine for people ages 16 and older.  In the United Kingdom, a widely publicized rollout of Pfizer's vaccine began on Dec. 8. News quickly spread about two workers in the National Health Service having allergic reactions following vaccination. Both of these workers carry adrenaline autoinjectors, suggesting they have suffered reactions in the past, the Guardian reported. These kinds of autoinjectors are well known in the United States under the brand name EpiPen.

A noted vaccine expert serving on VRBPAC, Paul Offit, MD, of Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, urged the FDA and Pfizer to investigate any connection between reaction to the vaccine and known allergies. If not fully addressed, reports of the reactions seen in initial vaccinations in the UK could prove to unnecessarily frighten people who have allergies away from getting the COVID shot, he said.

Offit suggested running tests where people with egg and peanut allergies would get the Pfizer vaccine under close medical observation "to prove that this is not going to be a problem."

"This is a practical solution because this issue is not going to die until we have better data," Offit said.

More than a dozen COVID-19 vaccines have reached advanced stages of testing, including ones developed in Russia and China, according to the World Health Organization (WHO). The two leading candidates for the US market are the Pfizer/BioNTech vaccine and a similar vaccine developed by Moderna and the National Institute of Allergy and Infectious Diseases. Johnson & Johnson and AstraZeneca are among the other companies with COVID-19 vaccines in testing.

The rapid development of COVID vaccines will create challenges in testing these products. A key issue will be how and whether to continue with placebo-controlled trials, even though such research would be helpful, FDA advisers said.

The FDA tasked Steven Goodman, MD, MHS, PhD, of Stanford University with presenting an overview of considerations for continuing a placebo-controlled trial as COVID vaccines become available. Once a COVID-19 vaccine becomes available to the public, people who have received placebo in the Pfizer trial should not be allowed to immediately receive the vaccine, Goodman said.

There isn't a strong medically-based argument against placebo-controlled research in COVID-19, as many people can take steps to reduce their risk for the infection, Goodman said.

"So as long as there are still important things to learn about the vaccine, placebo-controlled trials should not be regarded as unethical," Goodman said. " I think, however, they might be infeasible. And that is a big issue, because people may not be willing to either remain in the study or to enroll."

During the public comment session, a former FDA official spoke of a need for careful consideration of study volunteers' needs in designing trials of COVID-19 vaccines.

"Reasonable people can disagree over whether study subjects should have priority access to a product whose efficacy they helped demonstrate," said Peter Lurie, MD, president of the nonprofit Center for Science in the Public Interest. "But we ought to be able to agree on this: No subject who has put their body on the line in a vaccine study should be at a disadvantage in terms of vaccine access as a result of their participation."

Lurie argued against extended periods of blinded follow-up after authorization of a COVID-19 vaccine. Such a requirement would be "hard to justify ethically, if it is inconsistent with public health recommendations, particularly with rapidly rising case rates and the reported levels of effectiveness" of the Pfizer vaccine, said Lurie, who served as an associate commissioner at FDA from 2014 to 2017.

Lurie also noted the FDA staff's identification of what he called "disproportionate numbers of Bell's Palsy cases (4 in the vaccine groups vs. 0 in the placebo group)" as a matter that should continue to be monitored, including in the postmarketing phase. He raised no objections to the EUA.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen's Health Research Group, also spoke at the public comment session, citing no objection to an EUA for the Pfizer vaccine. Like Lurie, he urged special consideration of people who have or will receive placebo in COVID-19 vaccine trials.

The Thursday advisory committee on the Pfizer vaccine differed from those held for many other products. The discussion focused more on how to monitor and evaluate the vaccine once approved, while advisory committees sometimes include a detailed look at whether a company has proven that its product works. One of the special advisers serving temporarily on VRBPAC, Eric J. Rubin, MD, PhD, also today published an editorial in The New England Journal of Medicine, titled "SARS-CoV-2 Vaccination — An Ounce (Actually, Much Less) of Prevention."

In the editorial, Rubin and coauthor, Dan L. Longo, MD, called the Pfizer vaccine results seen so far "impressive."

"In the primary analysis, only 8 cases of Covid-19 were seen in the vaccine group, as compared with 162 in the placebo group, for an overall efficacy of 95% (with a 95% credible interval of 90.3 to 97.6%)," they write. "Although the trial does not have the statistical power to assess subgroups, efficacy appeared to be similar in low-risk and high-risk persons, including some from communities that have been disproportionately affected by disease, and in participants older than 55 years of age and those younger than 55."

Intense Scrutiny

The FDA has come under intense scrutiny this year in part because of the aggressive — and ultimately unrealistic — timelines for COVID-19 treatments promoted by the Trump administration. President Donald Trump several times suggested a COVID-19 vaccine could be approved before the November election. Many concerned physicians and scientists including Medscape Editor-in-Chief Eric Topol, MD, called on FDA staff to fight back against any bid to inappropriately speed the approval process for political reasons.

"Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA," Topol wrote in an August open letter to FDA Commissioner Stephen Hahn, MD.

In an October interview with Topol, Hahn noted that there has been some pushback against the idea of an EUA for a COVID-19 vaccine, with some people preferring to wait for a more complete biological license application.

"When you're talking about a pandemic where people are dying, you want to expedite it as much as possible," Hahn told Topol in the interview.

On Thursday, Hahn issued a public statement about the VRBPAC meeting. Hahn said the FDA's "career staff — made up of physicians, biologists, chemists, epidemiologists, statisticians, and other professionals — have been working around the clock to thoroughly evaluate the data and information in the EUA request."

"I can assure you that no vaccine will be authorized for use in the United States until FDA career officials feel confident in allowing their own families to receive it," Hahn said.

Many clinicians offered their views on the FDA meeting during the day on Twitter.

Robert Wachter, MD, chair of the Department of Medicine at the University of California, San Francisco, who has been a vocal opponent of some of Trump's public statements on COVID-19, urged state officials to stick with the FDA's call on the Pfizer vaccine. In a tweet, he noted that officials in California and several other states have called for independent reviews of COVID-19 vaccines.

If such reviews were to delay distribution of vaccines, this would "lead to more harm than good," Wachter tweeted. "Once FDA says 'go', we should go."

This article was updated 12/10/20.

This article originally appeared on Medscape.com.

Federal advisers on Thursday told US regulators that the benefits of Pfizer's COVID vaccine outweigh its risks for people aged 16 years and older, moving this product closer to a special emergency clearance. 

The US Food and Drug Administration (FDA) put Pfizer's application before its Vaccines and Related Biological Products Advisory Committee (VRBPAC), seeking expert feedback on what is likely to be the first COVID-19 vaccine cleared for use in the United States.

New York-based Pfizer is seeking an emergency use authorization (EUA) for its vaccine, known as BNT162b2, which it developed with Germany's BioNTech. The FDA asked its advisers to vote on a single question regarding this product: "Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?"

The members of VRBPAC voted 17-4 in favor of the Pfizer vaccine, with one panelist abstaining. The FDA considers the recommendations of its panels, but is not bound by them. The agency is expected to quickly grant the special clearance to Pfizer's vaccine, with the company then expected to complete work needed for a more complete biologics license application (BLA).

The FDA often allows members of its advisory committees to explain the reasons for their decisions to vote for or against an application after the tallies are publicly counted.

But the FDA did not give VRBPAC members this opportunity on Thursday, leaving the public without detailed insight into their support or objections.

Before the vote, several panelists had asked if the FDA could rephrase the voting question, raising the age for the approved group to perhaps 18 years of age. During the day, panelists also had questioned whether Pfizer's studies give enough information to judge whether the vaccine works against severe cases of COVID. And there was a discussion about how Pfizer could address concerns about the potential for allergic reactions to the vaccine, given the news of two healthcare workers who experienced allergic reactions after having the vaccine but who have since recovered.

In closing the meeting, VRBPAC chairman, Arnold Monto, MD, noted that the panel will on Dec. 17 meet again to offer recommendations on Moderna Inc.'s COVID vaccine.

"I believe most of us are going to be revisiting some of these issues in about a week," he said.

The panelist who abstained was H. Cody Meissner, MD, an expert in pediatric infectious disease from Tufts University. He earlier was among the several panelists who raised questions about the limited data available about the benefit to those ages 16 and 17. Those voting against the application were Michael Kurilla, MD, PhD; Archana Chatterjee, MD, PhD; A. Oveta Fuller, PhD, and David Kim, MD, MA, according to a tally read by the FDA staff after the vote.

Meanwhile, Sheldon Toubman, JD, voted in favor of the application according to the FDA staff's tally. Toubman had been a chief critic among VRBPAC members in reviewing Pfizer's application at the meeting. He'd suggested limiting the EUA to healthcare workers and residents of nursing homes. Members of these two groups are expected to be the first in the US to get Pfizer's vaccine, for which there will be only a limited initial supply. That idea gained no traction.

Toubman also pressed for more evidence that Pfizer's vaccine will work against severe cases of COVID.

The FDA staff on December 8 released a largely positive agency review of Pfizer vaccine. The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, with eight COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group. The FDA staff said that the 95% credible interval for the vaccine efficacy was 90.3% to 97.6%.

In that review, the FDA staff said there may be a hint from the results observed to date that the Pfizer vaccine may help ward off severe cases of COVID-19. There were 10 study participants that had severe COVID-19 disease after the first dose: one who received the vaccine and nine who received placebo.

"The total number of severe cases is small, which limits the overall conclusions that can be drawn; however, the case split does suggest protection from severe COVID-19 disease," the FDA staff said.

At the meeting today, Doron Fink, MD, PhD, a lead FDA official on the COVID vaccine review, responded directly to Toubman's concerns. There are many examples of vaccines that protect as well if not better against severe disease as they do against mild to moderate disease, Fink said.

"Protecting against disease of any severity is actually a pretty good predictor of protection against severe disease," Fink said, adding that there's already been a "strong result" shown in terms of the efficacy of Pfizer's vaccine.

Rolling out

Canadian health regulators on December 9 announced their nation's conditional approval of Pfizer's vaccine for people ages 16 and older.  In the United Kingdom, a widely publicized rollout of Pfizer's vaccine began on Dec. 8. News quickly spread about two workers in the National Health Service having allergic reactions following vaccination. Both of these workers carry adrenaline autoinjectors, suggesting they have suffered reactions in the past, the Guardian reported. These kinds of autoinjectors are well known in the United States under the brand name EpiPen.

A noted vaccine expert serving on VRBPAC, Paul Offit, MD, of Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, urged the FDA and Pfizer to investigate any connection between reaction to the vaccine and known allergies. If not fully addressed, reports of the reactions seen in initial vaccinations in the UK could prove to unnecessarily frighten people who have allergies away from getting the COVID shot, he said.

Offit suggested running tests where people with egg and peanut allergies would get the Pfizer vaccine under close medical observation "to prove that this is not going to be a problem."

"This is a practical solution because this issue is not going to die until we have better data," Offit said.

More than a dozen COVID-19 vaccines have reached advanced stages of testing, including ones developed in Russia and China, according to the World Health Organization (WHO). The two leading candidates for the US market are the Pfizer/BioNTech vaccine and a similar vaccine developed by Moderna and the National Institute of Allergy and Infectious Diseases. Johnson & Johnson and AstraZeneca are among the other companies with COVID-19 vaccines in testing.

The rapid development of COVID vaccines will create challenges in testing these products. A key issue will be how and whether to continue with placebo-controlled trials, even though such research would be helpful, FDA advisers said.

The FDA tasked Steven Goodman, MD, MHS, PhD, of Stanford University with presenting an overview of considerations for continuing a placebo-controlled trial as COVID vaccines become available. Once a COVID-19 vaccine becomes available to the public, people who have received placebo in the Pfizer trial should not be allowed to immediately receive the vaccine, Goodman said.

There isn't a strong medically-based argument against placebo-controlled research in COVID-19, as many people can take steps to reduce their risk for the infection, Goodman said.

"So as long as there are still important things to learn about the vaccine, placebo-controlled trials should not be regarded as unethical," Goodman said. " I think, however, they might be infeasible. And that is a big issue, because people may not be willing to either remain in the study or to enroll."

During the public comment session, a former FDA official spoke of a need for careful consideration of study volunteers' needs in designing trials of COVID-19 vaccines.

"Reasonable people can disagree over whether study subjects should have priority access to a product whose efficacy they helped demonstrate," said Peter Lurie, MD, president of the nonprofit Center for Science in the Public Interest. "But we ought to be able to agree on this: No subject who has put their body on the line in a vaccine study should be at a disadvantage in terms of vaccine access as a result of their participation."

Lurie argued against extended periods of blinded follow-up after authorization of a COVID-19 vaccine. Such a requirement would be "hard to justify ethically, if it is inconsistent with public health recommendations, particularly with rapidly rising case rates and the reported levels of effectiveness" of the Pfizer vaccine, said Lurie, who served as an associate commissioner at FDA from 2014 to 2017.

Lurie also noted the FDA staff's identification of what he called "disproportionate numbers of Bell's Palsy cases (4 in the vaccine groups vs. 0 in the placebo group)" as a matter that should continue to be monitored, including in the postmarketing phase. He raised no objections to the EUA.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen's Health Research Group, also spoke at the public comment session, citing no objection to an EUA for the Pfizer vaccine. Like Lurie, he urged special consideration of people who have or will receive placebo in COVID-19 vaccine trials.

The Thursday advisory committee on the Pfizer vaccine differed from those held for many other products. The discussion focused more on how to monitor and evaluate the vaccine once approved, while advisory committees sometimes include a detailed look at whether a company has proven that its product works. One of the special advisers serving temporarily on VRBPAC, Eric J. Rubin, MD, PhD, also today published an editorial in The New England Journal of Medicine, titled "SARS-CoV-2 Vaccination — An Ounce (Actually, Much Less) of Prevention."

In the editorial, Rubin and coauthor, Dan L. Longo, MD, called the Pfizer vaccine results seen so far "impressive."

"In the primary analysis, only 8 cases of Covid-19 were seen in the vaccine group, as compared with 162 in the placebo group, for an overall efficacy of 95% (with a 95% credible interval of 90.3 to 97.6%)," they write. "Although the trial does not have the statistical power to assess subgroups, efficacy appeared to be similar in low-risk and high-risk persons, including some from communities that have been disproportionately affected by disease, and in participants older than 55 years of age and those younger than 55."

Intense Scrutiny

The FDA has come under intense scrutiny this year in part because of the aggressive — and ultimately unrealistic — timelines for COVID-19 treatments promoted by the Trump administration. President Donald Trump several times suggested a COVID-19 vaccine could be approved before the November election. Many concerned physicians and scientists including Medscape Editor-in-Chief Eric Topol, MD, called on FDA staff to fight back against any bid to inappropriately speed the approval process for political reasons.

"Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA," Topol wrote in an August open letter to FDA Commissioner Stephen Hahn, MD.

In an October interview with Topol, Hahn noted that there has been some pushback against the idea of an EUA for a COVID-19 vaccine, with some people preferring to wait for a more complete biological license application.

"When you're talking about a pandemic where people are dying, you want to expedite it as much as possible," Hahn told Topol in the interview.

On Thursday, Hahn issued a public statement about the VRBPAC meeting. Hahn said the FDA's "career staff — made up of physicians, biologists, chemists, epidemiologists, statisticians, and other professionals — have been working around the clock to thoroughly evaluate the data and information in the EUA request."

"I can assure you that no vaccine will be authorized for use in the United States until FDA career officials feel confident in allowing their own families to receive it," Hahn said.

Many clinicians offered their views on the FDA meeting during the day on Twitter.

Robert Wachter, MD, chair of the Department of Medicine at the University of California, San Francisco, who has been a vocal opponent of some of Trump's public statements on COVID-19, urged state officials to stick with the FDA's call on the Pfizer vaccine. In a tweet, he noted that officials in California and several other states have called for independent reviews of COVID-19 vaccines.

If such reviews were to delay distribution of vaccines, this would "lead to more harm than good," Wachter tweeted. "Once FDA says 'go', we should go."

This article was updated 12/10/20.

This article originally appeared on Medscape.com.

Federal advisers on Thursday told US regulators that the benefits of Pfizer's COVID vaccine outweigh its risks for people aged 16 years and older, moving this product closer to a special emergency clearance. 

The US Food and Drug Administration (FDA) put Pfizer's application before its Vaccines and Related Biological Products Advisory Committee (VRBPAC), seeking expert feedback on what is likely to be the first COVID-19 vaccine cleared for use in the United States.

New York-based Pfizer is seeking an emergency use authorization (EUA) for its vaccine, known as BNT162b2, which it developed with Germany's BioNTech. The FDA asked its advisers to vote on a single question regarding this product: "Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?"

The members of VRBPAC voted 17-4 in favor of the Pfizer vaccine, with one panelist abstaining. The FDA considers the recommendations of its panels, but is not bound by them. The agency is expected to quickly grant the special clearance to Pfizer's vaccine, with the company then expected to complete work needed for a more complete biologics license application (BLA).

The FDA often allows members of its advisory committees to explain the reasons for their decisions to vote for or against an application after the tallies are publicly counted.

But the FDA did not give VRBPAC members this opportunity on Thursday, leaving the public without detailed insight into their support or objections.

Before the vote, several panelists had asked if the FDA could rephrase the voting question, raising the age for the approved group to perhaps 18 years of age. During the day, panelists also had questioned whether Pfizer's studies give enough information to judge whether the vaccine works against severe cases of COVID. And there was a discussion about how Pfizer could address concerns about the potential for allergic reactions to the vaccine, given the news of two healthcare workers who experienced allergic reactions after having the vaccine but who have since recovered.

In closing the meeting, VRBPAC chairman, Arnold Monto, MD, noted that the panel will on Dec. 17 meet again to offer recommendations on Moderna Inc.'s COVID vaccine.

"I believe most of us are going to be revisiting some of these issues in about a week," he said.

The panelist who abstained was H. Cody Meissner, MD, an expert in pediatric infectious disease from Tufts University. He earlier was among the several panelists who raised questions about the limited data available about the benefit to those ages 16 and 17. Those voting against the application were Michael Kurilla, MD, PhD; Archana Chatterjee, MD, PhD; A. Oveta Fuller, PhD, and David Kim, MD, MA, according to a tally read by the FDA staff after the vote.

Meanwhile, Sheldon Toubman, JD, voted in favor of the application according to the FDA staff's tally. Toubman had been a chief critic among VRBPAC members in reviewing Pfizer's application at the meeting. He'd suggested limiting the EUA to healthcare workers and residents of nursing homes. Members of these two groups are expected to be the first in the US to get Pfizer's vaccine, for which there will be only a limited initial supply. That idea gained no traction.

Toubman also pressed for more evidence that Pfizer's vaccine will work against severe cases of COVID.

The FDA staff on December 8 released a largely positive agency review of Pfizer vaccine. The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, with eight COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group. The FDA staff said that the 95% credible interval for the vaccine efficacy was 90.3% to 97.6%.

In that review, the FDA staff said there may be a hint from the results observed to date that the Pfizer vaccine may help ward off severe cases of COVID-19. There were 10 study participants that had severe COVID-19 disease after the first dose: one who received the vaccine and nine who received placebo.

"The total number of severe cases is small, which limits the overall conclusions that can be drawn; however, the case split does suggest protection from severe COVID-19 disease," the FDA staff said.

At the meeting today, Doron Fink, MD, PhD, a lead FDA official on the COVID vaccine review, responded directly to Toubman's concerns. There are many examples of vaccines that protect as well if not better against severe disease as they do against mild to moderate disease, Fink said.

"Protecting against disease of any severity is actually a pretty good predictor of protection against severe disease," Fink said, adding that there's already been a "strong result" shown in terms of the efficacy of Pfizer's vaccine.

Rolling out

Canadian health regulators on December 9 announced their nation's conditional approval of Pfizer's vaccine for people ages 16 and older.  In the United Kingdom, a widely publicized rollout of Pfizer's vaccine began on Dec. 8. News quickly spread about two workers in the National Health Service having allergic reactions following vaccination. Both of these workers carry adrenaline autoinjectors, suggesting they have suffered reactions in the past, the Guardian reported. These kinds of autoinjectors are well known in the United States under the brand name EpiPen.

A noted vaccine expert serving on VRBPAC, Paul Offit, MD, of Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, urged the FDA and Pfizer to investigate any connection between reaction to the vaccine and known allergies. If not fully addressed, reports of the reactions seen in initial vaccinations in the UK could prove to unnecessarily frighten people who have allergies away from getting the COVID shot, he said.

Offit suggested running tests where people with egg and peanut allergies would get the Pfizer vaccine under close medical observation "to prove that this is not going to be a problem."

"This is a practical solution because this issue is not going to die until we have better data," Offit said.

More than a dozen COVID-19 vaccines have reached advanced stages of testing, including ones developed in Russia and China, according to the World Health Organization (WHO). The two leading candidates for the US market are the Pfizer/BioNTech vaccine and a similar vaccine developed by Moderna and the National Institute of Allergy and Infectious Diseases. Johnson & Johnson and AstraZeneca are among the other companies with COVID-19 vaccines in testing.

The rapid development of COVID vaccines will create challenges in testing these products. A key issue will be how and whether to continue with placebo-controlled trials, even though such research would be helpful, FDA advisers said.

The FDA tasked Steven Goodman, MD, MHS, PhD, of Stanford University with presenting an overview of considerations for continuing a placebo-controlled trial as COVID vaccines become available. Once a COVID-19 vaccine becomes available to the public, people who have received placebo in the Pfizer trial should not be allowed to immediately receive the vaccine, Goodman said.

There isn't a strong medically-based argument against placebo-controlled research in COVID-19, as many people can take steps to reduce their risk for the infection, Goodman said.

"So as long as there are still important things to learn about the vaccine, placebo-controlled trials should not be regarded as unethical," Goodman said. " I think, however, they might be infeasible. And that is a big issue, because people may not be willing to either remain in the study or to enroll."

During the public comment session, a former FDA official spoke of a need for careful consideration of study volunteers' needs in designing trials of COVID-19 vaccines.

"Reasonable people can disagree over whether study subjects should have priority access to a product whose efficacy they helped demonstrate," said Peter Lurie, MD, president of the nonprofit Center for Science in the Public Interest. "But we ought to be able to agree on this: No subject who has put their body on the line in a vaccine study should be at a disadvantage in terms of vaccine access as a result of their participation."

Lurie argued against extended periods of blinded follow-up after authorization of a COVID-19 vaccine. Such a requirement would be "hard to justify ethically, if it is inconsistent with public health recommendations, particularly with rapidly rising case rates and the reported levels of effectiveness" of the Pfizer vaccine, said Lurie, who served as an associate commissioner at FDA from 2014 to 2017.

Lurie also noted the FDA staff's identification of what he called "disproportionate numbers of Bell's Palsy cases (4 in the vaccine groups vs. 0 in the placebo group)" as a matter that should continue to be monitored, including in the postmarketing phase. He raised no objections to the EUA.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen's Health Research Group, also spoke at the public comment session, citing no objection to an EUA for the Pfizer vaccine. Like Lurie, he urged special consideration of people who have or will receive placebo in COVID-19 vaccine trials.

The Thursday advisory committee on the Pfizer vaccine differed from those held for many other products. The discussion focused more on how to monitor and evaluate the vaccine once approved, while advisory committees sometimes include a detailed look at whether a company has proven that its product works. One of the special advisers serving temporarily on VRBPAC, Eric J. Rubin, MD, PhD, also today published an editorial in The New England Journal of Medicine, titled "SARS-CoV-2 Vaccination — An Ounce (Actually, Much Less) of Prevention."

In the editorial, Rubin and coauthor, Dan L. Longo, MD, called the Pfizer vaccine results seen so far "impressive."

"In the primary analysis, only 8 cases of Covid-19 were seen in the vaccine group, as compared with 162 in the placebo group, for an overall efficacy of 95% (with a 95% credible interval of 90.3 to 97.6%)," they write. "Although the trial does not have the statistical power to assess subgroups, efficacy appeared to be similar in low-risk and high-risk persons, including some from communities that have been disproportionately affected by disease, and in participants older than 55 years of age and those younger than 55."

Intense Scrutiny

The FDA has come under intense scrutiny this year in part because of the aggressive — and ultimately unrealistic — timelines for COVID-19 treatments promoted by the Trump administration. President Donald Trump several times suggested a COVID-19 vaccine could be approved before the November election. Many concerned physicians and scientists including Medscape Editor-in-Chief Eric Topol, MD, called on FDA staff to fight back against any bid to inappropriately speed the approval process for political reasons.

"Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA," Topol wrote in an August open letter to FDA Commissioner Stephen Hahn, MD.

In an October interview with Topol, Hahn noted that there has been some pushback against the idea of an EUA for a COVID-19 vaccine, with some people preferring to wait for a more complete biological license application.

"When you're talking about a pandemic where people are dying, you want to expedite it as much as possible," Hahn told Topol in the interview.

On Thursday, Hahn issued a public statement about the VRBPAC meeting. Hahn said the FDA's "career staff — made up of physicians, biologists, chemists, epidemiologists, statisticians, and other professionals — have been working around the clock to thoroughly evaluate the data and information in the EUA request."

"I can assure you that no vaccine will be authorized for use in the United States until FDA career officials feel confident in allowing their own families to receive it," Hahn said.

Many clinicians offered their views on the FDA meeting during the day on Twitter.

Robert Wachter, MD, chair of the Department of Medicine at the University of California, San Francisco, who has been a vocal opponent of some of Trump's public statements on COVID-19, urged state officials to stick with the FDA's call on the Pfizer vaccine. In a tweet, he noted that officials in California and several other states have called for independent reviews of COVID-19 vaccines.

If such reviews were to delay distribution of vaccines, this would "lead to more harm than good," Wachter tweeted. "Once FDA says 'go', we should go."

This article was updated 12/10/20.

This article originally appeared on Medscape.com.

Hospitalists in the VA system see patients with symptoms of alcohol withdrawal frequently – there are about 33,000 hospital admissions each year for alcohol withdrawal syndrome (AWS), says Robert Patrick, MD, of the Louis Stokes Cleveland VA Medical Center.

“By contrast, the number of admissions for the largest ambulatory care sensitive condition (heart failure) is only about 28,000,” he said. “If alcohol detox were an ambulatory care sensitive condition, it would be the largest in the VA by a substantial margin.”The purpose of the project he and his co-author, Laura Brown, MD, created to address the problem was to increase the number of patients treated for AWS as outpatients and decrease hospital admissions – without increasing readmissions or clinical deterioration.

They introduced four core operational changes for their study:

1. Standardized risk stratification in the Emergency Department (ED) to identify low risk patients for outpatient treatment.

2. Benzodiazepine sparing symptom triggered medication regimen.

3. Daily clinical dashboard surveillance and risk stratification for continued hospital stay.

4. Telephone follow-up for patients discharged from the ED or hospital.

With these changes in place, eight months of data showed a 50% reduction in AWS admissions and a 40% reduction in length of stays.

Their conclusion? “A well designed and executed QI project can dramatically reduce hospitalist workload, while at the same time improving patient safety,” Dr. Patrick said. “Hospitalists just have to be willing to think outside the box, work with nursing and coordinate care outside of the hospital to make it happen.”

He added a caveat for hospital medicine groups still in a fee-for-service environment. “This saves money for the payer, not the hospital,” he said. “In our case they are one and the same, so the ROI is huge. If you are part of an ACO this is probably true for you, but I would check with your ACO first.”
 

Reference

1. Patrick RM, Brown LZ. Decreasing Admissions, Readmissions and Length of Stay While Improving Patent Safety for Alcohol Withdrawal Syndrome. Abstract published at Hospital Medicine 2019, March 24-27, National Harbor, Md. Abstract Plenary. https://www.shmabstracts.com/abstract/decreasing-admissions-readmissions-and-length-of-stay-while-improving-patient-safety-for-alcohol-withdrawal-syndrome/.

Hospitalists in the VA system see patients with symptoms of alcohol withdrawal frequently – there are about 33,000 hospital admissions each year for alcohol withdrawal syndrome (AWS), says Robert Patrick, MD, of the Louis Stokes Cleveland VA Medical Center.

“By contrast, the number of admissions for the largest ambulatory care sensitive condition (heart failure) is only about 28,000,” he said. “If alcohol detox were an ambulatory care sensitive condition, it would be the largest in the VA by a substantial margin.”The purpose of the project he and his co-author, Laura Brown, MD, created to address the problem was to increase the number of patients treated for AWS as outpatients and decrease hospital admissions – without increasing readmissions or clinical deterioration.

They introduced four core operational changes for their study:

1. Standardized risk stratification in the Emergency Department (ED) to identify low risk patients for outpatient treatment.

2. Benzodiazepine sparing symptom triggered medication regimen.

3. Daily clinical dashboard surveillance and risk stratification for continued hospital stay.

4. Telephone follow-up for patients discharged from the ED or hospital.

With these changes in place, eight months of data showed a 50% reduction in AWS admissions and a 40% reduction in length of stays.

Their conclusion? “A well designed and executed QI project can dramatically reduce hospitalist workload, while at the same time improving patient safety,” Dr. Patrick said. “Hospitalists just have to be willing to think outside the box, work with nursing and coordinate care outside of the hospital to make it happen.”

He added a caveat for hospital medicine groups still in a fee-for-service environment. “This saves money for the payer, not the hospital,” he said. “In our case they are one and the same, so the ROI is huge. If you are part of an ACO this is probably true for you, but I would check with your ACO first.”
 

Reference

1. Patrick RM, Brown LZ. Decreasing Admissions, Readmissions and Length of Stay While Improving Patent Safety for Alcohol Withdrawal Syndrome. Abstract published at Hospital Medicine 2019, March 24-27, National Harbor, Md. Abstract Plenary. https://www.shmabstracts.com/abstract/decreasing-admissions-readmissions-and-length-of-stay-while-improving-patient-safety-for-alcohol-withdrawal-syndrome/.

Hospitalists in the VA system see patients with symptoms of alcohol withdrawal frequently – there are about 33,000 hospital admissions each year for alcohol withdrawal syndrome (AWS), says Robert Patrick, MD, of the Louis Stokes Cleveland VA Medical Center.

“By contrast, the number of admissions for the largest ambulatory care sensitive condition (heart failure) is only about 28,000,” he said. “If alcohol detox were an ambulatory care sensitive condition, it would be the largest in the VA by a substantial margin.”The purpose of the project he and his co-author, Laura Brown, MD, created to address the problem was to increase the number of patients treated for AWS as outpatients and decrease hospital admissions – without increasing readmissions or clinical deterioration.

They introduced four core operational changes for their study:

1. Standardized risk stratification in the Emergency Department (ED) to identify low risk patients for outpatient treatment.

2. Benzodiazepine sparing symptom triggered medication regimen.

3. Daily clinical dashboard surveillance and risk stratification for continued hospital stay.

4. Telephone follow-up for patients discharged from the ED or hospital.

With these changes in place, eight months of data showed a 50% reduction in AWS admissions and a 40% reduction in length of stays.

Their conclusion? “A well designed and executed QI project can dramatically reduce hospitalist workload, while at the same time improving patient safety,” Dr. Patrick said. “Hospitalists just have to be willing to think outside the box, work with nursing and coordinate care outside of the hospital to make it happen.”

He added a caveat for hospital medicine groups still in a fee-for-service environment. “This saves money for the payer, not the hospital,” he said. “In our case they are one and the same, so the ROI is huge. If you are part of an ACO this is probably true for you, but I would check with your ACO first.”
 

Reference

1. Patrick RM, Brown LZ. Decreasing Admissions, Readmissions and Length of Stay While Improving Patent Safety for Alcohol Withdrawal Syndrome. Abstract published at Hospital Medicine 2019, March 24-27, National Harbor, Md. Abstract Plenary. https://www.shmabstracts.com/abstract/decreasing-admissions-readmissions-and-length-of-stay-while-improving-patient-safety-for-alcohol-withdrawal-syndrome/.

Pfizer won’t be able to provide more COVID-19 vaccine doses to the United States until late June or July because other countries have bought up the available supply, according to The Washington Post.

The U.S. government signed a deal with the giant pharmaceutical company earlier this year to provide 100 million doses for $1.95 billion – enough for 50 million Americans to receive the two-dose vaccine. At that time, Pfizer officials encouraged Operation Warp Speed officials to purchase an additional 100 million doses, The New York Times first reported Dec. 7, but the federal officials declined.

Since then, other countries have signed vaccine deals with Pfizer, so the U.S. may not be able to receive a second major allotment until the summer of 2021, The Washington Post reported. Without a substantial number of additional doses, the U.S. may not be able to follow its schedule of vaccinating the majority of Americans against COVID-19 by April or May.

However, Trump administration officials told the newspaper that there won’t be issues, citing other vaccine companies such as Moderna.

“I’m not concerned about our ability to buy vaccines to offer to all of the American public,” Gen. Paul Ostrowski, who oversees logistics for Operation Warp Speed, told The Washington Post.

“It’s clear that Pfizer made plans with other countries. Many have been announced. We understand those pieces,” he said.

With Pfizer’s COVID-19 vaccine on the verge of FDA approval, federal officials contacted the company last weekend to buy another 100 million doses, but the company said its current supply is already committed, the newspaper reported.

The vaccine from Pfizer and BioNTech is expected to win emergency approval within days and has been shown to be effective against COVID-19.

Pfizer added that it may be able to provide 50 million doses at the end of the second quarter and another 50 million doses during the third quarter. However, the company can’t offer anything “substantial” until next summer.

Beyond the initial 100 million doses that the U.S. has already secured, Pfizer and federal officials would need to negotiate a new, “separate and mutually acceptable agreement,” Amy Rose, a spokeswoman for Pfizer, told the newspaper.

On Dec. 8, President Donald Trump was expected to sign an executive order prioritizing vaccination for Americans first before providing doses to other countries, according to Fox News.

The order will provide guidelines to the Department of Health and Human Services, the U.S. Agency for International Development and the U.S. International Development Finance Corporation for foreign assistance with vaccines, the news outlet reported.

It’s unclear whether the executive order is related to the Pfizer issue, whether the president can prevent a private company from fulfilling contracts with other countries, and whether President-elect Joe Biden will create his own policy, according to CNBC. The order may prove to be mostly symbolic.

The FDA could issue an emergency use authorization for Pfizer’s coronavirus vaccine this week and will likely approve Moderna’s vaccine next week. The U.S. has signed a contract with Moderna for 100 million doses.

During a call with reporters on Dec. 7, a spokeswoman for the Department of Health and Human Services said, “We are confident that we will have 100 million doses of Pfizer’s vaccine as agreed to in our contract, and beyond that, we have five other vaccine candidates, including 100 million doses on the way from Moderna.”

Federal officials are counting on vaccine candidates from AstraZeneca and Johnson & Johnson to seek FDA approval in January and be ready for shipment in February.

“We could have all of them,” Moncef Slaoui, the chief science adviser for Operation Warp Speed, told The Washington Post on Dec. 7.

“And for this reason, we feel confident we could cover the needs without a specific cliff,” he said. “We have planned things in such a way as we would indeed avoid a cliff.”

This article first appeared on WebMD.com.

Pfizer won’t be able to provide more COVID-19 vaccine doses to the United States until late June or July because other countries have bought up the available supply, according to The Washington Post.

The U.S. government signed a deal with the giant pharmaceutical company earlier this year to provide 100 million doses for $1.95 billion – enough for 50 million Americans to receive the two-dose vaccine. At that time, Pfizer officials encouraged Operation Warp Speed officials to purchase an additional 100 million doses, The New York Times first reported Dec. 7, but the federal officials declined.

Since then, other countries have signed vaccine deals with Pfizer, so the U.S. may not be able to receive a second major allotment until the summer of 2021, The Washington Post reported. Without a substantial number of additional doses, the U.S. may not be able to follow its schedule of vaccinating the majority of Americans against COVID-19 by April or May.

However, Trump administration officials told the newspaper that there won’t be issues, citing other vaccine companies such as Moderna.

“I’m not concerned about our ability to buy vaccines to offer to all of the American public,” Gen. Paul Ostrowski, who oversees logistics for Operation Warp Speed, told The Washington Post.

“It’s clear that Pfizer made plans with other countries. Many have been announced. We understand those pieces,” he said.

With Pfizer’s COVID-19 vaccine on the verge of FDA approval, federal officials contacted the company last weekend to buy another 100 million doses, but the company said its current supply is already committed, the newspaper reported.

The vaccine from Pfizer and BioNTech is expected to win emergency approval within days and has been shown to be effective against COVID-19.

Pfizer added that it may be able to provide 50 million doses at the end of the second quarter and another 50 million doses during the third quarter. However, the company can’t offer anything “substantial” until next summer.

Beyond the initial 100 million doses that the U.S. has already secured, Pfizer and federal officials would need to negotiate a new, “separate and mutually acceptable agreement,” Amy Rose, a spokeswoman for Pfizer, told the newspaper.

On Dec. 8, President Donald Trump was expected to sign an executive order prioritizing vaccination for Americans first before providing doses to other countries, according to Fox News.

The order will provide guidelines to the Department of Health and Human Services, the U.S. Agency for International Development and the U.S. International Development Finance Corporation for foreign assistance with vaccines, the news outlet reported.

It’s unclear whether the executive order is related to the Pfizer issue, whether the president can prevent a private company from fulfilling contracts with other countries, and whether President-elect Joe Biden will create his own policy, according to CNBC. The order may prove to be mostly symbolic.

The FDA could issue an emergency use authorization for Pfizer’s coronavirus vaccine this week and will likely approve Moderna’s vaccine next week. The U.S. has signed a contract with Moderna for 100 million doses.

During a call with reporters on Dec. 7, a spokeswoman for the Department of Health and Human Services said, “We are confident that we will have 100 million doses of Pfizer’s vaccine as agreed to in our contract, and beyond that, we have five other vaccine candidates, including 100 million doses on the way from Moderna.”

Federal officials are counting on vaccine candidates from AstraZeneca and Johnson & Johnson to seek FDA approval in January and be ready for shipment in February.

“We could have all of them,” Moncef Slaoui, the chief science adviser for Operation Warp Speed, told The Washington Post on Dec. 7.

“And for this reason, we feel confident we could cover the needs without a specific cliff,” he said. “We have planned things in such a way as we would indeed avoid a cliff.”

This article first appeared on WebMD.com.

Pfizer won’t be able to provide more COVID-19 vaccine doses to the United States until late June or July because other countries have bought up the available supply, according to The Washington Post.

The U.S. government signed a deal with the giant pharmaceutical company earlier this year to provide 100 million doses for $1.95 billion – enough for 50 million Americans to receive the two-dose vaccine. At that time, Pfizer officials encouraged Operation Warp Speed officials to purchase an additional 100 million doses, The New York Times first reported Dec. 7, but the federal officials declined.

Since then, other countries have signed vaccine deals with Pfizer, so the U.S. may not be able to receive a second major allotment until the summer of 2021, The Washington Post reported. Without a substantial number of additional doses, the U.S. may not be able to follow its schedule of vaccinating the majority of Americans against COVID-19 by April or May.

However, Trump administration officials told the newspaper that there won’t be issues, citing other vaccine companies such as Moderna.

“I’m not concerned about our ability to buy vaccines to offer to all of the American public,” Gen. Paul Ostrowski, who oversees logistics for Operation Warp Speed, told The Washington Post.

“It’s clear that Pfizer made plans with other countries. Many have been announced. We understand those pieces,” he said.

With Pfizer’s COVID-19 vaccine on the verge of FDA approval, federal officials contacted the company last weekend to buy another 100 million doses, but the company said its current supply is already committed, the newspaper reported.

The vaccine from Pfizer and BioNTech is expected to win emergency approval within days and has been shown to be effective against COVID-19.

Pfizer added that it may be able to provide 50 million doses at the end of the second quarter and another 50 million doses during the third quarter. However, the company can’t offer anything “substantial” until next summer.

Beyond the initial 100 million doses that the U.S. has already secured, Pfizer and federal officials would need to negotiate a new, “separate and mutually acceptable agreement,” Amy Rose, a spokeswoman for Pfizer, told the newspaper.

On Dec. 8, President Donald Trump was expected to sign an executive order prioritizing vaccination for Americans first before providing doses to other countries, according to Fox News.

The order will provide guidelines to the Department of Health and Human Services, the U.S. Agency for International Development and the U.S. International Development Finance Corporation for foreign assistance with vaccines, the news outlet reported.

It’s unclear whether the executive order is related to the Pfizer issue, whether the president can prevent a private company from fulfilling contracts with other countries, and whether President-elect Joe Biden will create his own policy, according to CNBC. The order may prove to be mostly symbolic.

The FDA could issue an emergency use authorization for Pfizer’s coronavirus vaccine this week and will likely approve Moderna’s vaccine next week. The U.S. has signed a contract with Moderna for 100 million doses.

During a call with reporters on Dec. 7, a spokeswoman for the Department of Health and Human Services said, “We are confident that we will have 100 million doses of Pfizer’s vaccine as agreed to in our contract, and beyond that, we have five other vaccine candidates, including 100 million doses on the way from Moderna.”

Federal officials are counting on vaccine candidates from AstraZeneca and Johnson & Johnson to seek FDA approval in January and be ready for shipment in February.

“We could have all of them,” Moncef Slaoui, the chief science adviser for Operation Warp Speed, told The Washington Post on Dec. 7.

“And for this reason, we feel confident we could cover the needs without a specific cliff,” he said. “We have planned things in such a way as we would indeed avoid a cliff.”

This article first appeared on WebMD.com.

As hospitals across the country develop their plans to vaccinate their health care employees against COVID-19, a key question has come to the fore: What if an employee – whether nurse, physician, or other health care worker – refuses to receive the vaccine? Can hospitals require their employees to be vaccinated against COVID-19? And what consequences could an employee face for refusing the vaccine?

My answer needs to be based, in part, on the law related to previous vaccines – influenza, for example – because at the time of this writing (early December 2020), no vaccine for COVID-19 has been approved, although approval of at least one vaccine is expected within a week. So there have been no offers of vaccine and refusals yet, nor are there any cases to date involving an employee who refused a COVID-19 vaccine. As of December 2020, there are no state or federal laws that either require an employee to be vaccinated against COVID-19 or that protect an employee who refuses vaccination against COVID-19. It will take a while after the vaccine is approved and distributed before refusals, reactions, policies, cases, and laws begin to emerge.

If we look at the law related to health care workers refusing to be vaccinated against the closest relative to COVID-19 – influenza – then the answer would be yes, employers can require employees to be vaccinated.

An employer can fire an employee who refuses influenza vaccination. If an employee who refused and was fired sues the employer for wrongful termination, the employee has more or less chance of success depending on the reason for refusal. Some courts and the Equal Employment Opportunity Commission have held that a refusal on religious grounds is protected by the U.S. Constitution, as in this recent case. The Constitution protects freedom to practice one’s religion. Specific religions may have a range of tenets that support refusal to be vaccinated.

A refusal on medical grounds has been successful if the medical grounds fall under the protections of the Americans with Disabilities Act but may fail when the medical grounds for the claim are not covered by the ADA.

Refusal for secular, nonmedical reasons, such as a health care worker’s policy of treating their body as their temple, has not gone over well with employers or courts. However, in at least one case, a nurse who refused vaccination on secular, nonmedical grounds won her case against her employer, on appeal. The appeals court found that the hospital violated her First Amendment rights.

Employees who refuse vaccination for religious or medical reasons still will need to take measures to protect patients and other employees from infection. An employer such as a hospital can, rather than fire the employee, offer the employee an accommodation, such as requiring that the employee wear a mask or quarantine. There are no cases that have upheld an employee’s right to refuse to wear a mask or quarantine.

The situation with the COVID-19 vaccine is different from the situation surrounding influenza vaccines. There are plenty of data on effectiveness and side effects of influenza vaccines, but there is very little evidence of short- or long-term effects of the COVID-19 vaccines currently being tested and/or considered for approval. One could argue that the process of vaccine development is the same for all virus vaccines. However, public confidence in the vaccine vetting process is not what it once was. It has been widely publicized that the COVID-19 vaccine trials have been rushed. As of December 2020, only 60% of the general population say they would take the vaccine, although researchers say confidence is increasing.

The Centers for Disease Control and Prevention has designated health care workers as first in line to get the vaccine, but some health care workers may not want to be the first to try it. A CDC survey found that 63% of health care workers polled in recent months said they would get a COVID-19 vaccine.

Unions have entered the conversation. A coalition of unions that represent health care workers said, “we need a transparent, evidence-based federal vaccine strategy based on principles of equity, safety, and priority, as well as robust efforts to address a high degree of skepticism about safety of an authorized vaccine.” The organization declined to promote a vaccine until more is known.

As of publication date, the EEOC guidance for employers responding to COVID-19 does not address vaccines.

The CDC’s Interim Guidance for Businesses and Employers Responding to Coronavirus Disease 2019, May 2020, updated Dec. 4, 2020, does not address vaccines. The CDC’s page on COVID-19 vaccination for health care workers does not address a health care worker’s refusal. The site does assure health care workers that the vaccine development process is sound: “The current vaccine safety system is strong and robust, with the capacity to effectively monitor COVID-19 vaccine safety. Existing data systems have validated analytic methods that can rapidly detect statistical signals for possible vaccine safety problems. These systems are being scaled up to fully meet the needs of the nation. Additional systems and data sources are also being developed to further enhance safety monitoring capabilities. CDC is committed to ensuring that COVID-19 vaccines are safe.”

In the coming months, government officials and vaccine manufacturers will be working to reassure the public of the safety of the vaccine and the rigor of the vaccine development process. In November 2020, National Institute of Allergy and Infectious Diseases Director Anthony Fauci, MD, told Kaiser Health News: “The company looks at the data. I look at the data. Then the company puts the data to the FDA. The FDA will make the decision to do an emergency-use authorization or a license application approval. And they have career scientists who are really independent. They’re not beholden to anybody. Then there’s another independent group, the Vaccines and Related Biological Products Advisory Committee. The FDA commissioner has vowed publicly that he will go according to the opinion of the career scientists and the advisory board.” President-elect Joe Biden said he would get a vaccine when Dr. Fauci thinks it is safe.

An employee who, after researching the vaccine and the process, still wants to refuse when offered the vaccine is not likely to be fired for that reason right away, as long as the employee takes other precautions, such as wearing a mask. If the employer does fire the employee and the employee sues the employer, it is impossible to predict how a court would decide the case.

Related legal questions may arise in the coming months. For example:

• Is an employer exempt from paying workers’ compensation to an employee who refuses to be vaccinated and then contracts the virus while on the job?
• Can a prospective employer require COVID-19 vaccination as a precondition of employment?
• Is it within a patient’s rights to receive an answer to the question: Has my health care worker been vaccinated against COVID-19?
• If a hospital allows employees to refuse vaccination and keep working, and an outbreak occurs, and it is suggested through contact tracing that unvaccinated workers infected patients, will a court hold the hospital liable for patients’ damages?

Answers to these questions are yet to be determined.

Carolyn Buppert (www.buppert.com) is an attorney and former nurse practitioner who focuses on the legal issues affecting nurse practitioners.

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

As hospitals across the country develop their plans to vaccinate their health care employees against COVID-19, a key question has come to the fore: What if an employee – whether nurse, physician, or other health care worker – refuses to receive the vaccine? Can hospitals require their employees to be vaccinated against COVID-19? And what consequences could an employee face for refusing the vaccine?

My answer needs to be based, in part, on the law related to previous vaccines – influenza, for example – because at the time of this writing (early December 2020), no vaccine for COVID-19 has been approved, although approval of at least one vaccine is expected within a week. So there have been no offers of vaccine and refusals yet, nor are there any cases to date involving an employee who refused a COVID-19 vaccine. As of December 2020, there are no state or federal laws that either require an employee to be vaccinated against COVID-19 or that protect an employee who refuses vaccination against COVID-19. It will take a while after the vaccine is approved and distributed before refusals, reactions, policies, cases, and laws begin to emerge.

If we look at the law related to health care workers refusing to be vaccinated against the closest relative to COVID-19 – influenza – then the answer would be yes, employers can require employees to be vaccinated.

An employer can fire an employee who refuses influenza vaccination. If an employee who refused and was fired sues the employer for wrongful termination, the employee has more or less chance of success depending on the reason for refusal. Some courts and the Equal Employment Opportunity Commission have held that a refusal on religious grounds is protected by the U.S. Constitution, as in this recent case. The Constitution protects freedom to practice one’s religion. Specific religions may have a range of tenets that support refusal to be vaccinated.

A refusal on medical grounds has been successful if the medical grounds fall under the protections of the Americans with Disabilities Act but may fail when the medical grounds for the claim are not covered by the ADA.

Refusal for secular, nonmedical reasons, such as a health care worker’s policy of treating their body as their temple, has not gone over well with employers or courts. However, in at least one case, a nurse who refused vaccination on secular, nonmedical grounds won her case against her employer, on appeal. The appeals court found that the hospital violated her First Amendment rights.

Employees who refuse vaccination for religious or medical reasons still will need to take measures to protect patients and other employees from infection. An employer such as a hospital can, rather than fire the employee, offer the employee an accommodation, such as requiring that the employee wear a mask or quarantine. There are no cases that have upheld an employee’s right to refuse to wear a mask or quarantine.

The situation with the COVID-19 vaccine is different from the situation surrounding influenza vaccines. There are plenty of data on effectiveness and side effects of influenza vaccines, but there is very little evidence of short- or long-term effects of the COVID-19 vaccines currently being tested and/or considered for approval. One could argue that the process of vaccine development is the same for all virus vaccines. However, public confidence in the vaccine vetting process is not what it once was. It has been widely publicized that the COVID-19 vaccine trials have been rushed. As of December 2020, only 60% of the general population say they would take the vaccine, although researchers say confidence is increasing.

The Centers for Disease Control and Prevention has designated health care workers as first in line to get the vaccine, but some health care workers may not want to be the first to try it. A CDC survey found that 63% of health care workers polled in recent months said they would get a COVID-19 vaccine.

Unions have entered the conversation. A coalition of unions that represent health care workers said, “we need a transparent, evidence-based federal vaccine strategy based on principles of equity, safety, and priority, as well as robust efforts to address a high degree of skepticism about safety of an authorized vaccine.” The organization declined to promote a vaccine until more is known.

As of publication date, the EEOC guidance for employers responding to COVID-19 does not address vaccines.

The CDC’s Interim Guidance for Businesses and Employers Responding to Coronavirus Disease 2019, May 2020, updated Dec. 4, 2020, does not address vaccines. The CDC’s page on COVID-19 vaccination for health care workers does not address a health care worker’s refusal. The site does assure health care workers that the vaccine development process is sound: “The current vaccine safety system is strong and robust, with the capacity to effectively monitor COVID-19 vaccine safety. Existing data systems have validated analytic methods that can rapidly detect statistical signals for possible vaccine safety problems. These systems are being scaled up to fully meet the needs of the nation. Additional systems and data sources are also being developed to further enhance safety monitoring capabilities. CDC is committed to ensuring that COVID-19 vaccines are safe.”

In the coming months, government officials and vaccine manufacturers will be working to reassure the public of the safety of the vaccine and the rigor of the vaccine development process. In November 2020, National Institute of Allergy and Infectious Diseases Director Anthony Fauci, MD, told Kaiser Health News: “The company looks at the data. I look at the data. Then the company puts the data to the FDA. The FDA will make the decision to do an emergency-use authorization or a license application approval. And they have career scientists who are really independent. They’re not beholden to anybody. Then there’s another independent group, the Vaccines and Related Biological Products Advisory Committee. The FDA commissioner has vowed publicly that he will go according to the opinion of the career scientists and the advisory board.” President-elect Joe Biden said he would get a vaccine when Dr. Fauci thinks it is safe.

An employee who, after researching the vaccine and the process, still wants to refuse when offered the vaccine is not likely to be fired for that reason right away, as long as the employee takes other precautions, such as wearing a mask. If the employer does fire the employee and the employee sues the employer, it is impossible to predict how a court would decide the case.

Related legal questions may arise in the coming months. For example:

• Is an employer exempt from paying workers’ compensation to an employee who refuses to be vaccinated and then contracts the virus while on the job?
• Can a prospective employer require COVID-19 vaccination as a precondition of employment?
• Is it within a patient’s rights to receive an answer to the question: Has my health care worker been vaccinated against COVID-19?
• If a hospital allows employees to refuse vaccination and keep working, and an outbreak occurs, and it is suggested through contact tracing that unvaccinated workers infected patients, will a court hold the hospital liable for patients’ damages?

Answers to these questions are yet to be determined.

Carolyn Buppert (www.buppert.com) is an attorney and former nurse practitioner who focuses on the legal issues affecting nurse practitioners.

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

As hospitals across the country develop their plans to vaccinate their health care employees against COVID-19, a key question has come to the fore: What if an employee – whether nurse, physician, or other health care worker – refuses to receive the vaccine? Can hospitals require their employees to be vaccinated against COVID-19? And what consequences could an employee face for refusing the vaccine?

My answer needs to be based, in part, on the law related to previous vaccines – influenza, for example – because at the time of this writing (early December 2020), no vaccine for COVID-19 has been approved, although approval of at least one vaccine is expected within a week. So there have been no offers of vaccine and refusals yet, nor are there any cases to date involving an employee who refused a COVID-19 vaccine. As of December 2020, there are no state or federal laws that either require an employee to be vaccinated against COVID-19 or that protect an employee who refuses vaccination against COVID-19. It will take a while after the vaccine is approved and distributed before refusals, reactions, policies, cases, and laws begin to emerge.

If we look at the law related to health care workers refusing to be vaccinated against the closest relative to COVID-19 – influenza – then the answer would be yes, employers can require employees to be vaccinated.

An employer can fire an employee who refuses influenza vaccination. If an employee who refused and was fired sues the employer for wrongful termination, the employee has more or less chance of success depending on the reason for refusal. Some courts and the Equal Employment Opportunity Commission have held that a refusal on religious grounds is protected by the U.S. Constitution, as in this recent case. The Constitution protects freedom to practice one’s religion. Specific religions may have a range of tenets that support refusal to be vaccinated.

A refusal on medical grounds has been successful if the medical grounds fall under the protections of the Americans with Disabilities Act but may fail when the medical grounds for the claim are not covered by the ADA.

Refusal for secular, nonmedical reasons, such as a health care worker’s policy of treating their body as their temple, has not gone over well with employers or courts. However, in at least one case, a nurse who refused vaccination on secular, nonmedical grounds won her case against her employer, on appeal. The appeals court found that the hospital violated her First Amendment rights.

Employees who refuse vaccination for religious or medical reasons still will need to take measures to protect patients and other employees from infection. An employer such as a hospital can, rather than fire the employee, offer the employee an accommodation, such as requiring that the employee wear a mask or quarantine. There are no cases that have upheld an employee’s right to refuse to wear a mask or quarantine.

The situation with the COVID-19 vaccine is different from the situation surrounding influenza vaccines. There are plenty of data on effectiveness and side effects of influenza vaccines, but there is very little evidence of short- or long-term effects of the COVID-19 vaccines currently being tested and/or considered for approval. One could argue that the process of vaccine development is the same for all virus vaccines. However, public confidence in the vaccine vetting process is not what it once was. It has been widely publicized that the COVID-19 vaccine trials have been rushed. As of December 2020, only 60% of the general population say they would take the vaccine, although researchers say confidence is increasing.

The Centers for Disease Control and Prevention has designated health care workers as first in line to get the vaccine, but some health care workers may not want to be the first to try it. A CDC survey found that 63% of health care workers polled in recent months said they would get a COVID-19 vaccine.

Unions have entered the conversation. A coalition of unions that represent health care workers said, “we need a transparent, evidence-based federal vaccine strategy based on principles of equity, safety, and priority, as well as robust efforts to address a high degree of skepticism about safety of an authorized vaccine.” The organization declined to promote a vaccine until more is known.

As of publication date, the EEOC guidance for employers responding to COVID-19 does not address vaccines.

The CDC’s Interim Guidance for Businesses and Employers Responding to Coronavirus Disease 2019, May 2020, updated Dec. 4, 2020, does not address vaccines. The CDC’s page on COVID-19 vaccination for health care workers does not address a health care worker’s refusal. The site does assure health care workers that the vaccine development process is sound: “The current vaccine safety system is strong and robust, with the capacity to effectively monitor COVID-19 vaccine safety. Existing data systems have validated analytic methods that can rapidly detect statistical signals for possible vaccine safety problems. These systems are being scaled up to fully meet the needs of the nation. Additional systems and data sources are also being developed to further enhance safety monitoring capabilities. CDC is committed to ensuring that COVID-19 vaccines are safe.”

In the coming months, government officials and vaccine manufacturers will be working to reassure the public of the safety of the vaccine and the rigor of the vaccine development process. In November 2020, National Institute of Allergy and Infectious Diseases Director Anthony Fauci, MD, told Kaiser Health News: “The company looks at the data. I look at the data. Then the company puts the data to the FDA. The FDA will make the decision to do an emergency-use authorization or a license application approval. And they have career scientists who are really independent. They’re not beholden to anybody. Then there’s another independent group, the Vaccines and Related Biological Products Advisory Committee. The FDA commissioner has vowed publicly that he will go according to the opinion of the career scientists and the advisory board.” President-elect Joe Biden said he would get a vaccine when Dr. Fauci thinks it is safe.

An employee who, after researching the vaccine and the process, still wants to refuse when offered the vaccine is not likely to be fired for that reason right away, as long as the employee takes other precautions, such as wearing a mask. If the employer does fire the employee and the employee sues the employer, it is impossible to predict how a court would decide the case.

Related legal questions may arise in the coming months. For example:

• Is an employer exempt from paying workers’ compensation to an employee who refuses to be vaccinated and then contracts the virus while on the job?
• Can a prospective employer require COVID-19 vaccination as a precondition of employment?
• Is it within a patient’s rights to receive an answer to the question: Has my health care worker been vaccinated against COVID-19?
• If a hospital allows employees to refuse vaccination and keep working, and an outbreak occurs, and it is suggested through contact tracing that unvaccinated workers infected patients, will a court hold the hospital liable for patients’ damages?

Answers to these questions are yet to be determined.

Carolyn Buppert (www.buppert.com) is an attorney and former nurse practitioner who focuses on the legal issues affecting nurse practitioners.

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

Background: Studies have suggested that adrenal incidentalomas may increase risk of cardiometabolic disease in patients. Guidelines for repeat imaging and hormonal assessment of adrenal incidentalomas are inconsistent because of inadequate studies.

Bottom line: Patients with adrenal adenomas should be counseled on modifying cardiovascular risk factors whereas tumor growth, change in hormone production, and malignant transformation are less concerning based on the studies included.

Citation: Elhassan YS et al. Natural history of adrenal incidentalomas with and without mild autonomous cortisol excess: A systematic review and meta-analysis. Ann Intern Med. 2019 Jun 25;121:107-16.

Dr. Thompson is a hospitalist and assistant professor of medicine in the division of general internal medicine at Saint Louis University School of Medicine.

Background: Studies have suggested that adrenal incidentalomas may increase risk of cardiometabolic disease in patients. Guidelines for repeat imaging and hormonal assessment of adrenal incidentalomas are inconsistent because of inadequate studies.

Bottom line: Patients with adrenal adenomas should be counseled on modifying cardiovascular risk factors whereas tumor growth, change in hormone production, and malignant transformation are less concerning based on the studies included.

Citation: Elhassan YS et al. Natural history of adrenal incidentalomas with and without mild autonomous cortisol excess: A systematic review and meta-analysis. Ann Intern Med. 2019 Jun 25;121:107-16.

Dr. Thompson is a hospitalist and assistant professor of medicine in the division of general internal medicine at Saint Louis University School of Medicine.

Background: Studies have suggested that adrenal incidentalomas may increase risk of cardiometabolic disease in patients. Guidelines for repeat imaging and hormonal assessment of adrenal incidentalomas are inconsistent because of inadequate studies.

Bottom line: Patients with adrenal adenomas should be counseled on modifying cardiovascular risk factors whereas tumor growth, change in hormone production, and malignant transformation are less concerning based on the studies included.

Citation: Elhassan YS et al. Natural history of adrenal incidentalomas with and without mild autonomous cortisol excess: A systematic review and meta-analysis. Ann Intern Med. 2019 Jun 25;121:107-16.

Dr. Thompson is a hospitalist and assistant professor of medicine in the division of general internal medicine at Saint Louis University School of Medicine.

Living near hydraulic fracturing is associated with increased risk of hospitalization in people with heart failure (HF), a new study from Pennsylvania suggests.

The link was strongest among those with more severe heart failure but patients with either HF phenotype showed this association of increased risk with exposure to fracking activities, according to the investigators, led by Tara P. McAlexander, PhD, MPH, Drexel University Dornsife School of Public Health in Philadelphia.

“Our understanding has expanded well beyond the famous Harvard Six Cities study to know that it’s not just a short-term uptick in air pollution that›s going to send someone to the hospital a couple days later,” said Dr. McAlexander in an interview, referring to the study conducted from the mid-1970s through 1991. “We know that people who live in these environments and are exposed for long periods of time may have long-term detrimental effects.”

Although questions remain about specific mechanisms and how best to assess exposure, the evidence is mounting in a way that is consistent with the biologic hypotheses of how fracking would adversely affect health, Dr. McAlexander said. “We have many studies now on adverse pregnancy and birth outcomes, and that’s just the tip of the iceberg.”

Pennsylvania is a hot spot for fracking, also known as unconventional natural gas development (UNGD), with more than 12,000 wells drilled in the Marcellus shale since 2004. The shale extends from upstate New York in the north to northeastern Kentucky and Tennessee in the south and covers about 72,000 square miles. Last year, Pennsylvania pledged $3 million to study clusters of rare pediatric cancers and asthma near fracking operations. A recent grand jury report concluded government officials failed to protect residents from the health effects of fracking.

Fracking involves a cascade of activities that can trigger neural circuitry, sympathetic activation, and inflammation – all well-known pathways that potentiate heart failure, said Sanjay Rajagopalan, MD, who has researched the health effects of air pollution for two decades and was not involved with the study.

“If you think about it, it’s like environmental perturbation on steroids in some ways where they are pulling the trigger from a variety of different ways: noise, air pollution, social displacement, psychosocial impacts, economic disparities. So it’s not at all surprising that they saw an association,” said Dr. Rajagopalan, chief of cardiovascular medicine at University Hospitals Harrington Heart & Vascular Institute and director of the Case Western Cardiovascular Research Institute, both in Cleveland, Ohio.

As reported in the Journal of the American College of Cardiology, Dr. McAlexander and colleagues at Johns Hopkins University, Baltimore, used electronic health data from the Geisinger Health System to identify 9,054 patients with heart failure seen between 2008 and 2015. Of these, 5,839 patients had an incident HF hospitalization and 3,215 served as controls. Geisinger operates 13 hospitals and two research centers in 45 of Pennsylvania’s 67 counties, serving more than 3 million of the state’s residents.

Patients’ residential addresses were used to identify latitude and longitude coordinates that were matched with 9,669 UNGD wells in Pennsylvania and the location of major and minor roadways. The researchers also calculated a measure of community socioeconomic deprivation.

The adjusted odds of hospitalization were higher for patients in the highest quartile of exposure for three of the four UNGD phases: pad preparation (odds ratio, 1.70; 95% confidence interval, 1.35-2.13), stimulation or the actual fracking (OR, 1.80; 95% CI, 1.35-2.40), and production (OR, 1.62; 95% CI, 1.07-2.45).

Dr. McAlexander said she initially thought the lack of association with drilling (OR, 0.97; 95% CI, 0.75-1.27) was a mistake but noted that the drilling metric reflects a shorter time period than, for example, 30 days needed to clear the well pad and bring in the necessary equipment.

Stronger associations between pad preparation, fracking, and production are also consistent with the known increases in air pollution, traffic, and noise associated with these phases.

Individuals with more severe HF had greater odds of hospitalization, but the effect sizes were generally comparable between HF with preserved versus reduced ejection fraction. For those with the highest exposure to fracking, the odds ratios for hospitalization reached 2.25 (95% CI, 1.56-3.25) and 2.09 (95% CI, 1.44-3.03), respectively.

Notably, patients who could be phenotyped versus those who could not were more likely to die, to be hospitalized for HF, and to have a higher Charlson Comorbidity Index and other relevant diagnoses like myocardial infarction.

“Clinicians need to be increasingly aware that the environments their patients are in are a huge factor in their disease progression and outlook,” McAlexander said. “We know that UNGD, specifically now, is something that could be impacting a heart failure patient’s survival.”

She also suggested that the findings may also spur more advocacy work and “across-silo” collaboration between clinicians and environmental researchers.

Dr. Rajagopalan said there is increasing recognition that physicians need to be aware of environmental health links as extreme events like the California and Oregon wildfires and coastal flooding become increasingly common. “Unfortunately, unconventional is becoming the new convention.”

The problem for many physicians, however, is just having enough bandwidth to get through the day and get enough learning to keep above water, he said. Artificial intelligence could be used to seed electronic medical records with other personalized information from a bevy of sources including smartphones and the internet of things, but fundamental changes are also needed in the educational process to emphasize the environment.

“It’s going to take a huge societal shift in the way we view commodities, what we consider healthy, etc, but it can happen very quickly because all it takes is a crisis like COVID-19 to bring people to their knees and make them understand how this is going to take over our lives over the next decade,” Dr. Rajagopalan said.

The scientific community has been calling for “good” epidemiologic studies on the health effects of fracking since the early 2010s, Barrak Alahmad, MBChB, MPH, Harvard T.H. Chan School of Public Health, and Haitham Khraishah, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, point out in an accompanying editorial.

The current study applied “extensive and rigorous methods” involving both the design and statistical approach, including use of a negative control analysis to assess for sources of spurious causal inference, several sensitivity analyses, and controlled for a wide range of covariates.

“Their results were consistent and robust across all these measures,” the editorialists wrote. “Most importantly, the effect size is probably too large to be explained away by an unmeasured confounder.”

Dr. Alahmad and Dr. Khraishah call for advancements in exposure assessment, citing a recent study reporting that ambient particle radioactivity near unconventional oil and gas sites could induce adverse health effects. Other unmet needs include a better understanding of racial disparities in the impacts of fracking and a fine-tuning of cause-specific cardiovascular morbidity and mortality.

The study was supported by training grants from the National Institute of Environmental Health Sciences to Dr. McAlexander and principal investigator Brian Schwartz, MD. The authors, Dr. Rajagopalan, Dr. Alahmad, and Dr. Khraishah have disclosed no relevant financial relationships.
 

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

Living near hydraulic fracturing is associated with increased risk of hospitalization in people with heart failure (HF), a new study from Pennsylvania suggests.

The link was strongest among those with more severe heart failure but patients with either HF phenotype showed this association of increased risk with exposure to fracking activities, according to the investigators, led by Tara P. McAlexander, PhD, MPH, Drexel University Dornsife School of Public Health in Philadelphia.

“Our understanding has expanded well beyond the famous Harvard Six Cities study to know that it’s not just a short-term uptick in air pollution that›s going to send someone to the hospital a couple days later,” said Dr. McAlexander in an interview, referring to the study conducted from the mid-1970s through 1991. “We know that people who live in these environments and are exposed for long periods of time may have long-term detrimental effects.”

Although questions remain about specific mechanisms and how best to assess exposure, the evidence is mounting in a way that is consistent with the biologic hypotheses of how fracking would adversely affect health, Dr. McAlexander said. “We have many studies now on adverse pregnancy and birth outcomes, and that’s just the tip of the iceberg.”

Pennsylvania is a hot spot for fracking, also known as unconventional natural gas development (UNGD), with more than 12,000 wells drilled in the Marcellus shale since 2004. The shale extends from upstate New York in the north to northeastern Kentucky and Tennessee in the south and covers about 72,000 square miles. Last year, Pennsylvania pledged $3 million to study clusters of rare pediatric cancers and asthma near fracking operations. A recent grand jury report concluded government officials failed to protect residents from the health effects of fracking.

Fracking involves a cascade of activities that can trigger neural circuitry, sympathetic activation, and inflammation – all well-known pathways that potentiate heart failure, said Sanjay Rajagopalan, MD, who has researched the health effects of air pollution for two decades and was not involved with the study.

“If you think about it, it’s like environmental perturbation on steroids in some ways where they are pulling the trigger from a variety of different ways: noise, air pollution, social displacement, psychosocial impacts, economic disparities. So it’s not at all surprising that they saw an association,” said Dr. Rajagopalan, chief of cardiovascular medicine at University Hospitals Harrington Heart & Vascular Institute and director of the Case Western Cardiovascular Research Institute, both in Cleveland, Ohio.

As reported in the Journal of the American College of Cardiology, Dr. McAlexander and colleagues at Johns Hopkins University, Baltimore, used electronic health data from the Geisinger Health System to identify 9,054 patients with heart failure seen between 2008 and 2015. Of these, 5,839 patients had an incident HF hospitalization and 3,215 served as controls. Geisinger operates 13 hospitals and two research centers in 45 of Pennsylvania’s 67 counties, serving more than 3 million of the state’s residents.

Patients’ residential addresses were used to identify latitude and longitude coordinates that were matched with 9,669 UNGD wells in Pennsylvania and the location of major and minor roadways. The researchers also calculated a measure of community socioeconomic deprivation.

The adjusted odds of hospitalization were higher for patients in the highest quartile of exposure for three of the four UNGD phases: pad preparation (odds ratio, 1.70; 95% confidence interval, 1.35-2.13), stimulation or the actual fracking (OR, 1.80; 95% CI, 1.35-2.40), and production (OR, 1.62; 95% CI, 1.07-2.45).

Dr. McAlexander said she initially thought the lack of association with drilling (OR, 0.97; 95% CI, 0.75-1.27) was a mistake but noted that the drilling metric reflects a shorter time period than, for example, 30 days needed to clear the well pad and bring in the necessary equipment.

Stronger associations between pad preparation, fracking, and production are also consistent with the known increases in air pollution, traffic, and noise associated with these phases.

Individuals with more severe HF had greater odds of hospitalization, but the effect sizes were generally comparable between HF with preserved versus reduced ejection fraction. For those with the highest exposure to fracking, the odds ratios for hospitalization reached 2.25 (95% CI, 1.56-3.25) and 2.09 (95% CI, 1.44-3.03), respectively.

Notably, patients who could be phenotyped versus those who could not were more likely to die, to be hospitalized for HF, and to have a higher Charlson Comorbidity Index and other relevant diagnoses like myocardial infarction.

“Clinicians need to be increasingly aware that the environments their patients are in are a huge factor in their disease progression and outlook,” McAlexander said. “We know that UNGD, specifically now, is something that could be impacting a heart failure patient’s survival.”

She also suggested that the findings may also spur more advocacy work and “across-silo” collaboration between clinicians and environmental researchers.

Dr. Rajagopalan said there is increasing recognition that physicians need to be aware of environmental health links as extreme events like the California and Oregon wildfires and coastal flooding become increasingly common. “Unfortunately, unconventional is becoming the new convention.”

The problem for many physicians, however, is just having enough bandwidth to get through the day and get enough learning to keep above water, he said. Artificial intelligence could be used to seed electronic medical records with other personalized information from a bevy of sources including smartphones and the internet of things, but fundamental changes are also needed in the educational process to emphasize the environment.

“It’s going to take a huge societal shift in the way we view commodities, what we consider healthy, etc, but it can happen very quickly because all it takes is a crisis like COVID-19 to bring people to their knees and make them understand how this is going to take over our lives over the next decade,” Dr. Rajagopalan said.

The scientific community has been calling for “good” epidemiologic studies on the health effects of fracking since the early 2010s, Barrak Alahmad, MBChB, MPH, Harvard T.H. Chan School of Public Health, and Haitham Khraishah, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, point out in an accompanying editorial.

The current study applied “extensive and rigorous methods” involving both the design and statistical approach, including use of a negative control analysis to assess for sources of spurious causal inference, several sensitivity analyses, and controlled for a wide range of covariates.

“Their results were consistent and robust across all these measures,” the editorialists wrote. “Most importantly, the effect size is probably too large to be explained away by an unmeasured confounder.”

Dr. Alahmad and Dr. Khraishah call for advancements in exposure assessment, citing a recent study reporting that ambient particle radioactivity near unconventional oil and gas sites could induce adverse health effects. Other unmet needs include a better understanding of racial disparities in the impacts of fracking and a fine-tuning of cause-specific cardiovascular morbidity and mortality.

The study was supported by training grants from the National Institute of Environmental Health Sciences to Dr. McAlexander and principal investigator Brian Schwartz, MD. The authors, Dr. Rajagopalan, Dr. Alahmad, and Dr. Khraishah have disclosed no relevant financial relationships.
 

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

Living near hydraulic fracturing is associated with increased risk of hospitalization in people with heart failure (HF), a new study from Pennsylvania suggests.

The link was strongest among those with more severe heart failure but patients with either HF phenotype showed this association of increased risk with exposure to fracking activities, according to the investigators, led by Tara P. McAlexander, PhD, MPH, Drexel University Dornsife School of Public Health in Philadelphia.

“Our understanding has expanded well beyond the famous Harvard Six Cities study to know that it’s not just a short-term uptick in air pollution that›s going to send someone to the hospital a couple days later,” said Dr. McAlexander in an interview, referring to the study conducted from the mid-1970s through 1991. “We know that people who live in these environments and are exposed for long periods of time may have long-term detrimental effects.”

Although questions remain about specific mechanisms and how best to assess exposure, the evidence is mounting in a way that is consistent with the biologic hypotheses of how fracking would adversely affect health, Dr. McAlexander said. “We have many studies now on adverse pregnancy and birth outcomes, and that’s just the tip of the iceberg.”

Pennsylvania is a hot spot for fracking, also known as unconventional natural gas development (UNGD), with more than 12,000 wells drilled in the Marcellus shale since 2004. The shale extends from upstate New York in the north to northeastern Kentucky and Tennessee in the south and covers about 72,000 square miles. Last year, Pennsylvania pledged $3 million to study clusters of rare pediatric cancers and asthma near fracking operations. A recent grand jury report concluded government officials failed to protect residents from the health effects of fracking.

Fracking involves a cascade of activities that can trigger neural circuitry, sympathetic activation, and inflammation – all well-known pathways that potentiate heart failure, said Sanjay Rajagopalan, MD, who has researched the health effects of air pollution for two decades and was not involved with the study.

“If you think about it, it’s like environmental perturbation on steroids in some ways where they are pulling the trigger from a variety of different ways: noise, air pollution, social displacement, psychosocial impacts, economic disparities. So it’s not at all surprising that they saw an association,” said Dr. Rajagopalan, chief of cardiovascular medicine at University Hospitals Harrington Heart & Vascular Institute and director of the Case Western Cardiovascular Research Institute, both in Cleveland, Ohio.

As reported in the Journal of the American College of Cardiology, Dr. McAlexander and colleagues at Johns Hopkins University, Baltimore, used electronic health data from the Geisinger Health System to identify 9,054 patients with heart failure seen between 2008 and 2015. Of these, 5,839 patients had an incident HF hospitalization and 3,215 served as controls. Geisinger operates 13 hospitals and two research centers in 45 of Pennsylvania’s 67 counties, serving more than 3 million of the state’s residents.

Patients’ residential addresses were used to identify latitude and longitude coordinates that were matched with 9,669 UNGD wells in Pennsylvania and the location of major and minor roadways. The researchers also calculated a measure of community socioeconomic deprivation.

The adjusted odds of hospitalization were higher for patients in the highest quartile of exposure for three of the four UNGD phases: pad preparation (odds ratio, 1.70; 95% confidence interval, 1.35-2.13), stimulation or the actual fracking (OR, 1.80; 95% CI, 1.35-2.40), and production (OR, 1.62; 95% CI, 1.07-2.45).

Dr. McAlexander said she initially thought the lack of association with drilling (OR, 0.97; 95% CI, 0.75-1.27) was a mistake but noted that the drilling metric reflects a shorter time period than, for example, 30 days needed to clear the well pad and bring in the necessary equipment.

Stronger associations between pad preparation, fracking, and production are also consistent with the known increases in air pollution, traffic, and noise associated with these phases.

Individuals with more severe HF had greater odds of hospitalization, but the effect sizes were generally comparable between HF with preserved versus reduced ejection fraction. For those with the highest exposure to fracking, the odds ratios for hospitalization reached 2.25 (95% CI, 1.56-3.25) and 2.09 (95% CI, 1.44-3.03), respectively.

Notably, patients who could be phenotyped versus those who could not were more likely to die, to be hospitalized for HF, and to have a higher Charlson Comorbidity Index and other relevant diagnoses like myocardial infarction.

“Clinicians need to be increasingly aware that the environments their patients are in are a huge factor in their disease progression and outlook,” McAlexander said. “We know that UNGD, specifically now, is something that could be impacting a heart failure patient’s survival.”

She also suggested that the findings may also spur more advocacy work and “across-silo” collaboration between clinicians and environmental researchers.

Dr. Rajagopalan said there is increasing recognition that physicians need to be aware of environmental health links as extreme events like the California and Oregon wildfires and coastal flooding become increasingly common. “Unfortunately, unconventional is becoming the new convention.”

The problem for many physicians, however, is just having enough bandwidth to get through the day and get enough learning to keep above water, he said. Artificial intelligence could be used to seed electronic medical records with other personalized information from a bevy of sources including smartphones and the internet of things, but fundamental changes are also needed in the educational process to emphasize the environment.

“It’s going to take a huge societal shift in the way we view commodities, what we consider healthy, etc, but it can happen very quickly because all it takes is a crisis like COVID-19 to bring people to their knees and make them understand how this is going to take over our lives over the next decade,” Dr. Rajagopalan said.

The scientific community has been calling for “good” epidemiologic studies on the health effects of fracking since the early 2010s, Barrak Alahmad, MBChB, MPH, Harvard T.H. Chan School of Public Health, and Haitham Khraishah, MD, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, point out in an accompanying editorial.

The current study applied “extensive and rigorous methods” involving both the design and statistical approach, including use of a negative control analysis to assess for sources of spurious causal inference, several sensitivity analyses, and controlled for a wide range of covariates.

“Their results were consistent and robust across all these measures,” the editorialists wrote. “Most importantly, the effect size is probably too large to be explained away by an unmeasured confounder.”

Dr. Alahmad and Dr. Khraishah call for advancements in exposure assessment, citing a recent study reporting that ambient particle radioactivity near unconventional oil and gas sites could induce adverse health effects. Other unmet needs include a better understanding of racial disparities in the impacts of fracking and a fine-tuning of cause-specific cardiovascular morbidity and mortality.

The study was supported by training grants from the National Institute of Environmental Health Sciences to Dr. McAlexander and principal investigator Brian Schwartz, MD. The authors, Dr. Rajagopalan, Dr. Alahmad, and Dr. Khraishah have disclosed no relevant financial relationships.
 

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

Coronary artery calcium (CAC) score as a measure of plaque burden more reliably predicts future cardiovascular (CV) risk in patients with suspected coronary disease (CAD) than whether or not the disease is obstructive, a large retrospective study suggests.

Indeed, CV risk went up in tandem with growing plaque burden regardless of whether there was obstructive disease in any coronary artery, defined as a 50% or greater stenosis by computed tomographic angiography (CTA).

The findings argue for plaque burden as measured by CAC score, rather than percent-stenosis severity, for guiding further treatment decisions in such patients, researchers say.

The research was based on more than 20,000 symptomatic patients referred to diagnostic CTA in the Western Denmark Heart Registry who were then followed for about 4 years for major CV events, including death, myocardial infarction, or stroke.

“What we show is that CAC is important for prognosis, and that patients with no stenosis have similar high risk as patients with stenosis when CAC burden is similar,” Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, said in an interview.

The guidelines “distinguish between primary and secondary prevention patients” based on the presence or absence of obstructive CAD, he said, but “our results challenge this long-held approach. We show that patients with nonobstructive CAD carry similar risk as patients with obstructive CAD.”

In practice, risk tends to be greater in patients with obstructive compared with nonobstructive CAD. But the reason “is simply that they normally have higher atherosclerosis burden,” Dr. Mortensen said. “When you stratify based on atherosclerosis burden, then patients with obstructive and nonobstructive CAD have similar risk.”

The analysis was published online Dec. 7 in the Journal of the American College of Cardiology with Mortensen as lead author.

Until recently, it had long been believed that CV-event risk was driven by ischemia – but “ischemia is just a surrogate for the extent of atherosclerotic disease,” Armin Arbab Zadeh, MD, PhD, MPH, who is not connected with the current study, said in an interview.

The finding that CV risk climbs with growing coronary plaque burden “essentially confirms” other recent studies, but with “added value in showing how well the calcium scores, compared to obstructive disease, track with risk. So it’s definitely a nice extension of the evidence,” said Dr. Zadeh, director of cardiac CT at Johns Hopkins University, Baltimore.

“This study clearly shows that there is no ischemia ‘threshold,’ that the risk starts from mild and goes up with the burden of atherosclerotic disease. We were essentially taught wrong for decades.”

Dr. Mortensen said that the new results “are in line with previous studies showing that atherosclerosis burden is very important for risk.” They also help explain why revascularization of patients with stable angina failed to cut the risk of MI or death in trials like COURAGE, FAME-2, and ISCHEMIA. It’s because “stenosis per se explains little of the risk compared to atherosclerosis burden.”

In the current analysis, for example, about 65% of events were in patients who did not show obstructive CAD at CTA. Its 23,759 patients with symptoms suggestive of CAD were referred for CTA from 2008 through 2017; 5,043 (21.2%) were found to have obstructive disease and 18,716 (78.8%) either had no CAD or nonobstructive disease.

About 4.4% of patients experienced a first major CV event over a median follow-up of 4.3 years. Only events occurring later than 90 days after CTA were counted in an effort to exclude any directly related to revascularization, Dr. Mortensen noted.

The risk of events went up proportionally with both CAC score and the number of coronaries with obstructive disease.

The number of major CV events per 1,000 person-years was 6.2 for patients with a CAC score of 0, of whom 87% had no CAD by CTA, 7% had nonobstructive CAD, and 6% had obstructive CAD.

The corresponding rate was 17.5 among patients with a CAC score >100-399 for a hazard ratio (HR) of 1.7 (95% confidence interval [CI] 1.4-2.1) vs. a CAC score of 0.

And it was 42.3 per 1,000 patient-years among patients with CAC score >1000, HR 3.4 (95% CI, 2.5-4.6) vs. a CAC score of 0. Among those with the highest-tier CAC score, none were without CAD by CTA, 17% had nonobstructive disease, and 83% had obstructive CAD.

The major CV event rate rose similarly by number of coronaries with obstructive disease. It was 6.1 per 1,000 person-years in patients with no CAD. But it was 12.3 in those with nonobstructive disease, HR 1.3 (95% CI 1.1-1.6), up to 34.7 in those with triple-vessel obstructive disease, HR 2.9 (95% CI 2.2-3.9), vs. no CAD.

However, in an analysis with stratification by CAC score tier (0, 1-99, 100-399, 400-1,000, and >1,000), obstructive CAD was not associated with increased major CV-event risk in any stratum. The findings were similar in each subgroup with 1-vessel, 2-vessel, or 3-vessel CAD when stratified by CAC score.

Nor did major CV event risk track with obstructive CAD in analyses by age or after excluding all patients who underwent coronary revascularization within 90 days of CTA, the group reported.

“I believe these results support the use of CTA as a first-line test in patients with symptoms suggestive of CAD, as it provides valuable information for both diagnosis and prognosis in symptomatic patients,” Dr. Mortensen said. Those found to have a higher burden of atherosclerosis, he added, should receive aggressive preventive therapy regardless of whether or not they have obstructive disease.

The evidence from this study and others “supports a CTA-based approach” in such patients, Dr. Zadeh said. “And I would go further to say that a stress test is really inadequate,” in that it “detects the disease at such a late stage, you’re missing the opportunity to identify these patients who have atherosclerotic disease while you can do something about it.”

Its continued use as a first-line test, Dr. Zadeh said, “is essentially, in my mind, dismissing the evidence.”

An accompanying editorial Todd C. Villines, MD, and Patricia Rodriguez Lozano, MD, of the University of Virginia, Charlottesville agreed that “it is time that the traditional definitions of primary and secondary prevention evolve to incorporate CAC and CTA measures of patient risk based on coronary artery plaque burden.”

But they pointed out some limitations of the current study.

“The authors compared CAC with ≥50% stenosis, not CAC to comprehensive, contemporary coronary CTA,” and so “did not assess numerous other well-validated measures of coronary plaque burden that are routinely obtained from coronary CTA that typically improve the prognostic accuracy of coronary CTA beyond stenosis alone.” Also not performed was “plaque quantification on coronary CTA, an emerging field of study.”

The editorialists noted that noncontrast CT as used in the study for CAC scoring “is generally not recommended as a standalone test in symptomatic patients. Most studies have shown that coronary CTA, a test that accurately detects stenosis and identifies all types of coronary atherosclerosis (calcified and noncalcified), has significantly higher diagnostic and prognostic accuracy than CAC when performed in symptomatic patients without known coronary artery disease.”

Dr. Mortensen has disclosed no relevant financial relationships. Disclosures for the other authors are in the report. Dr. Villines and Dr. Rodriguez Lozano have disclosed no relevant financial relationships. Dr. Zadeh disclosed receiving grant support from Canon Medical Systems.

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

Coronary artery calcium (CAC) score as a measure of plaque burden more reliably predicts future cardiovascular (CV) risk in patients with suspected coronary disease (CAD) than whether or not the disease is obstructive, a large retrospective study suggests.

Indeed, CV risk went up in tandem with growing plaque burden regardless of whether there was obstructive disease in any coronary artery, defined as a 50% or greater stenosis by computed tomographic angiography (CTA).

The findings argue for plaque burden as measured by CAC score, rather than percent-stenosis severity, for guiding further treatment decisions in such patients, researchers say.

The research was based on more than 20,000 symptomatic patients referred to diagnostic CTA in the Western Denmark Heart Registry who were then followed for about 4 years for major CV events, including death, myocardial infarction, or stroke.

“What we show is that CAC is important for prognosis, and that patients with no stenosis have similar high risk as patients with stenosis when CAC burden is similar,” Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, said in an interview.

The guidelines “distinguish between primary and secondary prevention patients” based on the presence or absence of obstructive CAD, he said, but “our results challenge this long-held approach. We show that patients with nonobstructive CAD carry similar risk as patients with obstructive CAD.”

In practice, risk tends to be greater in patients with obstructive compared with nonobstructive CAD. But the reason “is simply that they normally have higher atherosclerosis burden,” Dr. Mortensen said. “When you stratify based on atherosclerosis burden, then patients with obstructive and nonobstructive CAD have similar risk.”

The analysis was published online Dec. 7 in the Journal of the American College of Cardiology with Mortensen as lead author.

Until recently, it had long been believed that CV-event risk was driven by ischemia – but “ischemia is just a surrogate for the extent of atherosclerotic disease,” Armin Arbab Zadeh, MD, PhD, MPH, who is not connected with the current study, said in an interview.

The finding that CV risk climbs with growing coronary plaque burden “essentially confirms” other recent studies, but with “added value in showing how well the calcium scores, compared to obstructive disease, track with risk. So it’s definitely a nice extension of the evidence,” said Dr. Zadeh, director of cardiac CT at Johns Hopkins University, Baltimore.

“This study clearly shows that there is no ischemia ‘threshold,’ that the risk starts from mild and goes up with the burden of atherosclerotic disease. We were essentially taught wrong for decades.”

Dr. Mortensen said that the new results “are in line with previous studies showing that atherosclerosis burden is very important for risk.” They also help explain why revascularization of patients with stable angina failed to cut the risk of MI or death in trials like COURAGE, FAME-2, and ISCHEMIA. It’s because “stenosis per se explains little of the risk compared to atherosclerosis burden.”

In the current analysis, for example, about 65% of events were in patients who did not show obstructive CAD at CTA. Its 23,759 patients with symptoms suggestive of CAD were referred for CTA from 2008 through 2017; 5,043 (21.2%) were found to have obstructive disease and 18,716 (78.8%) either had no CAD or nonobstructive disease.

About 4.4% of patients experienced a first major CV event over a median follow-up of 4.3 years. Only events occurring later than 90 days after CTA were counted in an effort to exclude any directly related to revascularization, Dr. Mortensen noted.

The risk of events went up proportionally with both CAC score and the number of coronaries with obstructive disease.

The number of major CV events per 1,000 person-years was 6.2 for patients with a CAC score of 0, of whom 87% had no CAD by CTA, 7% had nonobstructive CAD, and 6% had obstructive CAD.

The corresponding rate was 17.5 among patients with a CAC score >100-399 for a hazard ratio (HR) of 1.7 (95% confidence interval [CI] 1.4-2.1) vs. a CAC score of 0.

And it was 42.3 per 1,000 patient-years among patients with CAC score >1000, HR 3.4 (95% CI, 2.5-4.6) vs. a CAC score of 0. Among those with the highest-tier CAC score, none were without CAD by CTA, 17% had nonobstructive disease, and 83% had obstructive CAD.

The major CV event rate rose similarly by number of coronaries with obstructive disease. It was 6.1 per 1,000 person-years in patients with no CAD. But it was 12.3 in those with nonobstructive disease, HR 1.3 (95% CI 1.1-1.6), up to 34.7 in those with triple-vessel obstructive disease, HR 2.9 (95% CI 2.2-3.9), vs. no CAD.

However, in an analysis with stratification by CAC score tier (0, 1-99, 100-399, 400-1,000, and >1,000), obstructive CAD was not associated with increased major CV-event risk in any stratum. The findings were similar in each subgroup with 1-vessel, 2-vessel, or 3-vessel CAD when stratified by CAC score.

Nor did major CV event risk track with obstructive CAD in analyses by age or after excluding all patients who underwent coronary revascularization within 90 days of CTA, the group reported.

“I believe these results support the use of CTA as a first-line test in patients with symptoms suggestive of CAD, as it provides valuable information for both diagnosis and prognosis in symptomatic patients,” Dr. Mortensen said. Those found to have a higher burden of atherosclerosis, he added, should receive aggressive preventive therapy regardless of whether or not they have obstructive disease.

The evidence from this study and others “supports a CTA-based approach” in such patients, Dr. Zadeh said. “And I would go further to say that a stress test is really inadequate,” in that it “detects the disease at such a late stage, you’re missing the opportunity to identify these patients who have atherosclerotic disease while you can do something about it.”

Its continued use as a first-line test, Dr. Zadeh said, “is essentially, in my mind, dismissing the evidence.”

An accompanying editorial Todd C. Villines, MD, and Patricia Rodriguez Lozano, MD, of the University of Virginia, Charlottesville agreed that “it is time that the traditional definitions of primary and secondary prevention evolve to incorporate CAC and CTA measures of patient risk based on coronary artery plaque burden.”

But they pointed out some limitations of the current study.

“The authors compared CAC with ≥50% stenosis, not CAC to comprehensive, contemporary coronary CTA,” and so “did not assess numerous other well-validated measures of coronary plaque burden that are routinely obtained from coronary CTA that typically improve the prognostic accuracy of coronary CTA beyond stenosis alone.” Also not performed was “plaque quantification on coronary CTA, an emerging field of study.”

The editorialists noted that noncontrast CT as used in the study for CAC scoring “is generally not recommended as a standalone test in symptomatic patients. Most studies have shown that coronary CTA, a test that accurately detects stenosis and identifies all types of coronary atherosclerosis (calcified and noncalcified), has significantly higher diagnostic and prognostic accuracy than CAC when performed in symptomatic patients without known coronary artery disease.”

Dr. Mortensen has disclosed no relevant financial relationships. Disclosures for the other authors are in the report. Dr. Villines and Dr. Rodriguez Lozano have disclosed no relevant financial relationships. Dr. Zadeh disclosed receiving grant support from Canon Medical Systems.

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

Coronary artery calcium (CAC) score as a measure of plaque burden more reliably predicts future cardiovascular (CV) risk in patients with suspected coronary disease (CAD) than whether or not the disease is obstructive, a large retrospective study suggests.

Indeed, CV risk went up in tandem with growing plaque burden regardless of whether there was obstructive disease in any coronary artery, defined as a 50% or greater stenosis by computed tomographic angiography (CTA).

The findings argue for plaque burden as measured by CAC score, rather than percent-stenosis severity, for guiding further treatment decisions in such patients, researchers say.

The research was based on more than 20,000 symptomatic patients referred to diagnostic CTA in the Western Denmark Heart Registry who were then followed for about 4 years for major CV events, including death, myocardial infarction, or stroke.

“What we show is that CAC is important for prognosis, and that patients with no stenosis have similar high risk as patients with stenosis when CAC burden is similar,” Martin Bødtker Mortensen, MD, PhD, Aarhus (Denmark) University Hospital, said in an interview.

The guidelines “distinguish between primary and secondary prevention patients” based on the presence or absence of obstructive CAD, he said, but “our results challenge this long-held approach. We show that patients with nonobstructive CAD carry similar risk as patients with obstructive CAD.”

In practice, risk tends to be greater in patients with obstructive compared with nonobstructive CAD. But the reason “is simply that they normally have higher atherosclerosis burden,” Dr. Mortensen said. “When you stratify based on atherosclerosis burden, then patients with obstructive and nonobstructive CAD have similar risk.”

The analysis was published online Dec. 7 in the Journal of the American College of Cardiology with Mortensen as lead author.

Until recently, it had long been believed that CV-event risk was driven by ischemia – but “ischemia is just a surrogate for the extent of atherosclerotic disease,” Armin Arbab Zadeh, MD, PhD, MPH, who is not connected with the current study, said in an interview.

The finding that CV risk climbs with growing coronary plaque burden “essentially confirms” other recent studies, but with “added value in showing how well the calcium scores, compared to obstructive disease, track with risk. So it’s definitely a nice extension of the evidence,” said Dr. Zadeh, director of cardiac CT at Johns Hopkins University, Baltimore.

“This study clearly shows that there is no ischemia ‘threshold,’ that the risk starts from mild and goes up with the burden of atherosclerotic disease. We were essentially taught wrong for decades.”

Dr. Mortensen said that the new results “are in line with previous studies showing that atherosclerosis burden is very important for risk.” They also help explain why revascularization of patients with stable angina failed to cut the risk of MI or death in trials like COURAGE, FAME-2, and ISCHEMIA. It’s because “stenosis per se explains little of the risk compared to atherosclerosis burden.”

In the current analysis, for example, about 65% of events were in patients who did not show obstructive CAD at CTA. Its 23,759 patients with symptoms suggestive of CAD were referred for CTA from 2008 through 2017; 5,043 (21.2%) were found to have obstructive disease and 18,716 (78.8%) either had no CAD or nonobstructive disease.

About 4.4% of patients experienced a first major CV event over a median follow-up of 4.3 years. Only events occurring later than 90 days after CTA were counted in an effort to exclude any directly related to revascularization, Dr. Mortensen noted.

The risk of events went up proportionally with both CAC score and the number of coronaries with obstructive disease.

The number of major CV events per 1,000 person-years was 6.2 for patients with a CAC score of 0, of whom 87% had no CAD by CTA, 7% had nonobstructive CAD, and 6% had obstructive CAD.

The corresponding rate was 17.5 among patients with a CAC score >100-399 for a hazard ratio (HR) of 1.7 (95% confidence interval [CI] 1.4-2.1) vs. a CAC score of 0.

And it was 42.3 per 1,000 patient-years among patients with CAC score >1000, HR 3.4 (95% CI, 2.5-4.6) vs. a CAC score of 0. Among those with the highest-tier CAC score, none were without CAD by CTA, 17% had nonobstructive disease, and 83% had obstructive CAD.

The major CV event rate rose similarly by number of coronaries with obstructive disease. It was 6.1 per 1,000 person-years in patients with no CAD. But it was 12.3 in those with nonobstructive disease, HR 1.3 (95% CI 1.1-1.6), up to 34.7 in those with triple-vessel obstructive disease, HR 2.9 (95% CI 2.2-3.9), vs. no CAD.

However, in an analysis with stratification by CAC score tier (0, 1-99, 100-399, 400-1,000, and >1,000), obstructive CAD was not associated with increased major CV-event risk in any stratum. The findings were similar in each subgroup with 1-vessel, 2-vessel, or 3-vessel CAD when stratified by CAC score.

Nor did major CV event risk track with obstructive CAD in analyses by age or after excluding all patients who underwent coronary revascularization within 90 days of CTA, the group reported.

“I believe these results support the use of CTA as a first-line test in patients with symptoms suggestive of CAD, as it provides valuable information for both diagnosis and prognosis in symptomatic patients,” Dr. Mortensen said. Those found to have a higher burden of atherosclerosis, he added, should receive aggressive preventive therapy regardless of whether or not they have obstructive disease.

The evidence from this study and others “supports a CTA-based approach” in such patients, Dr. Zadeh said. “And I would go further to say that a stress test is really inadequate,” in that it “detects the disease at such a late stage, you’re missing the opportunity to identify these patients who have atherosclerotic disease while you can do something about it.”

Its continued use as a first-line test, Dr. Zadeh said, “is essentially, in my mind, dismissing the evidence.”

An accompanying editorial Todd C. Villines, MD, and Patricia Rodriguez Lozano, MD, of the University of Virginia, Charlottesville agreed that “it is time that the traditional definitions of primary and secondary prevention evolve to incorporate CAC and CTA measures of patient risk based on coronary artery plaque burden.”

But they pointed out some limitations of the current study.

“The authors compared CAC with ≥50% stenosis, not CAC to comprehensive, contemporary coronary CTA,” and so “did not assess numerous other well-validated measures of coronary plaque burden that are routinely obtained from coronary CTA that typically improve the prognostic accuracy of coronary CTA beyond stenosis alone.” Also not performed was “plaque quantification on coronary CTA, an emerging field of study.”

The editorialists noted that noncontrast CT as used in the study for CAC scoring “is generally not recommended as a standalone test in symptomatic patients. Most studies have shown that coronary CTA, a test that accurately detects stenosis and identifies all types of coronary atherosclerosis (calcified and noncalcified), has significantly higher diagnostic and prognostic accuracy than CAC when performed in symptomatic patients without known coronary artery disease.”

Dr. Mortensen has disclosed no relevant financial relationships. Disclosures for the other authors are in the report. Dr. Villines and Dr. Rodriguez Lozano have disclosed no relevant financial relationships. Dr. Zadeh disclosed receiving grant support from Canon Medical Systems.

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

The World Health Organization estimates that 14.9 million of 57 million annual deaths worldwide (25%) are related directly to diseases caused by bacterial and/or viral infections.

The first crucial step in order to build a successful surveillance system is to accurately identify and diagnose disease, Ivana Pennisi reminded the audience at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. A problem, particularly in primary care, is differentiating between patients with bacterial infections who might benefit from antibiotics and those with viral infections where supportive treatment is generally required. One solution might a rapid point-of-care tool.

Ms. Pennisi described early experiences of using microchip technology to detect RNA biomarkers in the blood rather than look for the pathogen itself. Early results suggest high diagnostic accuracy at low cost.

It is known that when a bacteria or virus enters the body, it stimulates the immune system in a unique way leading to the expression of different genes in the host blood. As part of the Personalized Management of Febrile Illnesses study, researchers have demonstrated a number of high correlated transcripts. Of current interest are two genes which are upregulated in childhood febrile illnesses.

Ms. Pennisi, a PhD student working as part of a multidisciplinary at the department of infectious disease and Centre for Bioinspired Technology at Imperial College, London, developed loop-mediated isothermal amplification (LAMP) assays to detect for the first time host RNA signatures on a nucleic acid–based point-of-care handheld system to discriminate bacterial from viral infection. The amplification reaction is then combined with microchip technology in the well of a portable point-of-care device named Lacewing. It translates the nucleic acid amplification signal into a quantitative electrochemical signal without the need for a thermal cycler.

The combination of genomic expertise in the section of paediatrics lead by Michael Levin, PhD, and microchip-based technologies in the department of electrical and electronic engineering under the guidance of Pantelis Georgiou, PhD, enabled the team overcome many clinical challenges.

Ms. Pennisi presented her team’s early experiences with clinical samples from 455 febrile children. First, transcription isothermal amplification techniques were employed to confirm bacterial and viral infections. Results were then validated using standard fluorescent-based quantitative polymerase chain reaction (PCR) instruments. In order to define a decision boundary between bacterial and viral patients, cutoff levels were determined using multivariate logistic regression analysis. Results then were evaluated using microarrays, reverse transcriptase PCR (RT-PCR), and the eLAMP to confirm comparability with preferred techniques.

In conclusion, Ms. Pennisi reported that the two-gene signature combined with the use of eLAMP technology in a point-of-care tool offered the potential of low cost and accurate discrimination between bacterial and viral infection in febrile children. She outlined her vision for the future: “The patient sample and reagent are loaded into a disposable cartridge. This is then placed into a device to monitor in real time the reaction and share all the data via a Bluetooth to a dedicated app on a smart phone. All data and location of the outbreak are then stored in [the] cloud, making it easier for epidemiological studies and tracking of new outbreaks. We hope that by enhancing the capability of our platform, we contribute to better patient care.”

“Distinguishing between bacterial and viral infections remains one of the key questions in the daily pediatric acute care,” commented Lauri Ivaska, MD, from the department of pediatrics and adolescent medicine at Turku (Finland) University Hospital. “One of the most promising laboratory methods to do this is by measuring quantities of two specific host RNA transcripts from a blood sample. It would be of great importance if this could be done reliably by using a fast and cheap method as presented here by Ivana Pennisi.”

Ms. Pennisi had no relevant financial disclosures.

The World Health Organization estimates that 14.9 million of 57 million annual deaths worldwide (25%) are related directly to diseases caused by bacterial and/or viral infections.

The first crucial step in order to build a successful surveillance system is to accurately identify and diagnose disease, Ivana Pennisi reminded the audience at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. A problem, particularly in primary care, is differentiating between patients with bacterial infections who might benefit from antibiotics and those with viral infections where supportive treatment is generally required. One solution might a rapid point-of-care tool.

Ms. Pennisi described early experiences of using microchip technology to detect RNA biomarkers in the blood rather than look for the pathogen itself. Early results suggest high diagnostic accuracy at low cost.

It is known that when a bacteria or virus enters the body, it stimulates the immune system in a unique way leading to the expression of different genes in the host blood. As part of the Personalized Management of Febrile Illnesses study, researchers have demonstrated a number of high correlated transcripts. Of current interest are two genes which are upregulated in childhood febrile illnesses.

Ms. Pennisi, a PhD student working as part of a multidisciplinary at the department of infectious disease and Centre for Bioinspired Technology at Imperial College, London, developed loop-mediated isothermal amplification (LAMP) assays to detect for the first time host RNA signatures on a nucleic acid–based point-of-care handheld system to discriminate bacterial from viral infection. The amplification reaction is then combined with microchip technology in the well of a portable point-of-care device named Lacewing. It translates the nucleic acid amplification signal into a quantitative electrochemical signal without the need for a thermal cycler.

The combination of genomic expertise in the section of paediatrics lead by Michael Levin, PhD, and microchip-based technologies in the department of electrical and electronic engineering under the guidance of Pantelis Georgiou, PhD, enabled the team overcome many clinical challenges.

Ms. Pennisi presented her team’s early experiences with clinical samples from 455 febrile children. First, transcription isothermal amplification techniques were employed to confirm bacterial and viral infections. Results were then validated using standard fluorescent-based quantitative polymerase chain reaction (PCR) instruments. In order to define a decision boundary between bacterial and viral patients, cutoff levels were determined using multivariate logistic regression analysis. Results then were evaluated using microarrays, reverse transcriptase PCR (RT-PCR), and the eLAMP to confirm comparability with preferred techniques.

In conclusion, Ms. Pennisi reported that the two-gene signature combined with the use of eLAMP technology in a point-of-care tool offered the potential of low cost and accurate discrimination between bacterial and viral infection in febrile children. She outlined her vision for the future: “The patient sample and reagent are loaded into a disposable cartridge. This is then placed into a device to monitor in real time the reaction and share all the data via a Bluetooth to a dedicated app on a smart phone. All data and location of the outbreak are then stored in [the] cloud, making it easier for epidemiological studies and tracking of new outbreaks. We hope that by enhancing the capability of our platform, we contribute to better patient care.”

“Distinguishing between bacterial and viral infections remains one of the key questions in the daily pediatric acute care,” commented Lauri Ivaska, MD, from the department of pediatrics and adolescent medicine at Turku (Finland) University Hospital. “One of the most promising laboratory methods to do this is by measuring quantities of two specific host RNA transcripts from a blood sample. It would be of great importance if this could be done reliably by using a fast and cheap method as presented here by Ivana Pennisi.”

Ms. Pennisi had no relevant financial disclosures.

The World Health Organization estimates that 14.9 million of 57 million annual deaths worldwide (25%) are related directly to diseases caused by bacterial and/or viral infections.

The first crucial step in order to build a successful surveillance system is to accurately identify and diagnose disease, Ivana Pennisi reminded the audience at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. A problem, particularly in primary care, is differentiating between patients with bacterial infections who might benefit from antibiotics and those with viral infections where supportive treatment is generally required. One solution might a rapid point-of-care tool.

Ms. Pennisi described early experiences of using microchip technology to detect RNA biomarkers in the blood rather than look for the pathogen itself. Early results suggest high diagnostic accuracy at low cost.

It is known that when a bacteria or virus enters the body, it stimulates the immune system in a unique way leading to the expression of different genes in the host blood. As part of the Personalized Management of Febrile Illnesses study, researchers have demonstrated a number of high correlated transcripts. Of current interest are two genes which are upregulated in childhood febrile illnesses.

Ms. Pennisi, a PhD student working as part of a multidisciplinary at the department of infectious disease and Centre for Bioinspired Technology at Imperial College, London, developed loop-mediated isothermal amplification (LAMP) assays to detect for the first time host RNA signatures on a nucleic acid–based point-of-care handheld system to discriminate bacterial from viral infection. The amplification reaction is then combined with microchip technology in the well of a portable point-of-care device named Lacewing. It translates the nucleic acid amplification signal into a quantitative electrochemical signal without the need for a thermal cycler.

The combination of genomic expertise in the section of paediatrics lead by Michael Levin, PhD, and microchip-based technologies in the department of electrical and electronic engineering under the guidance of Pantelis Georgiou, PhD, enabled the team overcome many clinical challenges.

Ms. Pennisi presented her team’s early experiences with clinical samples from 455 febrile children. First, transcription isothermal amplification techniques were employed to confirm bacterial and viral infections. Results were then validated using standard fluorescent-based quantitative polymerase chain reaction (PCR) instruments. In order to define a decision boundary between bacterial and viral patients, cutoff levels were determined using multivariate logistic regression analysis. Results then were evaluated using microarrays, reverse transcriptase PCR (RT-PCR), and the eLAMP to confirm comparability with preferred techniques.

In conclusion, Ms. Pennisi reported that the two-gene signature combined with the use of eLAMP technology in a point-of-care tool offered the potential of low cost and accurate discrimination between bacterial and viral infection in febrile children. She outlined her vision for the future: “The patient sample and reagent are loaded into a disposable cartridge. This is then placed into a device to monitor in real time the reaction and share all the data via a Bluetooth to a dedicated app on a smart phone. All data and location of the outbreak are then stored in [the] cloud, making it easier for epidemiological studies and tracking of new outbreaks. We hope that by enhancing the capability of our platform, we contribute to better patient care.”

“Distinguishing between bacterial and viral infections remains one of the key questions in the daily pediatric acute care,” commented Lauri Ivaska, MD, from the department of pediatrics and adolescent medicine at Turku (Finland) University Hospital. “One of the most promising laboratory methods to do this is by measuring quantities of two specific host RNA transcripts from a blood sample. It would be of great importance if this could be done reliably by using a fast and cheap method as presented here by Ivana Pennisi.”

Ms. Pennisi had no relevant financial disclosures.

Clostridioides difficile (C. diff) infection (CDI) is a pathogen of both humans and animals, and to control it will require an integrated approach that encompasses human health care, veterinary health care, environmental regulation, and public policy. That is the conclusion of a group led by Su-Chen Lim, MD, and Tom Riley, MD, of Edith Cowan University in Australia, who published a review in Clinical Microbiology and Infection.

CDI was generally considered a nuisance infection until the early 21st century, when a hypervirulent fluoroquinolone-resistant strain emerged in North America. The strain is now documented In the United States, Canada, and most countries in Europe.

Another new feature of CDI is increased evidence of community transmission, which was previously rare. This is defined as cases where the patient experienced symptom onset outside the hospital, and had no history of hospitalization in the previous 12 weeks or symptom onset within 48 hours of hospital admission. Community-associated CDI now accounts for 41% of U.S. cases, nearly 30% of Australian cases, and about 14% in Europe, according to recent studies.

Several features of CDI suggest a need for an integrated management plan. The preferred habitat of C. diff is the gastrointestinal track of mammals, and likely colonizes all mammalian neonates. Over time, colonization by other microbes likely crowd it out and prevent overgrowth. But widespread use of antimicrobials in animal production can lead to the creation of an environment resembling that of the neonate, allowing C. diff to expand. That has led to food animals becoming a major C. diff reservoir, and whole-genome studies showed that strains found in humans, food, animals, and the environment are closely related and sometimes genetically indistinguishable, suggesting transmission between humans and animals that may be attributable to contaminated food and environments.

The authors suggest that C. diff infection control should be guided by the One Health initiative, which seeks cooperation between physicians, osteopathic physicians, veterinarians, dentists, nurses, and other scientific and environmental disciplines. The goal is to enhance surveillance and interdisciplinary communication, as well as integrated policies. The authors note that C. diff is often thought of by physicians as primarily a hospital problem, who may be unaware of the increased prevalence of community-acquired disease. It is also a significant problem in agriculture, since as many as 50% of piglets succumb to the disease. Other studies have recently shown that asymptomatic carriers of toxigenic strains are likely to transmit the bacteria to C. diff-negative patients. Asymptomatic carriers cluster with symptomatic patients. In one Cleveland hospital, more than 25% of hospital-associated CDI cases were found to have been colonized prior to admission, suggesting that these were not true hospital-associated cases.

C. diff has been isolated from a wide range of sources, including food animals, meat, seafood, vegetables, household environments, and natural environments like rivers, lakes, and soil. About 20% of calves and 70% of piglets are colonized with C. diff. It has a high prevalence in meat products in the United States, but lower in the Europe, possibly because of different slaughtering practices.

The authors suggest that zoonotic C. diff spread is unlikely to be confined to any geographic region or population, and that widespread C. diff contamination is occurring through food or the environment. This could be occurring because spores can withstand cooking temperatures and disseminate through the air, and even through manure from food animals made into compost or fertilizer.

Veterinary efforts mimicking hospital measures have reduced animal CDI, but there are no rapid diagnostic tests for CDI in animals, making it challenging to control its spread in this context.

The authors call for enhanced antimicrobial stewardship in both human and animal settings, including banning of antimicrobial agents as growth promoters. This has been done in the United States and Europe, but not in Brazil, China, Canada, India, and Australia. They also call for research on inactivation of C. diff spores during waste treatment.

Even better, the authors suggest that vaccines should be developed and employed in both animals and humans. No such vaccine exists in animals, but Pfizer has one for humans in a phase 3 clinical trial, but it does not prevent colonization. Others are in development.

The epidemiology of CDI is an ongoing challenge, with emerging new strains and changing social and environmental conditions. “However, it is with the collaborative efforts of industry partners, policymakers, veterinarians, clinicians, and researchers that CDI needs to be approached, a perfect example of One Health. Opening an interdisciplinary dialogue to address CDI and One Health issues has to be the focus of future studies,” the authors concluded.

SOURCE: SC Lim et al. Clinical Microbiology and Infection. 2020;26:85-863.

Clostridioides difficile (C. diff) infection (CDI) is a pathogen of both humans and animals, and to control it will require an integrated approach that encompasses human health care, veterinary health care, environmental regulation, and public policy. That is the conclusion of a group led by Su-Chen Lim, MD, and Tom Riley, MD, of Edith Cowan University in Australia, who published a review in Clinical Microbiology and Infection.

CDI was generally considered a nuisance infection until the early 21st century, when a hypervirulent fluoroquinolone-resistant strain emerged in North America. The strain is now documented In the United States, Canada, and most countries in Europe.

Another new feature of CDI is increased evidence of community transmission, which was previously rare. This is defined as cases where the patient experienced symptom onset outside the hospital, and had no history of hospitalization in the previous 12 weeks or symptom onset within 48 hours of hospital admission. Community-associated CDI now accounts for 41% of U.S. cases, nearly 30% of Australian cases, and about 14% in Europe, according to recent studies.

Several features of CDI suggest a need for an integrated management plan. The preferred habitat of C. diff is the gastrointestinal track of mammals, and likely colonizes all mammalian neonates. Over time, colonization by other microbes likely crowd it out and prevent overgrowth. But widespread use of antimicrobials in animal production can lead to the creation of an environment resembling that of the neonate, allowing C. diff to expand. That has led to food animals becoming a major C. diff reservoir, and whole-genome studies showed that strains found in humans, food, animals, and the environment are closely related and sometimes genetically indistinguishable, suggesting transmission between humans and animals that may be attributable to contaminated food and environments.

The authors suggest that C. diff infection control should be guided by the One Health initiative, which seeks cooperation between physicians, osteopathic physicians, veterinarians, dentists, nurses, and other scientific and environmental disciplines. The goal is to enhance surveillance and interdisciplinary communication, as well as integrated policies. The authors note that C. diff is often thought of by physicians as primarily a hospital problem, who may be unaware of the increased prevalence of community-acquired disease. It is also a significant problem in agriculture, since as many as 50% of piglets succumb to the disease. Other studies have recently shown that asymptomatic carriers of toxigenic strains are likely to transmit the bacteria to C. diff-negative patients. Asymptomatic carriers cluster with symptomatic patients. In one Cleveland hospital, more than 25% of hospital-associated CDI cases were found to have been colonized prior to admission, suggesting that these were not true hospital-associated cases.

C. diff has been isolated from a wide range of sources, including food animals, meat, seafood, vegetables, household environments, and natural environments like rivers, lakes, and soil. About 20% of calves and 70% of piglets are colonized with C. diff. It has a high prevalence in meat products in the United States, but lower in the Europe, possibly because of different slaughtering practices.

The authors suggest that zoonotic C. diff spread is unlikely to be confined to any geographic region or population, and that widespread C. diff contamination is occurring through food or the environment. This could be occurring because spores can withstand cooking temperatures and disseminate through the air, and even through manure from food animals made into compost or fertilizer.

Veterinary efforts mimicking hospital measures have reduced animal CDI, but there are no rapid diagnostic tests for CDI in animals, making it challenging to control its spread in this context.

The authors call for enhanced antimicrobial stewardship in both human and animal settings, including banning of antimicrobial agents as growth promoters. This has been done in the United States and Europe, but not in Brazil, China, Canada, India, and Australia. They also call for research on inactivation of C. diff spores during waste treatment.

Even better, the authors suggest that vaccines should be developed and employed in both animals and humans. No such vaccine exists in animals, but Pfizer has one for humans in a phase 3 clinical trial, but it does not prevent colonization. Others are in development.

The epidemiology of CDI is an ongoing challenge, with emerging new strains and changing social and environmental conditions. “However, it is with the collaborative efforts of industry partners, policymakers, veterinarians, clinicians, and researchers that CDI needs to be approached, a perfect example of One Health. Opening an interdisciplinary dialogue to address CDI and One Health issues has to be the focus of future studies,” the authors concluded.

SOURCE: SC Lim et al. Clinical Microbiology and Infection. 2020;26:85-863.

Clostridioides difficile (C. diff) infection (CDI) is a pathogen of both humans and animals, and to control it will require an integrated approach that encompasses human health care, veterinary health care, environmental regulation, and public policy. That is the conclusion of a group led by Su-Chen Lim, MD, and Tom Riley, MD, of Edith Cowan University in Australia, who published a review in Clinical Microbiology and Infection.

CDI was generally considered a nuisance infection until the early 21st century, when a hypervirulent fluoroquinolone-resistant strain emerged in North America. The strain is now documented In the United States, Canada, and most countries in Europe.

Another new feature of CDI is increased evidence of community transmission, which was previously rare. This is defined as cases where the patient experienced symptom onset outside the hospital, and had no history of hospitalization in the previous 12 weeks or symptom onset within 48 hours of hospital admission. Community-associated CDI now accounts for 41% of U.S. cases, nearly 30% of Australian cases, and about 14% in Europe, according to recent studies.

Several features of CDI suggest a need for an integrated management plan. The preferred habitat of C. diff is the gastrointestinal track of mammals, and likely colonizes all mammalian neonates. Over time, colonization by other microbes likely crowd it out and prevent overgrowth. But widespread use of antimicrobials in animal production can lead to the creation of an environment resembling that of the neonate, allowing C. diff to expand. That has led to food animals becoming a major C. diff reservoir, and whole-genome studies showed that strains found in humans, food, animals, and the environment are closely related and sometimes genetically indistinguishable, suggesting transmission between humans and animals that may be attributable to contaminated food and environments.

The authors suggest that C. diff infection control should be guided by the One Health initiative, which seeks cooperation between physicians, osteopathic physicians, veterinarians, dentists, nurses, and other scientific and environmental disciplines. The goal is to enhance surveillance and interdisciplinary communication, as well as integrated policies. The authors note that C. diff is often thought of by physicians as primarily a hospital problem, who may be unaware of the increased prevalence of community-acquired disease. It is also a significant problem in agriculture, since as many as 50% of piglets succumb to the disease. Other studies have recently shown that asymptomatic carriers of toxigenic strains are likely to transmit the bacteria to C. diff-negative patients. Asymptomatic carriers cluster with symptomatic patients. In one Cleveland hospital, more than 25% of hospital-associated CDI cases were found to have been colonized prior to admission, suggesting that these were not true hospital-associated cases.

C. diff has been isolated from a wide range of sources, including food animals, meat, seafood, vegetables, household environments, and natural environments like rivers, lakes, and soil. About 20% of calves and 70% of piglets are colonized with C. diff. It has a high prevalence in meat products in the United States, but lower in the Europe, possibly because of different slaughtering practices.

The authors suggest that zoonotic C. diff spread is unlikely to be confined to any geographic region or population, and that widespread C. diff contamination is occurring through food or the environment. This could be occurring because spores can withstand cooking temperatures and disseminate through the air, and even through manure from food animals made into compost or fertilizer.

Veterinary efforts mimicking hospital measures have reduced animal CDI, but there are no rapid diagnostic tests for CDI in animals, making it challenging to control its spread in this context.

The authors call for enhanced antimicrobial stewardship in both human and animal settings, including banning of antimicrobial agents as growth promoters. This has been done in the United States and Europe, but not in Brazil, China, Canada, India, and Australia. They also call for research on inactivation of C. diff spores during waste treatment.

Even better, the authors suggest that vaccines should be developed and employed in both animals and humans. No such vaccine exists in animals, but Pfizer has one for humans in a phase 3 clinical trial, but it does not prevent colonization. Others are in development.

The epidemiology of CDI is an ongoing challenge, with emerging new strains and changing social and environmental conditions. “However, it is with the collaborative efforts of industry partners, policymakers, veterinarians, clinicians, and researchers that CDI needs to be approached, a perfect example of One Health. Opening an interdisciplinary dialogue to address CDI and One Health issues has to be the focus of future studies,” the authors concluded.

SOURCE: SC Lim et al. Clinical Microbiology and Infection. 2020;26:85-863.

A Spanish survey of COVID-19 patients suggests that upper gastrointestinal bleeding (UGB) does not affect in-hospital mortality. It also found that fewer COVID-19–positive patients underwent endoscopies, but there was no statistically significant difference in in-hospital mortality outcome as a result of delays.

“In-hospital mortality in COVID-19 patients with upper-GI bleeding seemed to be more influenced by COVID-19 than by upper-GI bleeding, and that’s something I think is important for us to know,” Gyanprakash Ketwaroo, MD, associate professor at Baylor College of Medicine, Houston, said in an interview. Dr. Ketwaroo was not involved in the study.

The results weren’t a surprise, but they do provide some reassurance. “It’s probably what I expected. Initially, we thought there might be some COVID-19 related (GI) lesions, but that didn’t seem to be borne out. So we thought the bleeding was related to (the patient) being in a hospital or the typical reasons for bleeding. It’s also what I expected that less endoscopies would be performed in these patients, and even though fewer endoscopies were performed, the outcomes were still similar. I think it’s what most people expected,” said Dr. Ketwaroo.

The study was published online Nov. 25 in the Journal of Clinical Gastroenterology, and led by Rebeca González González, MD, of Severo Ochoa University Hospital in Leganés, Madrid, and Pascual Piñera-Salmerón, MD, of Reina Sofia University General Hospital in Murcia, Spain. The researchers retrospectively analyzed data on 71,904 COVID-19 patients at 62 emergency departments in Spain, and compared 83 patients who had COVID-19 and UGB to two control groups: 249 randomly selected COVID-19 patients without UGB, and 249 randomly selected non-COVID-19 patients with UGB.

They found that 1.11% of COVID-19 patients presented with UGB, compared with 1.78% of non-COVID-19 patients at emergency departments. In patients with COVID-19, risk of UGB was associated with hemoglobin values < 10 g/L (odds ratio [OR], 34.255, 95% confidence interval [CI], 12.752-92.021), abdominal pain (OR, 11.4; 95% CI, 5.092-25.944), and systolic blood pressure < 90 mm Hg (OR, 11.096; 95% CI, 2.975-41.390).

Compared with non-COVID-19 patients with UGB, those COVID-19 patients with UGB were more likely to have interstitial lung infiltrates (OR, 66.42; 95% CI, 15.364-287.223) and ground-glass opacities (OR, 21.27; 95% CI, 9.720-46.567) in chest radiograph, as well as fever (OR, 34.67; 95% CI, 11.719-102.572) and cough (OR, 26.4; 95% CI, 8.845-78.806).

Gastroscopy and endoscopic procedures were lower in patients with COVID-19 than in the general population (gastroscopy OR, 0.269; 95% CI, 0.160-0.453: endoscopy OR, 0.26; 95% CI, 0.165-0.623). There was no difference between the two groups with respect to endoscopic findings. After adjustment for age and sex, the only significant difference between COVID-19 patients with UGB and COVID-19 patients without UGB was a higher rate of intensive care unit admission (OR, 2.98; 95% CI, 1.16-7.65). Differences between COVID-19 patients with UGB and non–COVID-19 patients with UGB included higher rates of ICU admission (OR, 3.29; 95% CI, 1.28-8.47), prolonged hospitalizations (OR, 2.02; 95% CI, 1.15-3.55), and in-hospital mortality (OR, 2.05; 95% CI, 1.09-3.86).

UGB development was not associated with increased in-hospital mortality in COVID-19 patients (OR, 1.14; 95% CI, 0.59-2.19).

A limitation to the study it was that it was performed in Spain, where endoscopies are performed in the emergency department, and where there are different thresholds for admission to the intensive care unit than in the United States.

The authors did not report a funding source. Dr. Ketwaroo has no relevant financial disclosures.

SOURCE: González González R et al. J Clin Gastroenterol. 10.1097/MCG.0000000000001465.

A Spanish survey of COVID-19 patients suggests that upper gastrointestinal bleeding (UGB) does not affect in-hospital mortality. It also found that fewer COVID-19–positive patients underwent endoscopies, but there was no statistically significant difference in in-hospital mortality outcome as a result of delays.

“In-hospital mortality in COVID-19 patients with upper-GI bleeding seemed to be more influenced by COVID-19 than by upper-GI bleeding, and that’s something I think is important for us to know,” Gyanprakash Ketwaroo, MD, associate professor at Baylor College of Medicine, Houston, said in an interview. Dr. Ketwaroo was not involved in the study.

The results weren’t a surprise, but they do provide some reassurance. “It’s probably what I expected. Initially, we thought there might be some COVID-19 related (GI) lesions, but that didn’t seem to be borne out. So we thought the bleeding was related to (the patient) being in a hospital or the typical reasons for bleeding. It’s also what I expected that less endoscopies would be performed in these patients, and even though fewer endoscopies were performed, the outcomes were still similar. I think it’s what most people expected,” said Dr. Ketwaroo.

The study was published online Nov. 25 in the Journal of Clinical Gastroenterology, and led by Rebeca González González, MD, of Severo Ochoa University Hospital in Leganés, Madrid, and Pascual Piñera-Salmerón, MD, of Reina Sofia University General Hospital in Murcia, Spain. The researchers retrospectively analyzed data on 71,904 COVID-19 patients at 62 emergency departments in Spain, and compared 83 patients who had COVID-19 and UGB to two control groups: 249 randomly selected COVID-19 patients without UGB, and 249 randomly selected non-COVID-19 patients with UGB.

They found that 1.11% of COVID-19 patients presented with UGB, compared with 1.78% of non-COVID-19 patients at emergency departments. In patients with COVID-19, risk of UGB was associated with hemoglobin values < 10 g/L (odds ratio [OR], 34.255, 95% confidence interval [CI], 12.752-92.021), abdominal pain (OR, 11.4; 95% CI, 5.092-25.944), and systolic blood pressure < 90 mm Hg (OR, 11.096; 95% CI, 2.975-41.390).

Compared with non-COVID-19 patients with UGB, those COVID-19 patients with UGB were more likely to have interstitial lung infiltrates (OR, 66.42; 95% CI, 15.364-287.223) and ground-glass opacities (OR, 21.27; 95% CI, 9.720-46.567) in chest radiograph, as well as fever (OR, 34.67; 95% CI, 11.719-102.572) and cough (OR, 26.4; 95% CI, 8.845-78.806).

Gastroscopy and endoscopic procedures were lower in patients with COVID-19 than in the general population (gastroscopy OR, 0.269; 95% CI, 0.160-0.453: endoscopy OR, 0.26; 95% CI, 0.165-0.623). There was no difference between the two groups with respect to endoscopic findings. After adjustment for age and sex, the only significant difference between COVID-19 patients with UGB and COVID-19 patients without UGB was a higher rate of intensive care unit admission (OR, 2.98; 95% CI, 1.16-7.65). Differences between COVID-19 patients with UGB and non–COVID-19 patients with UGB included higher rates of ICU admission (OR, 3.29; 95% CI, 1.28-8.47), prolonged hospitalizations (OR, 2.02; 95% CI, 1.15-3.55), and in-hospital mortality (OR, 2.05; 95% CI, 1.09-3.86).

UGB development was not associated with increased in-hospital mortality in COVID-19 patients (OR, 1.14; 95% CI, 0.59-2.19).

A limitation to the study it was that it was performed in Spain, where endoscopies are performed in the emergency department, and where there are different thresholds for admission to the intensive care unit than in the United States.

The authors did not report a funding source. Dr. Ketwaroo has no relevant financial disclosures.

SOURCE: González González R et al. J Clin Gastroenterol. 10.1097/MCG.0000000000001465.

A Spanish survey of COVID-19 patients suggests that upper gastrointestinal bleeding (UGB) does not affect in-hospital mortality. It also found that fewer COVID-19–positive patients underwent endoscopies, but there was no statistically significant difference in in-hospital mortality outcome as a result of delays.

“In-hospital mortality in COVID-19 patients with upper-GI bleeding seemed to be more influenced by COVID-19 than by upper-GI bleeding, and that’s something I think is important for us to know,” Gyanprakash Ketwaroo, MD, associate professor at Baylor College of Medicine, Houston, said in an interview. Dr. Ketwaroo was not involved in the study.

The results weren’t a surprise, but they do provide some reassurance. “It’s probably what I expected. Initially, we thought there might be some COVID-19 related (GI) lesions, but that didn’t seem to be borne out. So we thought the bleeding was related to (the patient) being in a hospital or the typical reasons for bleeding. It’s also what I expected that less endoscopies would be performed in these patients, and even though fewer endoscopies were performed, the outcomes were still similar. I think it’s what most people expected,” said Dr. Ketwaroo.

The study was published online Nov. 25 in the Journal of Clinical Gastroenterology, and led by Rebeca González González, MD, of Severo Ochoa University Hospital in Leganés, Madrid, and Pascual Piñera-Salmerón, MD, of Reina Sofia University General Hospital in Murcia, Spain. The researchers retrospectively analyzed data on 71,904 COVID-19 patients at 62 emergency departments in Spain, and compared 83 patients who had COVID-19 and UGB to two control groups: 249 randomly selected COVID-19 patients without UGB, and 249 randomly selected non-COVID-19 patients with UGB.

They found that 1.11% of COVID-19 patients presented with UGB, compared with 1.78% of non-COVID-19 patients at emergency departments. In patients with COVID-19, risk of UGB was associated with hemoglobin values < 10 g/L (odds ratio [OR], 34.255, 95% confidence interval [CI], 12.752-92.021), abdominal pain (OR, 11.4; 95% CI, 5.092-25.944), and systolic blood pressure < 90 mm Hg (OR, 11.096; 95% CI, 2.975-41.390).

Compared with non-COVID-19 patients with UGB, those COVID-19 patients with UGB were more likely to have interstitial lung infiltrates (OR, 66.42; 95% CI, 15.364-287.223) and ground-glass opacities (OR, 21.27; 95% CI, 9.720-46.567) in chest radiograph, as well as fever (OR, 34.67; 95% CI, 11.719-102.572) and cough (OR, 26.4; 95% CI, 8.845-78.806).

Gastroscopy and endoscopic procedures were lower in patients with COVID-19 than in the general population (gastroscopy OR, 0.269; 95% CI, 0.160-0.453: endoscopy OR, 0.26; 95% CI, 0.165-0.623). There was no difference between the two groups with respect to endoscopic findings. After adjustment for age and sex, the only significant difference between COVID-19 patients with UGB and COVID-19 patients without UGB was a higher rate of intensive care unit admission (OR, 2.98; 95% CI, 1.16-7.65). Differences between COVID-19 patients with UGB and non–COVID-19 patients with UGB included higher rates of ICU admission (OR, 3.29; 95% CI, 1.28-8.47), prolonged hospitalizations (OR, 2.02; 95% CI, 1.15-3.55), and in-hospital mortality (OR, 2.05; 95% CI, 1.09-3.86).

UGB development was not associated with increased in-hospital mortality in COVID-19 patients (OR, 1.14; 95% CI, 0.59-2.19).

A limitation to the study it was that it was performed in Spain, where endoscopies are performed in the emergency department, and where there are different thresholds for admission to the intensive care unit than in the United States.

The authors did not report a funding source. Dr. Ketwaroo has no relevant financial disclosures.

SOURCE: González González R et al. J Clin Gastroenterol. 10.1097/MCG.0000000000001465.