Clinical

In recent years, social media platforms like Twitter, Facebook, and Instagram have become popular gathering spots for clinicians to connect, engage, and share medical content. Medical journals, which often act as purveyors of this content, have recognized social media’s growing power and influence and have begun looking for ways to better engage their audiences.

In 2016, the Annals of Surgery was looking to better disseminate the work being published in its pages and looked to Twitter as one way of accomplishing this. At the time, most journals were only posting the title or a brief description of the published manuscript and hoping their Twitter followers would click on the article link. As journal editors were finding, if the audience was not immediately familiar with the topic or able to quickly capture the nuances of the study, there was a good chance the reader would continue to scroll past the post and never view the article.

Recognizing that social media heavily relies on visual material to garner attention, Annals turned to Andrew Ibrahim, MD, an architect turned surgeon, to help them rethink their social media strategy. Using the design training he had previously received in his career as an architect, Dr. Ibrahim created a simple visual tool that could be used to capture the often complicated and nuanced aspects of a research study. He called his creation a “visual abstract.”

But what is a visual abstract? Simply, they are visual representations of the key findings of a published manuscript; or put another way, a “movie trailer” to the full manuscript. While they can take many different forms and designs, they often consist of three key components: (1) a simple, easy to understand title, (2) a primary focus on outcomes, and (3) the use of visual cues or images to help the reader absorb and remember the take home message. This simplified delivery of complex information allows the producer to efficiently share complex findings in a format that allows for rapid visualization and interpretation.

Andrew M. Ibrahim

Since its inception, several studies have examined the influence visual abstracts have on disseminating research. One study conducted by Dr. Ibrahim and his colleagues found that articles tweeted with a visual abstract had an almost eightfold increase in the number of Twitter impressions (a measure of social media dissemination) and a threefold increase in article visits, compared with those manuscripts tweeted with the article title only.¹ These results reflect what behavioral scientists have long understood: Humans process visual data better than any other type of data.² For instance, according to research compiled by 3M, the company behind popular sticky notes, visual data is processed 60,000 times faster than text and has been shown to improve learning by 400%.³ Likewise, digital marketers have found that pages with videos and images draw on average 94% more views than their text-only counterparts.⁴

This knowledge, along with the substantial difference in engagement and dissemination characteristics from Dr. Ibrahim’s study, was far beyond what anyone might have expected and started a trend in medicine that continues to grow today. Medical journals across all practices and disciplines, including several leading journals, such as the New England Journal of Medicine, the Journal of the American Medical Association, and the Journal of Hospital Medicine (JHM), are utilizing this new tool to help disseminate their work in social media.

Visual abstracts have expanded beyond the social media sphere and are now frequently used in Grand Rounds presentations and as teaching tools among medical educators. JHM was one of the first journals to adopt the use of visual abstracts and has since published more than 150 in total. Given the growing popularity and expanded use of visual abstracts, JHM recently began archiving them on the journal’s website to allow clinicians to use the material in their own creative ways.

Visual abstracts are just one piece of the growing enterprise in social media for JHM. Recognizing the growing utilization of social media among physicians, JHM has taken a leading role in the use of online journal clubs. Since 2014, JHM has run a monthly Twitter-based journal club that discusses recently published articles and hospital medicine–based topics, called #JHMChat.⁵ This forum has allowed hospitalists from across the country, and around the world, to connect, network, and engage around topics important to the field of hospital medicine. The journal frequently reaches beyond hospital medicine borders and partners with other specialties and interest groups to gain perspective and insights into shared topic areas. To date, #JHMChat has one of the most robust online communities and continues to attract new followers each month.

As social media use continues to expand among clinicians, engagement tools like visual abstracts and Twitter chats will certainly continue to grow. Given that more clinicians are scrolling through websites than flipping through journal pages, medical journals like JHM will continually look for novel ways to engage their audiences and create communities among their followers. While a former architect who now practices as a surgeon led the way with visual abstracts, it remains to be seen who will create the next tool used to capture our attention on the ever-evolving sphere of social media.
 

Dr. Wray is a hospitalist at the University of California, San Francisco, and the San Francisco Veterans Affairs Medical Center. He also serves as a digital media and associate editor for the Journal of Hospital Medicine.

References

1. Ibrahim AM et al. Visual abstracts to disseminate research on social media: A prospective, case-control crossover study. Ann Surg. 2017;266(6):e46.

2. Tufte ER. The Visual Display of Quantitative Information. Second edition. Cheshire, Conn. Graphics Press, 2001. https://search.library.wisc.edu/catalog/999913808702121.

3. Polishing Your Presentation. http://web.archive.org/web/20001014041642/http://www.3m.com:80/meetingnetwork/files/meetingguide_pres.pdf. Accessed May 28, 2017.

4. 7 reasons you need visual content in your marketing strategy. https://medium.com/@nikos_iliopoulos/7-reasons-you-need-visual-content-in-your-marketing-strategy-bc77ca5521ac. Accessed May 28, 2017.

5. Wray CM et al. The adoption of an online journal club to improve research dissemination and social media engagement among hospitalists. J Hosp Med. 2018. doi: 10.12788/jhm.2987.

In recent years, social media platforms like Twitter, Facebook, and Instagram have become popular gathering spots for clinicians to connect, engage, and share medical content. Medical journals, which often act as purveyors of this content, have recognized social media’s growing power and influence and have begun looking for ways to better engage their audiences.

In 2016, the Annals of Surgery was looking to better disseminate the work being published in its pages and looked to Twitter as one way of accomplishing this. At the time, most journals were only posting the title or a brief description of the published manuscript and hoping their Twitter followers would click on the article link. As journal editors were finding, if the audience was not immediately familiar with the topic or able to quickly capture the nuances of the study, there was a good chance the reader would continue to scroll past the post and never view the article.

Recognizing that social media heavily relies on visual material to garner attention, Annals turned to Andrew Ibrahim, MD, an architect turned surgeon, to help them rethink their social media strategy. Using the design training he had previously received in his career as an architect, Dr. Ibrahim created a simple visual tool that could be used to capture the often complicated and nuanced aspects of a research study. He called his creation a “visual abstract.”

But what is a visual abstract? Simply, they are visual representations of the key findings of a published manuscript; or put another way, a “movie trailer” to the full manuscript. While they can take many different forms and designs, they often consist of three key components: (1) a simple, easy to understand title, (2) a primary focus on outcomes, and (3) the use of visual cues or images to help the reader absorb and remember the take home message. This simplified delivery of complex information allows the producer to efficiently share complex findings in a format that allows for rapid visualization and interpretation.

Andrew M. Ibrahim

Since its inception, several studies have examined the influence visual abstracts have on disseminating research. One study conducted by Dr. Ibrahim and his colleagues found that articles tweeted with a visual abstract had an almost eightfold increase in the number of Twitter impressions (a measure of social media dissemination) and a threefold increase in article visits, compared with those manuscripts tweeted with the article title only.¹ These results reflect what behavioral scientists have long understood: Humans process visual data better than any other type of data.² For instance, according to research compiled by 3M, the company behind popular sticky notes, visual data is processed 60,000 times faster than text and has been shown to improve learning by 400%.³ Likewise, digital marketers have found that pages with videos and images draw on average 94% more views than their text-only counterparts.⁴

This knowledge, along with the substantial difference in engagement and dissemination characteristics from Dr. Ibrahim’s study, was far beyond what anyone might have expected and started a trend in medicine that continues to grow today. Medical journals across all practices and disciplines, including several leading journals, such as the New England Journal of Medicine, the Journal of the American Medical Association, and the Journal of Hospital Medicine (JHM), are utilizing this new tool to help disseminate their work in social media.

Visual abstracts have expanded beyond the social media sphere and are now frequently used in Grand Rounds presentations and as teaching tools among medical educators. JHM was one of the first journals to adopt the use of visual abstracts and has since published more than 150 in total. Given the growing popularity and expanded use of visual abstracts, JHM recently began archiving them on the journal’s website to allow clinicians to use the material in their own creative ways.

Visual abstracts are just one piece of the growing enterprise in social media for JHM. Recognizing the growing utilization of social media among physicians, JHM has taken a leading role in the use of online journal clubs. Since 2014, JHM has run a monthly Twitter-based journal club that discusses recently published articles and hospital medicine–based topics, called #JHMChat.⁵ This forum has allowed hospitalists from across the country, and around the world, to connect, network, and engage around topics important to the field of hospital medicine. The journal frequently reaches beyond hospital medicine borders and partners with other specialties and interest groups to gain perspective and insights into shared topic areas. To date, #JHMChat has one of the most robust online communities and continues to attract new followers each month.

As social media use continues to expand among clinicians, engagement tools like visual abstracts and Twitter chats will certainly continue to grow. Given that more clinicians are scrolling through websites than flipping through journal pages, medical journals like JHM will continually look for novel ways to engage their audiences and create communities among their followers. While a former architect who now practices as a surgeon led the way with visual abstracts, it remains to be seen who will create the next tool used to capture our attention on the ever-evolving sphere of social media.
 

Dr. Wray is a hospitalist at the University of California, San Francisco, and the San Francisco Veterans Affairs Medical Center. He also serves as a digital media and associate editor for the Journal of Hospital Medicine.

References

1. Ibrahim AM et al. Visual abstracts to disseminate research on social media: A prospective, case-control crossover study. Ann Surg. 2017;266(6):e46.

2. Tufte ER. The Visual Display of Quantitative Information. Second edition. Cheshire, Conn. Graphics Press, 2001. https://search.library.wisc.edu/catalog/999913808702121.

3. Polishing Your Presentation. http://web.archive.org/web/20001014041642/http://www.3m.com:80/meetingnetwork/files/meetingguide_pres.pdf. Accessed May 28, 2017.

4. 7 reasons you need visual content in your marketing strategy. https://medium.com/@nikos_iliopoulos/7-reasons-you-need-visual-content-in-your-marketing-strategy-bc77ca5521ac. Accessed May 28, 2017.

5. Wray CM et al. The adoption of an online journal club to improve research dissemination and social media engagement among hospitalists. J Hosp Med. 2018. doi: 10.12788/jhm.2987.

In recent years, social media platforms like Twitter, Facebook, and Instagram have become popular gathering spots for clinicians to connect, engage, and share medical content. Medical journals, which often act as purveyors of this content, have recognized social media’s growing power and influence and have begun looking for ways to better engage their audiences.

In 2016, the Annals of Surgery was looking to better disseminate the work being published in its pages and looked to Twitter as one way of accomplishing this. At the time, most journals were only posting the title or a brief description of the published manuscript and hoping their Twitter followers would click on the article link. As journal editors were finding, if the audience was not immediately familiar with the topic or able to quickly capture the nuances of the study, there was a good chance the reader would continue to scroll past the post and never view the article.

Recognizing that social media heavily relies on visual material to garner attention, Annals turned to Andrew Ibrahim, MD, an architect turned surgeon, to help them rethink their social media strategy. Using the design training he had previously received in his career as an architect, Dr. Ibrahim created a simple visual tool that could be used to capture the often complicated and nuanced aspects of a research study. He called his creation a “visual abstract.”

But what is a visual abstract? Simply, they are visual representations of the key findings of a published manuscript; or put another way, a “movie trailer” to the full manuscript. While they can take many different forms and designs, they often consist of three key components: (1) a simple, easy to understand title, (2) a primary focus on outcomes, and (3) the use of visual cues or images to help the reader absorb and remember the take home message. This simplified delivery of complex information allows the producer to efficiently share complex findings in a format that allows for rapid visualization and interpretation.

Andrew M. Ibrahim

Since its inception, several studies have examined the influence visual abstracts have on disseminating research. One study conducted by Dr. Ibrahim and his colleagues found that articles tweeted with a visual abstract had an almost eightfold increase in the number of Twitter impressions (a measure of social media dissemination) and a threefold increase in article visits, compared with those manuscripts tweeted with the article title only.¹ These results reflect what behavioral scientists have long understood: Humans process visual data better than any other type of data.² For instance, according to research compiled by 3M, the company behind popular sticky notes, visual data is processed 60,000 times faster than text and has been shown to improve learning by 400%.³ Likewise, digital marketers have found that pages with videos and images draw on average 94% more views than their text-only counterparts.⁴

This knowledge, along with the substantial difference in engagement and dissemination characteristics from Dr. Ibrahim’s study, was far beyond what anyone might have expected and started a trend in medicine that continues to grow today. Medical journals across all practices and disciplines, including several leading journals, such as the New England Journal of Medicine, the Journal of the American Medical Association, and the Journal of Hospital Medicine (JHM), are utilizing this new tool to help disseminate their work in social media.

Visual abstracts have expanded beyond the social media sphere and are now frequently used in Grand Rounds presentations and as teaching tools among medical educators. JHM was one of the first journals to adopt the use of visual abstracts and has since published more than 150 in total. Given the growing popularity and expanded use of visual abstracts, JHM recently began archiving them on the journal’s website to allow clinicians to use the material in their own creative ways.

Visual abstracts are just one piece of the growing enterprise in social media for JHM. Recognizing the growing utilization of social media among physicians, JHM has taken a leading role in the use of online journal clubs. Since 2014, JHM has run a monthly Twitter-based journal club that discusses recently published articles and hospital medicine–based topics, called #JHMChat.⁵ This forum has allowed hospitalists from across the country, and around the world, to connect, network, and engage around topics important to the field of hospital medicine. The journal frequently reaches beyond hospital medicine borders and partners with other specialties and interest groups to gain perspective and insights into shared topic areas. To date, #JHMChat has one of the most robust online communities and continues to attract new followers each month.

As social media use continues to expand among clinicians, engagement tools like visual abstracts and Twitter chats will certainly continue to grow. Given that more clinicians are scrolling through websites than flipping through journal pages, medical journals like JHM will continually look for novel ways to engage their audiences and create communities among their followers. While a former architect who now practices as a surgeon led the way with visual abstracts, it remains to be seen who will create the next tool used to capture our attention on the ever-evolving sphere of social media.
 

Dr. Wray is a hospitalist at the University of California, San Francisco, and the San Francisco Veterans Affairs Medical Center. He also serves as a digital media and associate editor for the Journal of Hospital Medicine.

References

1. Ibrahim AM et al. Visual abstracts to disseminate research on social media: A prospective, case-control crossover study. Ann Surg. 2017;266(6):e46.

2. Tufte ER. The Visual Display of Quantitative Information. Second edition. Cheshire, Conn. Graphics Press, 2001. https://search.library.wisc.edu/catalog/999913808702121.

3. Polishing Your Presentation. http://web.archive.org/web/20001014041642/http://www.3m.com:80/meetingnetwork/files/meetingguide_pres.pdf. Accessed May 28, 2017.

4. 7 reasons you need visual content in your marketing strategy. https://medium.com/@nikos_iliopoulos/7-reasons-you-need-visual-content-in-your-marketing-strategy-bc77ca5521ac. Accessed May 28, 2017.

5. Wray CM et al. The adoption of an online journal club to improve research dissemination and social media engagement among hospitalists. J Hosp Med. 2018. doi: 10.12788/jhm.2987.

ORLANDO – The proportion of children and adolescents admitted to critical care for serious poisonings has increased in recent years, according to authors of a study of more than 750,000 reported opioid exposures.

Fuse/thinkstockphotos.com

Critical care units were involved in 10% of pediatric opioid poisoning cases registered in 2015-2018, up from 7% in 2005-2009, reported Megan E. Land, MD, of Emory University, Atlanta, and coinvestigators.

Attempted suicide has represented an increasingly large proportion of pediatric opioid poisonings from 2005 to 2018, according to the researchers, based on retrospective analysis of cases reported to U.S. poison centers.

Mortality related to these pediatric poisonings increased over time, and among children and adolescents admitted to a pediatric ICU, CPR and naloxone use also increased over time, Dr. Land and associates noted.

These serious consequences of opioid ingestion by children and adolescents emphasize the need for strategies to address suicidality and reduce access to opioids, said Dr. Land, who presented the findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

“I think that this really requires a two-pronged approach,” she explained. “One is that we need to increase mental health resources for kids to address adolescent suicidality, and secondly, we need to decrease access to opioids in the hands of pediatric patients by decreasing prescribing and then also getting those that are unused out of the homes.”

Jeffrey Zimmerman, MD, past president of SCCM, said these findings on pediatric opioid poisonings represent the “iceberg tip” of a much larger societal issue that has impacts well beyond critical care.

“I think acutely, we’re well equipped to deal with the situation in terms of interventions,” Dr. Zimmerman said in an interview. “The bigger issue is dealing with what happens afterward, when the patient leaves the ICU in the hospital.”

When the issue is chronic opioid use among adolescents or children, critical care specialists can help by initiating opioid tapering in the hospital setting, rather than allowing the complete weaning process to play out at home, he said.

All clinicians can help prevent future injury by asking questions of the child and family to ensure that any opiates and other prescription medications at home are locked up, he added.

“These aren’t very glamorous things, but they’re common sense, and there’s more need for this common sense now than there ever has been,” Dr. Zimmerman concluded.

The study by Dr. Land and colleagues included data on primary opioid ingestions registered at 55 poison control centers in the United States. They assessed trends over three time periods: 2005-2009, 2010-2014, and 2015-2018.

They found that children under 19 years of age accounted for 28% of the 753,592 opioid poisonings reported over that time period.

The overall number of reported opioid poisonings among children declined somewhat since about 2010. However, the proportion admitted to a critical care unit increased from 7% in the 2005-2009 period to 10% in the 2015-2018 period, said Dr. Land, who added that the probability of a moderate or major effect increased by 0.55% and 0.11% per year, respectively, over the 14 years studied.

Mortality – 0.21% overall – increased from 0.18% in the earliest era to 0.28% in the most recent era, according to the investigators.

Suicidal intent increased from 14% in the earliest era to 21% in the most recent era, and was linked to near tenfold odds of undergoing a pediatric ICU procedure, Dr. Land and colleagues reported.

Among those children admitted to a pediatric ICU, use of CPR increased from 1% to 3% in the earliest and latest time periods, respectively; likewise, naloxone administration increased from 42% to 51% over those two time periods. By contrast, there was no change in use of mechanical ventilation (12%) or vasopressors (3%) over time, they added.

The opioids most commonly linked to pediatric ICU procedures were fentanyl (odds ratio, 12), heroin (OR, 11), and methadone (OR, 15).

Some funding for the study came from the Georgia Poison Center. Dr. Land had no disclosures relevant to the research.

SOURCE: Land M et al. Crit Care Med. 2020 doi: 10.1097/01.ccm.0000618708.38414.ea.

ORLANDO – The proportion of children and adolescents admitted to critical care for serious poisonings has increased in recent years, according to authors of a study of more than 750,000 reported opioid exposures.

Fuse/thinkstockphotos.com

Critical care units were involved in 10% of pediatric opioid poisoning cases registered in 2015-2018, up from 7% in 2005-2009, reported Megan E. Land, MD, of Emory University, Atlanta, and coinvestigators.

Attempted suicide has represented an increasingly large proportion of pediatric opioid poisonings from 2005 to 2018, according to the researchers, based on retrospective analysis of cases reported to U.S. poison centers.

Mortality related to these pediatric poisonings increased over time, and among children and adolescents admitted to a pediatric ICU, CPR and naloxone use also increased over time, Dr. Land and associates noted.

These serious consequences of opioid ingestion by children and adolescents emphasize the need for strategies to address suicidality and reduce access to opioids, said Dr. Land, who presented the findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

“I think that this really requires a two-pronged approach,” she explained. “One is that we need to increase mental health resources for kids to address adolescent suicidality, and secondly, we need to decrease access to opioids in the hands of pediatric patients by decreasing prescribing and then also getting those that are unused out of the homes.”

Jeffrey Zimmerman, MD, past president of SCCM, said these findings on pediatric opioid poisonings represent the “iceberg tip” of a much larger societal issue that has impacts well beyond critical care.

“I think acutely, we’re well equipped to deal with the situation in terms of interventions,” Dr. Zimmerman said in an interview. “The bigger issue is dealing with what happens afterward, when the patient leaves the ICU in the hospital.”

When the issue is chronic opioid use among adolescents or children, critical care specialists can help by initiating opioid tapering in the hospital setting, rather than allowing the complete weaning process to play out at home, he said.

All clinicians can help prevent future injury by asking questions of the child and family to ensure that any opiates and other prescription medications at home are locked up, he added.

“These aren’t very glamorous things, but they’re common sense, and there’s more need for this common sense now than there ever has been,” Dr. Zimmerman concluded.

The study by Dr. Land and colleagues included data on primary opioid ingestions registered at 55 poison control centers in the United States. They assessed trends over three time periods: 2005-2009, 2010-2014, and 2015-2018.

They found that children under 19 years of age accounted for 28% of the 753,592 opioid poisonings reported over that time period.

The overall number of reported opioid poisonings among children declined somewhat since about 2010. However, the proportion admitted to a critical care unit increased from 7% in the 2005-2009 period to 10% in the 2015-2018 period, said Dr. Land, who added that the probability of a moderate or major effect increased by 0.55% and 0.11% per year, respectively, over the 14 years studied.

Mortality – 0.21% overall – increased from 0.18% in the earliest era to 0.28% in the most recent era, according to the investigators.

Suicidal intent increased from 14% in the earliest era to 21% in the most recent era, and was linked to near tenfold odds of undergoing a pediatric ICU procedure, Dr. Land and colleagues reported.

Among those children admitted to a pediatric ICU, use of CPR increased from 1% to 3% in the earliest and latest time periods, respectively; likewise, naloxone administration increased from 42% to 51% over those two time periods. By contrast, there was no change in use of mechanical ventilation (12%) or vasopressors (3%) over time, they added.

The opioids most commonly linked to pediatric ICU procedures were fentanyl (odds ratio, 12), heroin (OR, 11), and methadone (OR, 15).

Some funding for the study came from the Georgia Poison Center. Dr. Land had no disclosures relevant to the research.

SOURCE: Land M et al. Crit Care Med. 2020 doi: 10.1097/01.ccm.0000618708.38414.ea.

ORLANDO – The proportion of children and adolescents admitted to critical care for serious poisonings has increased in recent years, according to authors of a study of more than 750,000 reported opioid exposures.

Fuse/thinkstockphotos.com

Critical care units were involved in 10% of pediatric opioid poisoning cases registered in 2015-2018, up from 7% in 2005-2009, reported Megan E. Land, MD, of Emory University, Atlanta, and coinvestigators.

Attempted suicide has represented an increasingly large proportion of pediatric opioid poisonings from 2005 to 2018, according to the researchers, based on retrospective analysis of cases reported to U.S. poison centers.

Mortality related to these pediatric poisonings increased over time, and among children and adolescents admitted to a pediatric ICU, CPR and naloxone use also increased over time, Dr. Land and associates noted.

These serious consequences of opioid ingestion by children and adolescents emphasize the need for strategies to address suicidality and reduce access to opioids, said Dr. Land, who presented the findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

“I think that this really requires a two-pronged approach,” she explained. “One is that we need to increase mental health resources for kids to address adolescent suicidality, and secondly, we need to decrease access to opioids in the hands of pediatric patients by decreasing prescribing and then also getting those that are unused out of the homes.”

Jeffrey Zimmerman, MD, past president of SCCM, said these findings on pediatric opioid poisonings represent the “iceberg tip” of a much larger societal issue that has impacts well beyond critical care.

“I think acutely, we’re well equipped to deal with the situation in terms of interventions,” Dr. Zimmerman said in an interview. “The bigger issue is dealing with what happens afterward, when the patient leaves the ICU in the hospital.”

When the issue is chronic opioid use among adolescents or children, critical care specialists can help by initiating opioid tapering in the hospital setting, rather than allowing the complete weaning process to play out at home, he said.

All clinicians can help prevent future injury by asking questions of the child and family to ensure that any opiates and other prescription medications at home are locked up, he added.

“These aren’t very glamorous things, but they’re common sense, and there’s more need for this common sense now than there ever has been,” Dr. Zimmerman concluded.

The study by Dr. Land and colleagues included data on primary opioid ingestions registered at 55 poison control centers in the United States. They assessed trends over three time periods: 2005-2009, 2010-2014, and 2015-2018.

They found that children under 19 years of age accounted for 28% of the 753,592 opioid poisonings reported over that time period.

The overall number of reported opioid poisonings among children declined somewhat since about 2010. However, the proportion admitted to a critical care unit increased from 7% in the 2005-2009 period to 10% in the 2015-2018 period, said Dr. Land, who added that the probability of a moderate or major effect increased by 0.55% and 0.11% per year, respectively, over the 14 years studied.

Mortality – 0.21% overall – increased from 0.18% in the earliest era to 0.28% in the most recent era, according to the investigators.

Suicidal intent increased from 14% in the earliest era to 21% in the most recent era, and was linked to near tenfold odds of undergoing a pediatric ICU procedure, Dr. Land and colleagues reported.

Among those children admitted to a pediatric ICU, use of CPR increased from 1% to 3% in the earliest and latest time periods, respectively; likewise, naloxone administration increased from 42% to 51% over those two time periods. By contrast, there was no change in use of mechanical ventilation (12%) or vasopressors (3%) over time, they added.

The opioids most commonly linked to pediatric ICU procedures were fentanyl (odds ratio, 12), heroin (OR, 11), and methadone (OR, 15).

Some funding for the study came from the Georgia Poison Center. Dr. Land had no disclosures relevant to the research.

SOURCE: Land M et al. Crit Care Med. 2020 doi: 10.1097/01.ccm.0000618708.38414.ea.

Hospitalists encounter troponin elevations daily, but we have to use clinical judgment to determine if the troponin elevation represents either a myocardial infarction (MI), or a non-MI troponin elevation (i.e. a , nonischemic myocardial injury).

©decade3d/Thinkstock.com

It is important to remember that an MI specifically refers to myocardial injury due to acute myocardial ischemia to the myocardium. This lack of blood supply can be due to an acute absolute or relative deficiency in coronary artery blood flow. However, there are also many mechanisms of myocardial injury unrelated to reduced coronary artery blood flow, and these should be more appropriately termed non-MI troponin elevations.

Historically, when an ischemic mechanism of myocardial injury was suspected, providers would categorize troponin elevations into ST-elevation MI (STEMI) versus non-ST-elevation MI (NSTEMI) based on the electrocardiogram (ECG). We would further classify the NSTEMI into type 1 or type 2, depending on the mechanism of injury. The term “NSTEMI” served as a “catch-all” term to describe both type 1 NSTEMIs and type 2 MIs, but that classification system is no longer valid.

Classification of MI types

The Fourth Universal Definition of MI published in August 2018 further updated the definitions of MI (summarized in Figure 1).² This review focuses on type 1 and type 2 MIs, which are the most common types encountered by hospitalists. Types 3-5 MI (grouped under a common ICD-10 diagnosis code for “Other MI Types,” or I21.A9) would rarely be diagnosed by hospitalists.



Figure 1: Classification of MI
 

The diagnosis of a type 1 MIs (STEMI and NSTEMI) is supported by the presence of an acute coronary thrombus or plaque rupture/erosion on coronary angiography or a strong suspicion for these when angiography is unavailable or contraindicated. Type 1 MI (also referred to as spontaneous MI) is generally a primary reason (or “principal” diagnosis) for a patient’s presentation to a hospital.³ Please note that a very high or rising troponin level alone is not diagnostic for a type 1 or type 2 NSTEMI. The lab has to be taken in the context of the patient’s presentation and other supporting findings.

In contrast to a type 1 MI (STEMI and NSTEMI), at type 2 MI results from an imbalance between myocardial oxygen supply and demand unrelated to acute coronary artery thrombosis or plaque rupture. A type 2 MI is a relative (as opposed to an absolute) deficiency in coronary artery blood flow triggered by an abrupt increase in myocardial oxygen demand, drop in myocardial blood supply, or both. In type 2 MI, myocardial injury occurs secondary to an underlying process, and therefore requires correct documentation of the underlying cause as well. 

Common examples of underlying causes of type 2 MI include acute blood loss anemia (e.g. GI bleed), acute hypoxia (e.g. COPD exacerbation), shock states (cardiogenic, hypovolemic, hemorrhagic, or septic), coronary vasospasm (e.g. spontaneous), and bradyarrhythmias. Patients with type 2 MI often have a history of fixed obstructive coronary disease, which when coupled with the acute trigger facilitates the type 2 MI; however, underlying CAD is not always present. 

Diagnosing a type 2 MI requires evidence of acute myocardial ischemia (Figure 2) with an elevated troponin but must also have at least one of the following:²

• Symptoms of acute myocardial ischemia such as typical chest pain.
• New ischemic ECG changes.
• Development of pathological Q waves.
• Imaging evidence of new loss of viable myocardium, significant reversible perfusion defect on nuclear imaging, or new regional wall motion abnormality in a pattern consistent with an ischemic etiology.

Distinguishing a type 1 NSTEMI from a type 2 MI depends mainly on the clinical context and clinical judgment. A patient whose presenting symptoms include acute chest discomfort, acute ST-T wave changes, and a rise in troponin would be suspected of having a type 1 NSTEMI. However, in a patient presenting with other or vague complaints where an elevated troponin was found amongst a battery of tests, a type 2 MI may be favored, particularly if there is evidence of an underlying trigger for a supply-demand mismatch. In challenging cases, cardiology consultation can help determine the MI type and/or the next diagnostic and treatment considerations.

When there is only elevated troponin levels (or even a rise and fall in troponin) without new symptoms or ECG/imaging evidence of myocardial ischemia, it is most appropriate to document a non-MI troponin elevation due to a nonischemic mechanism of myocardial injury.
 

Non-MI troponin elevation (nonischemic myocardial injury)

The number of conditions known to cause myocardial injury through mechanisms other than myocardial ischemia (see Figure 2) is growing, especially in the current era of high-sensitivity troponin assays.⁴

Common examples of underlying causes of non-MI troponin elevation include:

• Acute (on chronic) systolic or diastolic heart failure: Usually due to acute ventricular wall stretch/strain. Troponin elevations tend to be mild, with more indolent (or even flat) troponin trajectories.
• Pericarditis and myocarditis: Due to direct injury from myocardial inflammation.
• Cardiopulmonary resuscitation (CPR): Due to physical injury to the heart from mechanical chest compressions and from electrical shocks of external defibrillation.
• Stress-induced (takotsubo) cardiomyopathy: Stress-induced release of neurohormonal factors and catecholamines that cause direct myocyte injury and transient dilatation of the ventricle.
• Acute pulmonary embolism: Result of acute right ventricular wall stretch/strain, not from myocardial ischemia.
• Sepsis without shock: Direct toxicity of circulating cytokines to cardiac myocytes. In the absence of evidence of shock and symptoms/signs of myocardial ischemia, do not document type 2 MI.
• Renal failure (acute kidney injury or chronic kidney disease): Multiple etiologies, but at least partially related to reduced renal clearance of troponin. In general, renal failure in the absence of symptoms/signs of ischemia is best classified as a non-MI troponin elevation. ESRD patients who present with volume overload due to missed dialysis also typically have a non-MI troponin elevation.
• Stroke/intracranial hemorrhage: Mechanisms of myocardial injury and troponin elevation are incompletely understood, but may include catecholamine surges that injure the heart.

Some underlying conditions can cause a type 2 MI or a non-MI troponin elevation depending on the clinical context. For example, hypertensive emergency, severe aortic valve stenosis, hypertrophic cardiomyopathy, and tachyarrhythmias (including atrial fibrillation with rapid ventricular response) may cause increased myocardial oxygen demand, and in patients with underlying CAD, could precipitate a type 2 MI.

However, these same conditions could cause a non-MI troponin elevation in patients without CAD and could also cause myocardial injury and troponin release by causing acute left ventricular stretch/strain. Distinguishing the diagnose of type 2 MI vs. non-MI troponin elevation depends on documenting whether there are ancillary ischemic symptoms, ECG findings, imaging, and/or cath findings of acute myocardial ischemia.
 

Case examples 

1. A 60-year-old male presents with fever, cough, shortness of breath, and an infiltrate on CXR and is diagnosed with sepsis secondary to pneumonia. His initial troponin of 0.07 (normal < 0.05) rises to 0.11, peaks at 0.23, then subsequently trends down.

While some may be tempted to diagnose a type 2 MI, remember that sepsis can cause direct myocardial cell injury via direct cell toxicity. Unless this patient had at least one additional criteria (anginal chest pain, new ischemic ECG changes, or imaging evidence of new loss of viable myocardium, which does not recover with treatment of sepsis), this was most likely myocardial injury via direct cell toxicity, and should be documented as a non-MI troponin elevation due to sepsis without shock.

If there were ischemic ECG changes and the patient had chest pain, one would have to use clinical suspicion to differentiate between a type 1 NSTEMI and a type 2 MI. If there is a high clinical suspicion for an acute plaque rupture/thrombus, one would call it an NSTEMI and would have to document treatment as such (e.g. start heparin drip). Again, cardiology consultation can be helpful in cases where it may be hard to decide how to manage. Many times, the true mechanism is not determined until the patient is taken to the cath lab and if no acute plaque rupture is seen, then it was likely a type 2 MI.

2. A 70-year-old male with chronic systolic heart failure, noncompliant with medications, presents with 3 days of dyspnea on exertion and lower extremity edema. He had no chest discomfort. Exam shows bibasilar crackles and hepatojugular reflux. ECG shows no ischemic changes. Serial troponin values over 48 hours were: 0.48, 0.58, 0.51. A transthoracic echocardiogram reveals an LVEF of 40% with poor movement in the apex, similar to his prior echo.

This patient had no overt evidence of ischemia (no chest pain, ischemic ECG, or imaging changes) so the troponin elevation was most likely a non-MI troponin elevation secondary to acute on chronic systolic heart failure (in which the mechanism of troponin elevation is left ventricular chamber stretch from volume overload, and not demand ischemia). Generally, it is uncommon for a heart failure exacerbation to cause a type 2 MI.
 

Why is it so important to get this diagnosis right?

Misdiagnosing an MI when the patient does not have one can have multiple downstream repercussions. Because it stays on their medical record, it impacts their ability to get insurance and their premium costs. We expose patients to additional medications (e.g. dual antiplatelet therapy, statins), which can have adverse effects. As a result, it is very important to classify the etiology of the troponin elevation and treat accordingly.

Finally, when we incorrectly label a patient as having an MI, this can impact billing and reimbursement, DRG denials, insurance premiums, and quality metrics for both the hospital and the physicians. Hospitals’ 30-day readmission rates for AMI will suffer and quality metrics can be significantly impacted. We must be diligent and as precise as possible with our diagnoses and documentation to ensure the maximum benefit for our patients and our health care system.
 

Dr. Nave is assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta. Dr. Goyal is associate professor of medicine (cardiology), at Emory University, and chief quality officer, Emory Heart and Vascular Center, Emory Healthcare. He is also codirector of nuclear cardiology at Emory University Hospital.

Key points

• A diagnosis of a type 1 MI is supported by evidence or strong suspicion of acute coronary artery thrombus or plaque rupture/erosion.
• A very high troponin level alone is not diagnostic for a type 1 or type 2 MI. It has to be contextualized with the patient’s presentation and other supporting findings.
• Type 2 MI is a mismatch between myocardial oxygen supply and demand unrelated to acute coronary thrombosis or plaque rupture triggered by an abrupt increase in myocardial oxygen demand, drop in myocardial blood supply, or both. Type 2 MI should be documented along with its underlying cause.
• To diagnose an MI (either type 1 or type 2 MI), in addition to the troponin elevation, the patient must have symptoms of acute ischemia, ischemic ECG findings, and/or imaging suggestive of new ischemia.
• An elevated troponin level without new symptoms or ECG/imaging evidence of myocardial ischemia should be documented as a non-MI troponin elevation secondary to an underlying cause.

References

1. Goyal A, Gluckman TJ, Tcheng JE. What’s in a name? The new ICD-10 (10th revision of the international statistical classification of diseases and related health problems) codes and type 2 myocardial infarction. Circulation. 2017;136:1180-2.

2. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol. 2018;Aug 25:[Epub ahead of print].

3. Goyal, et al. Translating the Fourth Universal Definition of Myocardial Infarction into Clinical Documentation: Ten Pearls For Frontline Clinicians. Cardiology Magazine. Nov 2018.

4. Roongsritong C, Warraich I, Bradley C. Common causes of troponin elevations in the absence of acute myocardial infarction: incidence and clinical significance. Chest. 2004;125:1877-84.

Hospitalists encounter troponin elevations daily, but we have to use clinical judgment to determine if the troponin elevation represents either a myocardial infarction (MI), or a non-MI troponin elevation (i.e. a , nonischemic myocardial injury).

©decade3d/Thinkstock.com

It is important to remember that an MI specifically refers to myocardial injury due to acute myocardial ischemia to the myocardium. This lack of blood supply can be due to an acute absolute or relative deficiency in coronary artery blood flow. However, there are also many mechanisms of myocardial injury unrelated to reduced coronary artery blood flow, and these should be more appropriately termed non-MI troponin elevations.

Historically, when an ischemic mechanism of myocardial injury was suspected, providers would categorize troponin elevations into ST-elevation MI (STEMI) versus non-ST-elevation MI (NSTEMI) based on the electrocardiogram (ECG). We would further classify the NSTEMI into type 1 or type 2, depending on the mechanism of injury. The term “NSTEMI” served as a “catch-all” term to describe both type 1 NSTEMIs and type 2 MIs, but that classification system is no longer valid.

Classification of MI types

The Fourth Universal Definition of MI published in August 2018 further updated the definitions of MI (summarized in Figure 1).² This review focuses on type 1 and type 2 MIs, which are the most common types encountered by hospitalists. Types 3-5 MI (grouped under a common ICD-10 diagnosis code for “Other MI Types,” or I21.A9) would rarely be diagnosed by hospitalists.



Figure 1: Classification of MI
 

The diagnosis of a type 1 MIs (STEMI and NSTEMI) is supported by the presence of an acute coronary thrombus or plaque rupture/erosion on coronary angiography or a strong suspicion for these when angiography is unavailable or contraindicated. Type 1 MI (also referred to as spontaneous MI) is generally a primary reason (or “principal” diagnosis) for a patient’s presentation to a hospital.³ Please note that a very high or rising troponin level alone is not diagnostic for a type 1 or type 2 NSTEMI. The lab has to be taken in the context of the patient’s presentation and other supporting findings.

In contrast to a type 1 MI (STEMI and NSTEMI), at type 2 MI results from an imbalance between myocardial oxygen supply and demand unrelated to acute coronary artery thrombosis or plaque rupture. A type 2 MI is a relative (as opposed to an absolute) deficiency in coronary artery blood flow triggered by an abrupt increase in myocardial oxygen demand, drop in myocardial blood supply, or both. In type 2 MI, myocardial injury occurs secondary to an underlying process, and therefore requires correct documentation of the underlying cause as well. 

Common examples of underlying causes of type 2 MI include acute blood loss anemia (e.g. GI bleed), acute hypoxia (e.g. COPD exacerbation), shock states (cardiogenic, hypovolemic, hemorrhagic, or septic), coronary vasospasm (e.g. spontaneous), and bradyarrhythmias. Patients with type 2 MI often have a history of fixed obstructive coronary disease, which when coupled with the acute trigger facilitates the type 2 MI; however, underlying CAD is not always present. 

Diagnosing a type 2 MI requires evidence of acute myocardial ischemia (Figure 2) with an elevated troponin but must also have at least one of the following:²

• Symptoms of acute myocardial ischemia such as typical chest pain.
• New ischemic ECG changes.
• Development of pathological Q waves.
• Imaging evidence of new loss of viable myocardium, significant reversible perfusion defect on nuclear imaging, or new regional wall motion abnormality in a pattern consistent with an ischemic etiology.

Distinguishing a type 1 NSTEMI from a type 2 MI depends mainly on the clinical context and clinical judgment. A patient whose presenting symptoms include acute chest discomfort, acute ST-T wave changes, and a rise in troponin would be suspected of having a type 1 NSTEMI. However, in a patient presenting with other or vague complaints where an elevated troponin was found amongst a battery of tests, a type 2 MI may be favored, particularly if there is evidence of an underlying trigger for a supply-demand mismatch. In challenging cases, cardiology consultation can help determine the MI type and/or the next diagnostic and treatment considerations.

When there is only elevated troponin levels (or even a rise and fall in troponin) without new symptoms or ECG/imaging evidence of myocardial ischemia, it is most appropriate to document a non-MI troponin elevation due to a nonischemic mechanism of myocardial injury.
 

Non-MI troponin elevation (nonischemic myocardial injury)

The number of conditions known to cause myocardial injury through mechanisms other than myocardial ischemia (see Figure 2) is growing, especially in the current era of high-sensitivity troponin assays.⁴

Common examples of underlying causes of non-MI troponin elevation include:

• Acute (on chronic) systolic or diastolic heart failure: Usually due to acute ventricular wall stretch/strain. Troponin elevations tend to be mild, with more indolent (or even flat) troponin trajectories.
• Pericarditis and myocarditis: Due to direct injury from myocardial inflammation.
• Cardiopulmonary resuscitation (CPR): Due to physical injury to the heart from mechanical chest compressions and from electrical shocks of external defibrillation.
• Stress-induced (takotsubo) cardiomyopathy: Stress-induced release of neurohormonal factors and catecholamines that cause direct myocyte injury and transient dilatation of the ventricle.
• Acute pulmonary embolism: Result of acute right ventricular wall stretch/strain, not from myocardial ischemia.
• Sepsis without shock: Direct toxicity of circulating cytokines to cardiac myocytes. In the absence of evidence of shock and symptoms/signs of myocardial ischemia, do not document type 2 MI.
• Renal failure (acute kidney injury or chronic kidney disease): Multiple etiologies, but at least partially related to reduced renal clearance of troponin. In general, renal failure in the absence of symptoms/signs of ischemia is best classified as a non-MI troponin elevation. ESRD patients who present with volume overload due to missed dialysis also typically have a non-MI troponin elevation.
• Stroke/intracranial hemorrhage: Mechanisms of myocardial injury and troponin elevation are incompletely understood, but may include catecholamine surges that injure the heart.

Some underlying conditions can cause a type 2 MI or a non-MI troponin elevation depending on the clinical context. For example, hypertensive emergency, severe aortic valve stenosis, hypertrophic cardiomyopathy, and tachyarrhythmias (including atrial fibrillation with rapid ventricular response) may cause increased myocardial oxygen demand, and in patients with underlying CAD, could precipitate a type 2 MI.

However, these same conditions could cause a non-MI troponin elevation in patients without CAD and could also cause myocardial injury and troponin release by causing acute left ventricular stretch/strain. Distinguishing the diagnose of type 2 MI vs. non-MI troponin elevation depends on documenting whether there are ancillary ischemic symptoms, ECG findings, imaging, and/or cath findings of acute myocardial ischemia.
 

Case examples 

1. A 60-year-old male presents with fever, cough, shortness of breath, and an infiltrate on CXR and is diagnosed with sepsis secondary to pneumonia. His initial troponin of 0.07 (normal < 0.05) rises to 0.11, peaks at 0.23, then subsequently trends down.

While some may be tempted to diagnose a type 2 MI, remember that sepsis can cause direct myocardial cell injury via direct cell toxicity. Unless this patient had at least one additional criteria (anginal chest pain, new ischemic ECG changes, or imaging evidence of new loss of viable myocardium, which does not recover with treatment of sepsis), this was most likely myocardial injury via direct cell toxicity, and should be documented as a non-MI troponin elevation due to sepsis without shock.

If there were ischemic ECG changes and the patient had chest pain, one would have to use clinical suspicion to differentiate between a type 1 NSTEMI and a type 2 MI. If there is a high clinical suspicion for an acute plaque rupture/thrombus, one would call it an NSTEMI and would have to document treatment as such (e.g. start heparin drip). Again, cardiology consultation can be helpful in cases where it may be hard to decide how to manage. Many times, the true mechanism is not determined until the patient is taken to the cath lab and if no acute plaque rupture is seen, then it was likely a type 2 MI.

2. A 70-year-old male with chronic systolic heart failure, noncompliant with medications, presents with 3 days of dyspnea on exertion and lower extremity edema. He had no chest discomfort. Exam shows bibasilar crackles and hepatojugular reflux. ECG shows no ischemic changes. Serial troponin values over 48 hours were: 0.48, 0.58, 0.51. A transthoracic echocardiogram reveals an LVEF of 40% with poor movement in the apex, similar to his prior echo.

This patient had no overt evidence of ischemia (no chest pain, ischemic ECG, or imaging changes) so the troponin elevation was most likely a non-MI troponin elevation secondary to acute on chronic systolic heart failure (in which the mechanism of troponin elevation is left ventricular chamber stretch from volume overload, and not demand ischemia). Generally, it is uncommon for a heart failure exacerbation to cause a type 2 MI.
 

Why is it so important to get this diagnosis right?

Misdiagnosing an MI when the patient does not have one can have multiple downstream repercussions. Because it stays on their medical record, it impacts their ability to get insurance and their premium costs. We expose patients to additional medications (e.g. dual antiplatelet therapy, statins), which can have adverse effects. As a result, it is very important to classify the etiology of the troponin elevation and treat accordingly.

Finally, when we incorrectly label a patient as having an MI, this can impact billing and reimbursement, DRG denials, insurance premiums, and quality metrics for both the hospital and the physicians. Hospitals’ 30-day readmission rates for AMI will suffer and quality metrics can be significantly impacted. We must be diligent and as precise as possible with our diagnoses and documentation to ensure the maximum benefit for our patients and our health care system.
 

Dr. Nave is assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta. Dr. Goyal is associate professor of medicine (cardiology), at Emory University, and chief quality officer, Emory Heart and Vascular Center, Emory Healthcare. He is also codirector of nuclear cardiology at Emory University Hospital.

Key points

• A diagnosis of a type 1 MI is supported by evidence or strong suspicion of acute coronary artery thrombus or plaque rupture/erosion.
• A very high troponin level alone is not diagnostic for a type 1 or type 2 MI. It has to be contextualized with the patient’s presentation and other supporting findings.
• Type 2 MI is a mismatch between myocardial oxygen supply and demand unrelated to acute coronary thrombosis or plaque rupture triggered by an abrupt increase in myocardial oxygen demand, drop in myocardial blood supply, or both. Type 2 MI should be documented along with its underlying cause.
• To diagnose an MI (either type 1 or type 2 MI), in addition to the troponin elevation, the patient must have symptoms of acute ischemia, ischemic ECG findings, and/or imaging suggestive of new ischemia.
• An elevated troponin level without new symptoms or ECG/imaging evidence of myocardial ischemia should be documented as a non-MI troponin elevation secondary to an underlying cause.

References

1. Goyal A, Gluckman TJ, Tcheng JE. What’s in a name? The new ICD-10 (10th revision of the international statistical classification of diseases and related health problems) codes and type 2 myocardial infarction. Circulation. 2017;136:1180-2.

2. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol. 2018;Aug 25:[Epub ahead of print].

3. Goyal, et al. Translating the Fourth Universal Definition of Myocardial Infarction into Clinical Documentation: Ten Pearls For Frontline Clinicians. Cardiology Magazine. Nov 2018.

4. Roongsritong C, Warraich I, Bradley C. Common causes of troponin elevations in the absence of acute myocardial infarction: incidence and clinical significance. Chest. 2004;125:1877-84.

Hospitalists encounter troponin elevations daily, but we have to use clinical judgment to determine if the troponin elevation represents either a myocardial infarction (MI), or a non-MI troponin elevation (i.e. a , nonischemic myocardial injury).

©decade3d/Thinkstock.com

It is important to remember that an MI specifically refers to myocardial injury due to acute myocardial ischemia to the myocardium. This lack of blood supply can be due to an acute absolute or relative deficiency in coronary artery blood flow. However, there are also many mechanisms of myocardial injury unrelated to reduced coronary artery blood flow, and these should be more appropriately termed non-MI troponin elevations.

Historically, when an ischemic mechanism of myocardial injury was suspected, providers would categorize troponin elevations into ST-elevation MI (STEMI) versus non-ST-elevation MI (NSTEMI) based on the electrocardiogram (ECG). We would further classify the NSTEMI into type 1 or type 2, depending on the mechanism of injury. The term “NSTEMI” served as a “catch-all” term to describe both type 1 NSTEMIs and type 2 MIs, but that classification system is no longer valid.

Classification of MI types

The Fourth Universal Definition of MI published in August 2018 further updated the definitions of MI (summarized in Figure 1).² This review focuses on type 1 and type 2 MIs, which are the most common types encountered by hospitalists. Types 3-5 MI (grouped under a common ICD-10 diagnosis code for “Other MI Types,” or I21.A9) would rarely be diagnosed by hospitalists.



Figure 1: Classification of MI
 

The diagnosis of a type 1 MIs (STEMI and NSTEMI) is supported by the presence of an acute coronary thrombus or plaque rupture/erosion on coronary angiography or a strong suspicion for these when angiography is unavailable or contraindicated. Type 1 MI (also referred to as spontaneous MI) is generally a primary reason (or “principal” diagnosis) for a patient’s presentation to a hospital.³ Please note that a very high or rising troponin level alone is not diagnostic for a type 1 or type 2 NSTEMI. The lab has to be taken in the context of the patient’s presentation and other supporting findings.

In contrast to a type 1 MI (STEMI and NSTEMI), at type 2 MI results from an imbalance between myocardial oxygen supply and demand unrelated to acute coronary artery thrombosis or plaque rupture. A type 2 MI is a relative (as opposed to an absolute) deficiency in coronary artery blood flow triggered by an abrupt increase in myocardial oxygen demand, drop in myocardial blood supply, or both. In type 2 MI, myocardial injury occurs secondary to an underlying process, and therefore requires correct documentation of the underlying cause as well. 

Common examples of underlying causes of type 2 MI include acute blood loss anemia (e.g. GI bleed), acute hypoxia (e.g. COPD exacerbation), shock states (cardiogenic, hypovolemic, hemorrhagic, or septic), coronary vasospasm (e.g. spontaneous), and bradyarrhythmias. Patients with type 2 MI often have a history of fixed obstructive coronary disease, which when coupled with the acute trigger facilitates the type 2 MI; however, underlying CAD is not always present. 

Diagnosing a type 2 MI requires evidence of acute myocardial ischemia (Figure 2) with an elevated troponin but must also have at least one of the following:²

• Symptoms of acute myocardial ischemia such as typical chest pain.
• New ischemic ECG changes.
• Development of pathological Q waves.
• Imaging evidence of new loss of viable myocardium, significant reversible perfusion defect on nuclear imaging, or new regional wall motion abnormality in a pattern consistent with an ischemic etiology.

Distinguishing a type 1 NSTEMI from a type 2 MI depends mainly on the clinical context and clinical judgment. A patient whose presenting symptoms include acute chest discomfort, acute ST-T wave changes, and a rise in troponin would be suspected of having a type 1 NSTEMI. However, in a patient presenting with other or vague complaints where an elevated troponin was found amongst a battery of tests, a type 2 MI may be favored, particularly if there is evidence of an underlying trigger for a supply-demand mismatch. In challenging cases, cardiology consultation can help determine the MI type and/or the next diagnostic and treatment considerations.

When there is only elevated troponin levels (or even a rise and fall in troponin) without new symptoms or ECG/imaging evidence of myocardial ischemia, it is most appropriate to document a non-MI troponin elevation due to a nonischemic mechanism of myocardial injury.
 

Non-MI troponin elevation (nonischemic myocardial injury)

The number of conditions known to cause myocardial injury through mechanisms other than myocardial ischemia (see Figure 2) is growing, especially in the current era of high-sensitivity troponin assays.⁴

Common examples of underlying causes of non-MI troponin elevation include:

• Acute (on chronic) systolic or diastolic heart failure: Usually due to acute ventricular wall stretch/strain. Troponin elevations tend to be mild, with more indolent (or even flat) troponin trajectories.
• Pericarditis and myocarditis: Due to direct injury from myocardial inflammation.
• Cardiopulmonary resuscitation (CPR): Due to physical injury to the heart from mechanical chest compressions and from electrical shocks of external defibrillation.
• Stress-induced (takotsubo) cardiomyopathy: Stress-induced release of neurohormonal factors and catecholamines that cause direct myocyte injury and transient dilatation of the ventricle.
• Acute pulmonary embolism: Result of acute right ventricular wall stretch/strain, not from myocardial ischemia.
• Sepsis without shock: Direct toxicity of circulating cytokines to cardiac myocytes. In the absence of evidence of shock and symptoms/signs of myocardial ischemia, do not document type 2 MI.
• Renal failure (acute kidney injury or chronic kidney disease): Multiple etiologies, but at least partially related to reduced renal clearance of troponin. In general, renal failure in the absence of symptoms/signs of ischemia is best classified as a non-MI troponin elevation. ESRD patients who present with volume overload due to missed dialysis also typically have a non-MI troponin elevation.
• Stroke/intracranial hemorrhage: Mechanisms of myocardial injury and troponin elevation are incompletely understood, but may include catecholamine surges that injure the heart.

Some underlying conditions can cause a type 2 MI or a non-MI troponin elevation depending on the clinical context. For example, hypertensive emergency, severe aortic valve stenosis, hypertrophic cardiomyopathy, and tachyarrhythmias (including atrial fibrillation with rapid ventricular response) may cause increased myocardial oxygen demand, and in patients with underlying CAD, could precipitate a type 2 MI.

However, these same conditions could cause a non-MI troponin elevation in patients without CAD and could also cause myocardial injury and troponin release by causing acute left ventricular stretch/strain. Distinguishing the diagnose of type 2 MI vs. non-MI troponin elevation depends on documenting whether there are ancillary ischemic symptoms, ECG findings, imaging, and/or cath findings of acute myocardial ischemia.
 

Case examples 

1. A 60-year-old male presents with fever, cough, shortness of breath, and an infiltrate on CXR and is diagnosed with sepsis secondary to pneumonia. His initial troponin of 0.07 (normal < 0.05) rises to 0.11, peaks at 0.23, then subsequently trends down.

While some may be tempted to diagnose a type 2 MI, remember that sepsis can cause direct myocardial cell injury via direct cell toxicity. Unless this patient had at least one additional criteria (anginal chest pain, new ischemic ECG changes, or imaging evidence of new loss of viable myocardium, which does not recover with treatment of sepsis), this was most likely myocardial injury via direct cell toxicity, and should be documented as a non-MI troponin elevation due to sepsis without shock.

If there were ischemic ECG changes and the patient had chest pain, one would have to use clinical suspicion to differentiate between a type 1 NSTEMI and a type 2 MI. If there is a high clinical suspicion for an acute plaque rupture/thrombus, one would call it an NSTEMI and would have to document treatment as such (e.g. start heparin drip). Again, cardiology consultation can be helpful in cases where it may be hard to decide how to manage. Many times, the true mechanism is not determined until the patient is taken to the cath lab and if no acute plaque rupture is seen, then it was likely a type 2 MI.

2. A 70-year-old male with chronic systolic heart failure, noncompliant with medications, presents with 3 days of dyspnea on exertion and lower extremity edema. He had no chest discomfort. Exam shows bibasilar crackles and hepatojugular reflux. ECG shows no ischemic changes. Serial troponin values over 48 hours were: 0.48, 0.58, 0.51. A transthoracic echocardiogram reveals an LVEF of 40% with poor movement in the apex, similar to his prior echo.

This patient had no overt evidence of ischemia (no chest pain, ischemic ECG, or imaging changes) so the troponin elevation was most likely a non-MI troponin elevation secondary to acute on chronic systolic heart failure (in which the mechanism of troponin elevation is left ventricular chamber stretch from volume overload, and not demand ischemia). Generally, it is uncommon for a heart failure exacerbation to cause a type 2 MI.
 

Why is it so important to get this diagnosis right?

Misdiagnosing an MI when the patient does not have one can have multiple downstream repercussions. Because it stays on their medical record, it impacts their ability to get insurance and their premium costs. We expose patients to additional medications (e.g. dual antiplatelet therapy, statins), which can have adverse effects. As a result, it is very important to classify the etiology of the troponin elevation and treat accordingly.

Finally, when we incorrectly label a patient as having an MI, this can impact billing and reimbursement, DRG denials, insurance premiums, and quality metrics for both the hospital and the physicians. Hospitals’ 30-day readmission rates for AMI will suffer and quality metrics can be significantly impacted. We must be diligent and as precise as possible with our diagnoses and documentation to ensure the maximum benefit for our patients and our health care system.
 

Dr. Nave is assistant professor of medicine in the division of hospital medicine at Emory University, Atlanta. Dr. Goyal is associate professor of medicine (cardiology), at Emory University, and chief quality officer, Emory Heart and Vascular Center, Emory Healthcare. He is also codirector of nuclear cardiology at Emory University Hospital.

Key points

• A diagnosis of a type 1 MI is supported by evidence or strong suspicion of acute coronary artery thrombus or plaque rupture/erosion.
• A very high troponin level alone is not diagnostic for a type 1 or type 2 MI. It has to be contextualized with the patient’s presentation and other supporting findings.
• Type 2 MI is a mismatch between myocardial oxygen supply and demand unrelated to acute coronary thrombosis or plaque rupture triggered by an abrupt increase in myocardial oxygen demand, drop in myocardial blood supply, or both. Type 2 MI should be documented along with its underlying cause.
• To diagnose an MI (either type 1 or type 2 MI), in addition to the troponin elevation, the patient must have symptoms of acute ischemia, ischemic ECG findings, and/or imaging suggestive of new ischemia.
• An elevated troponin level without new symptoms or ECG/imaging evidence of myocardial ischemia should be documented as a non-MI troponin elevation secondary to an underlying cause.

References

1. Goyal A, Gluckman TJ, Tcheng JE. What’s in a name? The new ICD-10 (10th revision of the international statistical classification of diseases and related health problems) codes and type 2 myocardial infarction. Circulation. 2017;136:1180-2.

2. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth universal definition of myocardial infarction (2018). J Am Coll Cardiol. 2018;Aug 25:[Epub ahead of print].

3. Goyal, et al. Translating the Fourth Universal Definition of Myocardial Infarction into Clinical Documentation: Ten Pearls For Frontline Clinicians. Cardiology Magazine. Nov 2018.

4. Roongsritong C, Warraich I, Bradley C. Common causes of troponin elevations in the absence of acute myocardial infarction: incidence and clinical significance. Chest. 2004;125:1877-84.

Nine infants younger than 1 year of age were infected with the virus that causes COVID-19 and hospitalized in China between Dec. 8, 2019, and Feb. 6, 2020, based on data from the Chinese central government and local health departments.

Courtesy NIAID-RML

“As of February 6, 2020, China reported 31,211 confirmed cases of COVID-19 and 637 fatalities,” wrote Min Wei, MD, of Wuhan University, China, and colleagues. However, “few infections in children have been reported.”

In a research letter published in JAMA, the investigators reviewed data from nine infants aged 28 days to 1 year who were hospitalized with a diagnosis of COVID-19 between Dec. 8, 2019, and Feb. 6, 2020. The ages of the infants ranged from 1 month to 11 months, and seven were female. The patients included two children from Beijing, two from Hainan, and one each from the areas of Guangdong, Anhui, Shanghai, Zhejiang, and Guizhou.

All infected infants had at least one infected family member, and the infants’ infections occurred after the family members’ infections; seven infants lived in Wuhan or had family members who had visited Wuhan.

One of the infants had no symptoms but tested positive for the 2019 novel coronavirus, and two others had a diagnosis but missing information on any symptoms. Fever occurred in four patients, and mild upper respiratory tract symptoms occurred in two patients.

None of the infants died, and none reported severe complications or the need for intensive care or mechanical ventilation, the investigators said. The fact that most of the infants were female might suggest that they are more susceptible to the virus than males, although overall COVID-19 viral infections have been more common in adult men, especially those with chronic comorbidities, Dr. Wei and associates noted.

The study findings were limited by the small sample size and lack of symptom data for some patients, the researchers said. However, the results confirm that the COVID-19 virus is transmissible to infants younger than 1 year, and adult caregivers should exercise protective measures including wearing masks, washing hands before contact with infants, and routinely sterilizing toys and tableware, they emphasized.

The study was supported by the National Natural Science Foundation of China and the Fundamental Research Funds for the Central Universities. The researchers had no financial conflicts to disclose.

SOURCE: Wei M et al. JAMA. 2020 Feb 14. doi:10.1001/jama.2020.2131.

Nine infants younger than 1 year of age were infected with the virus that causes COVID-19 and hospitalized in China between Dec. 8, 2019, and Feb. 6, 2020, based on data from the Chinese central government and local health departments.

Courtesy NIAID-RML

“As of February 6, 2020, China reported 31,211 confirmed cases of COVID-19 and 637 fatalities,” wrote Min Wei, MD, of Wuhan University, China, and colleagues. However, “few infections in children have been reported.”

In a research letter published in JAMA, the investigators reviewed data from nine infants aged 28 days to 1 year who were hospitalized with a diagnosis of COVID-19 between Dec. 8, 2019, and Feb. 6, 2020. The ages of the infants ranged from 1 month to 11 months, and seven were female. The patients included two children from Beijing, two from Hainan, and one each from the areas of Guangdong, Anhui, Shanghai, Zhejiang, and Guizhou.

All infected infants had at least one infected family member, and the infants’ infections occurred after the family members’ infections; seven infants lived in Wuhan or had family members who had visited Wuhan.

One of the infants had no symptoms but tested positive for the 2019 novel coronavirus, and two others had a diagnosis but missing information on any symptoms. Fever occurred in four patients, and mild upper respiratory tract symptoms occurred in two patients.

None of the infants died, and none reported severe complications or the need for intensive care or mechanical ventilation, the investigators said. The fact that most of the infants were female might suggest that they are more susceptible to the virus than males, although overall COVID-19 viral infections have been more common in adult men, especially those with chronic comorbidities, Dr. Wei and associates noted.

The study findings were limited by the small sample size and lack of symptom data for some patients, the researchers said. However, the results confirm that the COVID-19 virus is transmissible to infants younger than 1 year, and adult caregivers should exercise protective measures including wearing masks, washing hands before contact with infants, and routinely sterilizing toys and tableware, they emphasized.

The study was supported by the National Natural Science Foundation of China and the Fundamental Research Funds for the Central Universities. The researchers had no financial conflicts to disclose.

SOURCE: Wei M et al. JAMA. 2020 Feb 14. doi:10.1001/jama.2020.2131.

Nine infants younger than 1 year of age were infected with the virus that causes COVID-19 and hospitalized in China between Dec. 8, 2019, and Feb. 6, 2020, based on data from the Chinese central government and local health departments.

Courtesy NIAID-RML

“As of February 6, 2020, China reported 31,211 confirmed cases of COVID-19 and 637 fatalities,” wrote Min Wei, MD, of Wuhan University, China, and colleagues. However, “few infections in children have been reported.”

In a research letter published in JAMA, the investigators reviewed data from nine infants aged 28 days to 1 year who were hospitalized with a diagnosis of COVID-19 between Dec. 8, 2019, and Feb. 6, 2020. The ages of the infants ranged from 1 month to 11 months, and seven were female. The patients included two children from Beijing, two from Hainan, and one each from the areas of Guangdong, Anhui, Shanghai, Zhejiang, and Guizhou.

All infected infants had at least one infected family member, and the infants’ infections occurred after the family members’ infections; seven infants lived in Wuhan or had family members who had visited Wuhan.

One of the infants had no symptoms but tested positive for the 2019 novel coronavirus, and two others had a diagnosis but missing information on any symptoms. Fever occurred in four patients, and mild upper respiratory tract symptoms occurred in two patients.

None of the infants died, and none reported severe complications or the need for intensive care or mechanical ventilation, the investigators said. The fact that most of the infants were female might suggest that they are more susceptible to the virus than males, although overall COVID-19 viral infections have been more common in adult men, especially those with chronic comorbidities, Dr. Wei and associates noted.

The study findings were limited by the small sample size and lack of symptom data for some patients, the researchers said. However, the results confirm that the COVID-19 virus is transmissible to infants younger than 1 year, and adult caregivers should exercise protective measures including wearing masks, washing hands before contact with infants, and routinely sterilizing toys and tableware, they emphasized.

The study was supported by the National Natural Science Foundation of China and the Fundamental Research Funds for the Central Universities. The researchers had no financial conflicts to disclose.

SOURCE: Wei M et al. JAMA. 2020 Feb 14. doi:10.1001/jama.2020.2131.

ORLANDO – While the impact of the 2019 novel coronavirus outbreak on hospitals outside of China remains to be determined, there are several practical points critical care professionals need to know to be prepared in the face of this dynamic and rapidly evolving outbreak, speakers said at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Andrew Bowser/MDedge News

“Priorities for us in our hospitals are early detection, infection prevention, staff safety, and obviously, taking care of sick people,” said Ryan C. Maves, MD, of the Naval Medical Center San Diego in a special session on the 2019 Novel Coronavirus outbreak.*

Approximately 72,000 cases of coronavirus disease 2019 (COVID-19) had been reported as of Feb. 17, 2020, the day of Dr. Maves’ talk, according to statistics from Johns Hopkins Center for Science and Engineering in Baltimore. A total of 1,775 deaths had been recorded, nearly all of which were in Hubei Province, the central point of the outbreak. In the United States, the number of cases stood at 15, with no deaths reported.

While the dynamics of the 2019 novel coronavirus are still being learned, the estimated range of spread for droplet transmission is 2 meters, according to Dr. Maves. The duration of environmental persistence is not yet known, but he said that other coronaviruses persist in low-humidity conditions for up to 4 days.

The number of secondary cases that arise from a primary infection, or R0, is estimated to be between 1.5 and 3, though it can change as exposure evolves; by comparison, the R0 for H1N1 influenza has been reported as 1.5, while measles is 12-18, indicating that it is “very contagious,” said Dr. Maves. Severe acute respiratory syndrome had an initial R0 of about 3.5, which he said declined rapidly to 0.7 as environmental and policy controls were put into place.

Critical care professionals need to know how to identify patients at risk of having COVID-19 and determine whether they need further work-up, according to Dr. Maves, who highlighted recent criteria released by the Centers for Disease Control and Prevention.

The highest-risk category, he said, are individuals exposed to a laboratory-confirmed coronavirus case, which along with fever or signs and symptoms of a lower respiratory illness would be sufficient to classify them as a “person of interest” requiring further evaluation for disease. A history of travel from Hubei Province plus fever and signs/symptoms of lower respiratory illness would also meet criteria for evaluation, according to the CDC, while travel to mainland China would also meet the threshold, if those symptoms required hospitalization.

The CDC also published a step-wise flowchart to evaluate patients who may have been exposed to the 2019 novel coronavirus. According to that flowchart, if an individual has traveled to China or had close contact with someone infected with the 2019 Novel Coronavirus within 14 days of symptoms, and that individual has fever or symptoms of lower respiratory illness such as cough or shortness of breath, then providers should isolate that individual and assess clinical status, in addition to contacting the local health department.

Andrew Bowser/MDedge News

Laura E. Evans, MD, MS, FCCM, of New York University, said she might recommend providers “flip the script” on that CDC algorithm when it comes to identifying patients who may have been exposed.

“I think perhaps what we should be doing at sites of entry is not talking about travel as the first question, but rather fever or symptoms of lower respiratory illnesses as the first question, and use that as the opportunity to implement risk mitigation at that stage,” Dr. Evans said in a presentation on preparing for COVID-19.

Even with “substantial uncertainty” about the potential impact of the 2019 Novel Coronavirus, a significant influx of seriously ill patients would put strain the U.S. health care delivery system, she added.

“None of us have tons of extra capacity in our emergency departments, inpatient units, or ICUs, and I think we need to be prepared for that,” she added. “We need to know what our process is for ‘identify, isolate, and inform,’ and we need to be testing that now.”

Dr. Maves and Dr. Evans both reported that they had no financial conflicts of interest to report. Dr. Maves indicated that the views expressed in his presentation did not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States government.

*Correction, 2/19/20: An earlier version of this article misstated the location of the naval center.

ORLANDO – While the impact of the 2019 novel coronavirus outbreak on hospitals outside of China remains to be determined, there are several practical points critical care professionals need to know to be prepared in the face of this dynamic and rapidly evolving outbreak, speakers said at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Andrew Bowser/MDedge News

“Priorities for us in our hospitals are early detection, infection prevention, staff safety, and obviously, taking care of sick people,” said Ryan C. Maves, MD, of the Naval Medical Center San Diego in a special session on the 2019 Novel Coronavirus outbreak.*

Approximately 72,000 cases of coronavirus disease 2019 (COVID-19) had been reported as of Feb. 17, 2020, the day of Dr. Maves’ talk, according to statistics from Johns Hopkins Center for Science and Engineering in Baltimore. A total of 1,775 deaths had been recorded, nearly all of which were in Hubei Province, the central point of the outbreak. In the United States, the number of cases stood at 15, with no deaths reported.

While the dynamics of the 2019 novel coronavirus are still being learned, the estimated range of spread for droplet transmission is 2 meters, according to Dr. Maves. The duration of environmental persistence is not yet known, but he said that other coronaviruses persist in low-humidity conditions for up to 4 days.

The number of secondary cases that arise from a primary infection, or R0, is estimated to be between 1.5 and 3, though it can change as exposure evolves; by comparison, the R0 for H1N1 influenza has been reported as 1.5, while measles is 12-18, indicating that it is “very contagious,” said Dr. Maves. Severe acute respiratory syndrome had an initial R0 of about 3.5, which he said declined rapidly to 0.7 as environmental and policy controls were put into place.

Critical care professionals need to know how to identify patients at risk of having COVID-19 and determine whether they need further work-up, according to Dr. Maves, who highlighted recent criteria released by the Centers for Disease Control and Prevention.

The highest-risk category, he said, are individuals exposed to a laboratory-confirmed coronavirus case, which along with fever or signs and symptoms of a lower respiratory illness would be sufficient to classify them as a “person of interest” requiring further evaluation for disease. A history of travel from Hubei Province plus fever and signs/symptoms of lower respiratory illness would also meet criteria for evaluation, according to the CDC, while travel to mainland China would also meet the threshold, if those symptoms required hospitalization.

The CDC also published a step-wise flowchart to evaluate patients who may have been exposed to the 2019 novel coronavirus. According to that flowchart, if an individual has traveled to China or had close contact with someone infected with the 2019 Novel Coronavirus within 14 days of symptoms, and that individual has fever or symptoms of lower respiratory illness such as cough or shortness of breath, then providers should isolate that individual and assess clinical status, in addition to contacting the local health department.

Andrew Bowser/MDedge News

Laura E. Evans, MD, MS, FCCM, of New York University, said she might recommend providers “flip the script” on that CDC algorithm when it comes to identifying patients who may have been exposed.

“I think perhaps what we should be doing at sites of entry is not talking about travel as the first question, but rather fever or symptoms of lower respiratory illnesses as the first question, and use that as the opportunity to implement risk mitigation at that stage,” Dr. Evans said in a presentation on preparing for COVID-19.

Even with “substantial uncertainty” about the potential impact of the 2019 Novel Coronavirus, a significant influx of seriously ill patients would put strain the U.S. health care delivery system, she added.

“None of us have tons of extra capacity in our emergency departments, inpatient units, or ICUs, and I think we need to be prepared for that,” she added. “We need to know what our process is for ‘identify, isolate, and inform,’ and we need to be testing that now.”

Dr. Maves and Dr. Evans both reported that they had no financial conflicts of interest to report. Dr. Maves indicated that the views expressed in his presentation did not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States government.

*Correction, 2/19/20: An earlier version of this article misstated the location of the naval center.

ORLANDO – While the impact of the 2019 novel coronavirus outbreak on hospitals outside of China remains to be determined, there are several practical points critical care professionals need to know to be prepared in the face of this dynamic and rapidly evolving outbreak, speakers said at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Andrew Bowser/MDedge News

“Priorities for us in our hospitals are early detection, infection prevention, staff safety, and obviously, taking care of sick people,” said Ryan C. Maves, MD, of the Naval Medical Center San Diego in a special session on the 2019 Novel Coronavirus outbreak.*

Approximately 72,000 cases of coronavirus disease 2019 (COVID-19) had been reported as of Feb. 17, 2020, the day of Dr. Maves’ talk, according to statistics from Johns Hopkins Center for Science and Engineering in Baltimore. A total of 1,775 deaths had been recorded, nearly all of which were in Hubei Province, the central point of the outbreak. In the United States, the number of cases stood at 15, with no deaths reported.

While the dynamics of the 2019 novel coronavirus are still being learned, the estimated range of spread for droplet transmission is 2 meters, according to Dr. Maves. The duration of environmental persistence is not yet known, but he said that other coronaviruses persist in low-humidity conditions for up to 4 days.

The number of secondary cases that arise from a primary infection, or R0, is estimated to be between 1.5 and 3, though it can change as exposure evolves; by comparison, the R0 for H1N1 influenza has been reported as 1.5, while measles is 12-18, indicating that it is “very contagious,” said Dr. Maves. Severe acute respiratory syndrome had an initial R0 of about 3.5, which he said declined rapidly to 0.7 as environmental and policy controls were put into place.

Critical care professionals need to know how to identify patients at risk of having COVID-19 and determine whether they need further work-up, according to Dr. Maves, who highlighted recent criteria released by the Centers for Disease Control and Prevention.

The highest-risk category, he said, are individuals exposed to a laboratory-confirmed coronavirus case, which along with fever or signs and symptoms of a lower respiratory illness would be sufficient to classify them as a “person of interest” requiring further evaluation for disease. A history of travel from Hubei Province plus fever and signs/symptoms of lower respiratory illness would also meet criteria for evaluation, according to the CDC, while travel to mainland China would also meet the threshold, if those symptoms required hospitalization.

The CDC also published a step-wise flowchart to evaluate patients who may have been exposed to the 2019 novel coronavirus. According to that flowchart, if an individual has traveled to China or had close contact with someone infected with the 2019 Novel Coronavirus within 14 days of symptoms, and that individual has fever or symptoms of lower respiratory illness such as cough or shortness of breath, then providers should isolate that individual and assess clinical status, in addition to contacting the local health department.

Andrew Bowser/MDedge News

Laura E. Evans, MD, MS, FCCM, of New York University, said she might recommend providers “flip the script” on that CDC algorithm when it comes to identifying patients who may have been exposed.

“I think perhaps what we should be doing at sites of entry is not talking about travel as the first question, but rather fever or symptoms of lower respiratory illnesses as the first question, and use that as the opportunity to implement risk mitigation at that stage,” Dr. Evans said in a presentation on preparing for COVID-19.

Even with “substantial uncertainty” about the potential impact of the 2019 Novel Coronavirus, a significant influx of seriously ill patients would put strain the U.S. health care delivery system, she added.

“None of us have tons of extra capacity in our emergency departments, inpatient units, or ICUs, and I think we need to be prepared for that,” she added. “We need to know what our process is for ‘identify, isolate, and inform,’ and we need to be testing that now.”

Dr. Maves and Dr. Evans both reported that they had no financial conflicts of interest to report. Dr. Maves indicated that the views expressed in his presentation did not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States government.

*Correction, 2/19/20: An earlier version of this article misstated the location of the naval center.

Influenza activity continues to increase, but it has slowed down a bit, according to the Centers for Disease Control and Prevention.

The CDC’s latest report shows that 6.8% of outpatients visiting health care providers had influenza-like illness during the week ending Feb. 8. That’s up from the previous week’s 6.6%, but that rise of 0.2 percentage points is smaller than the 0.6-point rises that occurred each of the 2 weeks before, and that could mean that activity is slowing.

That slowing, however, is not noticeable from this week’s map, which puts 41 states (there were 35 last week) and Puerto Rico in the red at the highest level of activity on the CDC’s 1-10 scale and another three states in the “high” range with levels of 8 or 9, the CDC’s influenza division reported.

That leaves Nevada and Oregon at level 7; Alaska, Florida, and the District of Columbia at level 5; Idaho at level 3, and Delaware with insufficient data (it was at level 5 last week), the CDC said.

The 2019-2020 season’s high activity, fortunately, has not translated into high severity, as overall hospitalization and mortality rates continue to remain at fairly typical levels. Hospitalization rates are elevated among children and young adults, however, and pediatric deaths are now up to 92, the CDC said, which is high for this point in the season.

rfranki@mdedge.com

Influenza activity continues to increase, but it has slowed down a bit, according to the Centers for Disease Control and Prevention.

The CDC’s latest report shows that 6.8% of outpatients visiting health care providers had influenza-like illness during the week ending Feb. 8. That’s up from the previous week’s 6.6%, but that rise of 0.2 percentage points is smaller than the 0.6-point rises that occurred each of the 2 weeks before, and that could mean that activity is slowing.

That slowing, however, is not noticeable from this week’s map, which puts 41 states (there were 35 last week) and Puerto Rico in the red at the highest level of activity on the CDC’s 1-10 scale and another three states in the “high” range with levels of 8 or 9, the CDC’s influenza division reported.

That leaves Nevada and Oregon at level 7; Alaska, Florida, and the District of Columbia at level 5; Idaho at level 3, and Delaware with insufficient data (it was at level 5 last week), the CDC said.

The 2019-2020 season’s high activity, fortunately, has not translated into high severity, as overall hospitalization and mortality rates continue to remain at fairly typical levels. Hospitalization rates are elevated among children and young adults, however, and pediatric deaths are now up to 92, the CDC said, which is high for this point in the season.

rfranki@mdedge.com

Influenza activity continues to increase, but it has slowed down a bit, according to the Centers for Disease Control and Prevention.

The CDC’s latest report shows that 6.8% of outpatients visiting health care providers had influenza-like illness during the week ending Feb. 8. That’s up from the previous week’s 6.6%, but that rise of 0.2 percentage points is smaller than the 0.6-point rises that occurred each of the 2 weeks before, and that could mean that activity is slowing.

That slowing, however, is not noticeable from this week’s map, which puts 41 states (there were 35 last week) and Puerto Rico in the red at the highest level of activity on the CDC’s 1-10 scale and another three states in the “high” range with levels of 8 or 9, the CDC’s influenza division reported.

That leaves Nevada and Oregon at level 7; Alaska, Florida, and the District of Columbia at level 5; Idaho at level 3, and Delaware with insufficient data (it was at level 5 last week), the CDC said.

The 2019-2020 season’s high activity, fortunately, has not translated into high severity, as overall hospitalization and mortality rates continue to remain at fairly typical levels. Hospitalization rates are elevated among children and young adults, however, and pediatric deaths are now up to 92, the CDC said, which is high for this point in the season.

rfranki@mdedge.com

The American College of Cardiology on Feb. 13, 2020, released a clinical bulletin that aims to address cardiac implications of the current epidemic of the novel coronavirus, now known as COVID-19.

The bulletin, reviewed and approved by the college’s Science and Quality Oversight Committee, “provides background on the epidemic, which was first reported in late December 2019, and looks at early cardiac implications from case reports,” the ACC noted in a press release. “It also provides information on the potential cardiac implications from analog viral respiratory pandemics and offers early clinical guidance given current COVID-19 uncertainty.”

The document looks at some early cardiac implications of the infection. For example, early case reports suggest patients with underlying conditions are at higher risk of complications or mortality from the virus, with up to 50% of hospitalized patients having a chronic medical illness, the authors wrote.

About 40% of hospitalized patients confirmed to have the virus have cardiovascular or cerebrovascular disease, they noted.

In a recent case report on 138 hospitalized COVID-19 patients, they noted, 19.6% developed acute respiratory distress syndrome, 16.7% developed arrhythmia, 8.7% developed shock, 7.2% developed acute cardiac injury, and 3.6% developed acute kidney injury. “Rates of complication were universally higher for ICU patients,” they wrote.

“The first reported death was a 61-year-old male, with a long history of smoking, who succumbed to acute respiratory distress, heart failure, and cardiac arrest,” the document noted. “Early, unpublished first-hand reports suggest at least some patients develop myocarditis.”

Stressing the current uncertainty about the virus, the bulletin provides the following clinical guidance:

• COVID-19 is spread through droplets and can live for substantial periods outside the body; containment and prevention using standard public health and personal strategies for preventing the spread of communicable disease remains the priority.
• In geographies with active COVID-19 transmission (mainly China), it is reasonable to advise patients with underlying cardiovascular disease of the potential increased risk and to encourage additional, reasonable precautions.
• Older adults are less likely to present with fever, thus close assessment for other symptoms such as cough or shortness of breath is warranted.
• Some experts have suggested that the rigorous use of guideline-directed, plaque-stabilizing agents could offer additional protection to cardiovascular disease (CVD) patients during a widespread outbreak (statins, beta-blockers, ACE inhibitors, acetylsalicylic acid); however, such therapies should be tailored to individual patients.
• It is important for patients with CVD to remain current with vaccinations, including the pneumococcal vaccine, given the increased risk of secondary bacterial infection; it would also be prudent to receive vaccination to prevent another source of fever which could be initially confused with coronavirus infection.
• It may be reasonable to triage COVID-19 patients according to the presence of underlying cardiovascular, respiratory, renal, and other chronic diseases for prioritized treatment.
• Providers are cautioned that classic symptoms and presentation of acute MI may be overshadowed in the context of coronavirus, resulting in underdiagnosis.
• For CVD patients in geographies without widespread COVID-19, emphasis should remain on the threat from influenza, the importance of vaccination and frequent handwashing, and continued adherence to all guideline-directed therapy for underlying chronic conditions.
• COVID-19 is a fast-moving epidemic with an uncertain clinical profile; providers should be prepared for guidance to shift as more information becomes available.

The full clinical update is available here.

This article first appeared on Medscape.com.

The American College of Cardiology on Feb. 13, 2020, released a clinical bulletin that aims to address cardiac implications of the current epidemic of the novel coronavirus, now known as COVID-19.

The bulletin, reviewed and approved by the college’s Science and Quality Oversight Committee, “provides background on the epidemic, which was first reported in late December 2019, and looks at early cardiac implications from case reports,” the ACC noted in a press release. “It also provides information on the potential cardiac implications from analog viral respiratory pandemics and offers early clinical guidance given current COVID-19 uncertainty.”

The document looks at some early cardiac implications of the infection. For example, early case reports suggest patients with underlying conditions are at higher risk of complications or mortality from the virus, with up to 50% of hospitalized patients having a chronic medical illness, the authors wrote.

About 40% of hospitalized patients confirmed to have the virus have cardiovascular or cerebrovascular disease, they noted.

In a recent case report on 138 hospitalized COVID-19 patients, they noted, 19.6% developed acute respiratory distress syndrome, 16.7% developed arrhythmia, 8.7% developed shock, 7.2% developed acute cardiac injury, and 3.6% developed acute kidney injury. “Rates of complication were universally higher for ICU patients,” they wrote.

“The first reported death was a 61-year-old male, with a long history of smoking, who succumbed to acute respiratory distress, heart failure, and cardiac arrest,” the document noted. “Early, unpublished first-hand reports suggest at least some patients develop myocarditis.”

Stressing the current uncertainty about the virus, the bulletin provides the following clinical guidance:

• COVID-19 is spread through droplets and can live for substantial periods outside the body; containment and prevention using standard public health and personal strategies for preventing the spread of communicable disease remains the priority.
• In geographies with active COVID-19 transmission (mainly China), it is reasonable to advise patients with underlying cardiovascular disease of the potential increased risk and to encourage additional, reasonable precautions.
• Older adults are less likely to present with fever, thus close assessment for other symptoms such as cough or shortness of breath is warranted.
• Some experts have suggested that the rigorous use of guideline-directed, plaque-stabilizing agents could offer additional protection to cardiovascular disease (CVD) patients during a widespread outbreak (statins, beta-blockers, ACE inhibitors, acetylsalicylic acid); however, such therapies should be tailored to individual patients.
• It is important for patients with CVD to remain current with vaccinations, including the pneumococcal vaccine, given the increased risk of secondary bacterial infection; it would also be prudent to receive vaccination to prevent another source of fever which could be initially confused with coronavirus infection.
• It may be reasonable to triage COVID-19 patients according to the presence of underlying cardiovascular, respiratory, renal, and other chronic diseases for prioritized treatment.
• Providers are cautioned that classic symptoms and presentation of acute MI may be overshadowed in the context of coronavirus, resulting in underdiagnosis.
• For CVD patients in geographies without widespread COVID-19, emphasis should remain on the threat from influenza, the importance of vaccination and frequent handwashing, and continued adherence to all guideline-directed therapy for underlying chronic conditions.
• COVID-19 is a fast-moving epidemic with an uncertain clinical profile; providers should be prepared for guidance to shift as more information becomes available.

The full clinical update is available here.

This article first appeared on Medscape.com.

The American College of Cardiology on Feb. 13, 2020, released a clinical bulletin that aims to address cardiac implications of the current epidemic of the novel coronavirus, now known as COVID-19.

The bulletin, reviewed and approved by the college’s Science and Quality Oversight Committee, “provides background on the epidemic, which was first reported in late December 2019, and looks at early cardiac implications from case reports,” the ACC noted in a press release. “It also provides information on the potential cardiac implications from analog viral respiratory pandemics and offers early clinical guidance given current COVID-19 uncertainty.”

The document looks at some early cardiac implications of the infection. For example, early case reports suggest patients with underlying conditions are at higher risk of complications or mortality from the virus, with up to 50% of hospitalized patients having a chronic medical illness, the authors wrote.

About 40% of hospitalized patients confirmed to have the virus have cardiovascular or cerebrovascular disease, they noted.

In a recent case report on 138 hospitalized COVID-19 patients, they noted, 19.6% developed acute respiratory distress syndrome, 16.7% developed arrhythmia, 8.7% developed shock, 7.2% developed acute cardiac injury, and 3.6% developed acute kidney injury. “Rates of complication were universally higher for ICU patients,” they wrote.

“The first reported death was a 61-year-old male, with a long history of smoking, who succumbed to acute respiratory distress, heart failure, and cardiac arrest,” the document noted. “Early, unpublished first-hand reports suggest at least some patients develop myocarditis.”

Stressing the current uncertainty about the virus, the bulletin provides the following clinical guidance:

• COVID-19 is spread through droplets and can live for substantial periods outside the body; containment and prevention using standard public health and personal strategies for preventing the spread of communicable disease remains the priority.
• In geographies with active COVID-19 transmission (mainly China), it is reasonable to advise patients with underlying cardiovascular disease of the potential increased risk and to encourage additional, reasonable precautions.
• Older adults are less likely to present with fever, thus close assessment for other symptoms such as cough or shortness of breath is warranted.
• Some experts have suggested that the rigorous use of guideline-directed, plaque-stabilizing agents could offer additional protection to cardiovascular disease (CVD) patients during a widespread outbreak (statins, beta-blockers, ACE inhibitors, acetylsalicylic acid); however, such therapies should be tailored to individual patients.
• It is important for patients with CVD to remain current with vaccinations, including the pneumococcal vaccine, given the increased risk of secondary bacterial infection; it would also be prudent to receive vaccination to prevent another source of fever which could be initially confused with coronavirus infection.
• It may be reasonable to triage COVID-19 patients according to the presence of underlying cardiovascular, respiratory, renal, and other chronic diseases for prioritized treatment.
• Providers are cautioned that classic symptoms and presentation of acute MI may be overshadowed in the context of coronavirus, resulting in underdiagnosis.
• For CVD patients in geographies without widespread COVID-19, emphasis should remain on the threat from influenza, the importance of vaccination and frequent handwashing, and continued adherence to all guideline-directed therapy for underlying chronic conditions.
• COVID-19 is a fast-moving epidemic with an uncertain clinical profile; providers should be prepared for guidance to shift as more information becomes available.

The full clinical update is available here.

This article first appeared on Medscape.com.

The Centers for Disease Control and Prevention announced two new patients now have the 2019 Novel Coronavirus (2019-nCoV), bringing the case total in the United States to 15.

The 14th case was discovered in California among a group of people under federal quarantine after returning from the Hubei Province in China. That patient was on a U.S. State Department–chartered flight that arrived in the United States on Feb. 7.

The 15th case was discovered in Texas among a group of people who also are under federal quarantine. That patient arrived on a State Department–chartered flight that arrived on Feb. 7. It is the first person in Texas that has tested positive for 2019-nCoV.

CDC said in a statement announcing the Texas case that there “will likely be additional cases in the coming days and weeks, including among other people recently returned from Wuhan.” Officials noted that more than 600 people who have returned as part of State Department–chartered flights are currently under that 14-day quarantine.

The agency is preparing for more widespread cases of 2019-nCoV.

Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, said that containment has been the early focus for the agency.

“The goal of the measures we have taken to date are to slow the introduction and impact of this disease in the United States, but at some point, we are likely to see community spread in the U.S.,” Dr. Messonnier said during a Feb. 12 teleconference with reporters. She added that the federal response will change over time as the virus spreads.

Dr. Messonnier noted that public health officials are planning for the increased demands that a wider outbreak of 2019-nCov would place on the health care delivery system, including ensuring an adequate supply of medical equipment.

gtwachtman@mdedge.com

The Centers for Disease Control and Prevention announced two new patients now have the 2019 Novel Coronavirus (2019-nCoV), bringing the case total in the United States to 15.

The 14th case was discovered in California among a group of people under federal quarantine after returning from the Hubei Province in China. That patient was on a U.S. State Department–chartered flight that arrived in the United States on Feb. 7.

The 15th case was discovered in Texas among a group of people who also are under federal quarantine. That patient arrived on a State Department–chartered flight that arrived on Feb. 7. It is the first person in Texas that has tested positive for 2019-nCoV.

CDC said in a statement announcing the Texas case that there “will likely be additional cases in the coming days and weeks, including among other people recently returned from Wuhan.” Officials noted that more than 600 people who have returned as part of State Department–chartered flights are currently under that 14-day quarantine.

The agency is preparing for more widespread cases of 2019-nCoV.

Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, said that containment has been the early focus for the agency.

“The goal of the measures we have taken to date are to slow the introduction and impact of this disease in the United States, but at some point, we are likely to see community spread in the U.S.,” Dr. Messonnier said during a Feb. 12 teleconference with reporters. She added that the federal response will change over time as the virus spreads.

Dr. Messonnier noted that public health officials are planning for the increased demands that a wider outbreak of 2019-nCov would place on the health care delivery system, including ensuring an adequate supply of medical equipment.

gtwachtman@mdedge.com

The Centers for Disease Control and Prevention announced two new patients now have the 2019 Novel Coronavirus (2019-nCoV), bringing the case total in the United States to 15.

The 14th case was discovered in California among a group of people under federal quarantine after returning from the Hubei Province in China. That patient was on a U.S. State Department–chartered flight that arrived in the United States on Feb. 7.

The 15th case was discovered in Texas among a group of people who also are under federal quarantine. That patient arrived on a State Department–chartered flight that arrived on Feb. 7. It is the first person in Texas that has tested positive for 2019-nCoV.

CDC said in a statement announcing the Texas case that there “will likely be additional cases in the coming days and weeks, including among other people recently returned from Wuhan.” Officials noted that more than 600 people who have returned as part of State Department–chartered flights are currently under that 14-day quarantine.

The agency is preparing for more widespread cases of 2019-nCoV.

Nancy Messonnier, MD, director of the CDC National Center for Immunization and Respiratory Diseases, said that containment has been the early focus for the agency.

“The goal of the measures we have taken to date are to slow the introduction and impact of this disease in the United States, but at some point, we are likely to see community spread in the U.S.,” Dr. Messonnier said during a Feb. 12 teleconference with reporters. She added that the federal response will change over time as the virus spreads.

Dr. Messonnier noted that public health officials are planning for the increased demands that a wider outbreak of 2019-nCov would place on the health care delivery system, including ensuring an adequate supply of medical equipment.

gtwachtman@mdedge.com

No specific treatment is currently available for human coronaviruses to date, but numerous antiviral agents are being identified through a variety of approaches, according to Thanigaimalai Pillaiyar, PhD, and colleagues in a review published in Drug Discovery Today.

Using the six previously discovered human coronaviruses – human CoV 229E (HCoV-229E), OC43 (HCoV-OC43), NL63 (HCoV-NL63), HKU1 (HCoV-HKU1); severe acute respiratory syndrome (SARS) CoV; and Middle East respiratory syndrome (MERS) CoV – the investigators examined progress in the use and development of therapeutic drugs, focusing on the potential roles of virus inhibitors.

“Research has mainly been focused on SARS- and MERS-CoV infections, because they were responsible for severe illness when compared with other CoVs,” Dr. Pillaiyar, of the department of pharmaceutical and medicinal chemistry at the University of Bonn (Germany), and colleagues wrote.

2019-nCov has been linked genomically as most closely related to SARS, and the Coronavirus Study Group of the International Committee on Virus Taxonomy, which has the responsibility for naming viruses, has designated the new virus SARS-CoV-2.
 

Examining extant drugs

The first approach to identifying possible antiviral agents reevaluates known, broadly acting antiviral drugs that have been used for other viral infections or other indications. The initial research into coronavirus therapeutics, in particular, has examined current antiviral therapeutics for their effectiveness against both SARS-CoV and MERS-CoV, but with mixed results.

For example, in a search of potential antiviral agents against CoVs, researchers identified four drugs – chloroquine, chlorpromazine, loperamide, and lopinavir – by screening drug libraries approved by the Food and Drug Administration. They were all able to inhibit the replication of MERS-CoV, SARS-CoV, and HCoV-229E in the low-micromolar range, which suggested that they could be used for broad-spectrum antiviral activity, according to Dr. Pillaiyar and colleagues.

Other research groups have also reported the discovery of antiviral drugs using this drug-repurposing approach, which included a number of broad-spectrum inhibitors of HCoVs (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazopyridine, and pyrvinium pamoate) that showed strong inhibition of replication by four CoVs in vitro at low-micromolar concentrations and suppressed the replication of all CoVs in a dose-dependent manner. Findings from in vivo studies showed lycorine protected mice against lethal HCoV-OC43 infection.

Along with the aforementioned drugs, a number of others have also shown potential usefulness, but, as yet, none has been validated for use in humans.
 

Developing new antivirals

The second approach for anti-CoV drug discovery involves the development of new therapeutics based on the genomic and biophysical understanding of the individual CoV in order to interfere with the virus itself or to disrupt its direct metabolic requirements. This can take several approaches.

MERS-CoV and SARS-CoV PL protease inhibitors

Of particular interest are antiviral therapies that attack papain-like protease, which is an important target because it is a multifunctional protein involved in proteolytic deubiquitination and viral evasion of the innate immune response. One such potential therapeutic that takes advantage of this target is disulfiram, an FDA-approved drug for use in alcohol-aversion therapy. Disulfiram has been reported as an allosteric inhibitor of MERS-CoV papain-like protease. Numerous other drug categories are being examined, with promising results in targeting the papain-like protease enzymes of both SARS and MERS.

Replicase inhibitors

Helicase (nsP13) protein is a crucial component required for virus replication in host cells and could serve as a feasible target for anti-MERS and anti-SARS chemical therapies, the review authors wrote, citing as an example, the recent development of a small 1,2,4-triazole derivative that inhibited the viral NTPase/helicase of SARS- and MERS-CoVs and demonstrated high antiviral activity and low cytotoxicity.

Membrane-bound viral RNA synthesis inhibitors

Antiviral agents that target membrane-bound coronaviral RNA synthesis represent a novel and attractive approach, according to Dr. Pillaiyar and colleagues. And recently, an inhibitor was developed that targets membrane-bound coronaviral RNA synthesis and “showed potent antiviral activity of MERS-CoV infection with remarkable efficacy.”

Host-based, anti-CoV treatment options

An alternate therapeutic tactic is to bolster host defenses or to modify host susceptibilities to prevent virus infection or replication. The innate interferon response of the host is crucial for the control of viral replication after infection, and the addition of exogenous recombinant interferon or use of drugs to stimulate the normal host interferon response are both potential therapeutic avenues. For example, nitazoxanide is a potent type I interferon inducer that has been used in humans for parasitic infections, and a synthetic nitrothiazolyl-salicylamide derivative was found to exhibit broad-spectrum antiviral activities against RNA and DNA viruses, including some coronaviruses.

Numerous other host pathways are being investigated as potential areas to enhance defense against infection and replication, for example, using inhibitors to block nucleic acid synthesis has been shown to provide broad-spectrum activity against SARS-CoV and MERS-CoV.

One particular example is remdesivir, a novel nucleotide analog antiviral drug, that was developed as a therapy for Ebola virus disease and Marburg virus infections. It was later shown to provide “reasonable antiviral activity against more distantly related viruses, such as respiratory syncytial virus, Junin virus, Lassa fever virus, and MERS-CoV,” the authors wrote.

Also of interest regarding remdesivir’s potential broad-spectrum use is that it has shown potent in vitro “antiviral activity against Malaysian and Bangladesh genotypes of Nipah virus (an RNA virus, although not a coronavirus, that infects both humans and animals) and reduced replication of Malaysian Nipah virus in primary human lung microvascular endothelial cells by more than four orders of magnitude,” Dr. Pillaiyar and colleagues added. Of particular note, all remdesivir-treated, Nipah virus–infected animals “survived the lethal challenge, indicating that remdesivir represents a promising antiviral treatment.”

In a press briefing earlier this month, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, reported that a randomized, controlled, phase 3 trial of the antiviral drug remdesivir is currently underway in China to establish whether the drug would be an effective and safe treatment for adults patients with mild or moderate 2019 Novel Coronavirus (2019-nCoV) disease.

“Our increasing understanding of novel emerging coronaviruses will be accompanied by increasing opportunities for the reasonable design of therapeutics. Importantly, understanding this basic information about CoV protease targets will not only aid the public health against SARS-CoV and MERS-CoV but also help in advance to target new coronaviruses that might emerge in the future,” the authors concluded.

Dr. Pillaiyar and colleagues reported that they had no financial conflicts of interest.

mlesney@mdedge.com

SOURCE: Pillaiyar T et al. Drug Discov Today. 2020 Jan 30. doi: 10.1016/j.drudis.2020.01.015.

No specific treatment is currently available for human coronaviruses to date, but numerous antiviral agents are being identified through a variety of approaches, according to Thanigaimalai Pillaiyar, PhD, and colleagues in a review published in Drug Discovery Today.

Using the six previously discovered human coronaviruses – human CoV 229E (HCoV-229E), OC43 (HCoV-OC43), NL63 (HCoV-NL63), HKU1 (HCoV-HKU1); severe acute respiratory syndrome (SARS) CoV; and Middle East respiratory syndrome (MERS) CoV – the investigators examined progress in the use and development of therapeutic drugs, focusing on the potential roles of virus inhibitors.

“Research has mainly been focused on SARS- and MERS-CoV infections, because they were responsible for severe illness when compared with other CoVs,” Dr. Pillaiyar, of the department of pharmaceutical and medicinal chemistry at the University of Bonn (Germany), and colleagues wrote.

2019-nCov has been linked genomically as most closely related to SARS, and the Coronavirus Study Group of the International Committee on Virus Taxonomy, which has the responsibility for naming viruses, has designated the new virus SARS-CoV-2.
 

Examining extant drugs

The first approach to identifying possible antiviral agents reevaluates known, broadly acting antiviral drugs that have been used for other viral infections or other indications. The initial research into coronavirus therapeutics, in particular, has examined current antiviral therapeutics for their effectiveness against both SARS-CoV and MERS-CoV, but with mixed results.

For example, in a search of potential antiviral agents against CoVs, researchers identified four drugs – chloroquine, chlorpromazine, loperamide, and lopinavir – by screening drug libraries approved by the Food and Drug Administration. They were all able to inhibit the replication of MERS-CoV, SARS-CoV, and HCoV-229E in the low-micromolar range, which suggested that they could be used for broad-spectrum antiviral activity, according to Dr. Pillaiyar and colleagues.

Other research groups have also reported the discovery of antiviral drugs using this drug-repurposing approach, which included a number of broad-spectrum inhibitors of HCoVs (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazopyridine, and pyrvinium pamoate) that showed strong inhibition of replication by four CoVs in vitro at low-micromolar concentrations and suppressed the replication of all CoVs in a dose-dependent manner. Findings from in vivo studies showed lycorine protected mice against lethal HCoV-OC43 infection.

Along with the aforementioned drugs, a number of others have also shown potential usefulness, but, as yet, none has been validated for use in humans.
 

Developing new antivirals

The second approach for anti-CoV drug discovery involves the development of new therapeutics based on the genomic and biophysical understanding of the individual CoV in order to interfere with the virus itself or to disrupt its direct metabolic requirements. This can take several approaches.

MERS-CoV and SARS-CoV PL protease inhibitors

Of particular interest are antiviral therapies that attack papain-like protease, which is an important target because it is a multifunctional protein involved in proteolytic deubiquitination and viral evasion of the innate immune response. One such potential therapeutic that takes advantage of this target is disulfiram, an FDA-approved drug for use in alcohol-aversion therapy. Disulfiram has been reported as an allosteric inhibitor of MERS-CoV papain-like protease. Numerous other drug categories are being examined, with promising results in targeting the papain-like protease enzymes of both SARS and MERS.

Replicase inhibitors

Helicase (nsP13) protein is a crucial component required for virus replication in host cells and could serve as a feasible target for anti-MERS and anti-SARS chemical therapies, the review authors wrote, citing as an example, the recent development of a small 1,2,4-triazole derivative that inhibited the viral NTPase/helicase of SARS- and MERS-CoVs and demonstrated high antiviral activity and low cytotoxicity.

Membrane-bound viral RNA synthesis inhibitors

Antiviral agents that target membrane-bound coronaviral RNA synthesis represent a novel and attractive approach, according to Dr. Pillaiyar and colleagues. And recently, an inhibitor was developed that targets membrane-bound coronaviral RNA synthesis and “showed potent antiviral activity of MERS-CoV infection with remarkable efficacy.”

Host-based, anti-CoV treatment options

An alternate therapeutic tactic is to bolster host defenses or to modify host susceptibilities to prevent virus infection or replication. The innate interferon response of the host is crucial for the control of viral replication after infection, and the addition of exogenous recombinant interferon or use of drugs to stimulate the normal host interferon response are both potential therapeutic avenues. For example, nitazoxanide is a potent type I interferon inducer that has been used in humans for parasitic infections, and a synthetic nitrothiazolyl-salicylamide derivative was found to exhibit broad-spectrum antiviral activities against RNA and DNA viruses, including some coronaviruses.

Numerous other host pathways are being investigated as potential areas to enhance defense against infection and replication, for example, using inhibitors to block nucleic acid synthesis has been shown to provide broad-spectrum activity against SARS-CoV and MERS-CoV.

One particular example is remdesivir, a novel nucleotide analog antiviral drug, that was developed as a therapy for Ebola virus disease and Marburg virus infections. It was later shown to provide “reasonable antiviral activity against more distantly related viruses, such as respiratory syncytial virus, Junin virus, Lassa fever virus, and MERS-CoV,” the authors wrote.

Also of interest regarding remdesivir’s potential broad-spectrum use is that it has shown potent in vitro “antiviral activity against Malaysian and Bangladesh genotypes of Nipah virus (an RNA virus, although not a coronavirus, that infects both humans and animals) and reduced replication of Malaysian Nipah virus in primary human lung microvascular endothelial cells by more than four orders of magnitude,” Dr. Pillaiyar and colleagues added. Of particular note, all remdesivir-treated, Nipah virus–infected animals “survived the lethal challenge, indicating that remdesivir represents a promising antiviral treatment.”

In a press briefing earlier this month, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, reported that a randomized, controlled, phase 3 trial of the antiviral drug remdesivir is currently underway in China to establish whether the drug would be an effective and safe treatment for adults patients with mild or moderate 2019 Novel Coronavirus (2019-nCoV) disease.

“Our increasing understanding of novel emerging coronaviruses will be accompanied by increasing opportunities for the reasonable design of therapeutics. Importantly, understanding this basic information about CoV protease targets will not only aid the public health against SARS-CoV and MERS-CoV but also help in advance to target new coronaviruses that might emerge in the future,” the authors concluded.

Dr. Pillaiyar and colleagues reported that they had no financial conflicts of interest.

mlesney@mdedge.com

SOURCE: Pillaiyar T et al. Drug Discov Today. 2020 Jan 30. doi: 10.1016/j.drudis.2020.01.015.

No specific treatment is currently available for human coronaviruses to date, but numerous antiviral agents are being identified through a variety of approaches, according to Thanigaimalai Pillaiyar, PhD, and colleagues in a review published in Drug Discovery Today.

Using the six previously discovered human coronaviruses – human CoV 229E (HCoV-229E), OC43 (HCoV-OC43), NL63 (HCoV-NL63), HKU1 (HCoV-HKU1); severe acute respiratory syndrome (SARS) CoV; and Middle East respiratory syndrome (MERS) CoV – the investigators examined progress in the use and development of therapeutic drugs, focusing on the potential roles of virus inhibitors.

“Research has mainly been focused on SARS- and MERS-CoV infections, because they were responsible for severe illness when compared with other CoVs,” Dr. Pillaiyar, of the department of pharmaceutical and medicinal chemistry at the University of Bonn (Germany), and colleagues wrote.

2019-nCov has been linked genomically as most closely related to SARS, and the Coronavirus Study Group of the International Committee on Virus Taxonomy, which has the responsibility for naming viruses, has designated the new virus SARS-CoV-2.
 

Examining extant drugs

The first approach to identifying possible antiviral agents reevaluates known, broadly acting antiviral drugs that have been used for other viral infections or other indications. The initial research into coronavirus therapeutics, in particular, has examined current antiviral therapeutics for their effectiveness against both SARS-CoV and MERS-CoV, but with mixed results.

For example, in a search of potential antiviral agents against CoVs, researchers identified four drugs – chloroquine, chlorpromazine, loperamide, and lopinavir – by screening drug libraries approved by the Food and Drug Administration. They were all able to inhibit the replication of MERS-CoV, SARS-CoV, and HCoV-229E in the low-micromolar range, which suggested that they could be used for broad-spectrum antiviral activity, according to Dr. Pillaiyar and colleagues.

Other research groups have also reported the discovery of antiviral drugs using this drug-repurposing approach, which included a number of broad-spectrum inhibitors of HCoVs (lycorine, emetine, monensin sodium, mycophenolate mofetil, mycophenolic acid, phenazopyridine, and pyrvinium pamoate) that showed strong inhibition of replication by four CoVs in vitro at low-micromolar concentrations and suppressed the replication of all CoVs in a dose-dependent manner. Findings from in vivo studies showed lycorine protected mice against lethal HCoV-OC43 infection.

Along with the aforementioned drugs, a number of others have also shown potential usefulness, but, as yet, none has been validated for use in humans.
 

Developing new antivirals

The second approach for anti-CoV drug discovery involves the development of new therapeutics based on the genomic and biophysical understanding of the individual CoV in order to interfere with the virus itself or to disrupt its direct metabolic requirements. This can take several approaches.

MERS-CoV and SARS-CoV PL protease inhibitors

Of particular interest are antiviral therapies that attack papain-like protease, which is an important target because it is a multifunctional protein involved in proteolytic deubiquitination and viral evasion of the innate immune response. One such potential therapeutic that takes advantage of this target is disulfiram, an FDA-approved drug for use in alcohol-aversion therapy. Disulfiram has been reported as an allosteric inhibitor of MERS-CoV papain-like protease. Numerous other drug categories are being examined, with promising results in targeting the papain-like protease enzymes of both SARS and MERS.

Replicase inhibitors

Helicase (nsP13) protein is a crucial component required for virus replication in host cells and could serve as a feasible target for anti-MERS and anti-SARS chemical therapies, the review authors wrote, citing as an example, the recent development of a small 1,2,4-triazole derivative that inhibited the viral NTPase/helicase of SARS- and MERS-CoVs and demonstrated high antiviral activity and low cytotoxicity.

Membrane-bound viral RNA synthesis inhibitors

Antiviral agents that target membrane-bound coronaviral RNA synthesis represent a novel and attractive approach, according to Dr. Pillaiyar and colleagues. And recently, an inhibitor was developed that targets membrane-bound coronaviral RNA synthesis and “showed potent antiviral activity of MERS-CoV infection with remarkable efficacy.”

Host-based, anti-CoV treatment options

An alternate therapeutic tactic is to bolster host defenses or to modify host susceptibilities to prevent virus infection or replication. The innate interferon response of the host is crucial for the control of viral replication after infection, and the addition of exogenous recombinant interferon or use of drugs to stimulate the normal host interferon response are both potential therapeutic avenues. For example, nitazoxanide is a potent type I interferon inducer that has been used in humans for parasitic infections, and a synthetic nitrothiazolyl-salicylamide derivative was found to exhibit broad-spectrum antiviral activities against RNA and DNA viruses, including some coronaviruses.

Numerous other host pathways are being investigated as potential areas to enhance defense against infection and replication, for example, using inhibitors to block nucleic acid synthesis has been shown to provide broad-spectrum activity against SARS-CoV and MERS-CoV.

One particular example is remdesivir, a novel nucleotide analog antiviral drug, that was developed as a therapy for Ebola virus disease and Marburg virus infections. It was later shown to provide “reasonable antiviral activity against more distantly related viruses, such as respiratory syncytial virus, Junin virus, Lassa fever virus, and MERS-CoV,” the authors wrote.

Also of interest regarding remdesivir’s potential broad-spectrum use is that it has shown potent in vitro “antiviral activity against Malaysian and Bangladesh genotypes of Nipah virus (an RNA virus, although not a coronavirus, that infects both humans and animals) and reduced replication of Malaysian Nipah virus in primary human lung microvascular endothelial cells by more than four orders of magnitude,” Dr. Pillaiyar and colleagues added. Of particular note, all remdesivir-treated, Nipah virus–infected animals “survived the lethal challenge, indicating that remdesivir represents a promising antiviral treatment.”

In a press briefing earlier this month, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, reported that a randomized, controlled, phase 3 trial of the antiviral drug remdesivir is currently underway in China to establish whether the drug would be an effective and safe treatment for adults patients with mild or moderate 2019 Novel Coronavirus (2019-nCoV) disease.

“Our increasing understanding of novel emerging coronaviruses will be accompanied by increasing opportunities for the reasonable design of therapeutics. Importantly, understanding this basic information about CoV protease targets will not only aid the public health against SARS-CoV and MERS-CoV but also help in advance to target new coronaviruses that might emerge in the future,” the authors concluded.

Dr. Pillaiyar and colleagues reported that they had no financial conflicts of interest.

mlesney@mdedge.com

SOURCE: Pillaiyar T et al. Drug Discov Today. 2020 Jan 30. doi: 10.1016/j.drudis.2020.01.015.

Neonatal transfer was the factor most often associated with unexpected, severe complications at birth, particularly at hospitals that had the highest rates of complications, according to a cross-sectional study published online in JAMA Network Open (2020;3[2]:e1919498).

“Transfers were more likely to be necessary when infants were born in hospitals with lower levels of neonatal care,” Mark A. Clapp, MD, MPH, of Massachusetts General Hospital in Boston, and colleagues wrote. “Thus, if this metric is to be used in its current form, it would appear that accreditors, regulatory bodies, and payers should consider adjusting for or stratifying by a hospital’s level of neonatal care to avoid disincentivizing against appropriate transfers.”

The Joint Commission recently included unexpected complications in term newborns as a marker of quality of obstetric care, but it does not currently recommend any risk adjustment for the metric. The authors aimed to learn which factors regarding patients and hospitals were associated with such complications. Severe, unexpected newborn complications include death, seizure, use of assisted ventilation for at least 6 hours, transfer to another facility, or a 5-minute Apgar score of 3 or less.

“This measure has been proposed to serve as a balancing measure to maternal metrics, such as the rate of nulliparous, term, singleton, vertex-presenting cesarean deliveries,” the authors explained.

This study was supported by a Health Policy Award from the Society for Maternal-Fetal Medicine. The authors reported no relevant financial disclosures.

This story first appeared on Medscape.

Neonatal transfer was the factor most often associated with unexpected, severe complications at birth, particularly at hospitals that had the highest rates of complications, according to a cross-sectional study published online in JAMA Network Open (2020;3[2]:e1919498).

“Transfers were more likely to be necessary when infants were born in hospitals with lower levels of neonatal care,” Mark A. Clapp, MD, MPH, of Massachusetts General Hospital in Boston, and colleagues wrote. “Thus, if this metric is to be used in its current form, it would appear that accreditors, regulatory bodies, and payers should consider adjusting for or stratifying by a hospital’s level of neonatal care to avoid disincentivizing against appropriate transfers.”

The Joint Commission recently included unexpected complications in term newborns as a marker of quality of obstetric care, but it does not currently recommend any risk adjustment for the metric. The authors aimed to learn which factors regarding patients and hospitals were associated with such complications. Severe, unexpected newborn complications include death, seizure, use of assisted ventilation for at least 6 hours, transfer to another facility, or a 5-minute Apgar score of 3 or less.

“This measure has been proposed to serve as a balancing measure to maternal metrics, such as the rate of nulliparous, term, singleton, vertex-presenting cesarean deliveries,” the authors explained.

This study was supported by a Health Policy Award from the Society for Maternal-Fetal Medicine. The authors reported no relevant financial disclosures.

This story first appeared on Medscape.

Neonatal transfer was the factor most often associated with unexpected, severe complications at birth, particularly at hospitals that had the highest rates of complications, according to a cross-sectional study published online in JAMA Network Open (2020;3[2]:e1919498).

“Transfers were more likely to be necessary when infants were born in hospitals with lower levels of neonatal care,” Mark A. Clapp, MD, MPH, of Massachusetts General Hospital in Boston, and colleagues wrote. “Thus, if this metric is to be used in its current form, it would appear that accreditors, regulatory bodies, and payers should consider adjusting for or stratifying by a hospital’s level of neonatal care to avoid disincentivizing against appropriate transfers.”

The Joint Commission recently included unexpected complications in term newborns as a marker of quality of obstetric care, but it does not currently recommend any risk adjustment for the metric. The authors aimed to learn which factors regarding patients and hospitals were associated with such complications. Severe, unexpected newborn complications include death, seizure, use of assisted ventilation for at least 6 hours, transfer to another facility, or a 5-minute Apgar score of 3 or less.

“This measure has been proposed to serve as a balancing measure to maternal metrics, such as the rate of nulliparous, term, singleton, vertex-presenting cesarean deliveries,” the authors explained.

This study was supported by a Health Policy Award from the Society for Maternal-Fetal Medicine. The authors reported no relevant financial disclosures.

This story first appeared on Medscape.