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Among infants younger than 1 year of age, bacterial meningitis is associated with worse long-term mortality, even after recovery from the initial infection. Heightened mortality risk stretched out to 10 years, and was highest in the wake of infection from Streptococcus agalactiae, according to a retrospective analysis of children in the Netherlands.

“The adjusted hazard rates were high for the whole group of bacterial meningitis, especially within the first year after onset. (Staphylococcus agalactiae) meningitis has the highest mortality risk within one year of disease onset,” Linde Snoek said during her presentation of the study (abstract 913) at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. Ms. Snoek is a PhD student at Amsterdam University Medical Center.

Over longer time periods, the mortality associations were different. “The adjusted hazard rates were highest for pneumococcal meningitis compared to the other pathogens. And this was the case for 1 year, 5 years, and 10 years after disease onset,” said Ms. Snoek.

The study appears to be the first to look at extended mortality following bacterial meningitis in this age group, according to Marie Rohr, MD, who comoderated the session where the research was presented.

“In a quick review of the literature I did not find any [equivalent] study concerning short- and long-term mortality after bacterial meningitis in under 1 year of age,” said Dr. Rohr, a fellow in pediatric infectious diseases at University Hospitals of Geneva. But the message to physicians is clear. “Children with history of bacterial meningitis have a higher long-term mortality than children without a history of bacterial meningitis,” said Dr. Rohr.

The study did have a key limitation: For matched controls, it relied on anonymous data from the Municipal Personal Records Database in Statistics Netherlands. “Important information like cause of death is lacking,” said Dr. Rohr.

Bacterial meningitis is associated with significant mortality and morbidity. Pathogens behind the infections vary with age group and geographic location, as well as immunization status.

To examine long-term mortality after bacterial meningitis, the researchers collected 1,646 records from an exposed cohort, with a date range of 1995 to 2018, from the Netherlands Reference Laboratory for Bacterial Meningitis. Included patients had a positive culture diagnosis of bacterial meningitis during the first year of life. Each exposed subject was compared to 10 controls matched by birth month, birth year, and sex, who had no exposure to bacterial meningitis.

Staphylococcus pneumoniae accounted for the most cases, at 32.0% (median age of onset, 180 days), followed by Neisseria meningitidis at 29.0% (median age of onset, 203 days). Other pathogens included S. agalactiae (19.7%, 10 days), Escherichia coli (8.8%, 13 days), and Haemophilus influenzae (5.4%, 231 days).

The mortality risk within 1 year of disease onset was higher for all pathogens (6.2% vs. 0.2% unexposed). The highest mortality risk was seen for S. agalactiae (8.7%), followed by E. coli (6.4%), N. meningitidis (4.9%), and H. influenzae (3.4%).

Hazard ratios (HR) for mortality were also higher, particularly in the first year after disease onset. For all pathogens, mortality rates were higher within 1 year (HR, 39.2), 5 years (HR, 28.7), and 10 years (HR, 24.1). The consistently highest mortality rates were associated with S. pneumoniae over 1-year, 5-year, and 10-year follow-up (HR, 42.8; HR, 45.6; HR, 40.6, respectively). Within 1 year, the highest mortality rate was associated with N. meningitidis (HR, 58.4).

Ms. Snoek and Dr. Rohr have no relevant financial disclosures.

Among infants younger than 1 year of age, bacterial meningitis is associated with worse long-term mortality, even after recovery from the initial infection. Heightened mortality risk stretched out to 10 years, and was highest in the wake of infection from Streptococcus agalactiae, according to a retrospective analysis of children in the Netherlands.

“The adjusted hazard rates were high for the whole group of bacterial meningitis, especially within the first year after onset. (Staphylococcus agalactiae) meningitis has the highest mortality risk within one year of disease onset,” Linde Snoek said during her presentation of the study (abstract 913) at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. Ms. Snoek is a PhD student at Amsterdam University Medical Center.

Over longer time periods, the mortality associations were different. “The adjusted hazard rates were highest for pneumococcal meningitis compared to the other pathogens. And this was the case for 1 year, 5 years, and 10 years after disease onset,” said Ms. Snoek.

The study appears to be the first to look at extended mortality following bacterial meningitis in this age group, according to Marie Rohr, MD, who comoderated the session where the research was presented.

“In a quick review of the literature I did not find any [equivalent] study concerning short- and long-term mortality after bacterial meningitis in under 1 year of age,” said Dr. Rohr, a fellow in pediatric infectious diseases at University Hospitals of Geneva. But the message to physicians is clear. “Children with history of bacterial meningitis have a higher long-term mortality than children without a history of bacterial meningitis,” said Dr. Rohr.

The study did have a key limitation: For matched controls, it relied on anonymous data from the Municipal Personal Records Database in Statistics Netherlands. “Important information like cause of death is lacking,” said Dr. Rohr.

Bacterial meningitis is associated with significant mortality and morbidity. Pathogens behind the infections vary with age group and geographic location, as well as immunization status.

To examine long-term mortality after bacterial meningitis, the researchers collected 1,646 records from an exposed cohort, with a date range of 1995 to 2018, from the Netherlands Reference Laboratory for Bacterial Meningitis. Included patients had a positive culture diagnosis of bacterial meningitis during the first year of life. Each exposed subject was compared to 10 controls matched by birth month, birth year, and sex, who had no exposure to bacterial meningitis.

Staphylococcus pneumoniae accounted for the most cases, at 32.0% (median age of onset, 180 days), followed by Neisseria meningitidis at 29.0% (median age of onset, 203 days). Other pathogens included S. agalactiae (19.7%, 10 days), Escherichia coli (8.8%, 13 days), and Haemophilus influenzae (5.4%, 231 days).

The mortality risk within 1 year of disease onset was higher for all pathogens (6.2% vs. 0.2% unexposed). The highest mortality risk was seen for S. agalactiae (8.7%), followed by E. coli (6.4%), N. meningitidis (4.9%), and H. influenzae (3.4%).

Hazard ratios (HR) for mortality were also higher, particularly in the first year after disease onset. For all pathogens, mortality rates were higher within 1 year (HR, 39.2), 5 years (HR, 28.7), and 10 years (HR, 24.1). The consistently highest mortality rates were associated with S. pneumoniae over 1-year, 5-year, and 10-year follow-up (HR, 42.8; HR, 45.6; HR, 40.6, respectively). Within 1 year, the highest mortality rate was associated with N. meningitidis (HR, 58.4).

Ms. Snoek and Dr. Rohr have no relevant financial disclosures.

Among infants younger than 1 year of age, bacterial meningitis is associated with worse long-term mortality, even after recovery from the initial infection. Heightened mortality risk stretched out to 10 years, and was highest in the wake of infection from Streptococcus agalactiae, according to a retrospective analysis of children in the Netherlands.

“The adjusted hazard rates were high for the whole group of bacterial meningitis, especially within the first year after onset. (Staphylococcus agalactiae) meningitis has the highest mortality risk within one year of disease onset,” Linde Snoek said during her presentation of the study (abstract 913) at the annual meeting of the European Society for Paediatric Infectious Diseases, held virtually this year. Ms. Snoek is a PhD student at Amsterdam University Medical Center.

Over longer time periods, the mortality associations were different. “The adjusted hazard rates were highest for pneumococcal meningitis compared to the other pathogens. And this was the case for 1 year, 5 years, and 10 years after disease onset,” said Ms. Snoek.

The study appears to be the first to look at extended mortality following bacterial meningitis in this age group, according to Marie Rohr, MD, who comoderated the session where the research was presented.

“In a quick review of the literature I did not find any [equivalent] study concerning short- and long-term mortality after bacterial meningitis in under 1 year of age,” said Dr. Rohr, a fellow in pediatric infectious diseases at University Hospitals of Geneva. But the message to physicians is clear. “Children with history of bacterial meningitis have a higher long-term mortality than children without a history of bacterial meningitis,” said Dr. Rohr.

The study did have a key limitation: For matched controls, it relied on anonymous data from the Municipal Personal Records Database in Statistics Netherlands. “Important information like cause of death is lacking,” said Dr. Rohr.

Bacterial meningitis is associated with significant mortality and morbidity. Pathogens behind the infections vary with age group and geographic location, as well as immunization status.

To examine long-term mortality after bacterial meningitis, the researchers collected 1,646 records from an exposed cohort, with a date range of 1995 to 2018, from the Netherlands Reference Laboratory for Bacterial Meningitis. Included patients had a positive culture diagnosis of bacterial meningitis during the first year of life. Each exposed subject was compared to 10 controls matched by birth month, birth year, and sex, who had no exposure to bacterial meningitis.

Staphylococcus pneumoniae accounted for the most cases, at 32.0% (median age of onset, 180 days), followed by Neisseria meningitidis at 29.0% (median age of onset, 203 days). Other pathogens included S. agalactiae (19.7%, 10 days), Escherichia coli (8.8%, 13 days), and Haemophilus influenzae (5.4%, 231 days).

The mortality risk within 1 year of disease onset was higher for all pathogens (6.2% vs. 0.2% unexposed). The highest mortality risk was seen for S. agalactiae (8.7%), followed by E. coli (6.4%), N. meningitidis (4.9%), and H. influenzae (3.4%).

Hazard ratios (HR) for mortality were also higher, particularly in the first year after disease onset. For all pathogens, mortality rates were higher within 1 year (HR, 39.2), 5 years (HR, 28.7), and 10 years (HR, 24.1). The consistently highest mortality rates were associated with S. pneumoniae over 1-year, 5-year, and 10-year follow-up (HR, 42.8; HR, 45.6; HR, 40.6, respectively). Within 1 year, the highest mortality rate was associated with N. meningitidis (HR, 58.4).

Ms. Snoek and Dr. Rohr have no relevant financial disclosures.

When Marisha Burden, MD, division head of hospital medicine at the University of Colorado at Denver, Aurora, would go to medical conferences, it seemed as if very few women were giving talks. She wondered if she could be wrong.

“I started doing my own assessments at every conference I would go to, just to make sure I wasn’t biased in my own belief system,” she said in a session at SHM Converge 2021, the annual conference of the Society of Hospital Medicine.

She wasn’t wrong.

In 2015, only 35% of all speakers at the SHM annual conference were women, and only 23% of the plenary speakers were women. In the years after that, when the society put out open calls for speakers, the numbers of women who spoke increased substantially, to 47% overall and 45% of plenary speakers.

The results – part of the SPEAK UP study Dr. Burden led in 2020 – show how gender disparity can be improved with a systematic process that is designed to improve it. The results of the study also showed that as the percentages of female speakers increased, the attendee ratings of the sessions did, too.

“You can do these things, and the quality of your conference doesn’t get negatively impacted – and in this case, actually improved,” Dr. Burden said.

That study marked progress toward leveling a traditionally uneven playing field when it comes to men and women in medicine, and the panelists in the session called on the field to use a variety of tools and strategies to continue toward something closer to equality.

Sara Spilseth, MD, MBA, chief of staff at Regions Hospital, in St. Paul, Minn., said it’s well established that although almost 50% of medical school students are women, the percentage shrinks each step from faculty to full professor to dean – of which only 16% are women. She referred to what’s known as the “leaky pipe.”

In what Dr. Spilseth said was one of her favorite studies, researchers in 2015 found that only 13% of clinical department leaders at the top 50 U.S. medical schools were women – they were outnumbered by the percentage of department leaders with mustaches, at 19%, even though mustaches are dwindling in popularity.

“Why does this exist? Why did we end up like this?” Part of the problem is a “respect gap,” she said, pointing to a study on the tendency of women to use the formal title of “doctor” when introducing male colleagues, whereas men who introduce women use that title less than half the time.

The COVID-19 pandemic has only made these disparities worse. Women are responsible for childcare much more frequently than men, Dr. Burden said, although the pandemic has brought caregiving duties to the forefront.

Dr. Spilseth said mentoring can help women navigate the workplace so as to help overcome these disparities. At Regions, the mentoring program is robust.

“Even before a new hire steps foot in the hospital, we have established them with a mentor,” she said. Sponsoring – the “ability of someone with political capital to use it to help colleagues” – can also help boost women’s careers, she said.

Her hospital also has a Women in Medicine Cooperative, which provides a way for women to talk about common struggles and to network.

Flexible work opportunities – working in transitional care units, being a physician advisor, and doing research – can all help boost a career as well, Dr. Spilseth said.

She said that at the University of Colorado, leaders set out to reach salary equity in a year and a half – and “it was a painful, painful process.” They found that different people held different beliefs about how people were paid, which led to a lot of unnecessary stress as they tried to construct a fairer system.

“On the back end of having done that, while it was a rough year and half, it has saved so much time – and I think built a culture of trust and transparency,” she said.

Recruiting in a more thoughtful way can also have a big impact, Dr. Spilseth said. The manner in which people are told about opportunities could exclude people without intending to.

“Are you casting a wide net?” she asked.

Adia Ross, MD, MHA, chief medical officer at Duke Regional Hospital, Durham, N.C., said that even in the face of obvious disparities, women can take steps on their own to boost their careers. She encouraged taking on “stretch assignments,” a project or task that is a bit beyond one’s current comfort level or level of experience or knowledge. “It can be a little scary, and sometimes there are bumps along the way,” she said.

All of these measures, though incremental, are the way to make bigger change, she said. “We want to take small steps but big strides forward.”

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

When Marisha Burden, MD, division head of hospital medicine at the University of Colorado at Denver, Aurora, would go to medical conferences, it seemed as if very few women were giving talks. She wondered if she could be wrong.

“I started doing my own assessments at every conference I would go to, just to make sure I wasn’t biased in my own belief system,” she said in a session at SHM Converge 2021, the annual conference of the Society of Hospital Medicine.

She wasn’t wrong.

In 2015, only 35% of all speakers at the SHM annual conference were women, and only 23% of the plenary speakers were women. In the years after that, when the society put out open calls for speakers, the numbers of women who spoke increased substantially, to 47% overall and 45% of plenary speakers.

The results – part of the SPEAK UP study Dr. Burden led in 2020 – show how gender disparity can be improved with a systematic process that is designed to improve it. The results of the study also showed that as the percentages of female speakers increased, the attendee ratings of the sessions did, too.

“You can do these things, and the quality of your conference doesn’t get negatively impacted – and in this case, actually improved,” Dr. Burden said.

That study marked progress toward leveling a traditionally uneven playing field when it comes to men and women in medicine, and the panelists in the session called on the field to use a variety of tools and strategies to continue toward something closer to equality.

Sara Spilseth, MD, MBA, chief of staff at Regions Hospital, in St. Paul, Minn., said it’s well established that although almost 50% of medical school students are women, the percentage shrinks each step from faculty to full professor to dean – of which only 16% are women. She referred to what’s known as the “leaky pipe.”

In what Dr. Spilseth said was one of her favorite studies, researchers in 2015 found that only 13% of clinical department leaders at the top 50 U.S. medical schools were women – they were outnumbered by the percentage of department leaders with mustaches, at 19%, even though mustaches are dwindling in popularity.

“Why does this exist? Why did we end up like this?” Part of the problem is a “respect gap,” she said, pointing to a study on the tendency of women to use the formal title of “doctor” when introducing male colleagues, whereas men who introduce women use that title less than half the time.

The COVID-19 pandemic has only made these disparities worse. Women are responsible for childcare much more frequently than men, Dr. Burden said, although the pandemic has brought caregiving duties to the forefront.

Dr. Spilseth said mentoring can help women navigate the workplace so as to help overcome these disparities. At Regions, the mentoring program is robust.

“Even before a new hire steps foot in the hospital, we have established them with a mentor,” she said. Sponsoring – the “ability of someone with political capital to use it to help colleagues” – can also help boost women’s careers, she said.

Her hospital also has a Women in Medicine Cooperative, which provides a way for women to talk about common struggles and to network.

Flexible work opportunities – working in transitional care units, being a physician advisor, and doing research – can all help boost a career as well, Dr. Spilseth said.

She said that at the University of Colorado, leaders set out to reach salary equity in a year and a half – and “it was a painful, painful process.” They found that different people held different beliefs about how people were paid, which led to a lot of unnecessary stress as they tried to construct a fairer system.

“On the back end of having done that, while it was a rough year and half, it has saved so much time – and I think built a culture of trust and transparency,” she said.

Recruiting in a more thoughtful way can also have a big impact, Dr. Spilseth said. The manner in which people are told about opportunities could exclude people without intending to.

“Are you casting a wide net?” she asked.

Adia Ross, MD, MHA, chief medical officer at Duke Regional Hospital, Durham, N.C., said that even in the face of obvious disparities, women can take steps on their own to boost their careers. She encouraged taking on “stretch assignments,” a project or task that is a bit beyond one’s current comfort level or level of experience or knowledge. “It can be a little scary, and sometimes there are bumps along the way,” she said.

All of these measures, though incremental, are the way to make bigger change, she said. “We want to take small steps but big strides forward.”

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

When Marisha Burden, MD, division head of hospital medicine at the University of Colorado at Denver, Aurora, would go to medical conferences, it seemed as if very few women were giving talks. She wondered if she could be wrong.

“I started doing my own assessments at every conference I would go to, just to make sure I wasn’t biased in my own belief system,” she said in a session at SHM Converge 2021, the annual conference of the Society of Hospital Medicine.

She wasn’t wrong.

In 2015, only 35% of all speakers at the SHM annual conference were women, and only 23% of the plenary speakers were women. In the years after that, when the society put out open calls for speakers, the numbers of women who spoke increased substantially, to 47% overall and 45% of plenary speakers.

The results – part of the SPEAK UP study Dr. Burden led in 2020 – show how gender disparity can be improved with a systematic process that is designed to improve it. The results of the study also showed that as the percentages of female speakers increased, the attendee ratings of the sessions did, too.

“You can do these things, and the quality of your conference doesn’t get negatively impacted – and in this case, actually improved,” Dr. Burden said.

That study marked progress toward leveling a traditionally uneven playing field when it comes to men and women in medicine, and the panelists in the session called on the field to use a variety of tools and strategies to continue toward something closer to equality.

Sara Spilseth, MD, MBA, chief of staff at Regions Hospital, in St. Paul, Minn., said it’s well established that although almost 50% of medical school students are women, the percentage shrinks each step from faculty to full professor to dean – of which only 16% are women. She referred to what’s known as the “leaky pipe.”

In what Dr. Spilseth said was one of her favorite studies, researchers in 2015 found that only 13% of clinical department leaders at the top 50 U.S. medical schools were women – they were outnumbered by the percentage of department leaders with mustaches, at 19%, even though mustaches are dwindling in popularity.

“Why does this exist? Why did we end up like this?” Part of the problem is a “respect gap,” she said, pointing to a study on the tendency of women to use the formal title of “doctor” when introducing male colleagues, whereas men who introduce women use that title less than half the time.

The COVID-19 pandemic has only made these disparities worse. Women are responsible for childcare much more frequently than men, Dr. Burden said, although the pandemic has brought caregiving duties to the forefront.

Dr. Spilseth said mentoring can help women navigate the workplace so as to help overcome these disparities. At Regions, the mentoring program is robust.

“Even before a new hire steps foot in the hospital, we have established them with a mentor,” she said. Sponsoring – the “ability of someone with political capital to use it to help colleagues” – can also help boost women’s careers, she said.

Her hospital also has a Women in Medicine Cooperative, which provides a way for women to talk about common struggles and to network.

Flexible work opportunities – working in transitional care units, being a physician advisor, and doing research – can all help boost a career as well, Dr. Spilseth said.

She said that at the University of Colorado, leaders set out to reach salary equity in a year and a half – and “it was a painful, painful process.” They found that different people held different beliefs about how people were paid, which led to a lot of unnecessary stress as they tried to construct a fairer system.

“On the back end of having done that, while it was a rough year and half, it has saved so much time – and I think built a culture of trust and transparency,” she said.

Recruiting in a more thoughtful way can also have a big impact, Dr. Spilseth said. The manner in which people are told about opportunities could exclude people without intending to.

“Are you casting a wide net?” she asked.

Adia Ross, MD, MHA, chief medical officer at Duke Regional Hospital, Durham, N.C., said that even in the face of obvious disparities, women can take steps on their own to boost their careers. She encouraged taking on “stretch assignments,” a project or task that is a bit beyond one’s current comfort level or level of experience or knowledge. “It can be a little scary, and sometimes there are bumps along the way,” she said.

All of these measures, though incremental, are the way to make bigger change, she said. “We want to take small steps but big strides forward.”

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

Advance care planning (ACP) is a process that supports adults at any age or stage of health in understanding and sharing their personal values, life goals, and preferences for future medical care, according to Meredith A. MacMartin, MD, director of inpatient palliative care at the Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

ACP “is really about planning for care in advance,” and in many ways, the inpatient setting is uniquely suited to this process, Dr. MacMartin said in a presentation at SHM Converge 2021, the annual conference of the Society of Hospital Medicine. “The key part is the advance part. You want conversations to happen before the care is actually needed,” she said.

Dr. MacMartin emphasized the importance of distinguishing between ACP and advance directives (ADs). ACP is a process, whereas ADs are documentation, “ideally of the content of advance care planning discussions,” she explained. ACP involves discussion about what is important to the patients, their goals, what information is helpful for them, and whether their current care is aligned with their goals, Dr. MacMartin said. ADs might involve a designated power of attorney for health care, a living will, and, in some states, specific clinician-signed orders regarding resuscitation or transport to hospital.

ACP is “more than whether a patient wants CPR [cardiopulmonary resuscitation] or not,” said Dr. MacMartin. ACP matters because it helps ensure that the care a patient receives aligns with the patient’s wishes and values, she said. ACP increases the likelihood that patients will die in their preferred locations, it allows them to discuss their wishes and prepare for decline, and it relieves family members of the burden of decision making, she said. From a hospital perspective, data show that use of an ACP can decrease intensive care unit (ICU) utilization and overall health care costs. “Often, when people are given the opportunity to express their wishes, they get less unnecessary care,” Dr. MacMartin noted.

Although ACP often takes place in an outpatient setting, hospitalists are in a unique position to conduct some ACP conversations with their patients, Dr. MacMartin said. “Hospitalists are available” and are physically present at least once a day, so there is a pragmatic advantage. Also, some data suggest that patients may feel more comfortable having ACP conversations with a hospitalist than with a primary care provider with whom they have a long-standing relationship, Dr. MacMartin added.

Another important advantage of ACP in the hospital setting is that, “as hospitalists, you are the expert on inpatient illness; you know what sick looks like, and you have a unique perspective on prognostication that may be harder to recreate in the outpatient setting,” Dr. MacMartin said.
 

Barriers to ACP include patient identification, logistics, attitudes

Settings in which ACP is appropriate include those in which a patient is undergoing “sentinel hospitalization,” meaning that the patient is at a transition point in the disease course. Examples are a patient newly diagnosed with metastatic solid cancer, a patient with progressive chronic kidney disease who is considering hemodialysis, or a patient who receives treatment in the ICU for longer than 7 days, Dr. MacMartin said.

Guidelines for identifying patients who might benefit from ACP include the use of the “surprise question” (“would you be surprised if this patient dies in the next year?”) as well as functional status assessments using tools such as the Australia-modified Karnofsky Performance Status or the Eastern Cooperative Oncology Group score, said Dr. MacMartin. Some studies suggest that any hospitalized patient older than 65 years should have an ACP discussion, she added.

Time pressure remains a significant barrier to ACP conversations. Some strategies to overcome this problem include enlisting help from other specialists, particularly social workers, Dr. MacMartin said. Social workers report a higher comfort level for talking to patients about death than any other medical specialty; “this is something they want to be doing,” she said. Also, the possibility of reimbursement may act as a buffer to create more time to have ACP conversations with patients, she noted.

Addressing clinicians’ discomfort with ACP conversations can be “a tougher nut to crack,” Dr. MacMartin acknowledged. Clinicians report that they don’t want to cause their patients distress, and some report that having conversations about end-of-life care is distressing for them as well. Some of these barriers can be overcome with skills training, including use of a prepared guideline or framework to help increase the comfort level for both clinicians and patients, said Dr. MacMartin.
 

A look ahead: Training strategies and COVID-19 impact

“For hospitalists interested in developing their ACP skills, I highly recommend two resources,” Dr. MacMartin said in an interview. “The Serious Illness Conversation Guide, from Ariadne Labs, is an excellent tool for any clinician to guide discussion about a patient’s goals and values,” she said.

“For clinicians wanting to build or improve their communication, including advance care planning discussions but also topics like responding to patient’s emotions, VitalTalk training offers a deeper dive into core communications skills,” she added.

“If your hospital has a palliative care team, they may also have more local resources available to you. To learn more about billing for ACP discussions, I recommend starting with your institutional billing and coding group, as these practices vary some between practices, and they will be able to provide the best guidance for clinicians. These are new codes that aren’t yet being very widely used so it’s a chance to innovate,” Dr. MacMartin noted.

“The hospital setting is an opportunity for patients to reflect on their health, both present and in the future, with a physician who has expertise in acute illness and prognostication and who is available for discussion on a daily basis during the hospitalization,” Dr. MacMartin emphasized.

As for whether the COVID-19 pandemic has affected ACP in the inpatient setting, the data are limited, but more information is forthcoming, Dr. MacMartin said. “In my personal experience and in talking to colleagues elsewhere, the pandemic has highlighted the need for ACP in some ways, as we have tried to ensure that people who wouldn’t want things like intensive care are identified early,” she said. “I hope that some of the workflows developed to identify patients who should get ACP in the hospital stay in practice and are strengthened over time,” she added.

Dr. MacMartin has disclosed no relevant financial relationships.
 

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

Advance care planning (ACP) is a process that supports adults at any age or stage of health in understanding and sharing their personal values, life goals, and preferences for future medical care, according to Meredith A. MacMartin, MD, director of inpatient palliative care at the Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

ACP “is really about planning for care in advance,” and in many ways, the inpatient setting is uniquely suited to this process, Dr. MacMartin said in a presentation at SHM Converge 2021, the annual conference of the Society of Hospital Medicine. “The key part is the advance part. You want conversations to happen before the care is actually needed,” she said.

Dr. MacMartin emphasized the importance of distinguishing between ACP and advance directives (ADs). ACP is a process, whereas ADs are documentation, “ideally of the content of advance care planning discussions,” she explained. ACP involves discussion about what is important to the patients, their goals, what information is helpful for them, and whether their current care is aligned with their goals, Dr. MacMartin said. ADs might involve a designated power of attorney for health care, a living will, and, in some states, specific clinician-signed orders regarding resuscitation or transport to hospital.

ACP is “more than whether a patient wants CPR [cardiopulmonary resuscitation] or not,” said Dr. MacMartin. ACP matters because it helps ensure that the care a patient receives aligns with the patient’s wishes and values, she said. ACP increases the likelihood that patients will die in their preferred locations, it allows them to discuss their wishes and prepare for decline, and it relieves family members of the burden of decision making, she said. From a hospital perspective, data show that use of an ACP can decrease intensive care unit (ICU) utilization and overall health care costs. “Often, when people are given the opportunity to express their wishes, they get less unnecessary care,” Dr. MacMartin noted.

Although ACP often takes place in an outpatient setting, hospitalists are in a unique position to conduct some ACP conversations with their patients, Dr. MacMartin said. “Hospitalists are available” and are physically present at least once a day, so there is a pragmatic advantage. Also, some data suggest that patients may feel more comfortable having ACP conversations with a hospitalist than with a primary care provider with whom they have a long-standing relationship, Dr. MacMartin added.

Another important advantage of ACP in the hospital setting is that, “as hospitalists, you are the expert on inpatient illness; you know what sick looks like, and you have a unique perspective on prognostication that may be harder to recreate in the outpatient setting,” Dr. MacMartin said.
 

Barriers to ACP include patient identification, logistics, attitudes

Settings in which ACP is appropriate include those in which a patient is undergoing “sentinel hospitalization,” meaning that the patient is at a transition point in the disease course. Examples are a patient newly diagnosed with metastatic solid cancer, a patient with progressive chronic kidney disease who is considering hemodialysis, or a patient who receives treatment in the ICU for longer than 7 days, Dr. MacMartin said.

Guidelines for identifying patients who might benefit from ACP include the use of the “surprise question” (“would you be surprised if this patient dies in the next year?”) as well as functional status assessments using tools such as the Australia-modified Karnofsky Performance Status or the Eastern Cooperative Oncology Group score, said Dr. MacMartin. Some studies suggest that any hospitalized patient older than 65 years should have an ACP discussion, she added.

Time pressure remains a significant barrier to ACP conversations. Some strategies to overcome this problem include enlisting help from other specialists, particularly social workers, Dr. MacMartin said. Social workers report a higher comfort level for talking to patients about death than any other medical specialty; “this is something they want to be doing,” she said. Also, the possibility of reimbursement may act as a buffer to create more time to have ACP conversations with patients, she noted.

Addressing clinicians’ discomfort with ACP conversations can be “a tougher nut to crack,” Dr. MacMartin acknowledged. Clinicians report that they don’t want to cause their patients distress, and some report that having conversations about end-of-life care is distressing for them as well. Some of these barriers can be overcome with skills training, including use of a prepared guideline or framework to help increase the comfort level for both clinicians and patients, said Dr. MacMartin.
 

A look ahead: Training strategies and COVID-19 impact

“For hospitalists interested in developing their ACP skills, I highly recommend two resources,” Dr. MacMartin said in an interview. “The Serious Illness Conversation Guide, from Ariadne Labs, is an excellent tool for any clinician to guide discussion about a patient’s goals and values,” she said.

“For clinicians wanting to build or improve their communication, including advance care planning discussions but also topics like responding to patient’s emotions, VitalTalk training offers a deeper dive into core communications skills,” she added.

“If your hospital has a palliative care team, they may also have more local resources available to you. To learn more about billing for ACP discussions, I recommend starting with your institutional billing and coding group, as these practices vary some between practices, and they will be able to provide the best guidance for clinicians. These are new codes that aren’t yet being very widely used so it’s a chance to innovate,” Dr. MacMartin noted.

“The hospital setting is an opportunity for patients to reflect on their health, both present and in the future, with a physician who has expertise in acute illness and prognostication and who is available for discussion on a daily basis during the hospitalization,” Dr. MacMartin emphasized.

As for whether the COVID-19 pandemic has affected ACP in the inpatient setting, the data are limited, but more information is forthcoming, Dr. MacMartin said. “In my personal experience and in talking to colleagues elsewhere, the pandemic has highlighted the need for ACP in some ways, as we have tried to ensure that people who wouldn’t want things like intensive care are identified early,” she said. “I hope that some of the workflows developed to identify patients who should get ACP in the hospital stay in practice and are strengthened over time,” she added.

Dr. MacMartin has disclosed no relevant financial relationships.
 

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

Advance care planning (ACP) is a process that supports adults at any age or stage of health in understanding and sharing their personal values, life goals, and preferences for future medical care, according to Meredith A. MacMartin, MD, director of inpatient palliative care at the Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

ACP “is really about planning for care in advance,” and in many ways, the inpatient setting is uniquely suited to this process, Dr. MacMartin said in a presentation at SHM Converge 2021, the annual conference of the Society of Hospital Medicine. “The key part is the advance part. You want conversations to happen before the care is actually needed,” she said.

Dr. MacMartin emphasized the importance of distinguishing between ACP and advance directives (ADs). ACP is a process, whereas ADs are documentation, “ideally of the content of advance care planning discussions,” she explained. ACP involves discussion about what is important to the patients, their goals, what information is helpful for them, and whether their current care is aligned with their goals, Dr. MacMartin said. ADs might involve a designated power of attorney for health care, a living will, and, in some states, specific clinician-signed orders regarding resuscitation or transport to hospital.

ACP is “more than whether a patient wants CPR [cardiopulmonary resuscitation] or not,” said Dr. MacMartin. ACP matters because it helps ensure that the care a patient receives aligns with the patient’s wishes and values, she said. ACP increases the likelihood that patients will die in their preferred locations, it allows them to discuss their wishes and prepare for decline, and it relieves family members of the burden of decision making, she said. From a hospital perspective, data show that use of an ACP can decrease intensive care unit (ICU) utilization and overall health care costs. “Often, when people are given the opportunity to express their wishes, they get less unnecessary care,” Dr. MacMartin noted.

Although ACP often takes place in an outpatient setting, hospitalists are in a unique position to conduct some ACP conversations with their patients, Dr. MacMartin said. “Hospitalists are available” and are physically present at least once a day, so there is a pragmatic advantage. Also, some data suggest that patients may feel more comfortable having ACP conversations with a hospitalist than with a primary care provider with whom they have a long-standing relationship, Dr. MacMartin added.

Another important advantage of ACP in the hospital setting is that, “as hospitalists, you are the expert on inpatient illness; you know what sick looks like, and you have a unique perspective on prognostication that may be harder to recreate in the outpatient setting,” Dr. MacMartin said.
 

Barriers to ACP include patient identification, logistics, attitudes

Settings in which ACP is appropriate include those in which a patient is undergoing “sentinel hospitalization,” meaning that the patient is at a transition point in the disease course. Examples are a patient newly diagnosed with metastatic solid cancer, a patient with progressive chronic kidney disease who is considering hemodialysis, or a patient who receives treatment in the ICU for longer than 7 days, Dr. MacMartin said.

Guidelines for identifying patients who might benefit from ACP include the use of the “surprise question” (“would you be surprised if this patient dies in the next year?”) as well as functional status assessments using tools such as the Australia-modified Karnofsky Performance Status or the Eastern Cooperative Oncology Group score, said Dr. MacMartin. Some studies suggest that any hospitalized patient older than 65 years should have an ACP discussion, she added.

Time pressure remains a significant barrier to ACP conversations. Some strategies to overcome this problem include enlisting help from other specialists, particularly social workers, Dr. MacMartin said. Social workers report a higher comfort level for talking to patients about death than any other medical specialty; “this is something they want to be doing,” she said. Also, the possibility of reimbursement may act as a buffer to create more time to have ACP conversations with patients, she noted.

Addressing clinicians’ discomfort with ACP conversations can be “a tougher nut to crack,” Dr. MacMartin acknowledged. Clinicians report that they don’t want to cause their patients distress, and some report that having conversations about end-of-life care is distressing for them as well. Some of these barriers can be overcome with skills training, including use of a prepared guideline or framework to help increase the comfort level for both clinicians and patients, said Dr. MacMartin.
 

A look ahead: Training strategies and COVID-19 impact

“For hospitalists interested in developing their ACP skills, I highly recommend two resources,” Dr. MacMartin said in an interview. “The Serious Illness Conversation Guide, from Ariadne Labs, is an excellent tool for any clinician to guide discussion about a patient’s goals and values,” she said.

“For clinicians wanting to build or improve their communication, including advance care planning discussions but also topics like responding to patient’s emotions, VitalTalk training offers a deeper dive into core communications skills,” she added.

“If your hospital has a palliative care team, they may also have more local resources available to you. To learn more about billing for ACP discussions, I recommend starting with your institutional billing and coding group, as these practices vary some between practices, and they will be able to provide the best guidance for clinicians. These are new codes that aren’t yet being very widely used so it’s a chance to innovate,” Dr. MacMartin noted.

“The hospital setting is an opportunity for patients to reflect on their health, both present and in the future, with a physician who has expertise in acute illness and prognostication and who is available for discussion on a daily basis during the hospitalization,” Dr. MacMartin emphasized.

As for whether the COVID-19 pandemic has affected ACP in the inpatient setting, the data are limited, but more information is forthcoming, Dr. MacMartin said. “In my personal experience and in talking to colleagues elsewhere, the pandemic has highlighted the need for ACP in some ways, as we have tried to ensure that people who wouldn’t want things like intensive care are identified early,” she said. “I hope that some of the workflows developed to identify patients who should get ACP in the hospital stay in practice and are strengthened over time,” she added.

Dr. MacMartin has disclosed no relevant financial relationships.
 

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

Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose. 

Now the Centers for Disease Control and Prevention has published the first comprehensive guide to the diagnosis and treatment of botulism. The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in  Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.

In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.

Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”

While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.

Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
 

Diagnosis

Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.

Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).

Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.

Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.

With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.

Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”

It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.

Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
 

Treatment

Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.

Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.

While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.

Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.

Dr. Stone is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research,” the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.

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

Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose. 

Now the Centers for Disease Control and Prevention has published the first comprehensive guide to the diagnosis and treatment of botulism. The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in  Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.

In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.

Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”

While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.

Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
 

Diagnosis

Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.

Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).

Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.

Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.

With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.

Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”

It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.

Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
 

Treatment

Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.

Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.

While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.

Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.

Dr. Stone is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research,” the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.

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

Botulinum toxin is said to be the most lethal substance known. Inhaling just 1-3 nanograms of toxin per kilogram of body mass constitutes a lethal dose. 

Now the Centers for Disease Control and Prevention has published the first comprehensive guide to the diagnosis and treatment of botulism. The CDC has been working on these guidelines since 2015, initially establishing a technical development group and steering committee to prioritize topics for review and make recommendations. Since then, the agency published 15 systematic reviews in  Clinical Infectious Diseases early in 2018. The reviews addressed the recognition of botulism clinically, treatment with botulinum antitoxin, and complications from that treatment. They also looked at the epidemiology of botulism outbreaks and botulism in the special populations of vulnerable pediatric and pregnant patients.

In 2016, the CDC held two extended forums and convened a workshop with 72 experts. In addition to the more standard topics of diagnosis and treatment, attention was given to crisis standards of care, caring for multiple patients at once, and ethical considerations in management.

Amesh Adalja, MD, senior scholar, Johns Hopkins Center for Health Security, Baltimore, said in an interview that the new guidance “was really specific [and] was meant to address the gap in guidance for mass casualty settings.”

While clinicians are used to focusing on an individual patient, in times of crises, with multiple patients from a food-borne outbreak or a bioterrorism attack, the focus must shift to the population rather than the individual. The workshop explored issues of triaging, adding beds, and caring for patients when a hospital is overwhelmed with an acute influx of severely ill patients.

Such a mass casualty event is similar to the stress encountered this past year with COVID-19 patients swamping the hospitals, which had too little oxygen, too few ventilators, and too few staff members to care for the sudden influx of critically ill patients.
 

Diagnosis

Leslie Edwards, MHS, BSN, a CDC epidemiologist and botulism expert, said that “botulism is rare and [so] could be difficult to diagnose.” The CDC “wanted to highlight some of those key clinical factors” to speed recognition.

Hospitals and health officials are being urged to develop crisis protocols as part of emergency preparedness plans. And clinicians should be able to recognize four major syndromes: botulism from food, wounds, and inhalation, as well as iatrogenic botulism (from exposure via injection of the neurotoxin).

Botulism has a characteristic and unusual pattern of symptoms, which begin with cranial nerve palsies. Then there is typically a descending, symmetric flaccid paralysis. Symptoms might progress to respiratory failure and death. Other critical clues that implicate botulism include a lack of sensory deficits and the absence of pain.

Symptoms are most likely to be mistaken for myasthenia gravis or Guillain-Barré syndrome, but the latter has an ascending paralysis. Cranial nerve involvement can present as blurred vision, ptosis (drooping lid), diplopia (double vision), ophthalmoplegia (weak eye muscles), or difficulty with speech and swallowing. Shortness of breath and abdominal discomfort can also occur. Respiratory failure may occur from weakness or paralysis of cranial nerves. Cranial nerve signs and symptoms in the absence of fever, along with a descending paralysis, should strongly suggest the diagnosis.

With food-borne botulism, vomiting occurs in half the patients. Improperly sterilized home-canned food is the major risk factor. While the toxin is rapidly destroyed by heat, the bacterial spores are not. Wound botulism is most commonly associated with the injection of drugs, particularly black tar heroin.

Dr. Edwards stressed that “time is of the essence when it comes to botulism diagnostics and treating. Timely administration of the botulism antitoxin early in the course of illness can arrest the progression of paralysis and possibly avert the need for intubation or ventilation.”

It’s essential to note that botulism is an urgent diagnosis that has to be made on clinical grounds. Lab assays for botulinum neurotoxins take too long and are only conducted in public health laboratories. The decision to use antitoxin must not be delayed to wait for confirmation.

Clinicians should immediately contact the local or state health department’s emergency on-call team if botulism is suspected. They will arrange for expert consultation.
 

Treatment

Botulinum antitoxin is the only specific therapy for this infection. If given early – preferably within 24-48 hours of symptom onset – it can stop the progression of paralysis. But antitoxin will not reverse existing paralysis. If paralysis is still progressing outside of that 24- to 48-hour window, the antitoxin should still provide benefit. The antitoxin is available only through state health departments and a request to the CDC.

Botulism antitoxin is made from horse serum and therefore may cause a variety of allergic reactions. The risk for anaphylaxis is less than 2%, far lower than the mortality from untreated botulism.

While these guidelines have an important focus on triaging and treating mass casualties from botulism, it’s important to note that food-borne outbreaks and prevention issues are covered elsewhere on the CDC site.

Dr. Edwards has disclosed no relevant financial relationships. Dr. Adalja is a consultant for Emergent BioSolutions, which makes the heptavalent botulism antitoxin.

Dr. Stone is an infectious disease specialist and author of “Resilience: One Family’s Story of Hope and Triumph Over Evil” and of “Conducting Clinical Research,” the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone.

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

Myocarditis is present in a small percentage of competitive athletes after COVID-19 infection, even in those without symptoms, new research suggests.

In a cohort study of 1,597 competitive collegiate athletes undergoing comprehensive cardiovascular testing in the United States, the prevalence of clinical myocarditis based on a symptom-based screening strategy was only 0.31%.

But screening with cardiac MRI increased the prevalence of clinical and subclinical myocarditis by a factor of 7.4, to 2.3%, the authors reported.

The findings are published online May 27, 2021, in JAMA Cardiology.

“It was the largest study to evaluate college athletes who have had COVID with extensive cardiac testing, including MRI, and this gave us a very objective look at the cardiac findings, as they were not purely based upon a subjective evaluation of symptoms,” lead investigator Curt J. Daniels, MD, professor at Ohio State University Wexner Medical Center, Columbus, said in an interview.

“Unfortunately, our study showed that athletes can be asymptomatic, or at least not report symptoms. This is a very subjective feature, and we don’t know if they don’t report symptoms because they didn’t want to get tested. That is why we took a very objective approach,” Dr. Daniels said.

The finding that more than half of the asymptomatic athletes had myocarditis, or as the investigators called it, “subclinical myocarditis,” was a surprise, he acknowledged.

“More than half of the athletes found to have myocarditis reported no symptoms, and yes, that was a surprise, because prior to this study, the protocols that had been published stated that you had to have symptoms to even enter into the protocol for cardiac MRI. But, as our ... paper shows, if we had followed that protocol, we only would have found about 5 cases of myocarditis, as opposed to the total of 37 we found with cardiac MRI,” Dr. Daniels said.

In October 2020, the American College of Cardiology’s Sports and Exercise Council recommended that cardiac MRI be limited to athletes who exhibited symptoms as part of their guide to ensuring a safe return to play.

As reported by this news organization the council recommended a tiered approach to screening based on the presence of symptoms, followed by electrocardiography, injury biomarkers, and echocardiography. Any abnormalities detected were to be further characterized by the selective use of cardiac MRI.

At the time, there were relatively few data to support the recommendations, and all stakeholders called for larger datasets to better drive informed recommendations in the future.

In the current study, Dr. Daniels and associates conducted comprehensive cardiac screening – including ECG, troponin testing, echocardiography, and cardiac MRI – of 1,597 college athlete survivors of COVID-19.

The athletes were part of the Big Ten athletic conference, which consists of 13 major American universities.

AlexLMX/Getty Images

Cardiac MRI revealed that 37 (2.3%) of these athletes demonstrated diagnostic criteria for COVID-19 myocarditis; of these, 20 had no cardiovascular symptoms and had normal ECGs, echocardiography, and troponin test results.

“These patients would not have been identified without CMR imaging. If we were going according to the older protocol, we would not have made this discovery. Cardiac MRI is the most sensitive and specific test for myocardial inflammation, there is no argument about that,” Dr. Daniels said.

The catch is, cardiac MRI is expensive and often difficult to access, especially in remote, rural, or other underserviced areas.

“You can’t get an MRI for every person who has had COVID, it’s just not feasible,” Dr. Daniels said. “We are not advocating that everybody get an MRI. But we do hope that our study creates awareness among clinicians and athletes themselves that if you’ve had COVID, even if you’re asymptomatic, there may be some heart changes. So be aware when you start to exercise again, if you have any symptoms, pause and seek medical care.”
 

Kudos to the sports cardiology community

In an accompanying editorial, James E. Udelson, MD, Ethan J. Rowin, MD, and Barry J. Maron, MD, from the CardioVascular Center at Tufts Medical Center, Boston, applauded the sports cardiology community for its diligence in acquiring and publishing data about the post–COVID-19 prevalence of cardiac abnormalities in competitive athletes.

“It is a real tribute to the sports cardiology community. There has been an amazing growth of information, and they not only gathered this information, they analyzed and published it, starting out with a study of 29 or 30 athletes, and now thousands,” Dr. Udelson said in an interview.

At the start of the pandemic, it appeared that 15%-20% of athletes had myocarditis, and athletic conferences were discussing canceling sports events.

However, with greater numbers comes a more accurate picture of the extent of the problem.

“Once you get thousands of subjects in these studies, you can hone in on what the real number is, so now we understand that if you screen everybody with a cardiac MRI, 1%, 2%, or 3% will have some evidence of what looks like myocarditis,” he said.

Dr. Udelson agreed that doing cardiac imaging in everyone is not feasible.

“This study looked at a very large number of people who all had an MRI, but that doesn’t mean everyone should have them. If you just do an echo, an EKG, and a troponin test, and if everything is normal, which is kind of what current recommendations are, this paper tells us that we are going to miss one or two people out of a hundred, and that might be okay,” he said. “So, if you are at a huge university that has a large medical center and you want to screen all your athletes with MRI, great. But if you’re at a high school in a remote area, you know that the alternative, not having an MRI, isn’t so bad, either.”

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

Myocarditis is present in a small percentage of competitive athletes after COVID-19 infection, even in those without symptoms, new research suggests.

In a cohort study of 1,597 competitive collegiate athletes undergoing comprehensive cardiovascular testing in the United States, the prevalence of clinical myocarditis based on a symptom-based screening strategy was only 0.31%.

But screening with cardiac MRI increased the prevalence of clinical and subclinical myocarditis by a factor of 7.4, to 2.3%, the authors reported.

The findings are published online May 27, 2021, in JAMA Cardiology.

“It was the largest study to evaluate college athletes who have had COVID with extensive cardiac testing, including MRI, and this gave us a very objective look at the cardiac findings, as they were not purely based upon a subjective evaluation of symptoms,” lead investigator Curt J. Daniels, MD, professor at Ohio State University Wexner Medical Center, Columbus, said in an interview.

“Unfortunately, our study showed that athletes can be asymptomatic, or at least not report symptoms. This is a very subjective feature, and we don’t know if they don’t report symptoms because they didn’t want to get tested. That is why we took a very objective approach,” Dr. Daniels said.

The finding that more than half of the asymptomatic athletes had myocarditis, or as the investigators called it, “subclinical myocarditis,” was a surprise, he acknowledged.

“More than half of the athletes found to have myocarditis reported no symptoms, and yes, that was a surprise, because prior to this study, the protocols that had been published stated that you had to have symptoms to even enter into the protocol for cardiac MRI. But, as our ... paper shows, if we had followed that protocol, we only would have found about 5 cases of myocarditis, as opposed to the total of 37 we found with cardiac MRI,” Dr. Daniels said.

In October 2020, the American College of Cardiology’s Sports and Exercise Council recommended that cardiac MRI be limited to athletes who exhibited symptoms as part of their guide to ensuring a safe return to play.

As reported by this news organization the council recommended a tiered approach to screening based on the presence of symptoms, followed by electrocardiography, injury biomarkers, and echocardiography. Any abnormalities detected were to be further characterized by the selective use of cardiac MRI.

At the time, there were relatively few data to support the recommendations, and all stakeholders called for larger datasets to better drive informed recommendations in the future.

In the current study, Dr. Daniels and associates conducted comprehensive cardiac screening – including ECG, troponin testing, echocardiography, and cardiac MRI – of 1,597 college athlete survivors of COVID-19.

The athletes were part of the Big Ten athletic conference, which consists of 13 major American universities.

AlexLMX/Getty Images

Cardiac MRI revealed that 37 (2.3%) of these athletes demonstrated diagnostic criteria for COVID-19 myocarditis; of these, 20 had no cardiovascular symptoms and had normal ECGs, echocardiography, and troponin test results.

“These patients would not have been identified without CMR imaging. If we were going according to the older protocol, we would not have made this discovery. Cardiac MRI is the most sensitive and specific test for myocardial inflammation, there is no argument about that,” Dr. Daniels said.

The catch is, cardiac MRI is expensive and often difficult to access, especially in remote, rural, or other underserviced areas.

“You can’t get an MRI for every person who has had COVID, it’s just not feasible,” Dr. Daniels said. “We are not advocating that everybody get an MRI. But we do hope that our study creates awareness among clinicians and athletes themselves that if you’ve had COVID, even if you’re asymptomatic, there may be some heart changes. So be aware when you start to exercise again, if you have any symptoms, pause and seek medical care.”
 

Kudos to the sports cardiology community

In an accompanying editorial, James E. Udelson, MD, Ethan J. Rowin, MD, and Barry J. Maron, MD, from the CardioVascular Center at Tufts Medical Center, Boston, applauded the sports cardiology community for its diligence in acquiring and publishing data about the post–COVID-19 prevalence of cardiac abnormalities in competitive athletes.

“It is a real tribute to the sports cardiology community. There has been an amazing growth of information, and they not only gathered this information, they analyzed and published it, starting out with a study of 29 or 30 athletes, and now thousands,” Dr. Udelson said in an interview.

At the start of the pandemic, it appeared that 15%-20% of athletes had myocarditis, and athletic conferences were discussing canceling sports events.

However, with greater numbers comes a more accurate picture of the extent of the problem.

“Once you get thousands of subjects in these studies, you can hone in on what the real number is, so now we understand that if you screen everybody with a cardiac MRI, 1%, 2%, or 3% will have some evidence of what looks like myocarditis,” he said.

Dr. Udelson agreed that doing cardiac imaging in everyone is not feasible.

“This study looked at a very large number of people who all had an MRI, but that doesn’t mean everyone should have them. If you just do an echo, an EKG, and a troponin test, and if everything is normal, which is kind of what current recommendations are, this paper tells us that we are going to miss one or two people out of a hundred, and that might be okay,” he said. “So, if you are at a huge university that has a large medical center and you want to screen all your athletes with MRI, great. But if you’re at a high school in a remote area, you know that the alternative, not having an MRI, isn’t so bad, either.”

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

Myocarditis is present in a small percentage of competitive athletes after COVID-19 infection, even in those without symptoms, new research suggests.

In a cohort study of 1,597 competitive collegiate athletes undergoing comprehensive cardiovascular testing in the United States, the prevalence of clinical myocarditis based on a symptom-based screening strategy was only 0.31%.

But screening with cardiac MRI increased the prevalence of clinical and subclinical myocarditis by a factor of 7.4, to 2.3%, the authors reported.

The findings are published online May 27, 2021, in JAMA Cardiology.

“It was the largest study to evaluate college athletes who have had COVID with extensive cardiac testing, including MRI, and this gave us a very objective look at the cardiac findings, as they were not purely based upon a subjective evaluation of symptoms,” lead investigator Curt J. Daniels, MD, professor at Ohio State University Wexner Medical Center, Columbus, said in an interview.

“Unfortunately, our study showed that athletes can be asymptomatic, or at least not report symptoms. This is a very subjective feature, and we don’t know if they don’t report symptoms because they didn’t want to get tested. That is why we took a very objective approach,” Dr. Daniels said.

The finding that more than half of the asymptomatic athletes had myocarditis, or as the investigators called it, “subclinical myocarditis,” was a surprise, he acknowledged.

“More than half of the athletes found to have myocarditis reported no symptoms, and yes, that was a surprise, because prior to this study, the protocols that had been published stated that you had to have symptoms to even enter into the protocol for cardiac MRI. But, as our ... paper shows, if we had followed that protocol, we only would have found about 5 cases of myocarditis, as opposed to the total of 37 we found with cardiac MRI,” Dr. Daniels said.

In October 2020, the American College of Cardiology’s Sports and Exercise Council recommended that cardiac MRI be limited to athletes who exhibited symptoms as part of their guide to ensuring a safe return to play.

As reported by this news organization the council recommended a tiered approach to screening based on the presence of symptoms, followed by electrocardiography, injury biomarkers, and echocardiography. Any abnormalities detected were to be further characterized by the selective use of cardiac MRI.

At the time, there were relatively few data to support the recommendations, and all stakeholders called for larger datasets to better drive informed recommendations in the future.

In the current study, Dr. Daniels and associates conducted comprehensive cardiac screening – including ECG, troponin testing, echocardiography, and cardiac MRI – of 1,597 college athlete survivors of COVID-19.

The athletes were part of the Big Ten athletic conference, which consists of 13 major American universities.

AlexLMX/Getty Images

Cardiac MRI revealed that 37 (2.3%) of these athletes demonstrated diagnostic criteria for COVID-19 myocarditis; of these, 20 had no cardiovascular symptoms and had normal ECGs, echocardiography, and troponin test results.

“These patients would not have been identified without CMR imaging. If we were going according to the older protocol, we would not have made this discovery. Cardiac MRI is the most sensitive and specific test for myocardial inflammation, there is no argument about that,” Dr. Daniels said.

The catch is, cardiac MRI is expensive and often difficult to access, especially in remote, rural, or other underserviced areas.

“You can’t get an MRI for every person who has had COVID, it’s just not feasible,” Dr. Daniels said. “We are not advocating that everybody get an MRI. But we do hope that our study creates awareness among clinicians and athletes themselves that if you’ve had COVID, even if you’re asymptomatic, there may be some heart changes. So be aware when you start to exercise again, if you have any symptoms, pause and seek medical care.”
 

Kudos to the sports cardiology community

In an accompanying editorial, James E. Udelson, MD, Ethan J. Rowin, MD, and Barry J. Maron, MD, from the CardioVascular Center at Tufts Medical Center, Boston, applauded the sports cardiology community for its diligence in acquiring and publishing data about the post–COVID-19 prevalence of cardiac abnormalities in competitive athletes.

“It is a real tribute to the sports cardiology community. There has been an amazing growth of information, and they not only gathered this information, they analyzed and published it, starting out with a study of 29 or 30 athletes, and now thousands,” Dr. Udelson said in an interview.

At the start of the pandemic, it appeared that 15%-20% of athletes had myocarditis, and athletic conferences were discussing canceling sports events.

However, with greater numbers comes a more accurate picture of the extent of the problem.

“Once you get thousands of subjects in these studies, you can hone in on what the real number is, so now we understand that if you screen everybody with a cardiac MRI, 1%, 2%, or 3% will have some evidence of what looks like myocarditis,” he said.

Dr. Udelson agreed that doing cardiac imaging in everyone is not feasible.

“This study looked at a very large number of people who all had an MRI, but that doesn’t mean everyone should have them. If you just do an echo, an EKG, and a troponin test, and if everything is normal, which is kind of what current recommendations are, this paper tells us that we are going to miss one or two people out of a hundred, and that might be okay,” he said. “So, if you are at a huge university that has a large medical center and you want to screen all your athletes with MRI, great. But if you’re at a high school in a remote area, you know that the alternative, not having an MRI, isn’t so bad, either.”

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

Background: For patients receiving palliative care who develop respiratory distress, conventional oxygen therapy may not adequately relieve symptoms of dyspnea, and noninvasive ventilation may not promote comfort. Few randomized controlled trials have investigated the use of high-flow nasal cannula (HFNC) for treatment of palliative care patients who present to the hospital with respiratory distress.

Dr. Halford is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: For patients receiving palliative care who develop respiratory distress, conventional oxygen therapy may not adequately relieve symptoms of dyspnea, and noninvasive ventilation may not promote comfort. Few randomized controlled trials have investigated the use of high-flow nasal cannula (HFNC) for treatment of palliative care patients who present to the hospital with respiratory distress.

Dr. Halford is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: For patients receiving palliative care who develop respiratory distress, conventional oxygen therapy may not adequately relieve symptoms of dyspnea, and noninvasive ventilation may not promote comfort. Few randomized controlled trials have investigated the use of high-flow nasal cannula (HFNC) for treatment of palliative care patients who present to the hospital with respiratory distress.

Dr. Halford is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

The respiratory therapists at Mount Sinai Beth Israel, New York, know when Lina Miyakawa, MD, starts a week in the ICU, because she turns down the fraction of inspired oxygen (FiO₂) levels if patients tolerate it.

“Hyperoxia in mechanical ventilation is a topic that’s near and dear to my heart,” Dr. Miyakawa, a pulmonary and critical care medicine specialist at Mount Sinai Beth Israel, said during SHM Converge, the annual conference of the Society of Hospital Medicine. “You can always find ‘wean down FiO₂’ in my consult notes.”

While it is believed that humans have built up evolutionary defenses against hypoxia but not against hyperoxia, medical literature on the topic of hyperoxia with supplemental oxygen is fairly young. “In medical school we were taught to give oxygen for anybody with chest pain and concern about acute coronary syndrome,” she said. “This was until recent data suggested harm from liberal oxygen use.”

In a single-center trial of 434 critical care patients with an ICU length of stay of 72 hours or longer, Italian researchers examined the effects of a conservative protocol for oxygen therapy versus conventional therapy on ICU mortality (JAMA. 2016;316[15]:1583-9). The trial was stopped because the patients who were assigned to receive conservative therapy had a significantly lower mortality than the ones who received usual care (P = .01). “The study was not perfect, and the premature stoppage likely exaggerated the effect size,” said Dr. Miyakawa, who was not affiliated with the trial. “However, subsequent retrospective studies continue to support a benefit with conservative oxygen use, especially in different groups of patients. One of note is hyperoxia following cardiac arrest. There’s something called a two-hit model that speaks to worsening ischemia with reperfusion injury after the initial hypoxic event from the cardiac arrest itself” (See Intensive Care Med. 2015;41:534-6).

In a multicenter cohort study that drew from the Project IMPACT critical care database of ICUs at 120 U.S. hospitals between 2001 and 2005, researchers led by J. Hope Kilgannon, MD, tested the hypothesis that post-resuscitation hyperoxia is associated with increased in-hospital mortality (JAMA. 2010;303[21]:2165-71). The study population consisted of 6,326 patients who were divided into three groups: the hypoxic group (a PaO₂ of less than 60 mm Hg); the normoxic group (a PaO₂ of 60-299 mm Hg), and the hyperoxic group (a PaO₂ of over 300 mm Hg). The mortality for the hyperoxic group was 63%, the hypoxic group at 57%, and the normoxic group at 45%.

More recently, the ICU-ROX Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group evaluated conservative versus liberal approaches in providing oxygen to 965 patients who were mechanically ventilated between 2015 and 2018 at 21 ICUs (N Eng J Med. 2020;382:989-98). Of the 965 patients, 484 were randomly assigned to the conservative oxygen group (defined as an SpO₂ of 97% or lower) and 481 were assigned to the usual oxygen group (defined as having no specific measures limiting FiO₂ or the SpO₂). The primary outcome was the number of ventilator-free days from randomization until day 28, while the secondary outcome was mortality at 180 days. The researchers also performed a subgroup analysis of patients at risk for hypoxic-ischemic encephalopathy.

No significant differences were observed in the number of ventilator days between the two group (a median of 21 days in the conservative oxygen group versus 22 days in the usual oxygen group, respectively; P = .80) nor in mortality at 180 days (35.7% vs. 34.5%). However, in the subgroup analysis, patients with hypoxic-ischemic encephalopathy were noted to have more ventilator-free days (21 vs. 0 days), improved 180-day mortality (43% vs. 59%), and less functional impairment (55% vs. 68%) in the conservative-oxygen group.

“The results of this study suggest that conservative oxygen therapy has no additional advantage over standard oxygen therapy, but there may be benefits in those vulnerable to hyperoxia, which warrants further investigation,” Dr. Miyakawa said. “There are a few points to note on this topic. First, many of the previous studies had more liberal oxygen strategies than the ones used in this study, which could be the reason why we are seeing these results. In addition, O₂ titration relies on imperfect approximations. PaO₂ cannot be measured continuously; we really depend on the SpO₂ on a minute-by-minute basis. Critically ill patients can also undergo episodes of hypoperfusion and shock state minute-by-minute. That’s when they’re at risk for hypoxemia. This would not be captured continuously with just O₂ saturations.”

Dr. Miyakawa also highlighted the Liberal Oxygenation versus Conservative Oxygenation in Acute Respiratory Distress Syndrome trial (LOCO₂) a prospective, multicenter, randomized, open-label trial involving patients with ARDS. It was carried out at 13 ICUs in France between June 2016 and September 2018 in an effort determine whether conservative oxygenation would reduce mortality at 28 days compared with the usual liberal-oxygen strategy (N Eng J Med. 2020;382:999-1008). The researchers detected a signal of increased mortality in the conservative oxygen group (34% vs. 27%), which led to a premature stoppage of the trial. “I’d like to postulate that the higher incidence of proning in the liberal oxygenation group compared to the conservative oxygen group (51% to 34%) may be the reason for the difference in mortality,” said Dr. Miyakawa, who was not affiliated with LOCO₂. “This is supported from the 2013 PROSEVA Study Group, which reported that prone positioning in ARDS significantly decreases 28- and 90-day mortality” (see N Engl J Med. 2013; 368:2159-68).

She said that future trials on this topic “will have to address how a particular [oxygenation] target is both set and achieved in each group of patients, particularly those with specific organ injuries. In the meantime, in my opinion, avoiding excess oxygen seems sensible.”

Dr. Miyakawa reported having no financial disclosures.

The respiratory therapists at Mount Sinai Beth Israel, New York, know when Lina Miyakawa, MD, starts a week in the ICU, because she turns down the fraction of inspired oxygen (FiO₂) levels if patients tolerate it.

“Hyperoxia in mechanical ventilation is a topic that’s near and dear to my heart,” Dr. Miyakawa, a pulmonary and critical care medicine specialist at Mount Sinai Beth Israel, said during SHM Converge, the annual conference of the Society of Hospital Medicine. “You can always find ‘wean down FiO₂’ in my consult notes.”

While it is believed that humans have built up evolutionary defenses against hypoxia but not against hyperoxia, medical literature on the topic of hyperoxia with supplemental oxygen is fairly young. “In medical school we were taught to give oxygen for anybody with chest pain and concern about acute coronary syndrome,” she said. “This was until recent data suggested harm from liberal oxygen use.”

In a single-center trial of 434 critical care patients with an ICU length of stay of 72 hours or longer, Italian researchers examined the effects of a conservative protocol for oxygen therapy versus conventional therapy on ICU mortality (JAMA. 2016;316[15]:1583-9). The trial was stopped because the patients who were assigned to receive conservative therapy had a significantly lower mortality than the ones who received usual care (P = .01). “The study was not perfect, and the premature stoppage likely exaggerated the effect size,” said Dr. Miyakawa, who was not affiliated with the trial. “However, subsequent retrospective studies continue to support a benefit with conservative oxygen use, especially in different groups of patients. One of note is hyperoxia following cardiac arrest. There’s something called a two-hit model that speaks to worsening ischemia with reperfusion injury after the initial hypoxic event from the cardiac arrest itself” (See Intensive Care Med. 2015;41:534-6).

In a multicenter cohort study that drew from the Project IMPACT critical care database of ICUs at 120 U.S. hospitals between 2001 and 2005, researchers led by J. Hope Kilgannon, MD, tested the hypothesis that post-resuscitation hyperoxia is associated with increased in-hospital mortality (JAMA. 2010;303[21]:2165-71). The study population consisted of 6,326 patients who were divided into three groups: the hypoxic group (a PaO₂ of less than 60 mm Hg); the normoxic group (a PaO₂ of 60-299 mm Hg), and the hyperoxic group (a PaO₂ of over 300 mm Hg). The mortality for the hyperoxic group was 63%, the hypoxic group at 57%, and the normoxic group at 45%.

More recently, the ICU-ROX Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group evaluated conservative versus liberal approaches in providing oxygen to 965 patients who were mechanically ventilated between 2015 and 2018 at 21 ICUs (N Eng J Med. 2020;382:989-98). Of the 965 patients, 484 were randomly assigned to the conservative oxygen group (defined as an SpO₂ of 97% or lower) and 481 were assigned to the usual oxygen group (defined as having no specific measures limiting FiO₂ or the SpO₂). The primary outcome was the number of ventilator-free days from randomization until day 28, while the secondary outcome was mortality at 180 days. The researchers also performed a subgroup analysis of patients at risk for hypoxic-ischemic encephalopathy.

No significant differences were observed in the number of ventilator days between the two group (a median of 21 days in the conservative oxygen group versus 22 days in the usual oxygen group, respectively; P = .80) nor in mortality at 180 days (35.7% vs. 34.5%). However, in the subgroup analysis, patients with hypoxic-ischemic encephalopathy were noted to have more ventilator-free days (21 vs. 0 days), improved 180-day mortality (43% vs. 59%), and less functional impairment (55% vs. 68%) in the conservative-oxygen group.

“The results of this study suggest that conservative oxygen therapy has no additional advantage over standard oxygen therapy, but there may be benefits in those vulnerable to hyperoxia, which warrants further investigation,” Dr. Miyakawa said. “There are a few points to note on this topic. First, many of the previous studies had more liberal oxygen strategies than the ones used in this study, which could be the reason why we are seeing these results. In addition, O₂ titration relies on imperfect approximations. PaO₂ cannot be measured continuously; we really depend on the SpO₂ on a minute-by-minute basis. Critically ill patients can also undergo episodes of hypoperfusion and shock state minute-by-minute. That’s when they’re at risk for hypoxemia. This would not be captured continuously with just O₂ saturations.”

Dr. Miyakawa also highlighted the Liberal Oxygenation versus Conservative Oxygenation in Acute Respiratory Distress Syndrome trial (LOCO₂) a prospective, multicenter, randomized, open-label trial involving patients with ARDS. It was carried out at 13 ICUs in France between June 2016 and September 2018 in an effort determine whether conservative oxygenation would reduce mortality at 28 days compared with the usual liberal-oxygen strategy (N Eng J Med. 2020;382:999-1008). The researchers detected a signal of increased mortality in the conservative oxygen group (34% vs. 27%), which led to a premature stoppage of the trial. “I’d like to postulate that the higher incidence of proning in the liberal oxygenation group compared to the conservative oxygen group (51% to 34%) may be the reason for the difference in mortality,” said Dr. Miyakawa, who was not affiliated with LOCO₂. “This is supported from the 2013 PROSEVA Study Group, which reported that prone positioning in ARDS significantly decreases 28- and 90-day mortality” (see N Engl J Med. 2013; 368:2159-68).

She said that future trials on this topic “will have to address how a particular [oxygenation] target is both set and achieved in each group of patients, particularly those with specific organ injuries. In the meantime, in my opinion, avoiding excess oxygen seems sensible.”

Dr. Miyakawa reported having no financial disclosures.

The respiratory therapists at Mount Sinai Beth Israel, New York, know when Lina Miyakawa, MD, starts a week in the ICU, because she turns down the fraction of inspired oxygen (FiO₂) levels if patients tolerate it.

“Hyperoxia in mechanical ventilation is a topic that’s near and dear to my heart,” Dr. Miyakawa, a pulmonary and critical care medicine specialist at Mount Sinai Beth Israel, said during SHM Converge, the annual conference of the Society of Hospital Medicine. “You can always find ‘wean down FiO₂’ in my consult notes.”

While it is believed that humans have built up evolutionary defenses against hypoxia but not against hyperoxia, medical literature on the topic of hyperoxia with supplemental oxygen is fairly young. “In medical school we were taught to give oxygen for anybody with chest pain and concern about acute coronary syndrome,” she said. “This was until recent data suggested harm from liberal oxygen use.”

In a single-center trial of 434 critical care patients with an ICU length of stay of 72 hours or longer, Italian researchers examined the effects of a conservative protocol for oxygen therapy versus conventional therapy on ICU mortality (JAMA. 2016;316[15]:1583-9). The trial was stopped because the patients who were assigned to receive conservative therapy had a significantly lower mortality than the ones who received usual care (P = .01). “The study was not perfect, and the premature stoppage likely exaggerated the effect size,” said Dr. Miyakawa, who was not affiliated with the trial. “However, subsequent retrospective studies continue to support a benefit with conservative oxygen use, especially in different groups of patients. One of note is hyperoxia following cardiac arrest. There’s something called a two-hit model that speaks to worsening ischemia with reperfusion injury after the initial hypoxic event from the cardiac arrest itself” (See Intensive Care Med. 2015;41:534-6).

In a multicenter cohort study that drew from the Project IMPACT critical care database of ICUs at 120 U.S. hospitals between 2001 and 2005, researchers led by J. Hope Kilgannon, MD, tested the hypothesis that post-resuscitation hyperoxia is associated with increased in-hospital mortality (JAMA. 2010;303[21]:2165-71). The study population consisted of 6,326 patients who were divided into three groups: the hypoxic group (a PaO₂ of less than 60 mm Hg); the normoxic group (a PaO₂ of 60-299 mm Hg), and the hyperoxic group (a PaO₂ of over 300 mm Hg). The mortality for the hyperoxic group was 63%, the hypoxic group at 57%, and the normoxic group at 45%.

More recently, the ICU-ROX Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group evaluated conservative versus liberal approaches in providing oxygen to 965 patients who were mechanically ventilated between 2015 and 2018 at 21 ICUs (N Eng J Med. 2020;382:989-98). Of the 965 patients, 484 were randomly assigned to the conservative oxygen group (defined as an SpO₂ of 97% or lower) and 481 were assigned to the usual oxygen group (defined as having no specific measures limiting FiO₂ or the SpO₂). The primary outcome was the number of ventilator-free days from randomization until day 28, while the secondary outcome was mortality at 180 days. The researchers also performed a subgroup analysis of patients at risk for hypoxic-ischemic encephalopathy.

No significant differences were observed in the number of ventilator days between the two group (a median of 21 days in the conservative oxygen group versus 22 days in the usual oxygen group, respectively; P = .80) nor in mortality at 180 days (35.7% vs. 34.5%). However, in the subgroup analysis, patients with hypoxic-ischemic encephalopathy were noted to have more ventilator-free days (21 vs. 0 days), improved 180-day mortality (43% vs. 59%), and less functional impairment (55% vs. 68%) in the conservative-oxygen group.

“The results of this study suggest that conservative oxygen therapy has no additional advantage over standard oxygen therapy, but there may be benefits in those vulnerable to hyperoxia, which warrants further investigation,” Dr. Miyakawa said. “There are a few points to note on this topic. First, many of the previous studies had more liberal oxygen strategies than the ones used in this study, which could be the reason why we are seeing these results. In addition, O₂ titration relies on imperfect approximations. PaO₂ cannot be measured continuously; we really depend on the SpO₂ on a minute-by-minute basis. Critically ill patients can also undergo episodes of hypoperfusion and shock state minute-by-minute. That’s when they’re at risk for hypoxemia. This would not be captured continuously with just O₂ saturations.”

Dr. Miyakawa also highlighted the Liberal Oxygenation versus Conservative Oxygenation in Acute Respiratory Distress Syndrome trial (LOCO₂) a prospective, multicenter, randomized, open-label trial involving patients with ARDS. It was carried out at 13 ICUs in France between June 2016 and September 2018 in an effort determine whether conservative oxygenation would reduce mortality at 28 days compared with the usual liberal-oxygen strategy (N Eng J Med. 2020;382:999-1008). The researchers detected a signal of increased mortality in the conservative oxygen group (34% vs. 27%), which led to a premature stoppage of the trial. “I’d like to postulate that the higher incidence of proning in the liberal oxygenation group compared to the conservative oxygen group (51% to 34%) may be the reason for the difference in mortality,” said Dr. Miyakawa, who was not affiliated with LOCO₂. “This is supported from the 2013 PROSEVA Study Group, which reported that prone positioning in ARDS significantly decreases 28- and 90-day mortality” (see N Engl J Med. 2013; 368:2159-68).

She said that future trials on this topic “will have to address how a particular [oxygenation] target is both set and achieved in each group of patients, particularly those with specific organ injuries. In the meantime, in my opinion, avoiding excess oxygen seems sensible.”

Dr. Miyakawa reported having no financial disclosures.

The COVID-19 pandemic has been difficult for all hospitalists, especially those who are parents of young children. For hospitalist moms who are also immigrants working on temporary H1-B visas, this stress is exacerbated. Though each story is unique, the underlying themes are the same: Worries over visa renewals, the immigration process, family members back home, and the risk of illness, job loss, and deportation.

Supporting the family

Like all health care workers, Prasanna Palabindela, MD, a hospitalist at Jennie Stuart Health in Hopkinsville, Ky., has been worried about bringing COVID-19 home to her family, especially in the beginning. Her in-laws had just arrived from India for a visit in March 2020 when the pandemic began, everything was shut down, and her in-laws were forced to settle in for an unexpected months-long stay.

Along with her elderly in-laws, who also have chronic conditions, Dr. Palabindela had two small children to worry about – a then-5-month-old daughter and a 5-year-old son. “I was more worried about them than me,” she said. “I used to take showers before coming home and just do all precautions as much as I can. I’m glad that I did not bring COVID, so far, to the family.”

Once she could safely send her in-laws back to India, Dr. Palabindela began searching for a nanny. Daycare was out of the question because she didn’t want her children to be exposed to illness. After a long search, she found a nanny who could also help her son with virtual school. “It’s expensive, but still, my family and my family’s health is my priority,” she said.

Working on visas has caused multiple issues for Dr. Palabindela and her husband. After living in different states because of their jobs, her husband joined her in West Virginia for her residency and found a job there. When Dr. Palabindela took her current position, her husband had to quit his job in West Virginia and move with her to Kentucky for them to stay together. Unfortunately, he couldn’t find a good fit for work in Kentucky, so the couple decided to put him on her visa so they wouldn’t have to live apart.

Now Dr. Palabindela is the family’s sole breadwinner. “That means if something happens to me, I always worry what’s going to happen with my family because legally, my husband cannot work. Technically, everyone is deported back to home,” she said. Not being able to work is hard for her husband too. “It’s just so much stress in the family because he worked for 11 years,” said Dr. Palabindela.

Through all the upheavals, Dr. Palabindela has had support from all sides. Her husband has been the biggest source. “He’s my backbone. Every time, he supported me in each and every aspect,” she said. Her parents and her brothers check in on her constantly to make sure she’s staying safe. Even the chief at her hospital has played a significant role, going to bat for his physicians to ensure their safety.

Dr. Palabindela credits everyone who works with COVID-19 patients as heroes. “The nurses, the physicians, the housekeeping, respiratory therapist, speech therapist, physical therapy ... everybody has a role. Everybody is a hero,” she said. “Whoever is wearing a mask is a hero, too, because they are contributing to this community.”
 

Advocating for immigration reform

A lack of transparency and information in the beginning of the pandemic significantly contributed to anxiety, said Anuradha Amara, MD, MBBS, a hospitalist in Wilmington, Del. She felt that what was on the news and what was actually going on in the hospitals were quite different. Colleagues were getting sick, there wasn’t enough personal protective equipment, and planning went out the window. “It’s like a meteor hitting a place and then we start dealing with the aftermath, but we weren’t ready before,” Dr. Amara said. “We didn’t have a plan for a pandemic.”

Then there was the concern of either her or her husband, a cardiologist, getting sick and potentially losing their jobs and immigration status. “How am I going to go back to my country if I had to? What will happen to my family if I die? If I go on the ventilator? Those are the insecurities we found additional to the pandemic challenges we had,” Dr. Amara said.

Not being able to go see their family in India or have them come visit was difficult – “it was pretty bad up there,” said Dr. Amara. Fortunately, her family members in India remained safe, but there’s a very real uneasiness about returning should an emergency arise. “Should I go back and then take the risk of losing my job and losing my position and my kids are here, they’re going to school here. How do you decide that?” she asked.

One of the worst effects of her visa restrictions was not being able to help in New York when hospitals were so short-staffed, and the morgues were overflowing. “New York is 3 hours away from where I live, but I was in chains. I couldn’t help them because of these visa restrictions,” Dr. Amara said. During the emergency, the state allowed physicians from other states to practice without being licensed in New York, but immigrant physicians were not included. “Even if we wanted to, we couldn’t volunteer,” said Dr. Amara. “I have family in New York, and I was really worried. Out of compassion I wanted to help, but I couldn’t do anything.”

Before the pandemic, Dr. Amara joined in advocacy efforts for immigrant physicians through Physicians for American Healthcare Access (PAHA). “In uncertain times, like COVID, it gets worse that you’re challenged with everything on top of your health, your family, and you have to be worried about deportation,” she said. “We need to strengthen legislation. Nobody should suffer with immigration processes during an active pandemic or otherwise.”

In the United States, 28% of physicians are immigrants. Dr. Amara pointed out that these physicians go through years of expensive training with extensive background checks at every level, yet they’re classified as second preference (EB-2) workers. She believes that physicians as a group should be excluded from this category and allowed to automatically become citizens after 5 years of living in the United States and working in an underserved area.

There have been an estimated 15,000 unused green cards since 2005. And if Congress went back to 1992, there could be more than 220,000 previously unused green cards recaptured. These unused green cards are the basis behind bills H.R.2255 and S.1024, the Healthcare Workforce Resiliency Act, which has been championed by SHM and PAHA. “It will allow the frontline physicians, 15,000 of them, and 25,000 nurses, to obtain their permanent residency,” said Dr. Amara. “These are people who already applied for their permanent residencies and they’re still waiting.”

SHM has consistently advocated for the Act since it was first introduced, written multiple letters on the issue, and supported it both on and off Capitol Hill. The society says the legislation would be an “important first step toward addressing a critical shortage” in the U.S. health care system by “recognizing the vital role immigrant physicians and nurses are playing in the fight against COVID-19.”

Currently, SHM has a live action alert open for the reintroduced bill, and encourages members to contact their legislators and urge them to support the reintroduction of the Act by cosponsoring and working to pass the legislation

Dr. Amara encourages physicians to start engaging in advocacy efforts early. Though she didn’t begin participating until late in her career, she said being aware of and part of policies that affect medicine is important. If more physicians get involved, “there are so many things we can take care of,” said Dr. Amara. “The medical profession doesn’t have to be so difficult and so busy. There are ways we can make it better and I believe that. And obviously I’ll continue to work and advocate for the entire medical profession, their problems, their health and well-being, to prevent burnout.”
 

Making time for positivity and self-care

Sandhya Tagaram, MD, a hospitalist at UMass Memorial Medical Center in Worcester, Mass., and her husband, also a hospitalist physician, had only ever read about pandemics in books. They certainly never expected to be in the middle of one. “That was a totally different level of anxiety to work as frontline physicians with two kids under 5 years and families away back home in India,” she said.

UMass Memorial Medical Center

Dr. Tagaram and her husband work opposite shifts so that one of them is always home with their two young children. “Our schedules became more challenging when the pandemic started. Between both of our schedules and with minimal childcare facilities, we managed to strike a decent work-family balance, although we experience less vacation time together. We are fortunate to have an understanding work group,” said Dr. Tagaram.

Even before COVID-19, Dr. Tagaram found working on the temporary work visa challenging. “I think the pandemic has exposed the layer of uncertainty associated with it,” she said. “It’s incredibly stressful to imagine any minor turbulence that could alter our family and work lives. As a frontline physician mom, I take pride in raising my kids and taking care of my patients. We want to serve our communities and at the same time secure our families.”

Not being able to visit family back home and travel is exceedingly difficult. Dr. Tagaram said it would be helpful if there was a separate permanent residence pathway for physicians because they play a critical role in public health and they have been an integral part of the COVID-19 pandemic response team. A separate pathway could help keep their families secure and enable them to give their best to their communities.

Amid all the anxiety, Dr. Tagaram said she and her husband realized they could not keep living with so much pressure. As parents and as physicians, they did not want their stress to leak out and affect their ability and commitment to care for their children or their patients. They decided they needed to figure out how to be positive and constructive.

“We try some daily fun activities with the kids after returning home from work,” said Dr. Tagaram. They also formed a bubble group with two other physician families so the children could interact safely. She said that it’s critical that physicians take time for themselves. “We have to cultivate a serious hobby that helps to rejuvenate and calm our busy minds,” said Dr. Tagaram.

She makes time every day to exercise and to read at least a few pages from a good book. She is also learning Carnatic music along with one of her daughters. And every month since March 2020, she has journaled about her work and what she learned so her daughters can read it someday. “These things keep me jazzed up,” she said.

The pandemic has highlighted the fact that we are all part of one global community. “Although we hail from different backgrounds, we learned that we do have some common goals of being kind and supportive to each other and to give back to our communities. Hopefully we will continue this spirit,” said Dr. Tagaram. As a physician mother, “I feel it’s a privilege and honor to take care of my family and my community.”
 

Soldiering on in the COVID-19 war

The uncertainty everyone felt at the beginning of the pandemic was “very, very scary,” said Mamtha Balla, MD, MPH, a hospitalist and clinical assistant professor in northwest Ohio. “Initially, I was so involved in it and I felt like it was like a war, a COVID-19 war, and we are soldiers in that and trying to protect and do whatever we can.”

She and her husband, a geriatrician also working on an H-1B visa, have worked hard not to bring the virus home to their 2-year-old daughter. Going into 2021, the past 2 years have been “the most hectic and emotionally draining – and physically exhausting – years of my life,” said Dr. Balla.

The COVID-19 vaccine has helped reduce some pressure, but Dr. Balla is still concerned about the high risk to health care workers and the new COVID-19 strains coming out. “We are really not sure what we are dealing with and how the COVID will calm,” she said. “It is pretty challenging being a health care worker because not only are you responsible for your patients at the end of the day, but you are also responsible for your families.”

Initially in the United States from India on a student visa in 2008, Dr. Balla was placed on an H-1B visa when she started her residency. It was during this time that her mother was diagnosed with cancer and went through surgeries and chemotherapy. “She was pretty ill,” recalled Dr. Balla.

Despite the situation, Dr. Balla was afraid to go stay with her mother in case her visa application was rejected, and she couldn’t complete her third year of education. “I opted not to go to India at that time because I did not want to take a chance,” Dr. Balla said. “I have tears in my eyes because those are not easy moments, to withhold from seeing your parents, or to be in any other emergency where you cannot travel. That especially puts us at a higher risk emotionally and physically.”

She has not seen her parents in 2½ years. Between the very real possibility of not being able to get her visa stamp and the unpredictability of how other countries are dealing with COVID-19, Dr. Balla feels it is impossible to even think of going to visit. “Even if I go, what if something happens where my visa gets stuck, or the visa office is not open?” she said. If she could not get back to the United States as planned, she would have patients left behind here.

Recently, Dr. Balla did travel to India and her passport stamp did not come on time, so her husband had to come back to the United States by himself. She had to wait for her stamp for a couple more weeks before she could leave and, in the meantime, had to make arrangements at her hospital. “It is so much trauma,” she said.

There’s also the worry she has about getting sick or disabled and not being able to work anymore, resulting in deportation. “Is that what we are doing for people who are working like soldiers? Are we really treating them the correct way?” Dr. Balla asked.

Dr. Balla considers all health care workers to be soldiers in the COVID-19 war. As such, she believes the government should step up to make sure they are supporting and helping these immigrant physician-soldiers who are so necessary. She applauds France’s recent decision to grant citizenship to its frontline immigrant health care workers and feels that the same should be done in the United States. She filed her green card application in 2012, but she is nowhere close to getting it. (The backlog for employment-based green cards is more than 900,000 now.)

As people putting their own and their family’s lives at risk to care for patients with COVID-19, Dr. Balla and her husband have talked about moving to another country or even back to India. “I am a taxpayer; I am a good human being working for the community and for the job. This is my 13th year here. If I am not eligible [for citizenship] still, then I am not sure what else I have to do to prove myself,” she said. “I am owning United States citizens as my people, so please own us and help us out in this difficult scenario.”

The COVID-19 pandemic has been difficult for all hospitalists, especially those who are parents of young children. For hospitalist moms who are also immigrants working on temporary H1-B visas, this stress is exacerbated. Though each story is unique, the underlying themes are the same: Worries over visa renewals, the immigration process, family members back home, and the risk of illness, job loss, and deportation.

Supporting the family

Like all health care workers, Prasanna Palabindela, MD, a hospitalist at Jennie Stuart Health in Hopkinsville, Ky., has been worried about bringing COVID-19 home to her family, especially in the beginning. Her in-laws had just arrived from India for a visit in March 2020 when the pandemic began, everything was shut down, and her in-laws were forced to settle in for an unexpected months-long stay.

Along with her elderly in-laws, who also have chronic conditions, Dr. Palabindela had two small children to worry about – a then-5-month-old daughter and a 5-year-old son. “I was more worried about them than me,” she said. “I used to take showers before coming home and just do all precautions as much as I can. I’m glad that I did not bring COVID, so far, to the family.”

Once she could safely send her in-laws back to India, Dr. Palabindela began searching for a nanny. Daycare was out of the question because she didn’t want her children to be exposed to illness. After a long search, she found a nanny who could also help her son with virtual school. “It’s expensive, but still, my family and my family’s health is my priority,” she said.

Working on visas has caused multiple issues for Dr. Palabindela and her husband. After living in different states because of their jobs, her husband joined her in West Virginia for her residency and found a job there. When Dr. Palabindela took her current position, her husband had to quit his job in West Virginia and move with her to Kentucky for them to stay together. Unfortunately, he couldn’t find a good fit for work in Kentucky, so the couple decided to put him on her visa so they wouldn’t have to live apart.

Now Dr. Palabindela is the family’s sole breadwinner. “That means if something happens to me, I always worry what’s going to happen with my family because legally, my husband cannot work. Technically, everyone is deported back to home,” she said. Not being able to work is hard for her husband too. “It’s just so much stress in the family because he worked for 11 years,” said Dr. Palabindela.

Through all the upheavals, Dr. Palabindela has had support from all sides. Her husband has been the biggest source. “He’s my backbone. Every time, he supported me in each and every aspect,” she said. Her parents and her brothers check in on her constantly to make sure she’s staying safe. Even the chief at her hospital has played a significant role, going to bat for his physicians to ensure their safety.

Dr. Palabindela credits everyone who works with COVID-19 patients as heroes. “The nurses, the physicians, the housekeeping, respiratory therapist, speech therapist, physical therapy ... everybody has a role. Everybody is a hero,” she said. “Whoever is wearing a mask is a hero, too, because they are contributing to this community.”
 

Advocating for immigration reform

A lack of transparency and information in the beginning of the pandemic significantly contributed to anxiety, said Anuradha Amara, MD, MBBS, a hospitalist in Wilmington, Del. She felt that what was on the news and what was actually going on in the hospitals were quite different. Colleagues were getting sick, there wasn’t enough personal protective equipment, and planning went out the window. “It’s like a meteor hitting a place and then we start dealing with the aftermath, but we weren’t ready before,” Dr. Amara said. “We didn’t have a plan for a pandemic.”

Then there was the concern of either her or her husband, a cardiologist, getting sick and potentially losing their jobs and immigration status. “How am I going to go back to my country if I had to? What will happen to my family if I die? If I go on the ventilator? Those are the insecurities we found additional to the pandemic challenges we had,” Dr. Amara said.

Not being able to go see their family in India or have them come visit was difficult – “it was pretty bad up there,” said Dr. Amara. Fortunately, her family members in India remained safe, but there’s a very real uneasiness about returning should an emergency arise. “Should I go back and then take the risk of losing my job and losing my position and my kids are here, they’re going to school here. How do you decide that?” she asked.

One of the worst effects of her visa restrictions was not being able to help in New York when hospitals were so short-staffed, and the morgues were overflowing. “New York is 3 hours away from where I live, but I was in chains. I couldn’t help them because of these visa restrictions,” Dr. Amara said. During the emergency, the state allowed physicians from other states to practice without being licensed in New York, but immigrant physicians were not included. “Even if we wanted to, we couldn’t volunteer,” said Dr. Amara. “I have family in New York, and I was really worried. Out of compassion I wanted to help, but I couldn’t do anything.”

Before the pandemic, Dr. Amara joined in advocacy efforts for immigrant physicians through Physicians for American Healthcare Access (PAHA). “In uncertain times, like COVID, it gets worse that you’re challenged with everything on top of your health, your family, and you have to be worried about deportation,” she said. “We need to strengthen legislation. Nobody should suffer with immigration processes during an active pandemic or otherwise.”

In the United States, 28% of physicians are immigrants. Dr. Amara pointed out that these physicians go through years of expensive training with extensive background checks at every level, yet they’re classified as second preference (EB-2) workers. She believes that physicians as a group should be excluded from this category and allowed to automatically become citizens after 5 years of living in the United States and working in an underserved area.

There have been an estimated 15,000 unused green cards since 2005. And if Congress went back to 1992, there could be more than 220,000 previously unused green cards recaptured. These unused green cards are the basis behind bills H.R.2255 and S.1024, the Healthcare Workforce Resiliency Act, which has been championed by SHM and PAHA. “It will allow the frontline physicians, 15,000 of them, and 25,000 nurses, to obtain their permanent residency,” said Dr. Amara. “These are people who already applied for their permanent residencies and they’re still waiting.”

SHM has consistently advocated for the Act since it was first introduced, written multiple letters on the issue, and supported it both on and off Capitol Hill. The society says the legislation would be an “important first step toward addressing a critical shortage” in the U.S. health care system by “recognizing the vital role immigrant physicians and nurses are playing in the fight against COVID-19.”

Currently, SHM has a live action alert open for the reintroduced bill, and encourages members to contact their legislators and urge them to support the reintroduction of the Act by cosponsoring and working to pass the legislation

Dr. Amara encourages physicians to start engaging in advocacy efforts early. Though she didn’t begin participating until late in her career, she said being aware of and part of policies that affect medicine is important. If more physicians get involved, “there are so many things we can take care of,” said Dr. Amara. “The medical profession doesn’t have to be so difficult and so busy. There are ways we can make it better and I believe that. And obviously I’ll continue to work and advocate for the entire medical profession, their problems, their health and well-being, to prevent burnout.”
 

Making time for positivity and self-care

Sandhya Tagaram, MD, a hospitalist at UMass Memorial Medical Center in Worcester, Mass., and her husband, also a hospitalist physician, had only ever read about pandemics in books. They certainly never expected to be in the middle of one. “That was a totally different level of anxiety to work as frontline physicians with two kids under 5 years and families away back home in India,” she said.

UMass Memorial Medical Center

Dr. Tagaram and her husband work opposite shifts so that one of them is always home with their two young children. “Our schedules became more challenging when the pandemic started. Between both of our schedules and with minimal childcare facilities, we managed to strike a decent work-family balance, although we experience less vacation time together. We are fortunate to have an understanding work group,” said Dr. Tagaram.

Even before COVID-19, Dr. Tagaram found working on the temporary work visa challenging. “I think the pandemic has exposed the layer of uncertainty associated with it,” she said. “It’s incredibly stressful to imagine any minor turbulence that could alter our family and work lives. As a frontline physician mom, I take pride in raising my kids and taking care of my patients. We want to serve our communities and at the same time secure our families.”

Not being able to visit family back home and travel is exceedingly difficult. Dr. Tagaram said it would be helpful if there was a separate permanent residence pathway for physicians because they play a critical role in public health and they have been an integral part of the COVID-19 pandemic response team. A separate pathway could help keep their families secure and enable them to give their best to their communities.

Amid all the anxiety, Dr. Tagaram said she and her husband realized they could not keep living with so much pressure. As parents and as physicians, they did not want their stress to leak out and affect their ability and commitment to care for their children or their patients. They decided they needed to figure out how to be positive and constructive.

“We try some daily fun activities with the kids after returning home from work,” said Dr. Tagaram. They also formed a bubble group with two other physician families so the children could interact safely. She said that it’s critical that physicians take time for themselves. “We have to cultivate a serious hobby that helps to rejuvenate and calm our busy minds,” said Dr. Tagaram.

She makes time every day to exercise and to read at least a few pages from a good book. She is also learning Carnatic music along with one of her daughters. And every month since March 2020, she has journaled about her work and what she learned so her daughters can read it someday. “These things keep me jazzed up,” she said.

The pandemic has highlighted the fact that we are all part of one global community. “Although we hail from different backgrounds, we learned that we do have some common goals of being kind and supportive to each other and to give back to our communities. Hopefully we will continue this spirit,” said Dr. Tagaram. As a physician mother, “I feel it’s a privilege and honor to take care of my family and my community.”
 

Soldiering on in the COVID-19 war

The uncertainty everyone felt at the beginning of the pandemic was “very, very scary,” said Mamtha Balla, MD, MPH, a hospitalist and clinical assistant professor in northwest Ohio. “Initially, I was so involved in it and I felt like it was like a war, a COVID-19 war, and we are soldiers in that and trying to protect and do whatever we can.”

She and her husband, a geriatrician also working on an H-1B visa, have worked hard not to bring the virus home to their 2-year-old daughter. Going into 2021, the past 2 years have been “the most hectic and emotionally draining – and physically exhausting – years of my life,” said Dr. Balla.

The COVID-19 vaccine has helped reduce some pressure, but Dr. Balla is still concerned about the high risk to health care workers and the new COVID-19 strains coming out. “We are really not sure what we are dealing with and how the COVID will calm,” she said. “It is pretty challenging being a health care worker because not only are you responsible for your patients at the end of the day, but you are also responsible for your families.”

Initially in the United States from India on a student visa in 2008, Dr. Balla was placed on an H-1B visa when she started her residency. It was during this time that her mother was diagnosed with cancer and went through surgeries and chemotherapy. “She was pretty ill,” recalled Dr. Balla.

Despite the situation, Dr. Balla was afraid to go stay with her mother in case her visa application was rejected, and she couldn’t complete her third year of education. “I opted not to go to India at that time because I did not want to take a chance,” Dr. Balla said. “I have tears in my eyes because those are not easy moments, to withhold from seeing your parents, or to be in any other emergency where you cannot travel. That especially puts us at a higher risk emotionally and physically.”

She has not seen her parents in 2½ years. Between the very real possibility of not being able to get her visa stamp and the unpredictability of how other countries are dealing with COVID-19, Dr. Balla feels it is impossible to even think of going to visit. “Even if I go, what if something happens where my visa gets stuck, or the visa office is not open?” she said. If she could not get back to the United States as planned, she would have patients left behind here.

Recently, Dr. Balla did travel to India and her passport stamp did not come on time, so her husband had to come back to the United States by himself. She had to wait for her stamp for a couple more weeks before she could leave and, in the meantime, had to make arrangements at her hospital. “It is so much trauma,” she said.

There’s also the worry she has about getting sick or disabled and not being able to work anymore, resulting in deportation. “Is that what we are doing for people who are working like soldiers? Are we really treating them the correct way?” Dr. Balla asked.

Dr. Balla considers all health care workers to be soldiers in the COVID-19 war. As such, she believes the government should step up to make sure they are supporting and helping these immigrant physician-soldiers who are so necessary. She applauds France’s recent decision to grant citizenship to its frontline immigrant health care workers and feels that the same should be done in the United States. She filed her green card application in 2012, but she is nowhere close to getting it. (The backlog for employment-based green cards is more than 900,000 now.)

As people putting their own and their family’s lives at risk to care for patients with COVID-19, Dr. Balla and her husband have talked about moving to another country or even back to India. “I am a taxpayer; I am a good human being working for the community and for the job. This is my 13th year here. If I am not eligible [for citizenship] still, then I am not sure what else I have to do to prove myself,” she said. “I am owning United States citizens as my people, so please own us and help us out in this difficult scenario.”

The COVID-19 pandemic has been difficult for all hospitalists, especially those who are parents of young children. For hospitalist moms who are also immigrants working on temporary H1-B visas, this stress is exacerbated. Though each story is unique, the underlying themes are the same: Worries over visa renewals, the immigration process, family members back home, and the risk of illness, job loss, and deportation.

Supporting the family

Like all health care workers, Prasanna Palabindela, MD, a hospitalist at Jennie Stuart Health in Hopkinsville, Ky., has been worried about bringing COVID-19 home to her family, especially in the beginning. Her in-laws had just arrived from India for a visit in March 2020 when the pandemic began, everything was shut down, and her in-laws were forced to settle in for an unexpected months-long stay.

Along with her elderly in-laws, who also have chronic conditions, Dr. Palabindela had two small children to worry about – a then-5-month-old daughter and a 5-year-old son. “I was more worried about them than me,” she said. “I used to take showers before coming home and just do all precautions as much as I can. I’m glad that I did not bring COVID, so far, to the family.”

Once she could safely send her in-laws back to India, Dr. Palabindela began searching for a nanny. Daycare was out of the question because she didn’t want her children to be exposed to illness. After a long search, she found a nanny who could also help her son with virtual school. “It’s expensive, but still, my family and my family’s health is my priority,” she said.

Working on visas has caused multiple issues for Dr. Palabindela and her husband. After living in different states because of their jobs, her husband joined her in West Virginia for her residency and found a job there. When Dr. Palabindela took her current position, her husband had to quit his job in West Virginia and move with her to Kentucky for them to stay together. Unfortunately, he couldn’t find a good fit for work in Kentucky, so the couple decided to put him on her visa so they wouldn’t have to live apart.

Now Dr. Palabindela is the family’s sole breadwinner. “That means if something happens to me, I always worry what’s going to happen with my family because legally, my husband cannot work. Technically, everyone is deported back to home,” she said. Not being able to work is hard for her husband too. “It’s just so much stress in the family because he worked for 11 years,” said Dr. Palabindela.

Through all the upheavals, Dr. Palabindela has had support from all sides. Her husband has been the biggest source. “He’s my backbone. Every time, he supported me in each and every aspect,” she said. Her parents and her brothers check in on her constantly to make sure she’s staying safe. Even the chief at her hospital has played a significant role, going to bat for his physicians to ensure their safety.

Dr. Palabindela credits everyone who works with COVID-19 patients as heroes. “The nurses, the physicians, the housekeeping, respiratory therapist, speech therapist, physical therapy ... everybody has a role. Everybody is a hero,” she said. “Whoever is wearing a mask is a hero, too, because they are contributing to this community.”
 

Advocating for immigration reform

A lack of transparency and information in the beginning of the pandemic significantly contributed to anxiety, said Anuradha Amara, MD, MBBS, a hospitalist in Wilmington, Del. She felt that what was on the news and what was actually going on in the hospitals were quite different. Colleagues were getting sick, there wasn’t enough personal protective equipment, and planning went out the window. “It’s like a meteor hitting a place and then we start dealing with the aftermath, but we weren’t ready before,” Dr. Amara said. “We didn’t have a plan for a pandemic.”

Then there was the concern of either her or her husband, a cardiologist, getting sick and potentially losing their jobs and immigration status. “How am I going to go back to my country if I had to? What will happen to my family if I die? If I go on the ventilator? Those are the insecurities we found additional to the pandemic challenges we had,” Dr. Amara said.

Not being able to go see their family in India or have them come visit was difficult – “it was pretty bad up there,” said Dr. Amara. Fortunately, her family members in India remained safe, but there’s a very real uneasiness about returning should an emergency arise. “Should I go back and then take the risk of losing my job and losing my position and my kids are here, they’re going to school here. How do you decide that?” she asked.

One of the worst effects of her visa restrictions was not being able to help in New York when hospitals were so short-staffed, and the morgues were overflowing. “New York is 3 hours away from where I live, but I was in chains. I couldn’t help them because of these visa restrictions,” Dr. Amara said. During the emergency, the state allowed physicians from other states to practice without being licensed in New York, but immigrant physicians were not included. “Even if we wanted to, we couldn’t volunteer,” said Dr. Amara. “I have family in New York, and I was really worried. Out of compassion I wanted to help, but I couldn’t do anything.”

Before the pandemic, Dr. Amara joined in advocacy efforts for immigrant physicians through Physicians for American Healthcare Access (PAHA). “In uncertain times, like COVID, it gets worse that you’re challenged with everything on top of your health, your family, and you have to be worried about deportation,” she said. “We need to strengthen legislation. Nobody should suffer with immigration processes during an active pandemic or otherwise.”

In the United States, 28% of physicians are immigrants. Dr. Amara pointed out that these physicians go through years of expensive training with extensive background checks at every level, yet they’re classified as second preference (EB-2) workers. She believes that physicians as a group should be excluded from this category and allowed to automatically become citizens after 5 years of living in the United States and working in an underserved area.

There have been an estimated 15,000 unused green cards since 2005. And if Congress went back to 1992, there could be more than 220,000 previously unused green cards recaptured. These unused green cards are the basis behind bills H.R.2255 and S.1024, the Healthcare Workforce Resiliency Act, which has been championed by SHM and PAHA. “It will allow the frontline physicians, 15,000 of them, and 25,000 nurses, to obtain their permanent residency,” said Dr. Amara. “These are people who already applied for their permanent residencies and they’re still waiting.”

SHM has consistently advocated for the Act since it was first introduced, written multiple letters on the issue, and supported it both on and off Capitol Hill. The society says the legislation would be an “important first step toward addressing a critical shortage” in the U.S. health care system by “recognizing the vital role immigrant physicians and nurses are playing in the fight against COVID-19.”

Currently, SHM has a live action alert open for the reintroduced bill, and encourages members to contact their legislators and urge them to support the reintroduction of the Act by cosponsoring and working to pass the legislation

Dr. Amara encourages physicians to start engaging in advocacy efforts early. Though she didn’t begin participating until late in her career, she said being aware of and part of policies that affect medicine is important. If more physicians get involved, “there are so many things we can take care of,” said Dr. Amara. “The medical profession doesn’t have to be so difficult and so busy. There are ways we can make it better and I believe that. And obviously I’ll continue to work and advocate for the entire medical profession, their problems, their health and well-being, to prevent burnout.”
 

Making time for positivity and self-care

Sandhya Tagaram, MD, a hospitalist at UMass Memorial Medical Center in Worcester, Mass., and her husband, also a hospitalist physician, had only ever read about pandemics in books. They certainly never expected to be in the middle of one. “That was a totally different level of anxiety to work as frontline physicians with two kids under 5 years and families away back home in India,” she said.

UMass Memorial Medical Center

Dr. Tagaram and her husband work opposite shifts so that one of them is always home with their two young children. “Our schedules became more challenging when the pandemic started. Between both of our schedules and with minimal childcare facilities, we managed to strike a decent work-family balance, although we experience less vacation time together. We are fortunate to have an understanding work group,” said Dr. Tagaram.

Even before COVID-19, Dr. Tagaram found working on the temporary work visa challenging. “I think the pandemic has exposed the layer of uncertainty associated with it,” she said. “It’s incredibly stressful to imagine any minor turbulence that could alter our family and work lives. As a frontline physician mom, I take pride in raising my kids and taking care of my patients. We want to serve our communities and at the same time secure our families.”

Not being able to visit family back home and travel is exceedingly difficult. Dr. Tagaram said it would be helpful if there was a separate permanent residence pathway for physicians because they play a critical role in public health and they have been an integral part of the COVID-19 pandemic response team. A separate pathway could help keep their families secure and enable them to give their best to their communities.

Amid all the anxiety, Dr. Tagaram said she and her husband realized they could not keep living with so much pressure. As parents and as physicians, they did not want their stress to leak out and affect their ability and commitment to care for their children or their patients. They decided they needed to figure out how to be positive and constructive.

“We try some daily fun activities with the kids after returning home from work,” said Dr. Tagaram. They also formed a bubble group with two other physician families so the children could interact safely. She said that it’s critical that physicians take time for themselves. “We have to cultivate a serious hobby that helps to rejuvenate and calm our busy minds,” said Dr. Tagaram.

She makes time every day to exercise and to read at least a few pages from a good book. She is also learning Carnatic music along with one of her daughters. And every month since March 2020, she has journaled about her work and what she learned so her daughters can read it someday. “These things keep me jazzed up,” she said.

The pandemic has highlighted the fact that we are all part of one global community. “Although we hail from different backgrounds, we learned that we do have some common goals of being kind and supportive to each other and to give back to our communities. Hopefully we will continue this spirit,” said Dr. Tagaram. As a physician mother, “I feel it’s a privilege and honor to take care of my family and my community.”
 

Soldiering on in the COVID-19 war

The uncertainty everyone felt at the beginning of the pandemic was “very, very scary,” said Mamtha Balla, MD, MPH, a hospitalist and clinical assistant professor in northwest Ohio. “Initially, I was so involved in it and I felt like it was like a war, a COVID-19 war, and we are soldiers in that and trying to protect and do whatever we can.”

She and her husband, a geriatrician also working on an H-1B visa, have worked hard not to bring the virus home to their 2-year-old daughter. Going into 2021, the past 2 years have been “the most hectic and emotionally draining – and physically exhausting – years of my life,” said Dr. Balla.

The COVID-19 vaccine has helped reduce some pressure, but Dr. Balla is still concerned about the high risk to health care workers and the new COVID-19 strains coming out. “We are really not sure what we are dealing with and how the COVID will calm,” she said. “It is pretty challenging being a health care worker because not only are you responsible for your patients at the end of the day, but you are also responsible for your families.”

Initially in the United States from India on a student visa in 2008, Dr. Balla was placed on an H-1B visa when she started her residency. It was during this time that her mother was diagnosed with cancer and went through surgeries and chemotherapy. “She was pretty ill,” recalled Dr. Balla.

Despite the situation, Dr. Balla was afraid to go stay with her mother in case her visa application was rejected, and she couldn’t complete her third year of education. “I opted not to go to India at that time because I did not want to take a chance,” Dr. Balla said. “I have tears in my eyes because those are not easy moments, to withhold from seeing your parents, or to be in any other emergency where you cannot travel. That especially puts us at a higher risk emotionally and physically.”

She has not seen her parents in 2½ years. Between the very real possibility of not being able to get her visa stamp and the unpredictability of how other countries are dealing with COVID-19, Dr. Balla feels it is impossible to even think of going to visit. “Even if I go, what if something happens where my visa gets stuck, or the visa office is not open?” she said. If she could not get back to the United States as planned, she would have patients left behind here.

Recently, Dr. Balla did travel to India and her passport stamp did not come on time, so her husband had to come back to the United States by himself. She had to wait for her stamp for a couple more weeks before she could leave and, in the meantime, had to make arrangements at her hospital. “It is so much trauma,” she said.

There’s also the worry she has about getting sick or disabled and not being able to work anymore, resulting in deportation. “Is that what we are doing for people who are working like soldiers? Are we really treating them the correct way?” Dr. Balla asked.

Dr. Balla considers all health care workers to be soldiers in the COVID-19 war. As such, she believes the government should step up to make sure they are supporting and helping these immigrant physician-soldiers who are so necessary. She applauds France’s recent decision to grant citizenship to its frontline immigrant health care workers and feels that the same should be done in the United States. She filed her green card application in 2012, but she is nowhere close to getting it. (The backlog for employment-based green cards is more than 900,000 now.)

As people putting their own and their family’s lives at risk to care for patients with COVID-19, Dr. Balla and her husband have talked about moving to another country or even back to India. “I am a taxpayer; I am a good human being working for the community and for the job. This is my 13th year here. If I am not eligible [for citizenship] still, then I am not sure what else I have to do to prove myself,” she said. “I am owning United States citizens as my people, so please own us and help us out in this difficult scenario.”

A subcutaneous dose of the second-generation glycoprotein IIb/IIIa inhibitor RUC-4 achieved rapid dose-dependent platelet inhibition in patients with ST-segment elevation MI (STEMI) undergoing stenting in the CEL-02 study.

Platelet inhibition occurred within 15 minutes among the 27 patients, and wore off rapidly, with almost 50% of platelet function recovered within 122 minutes.

The drug was well tolerated, with no thrombocytopenia in the first 72 hours after administration, one injection-site reaction, and two major bleeds likely caused by catheter-based trauma to the proximal radial artery, reported Jurrien ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands.

The results were reported during the annual meeting of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021) and published simultaneously in EuroIntervention.

Dr. ten Berg noted that there is a need for drugs like RUC-4 in the early treatment of STEMI because oral P2Y12 inhibitors have a “seriously delayed” onset by about 2-4 hours. Prehospital use of the glycoprotein inhibitor (GPI) tirofiban was shown to improve reperfusion and late outcomes in the ON-TIME 2 trial, but GPIs require continuous intravenous administration and are associated with thrombocytopenia.

“Since RUC-4 is unique among small-molecule GPI in not inducing the receptor to undergo a major conformational change that has been implicated in the development of thrombocytopenia, it is possible that RUC-4 may be associated with fewer episodes of thrombocytopenia than current GPI,” the authors wrote.

RUC-4, also called zalunfiban, can be delivered with a single subcutaneous dose and, in a phase 1 study, demonstrated platelet inhibition within 15 minutes and was well tolerated up to a dose of 0.075 mg/kg among healthy volunteers and patients with stable coronary artery disease on aspirin.

In the CEL-02 study, 27 STEMI patients received a weight-adjusted subcutaneous injection of RUC-4 before primary percutaneous coronary intervention (PCI) in escalating doses of 0.075 mg/kg, 0.090 mg/kg, and 0.110 mg/kg. Patients were given standard treatment in the ambulance, which included aspirin (93%), ticagrelor (93%), and unfractionated heparin (96%). The activated clotting time was less than 200 seconds in 92% of patients who received additional heparin during cardiac catheterization.

The patients’ mean age was 62 years, 26% were women, and 96% were White. Pharmacodynamic data were available for 24 patients.

The average platelet inhibition 15 minutes after the injection was 77.5%, 87.5%, and 91.7%, respectively, for the three escalating doses (P = .002 for trend).

The primary endpoint of at least 77% inhibition of the iso-TRAP channel – which corresponds to 80% inhibition of light transmission aggregometry stimulated by 20 mcM adenosine diphosphate within 15 minutes – was achieved in three of eight patients at the lowest dose and in seven of eight patients at the middle and highest doses.

“Single-dose subcutaneous RUC-4 induces a fast, potent dose-dependent response of platelet inhibition in patients with STEMI presenting for primary PCI,” Dr. ten Berg concluded. “It is therefore promising for prehospital platelet inhibition in STEMI patients, and the results support further research on clinical benefit.”

The double-blind, randomized phase 2b CELEBRATE trial is underway, evaluating 1,668 STEMI patients treated with a 0.110 mg/kg or 0.130 mg/kg dose of RUC-4 or placebo in the ambulance. The coprimary outcomes are restoration of coronary artery blood flow and resolution of ST-segment deviation post-PCI/angiography. Primary completion is set for March 2023.

MDedge News

Marco Valgimigli, MD, who was not involved in the study, said in an interview that RUC-4 has “some theoretical advantages, compared with conventional IIb/IIIa inhibitors, namely the absence of thrombocytopenia which is, however, relatively rare, especially with tirofiban or eptifibatide.”

The subcutaneous approach may also offer an advantage. Yet, if the administration of RUC-4 is “to happen in the ambulance – a setting where an IV line is usually established – whether the subcutaneous versus IV administration of the treatment proves to be advantageous remains to be seen,” said Dr. Valgimigli, from Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.

“We would need to see the results of large randomized trials embracing this treatment option before a clinical decision can be made, especially considering that IIb/IIa inhibitors in the ambulance have been tested in the past but ultimately abandoned,” he said.

Limitations of the study are its open-label design, the fact that iso-TRAP channel assay data were not reported by the VeryifyNow instrument and had to be calculated from the raw data, and the fact that the timing of the RUC-4 injection immediately before PCI does not fully resemble the expected use of RUC-4 in clinical practice, where RUC-4 would be administered at the same time as the aspirin, ticagrelor, and heparin, and about an hour before PCI, ten Berg and colleagues wrote.

CeleCor Therapeutics sponsored the study and provided study materials. Dr. ten Berg reported receiving lecture or consultancy fees from AstraZeneca, Eli Lilly, Daiichi Sankyo, The Medicines Company, AccuMetrics, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, Ferrer, and Idorsia, and institutional research grants from ZonMw and AstraZeneca. Coauthor Barry S. Coller is an inventor of RUC-4 and a founder, equity holder, and consultant to CeleCor. He also receives royalties from Centocor/Janssen and the VerifyNow assays. Dr. Valgimigli has received grants from Abbott, Terumo, Medicure, and AstraZeneca, and personal fees from Abbott, Chiesi, Bayer, Daiichi Sankyo, Amgen, Terumo, Alvimedica, AstraZeneca, Biosensors, and Idorsia.

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

A subcutaneous dose of the second-generation glycoprotein IIb/IIIa inhibitor RUC-4 achieved rapid dose-dependent platelet inhibition in patients with ST-segment elevation MI (STEMI) undergoing stenting in the CEL-02 study.

Platelet inhibition occurred within 15 minutes among the 27 patients, and wore off rapidly, with almost 50% of platelet function recovered within 122 minutes.

The drug was well tolerated, with no thrombocytopenia in the first 72 hours after administration, one injection-site reaction, and two major bleeds likely caused by catheter-based trauma to the proximal radial artery, reported Jurrien ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands.

The results were reported during the annual meeting of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021) and published simultaneously in EuroIntervention.

Dr. ten Berg noted that there is a need for drugs like RUC-4 in the early treatment of STEMI because oral P2Y12 inhibitors have a “seriously delayed” onset by about 2-4 hours. Prehospital use of the glycoprotein inhibitor (GPI) tirofiban was shown to improve reperfusion and late outcomes in the ON-TIME 2 trial, but GPIs require continuous intravenous administration and are associated with thrombocytopenia.

“Since RUC-4 is unique among small-molecule GPI in not inducing the receptor to undergo a major conformational change that has been implicated in the development of thrombocytopenia, it is possible that RUC-4 may be associated with fewer episodes of thrombocytopenia than current GPI,” the authors wrote.

RUC-4, also called zalunfiban, can be delivered with a single subcutaneous dose and, in a phase 1 study, demonstrated platelet inhibition within 15 minutes and was well tolerated up to a dose of 0.075 mg/kg among healthy volunteers and patients with stable coronary artery disease on aspirin.

In the CEL-02 study, 27 STEMI patients received a weight-adjusted subcutaneous injection of RUC-4 before primary percutaneous coronary intervention (PCI) in escalating doses of 0.075 mg/kg, 0.090 mg/kg, and 0.110 mg/kg. Patients were given standard treatment in the ambulance, which included aspirin (93%), ticagrelor (93%), and unfractionated heparin (96%). The activated clotting time was less than 200 seconds in 92% of patients who received additional heparin during cardiac catheterization.

The patients’ mean age was 62 years, 26% were women, and 96% were White. Pharmacodynamic data were available for 24 patients.

The average platelet inhibition 15 minutes after the injection was 77.5%, 87.5%, and 91.7%, respectively, for the three escalating doses (P = .002 for trend).

The primary endpoint of at least 77% inhibition of the iso-TRAP channel – which corresponds to 80% inhibition of light transmission aggregometry stimulated by 20 mcM adenosine diphosphate within 15 minutes – was achieved in three of eight patients at the lowest dose and in seven of eight patients at the middle and highest doses.

“Single-dose subcutaneous RUC-4 induces a fast, potent dose-dependent response of platelet inhibition in patients with STEMI presenting for primary PCI,” Dr. ten Berg concluded. “It is therefore promising for prehospital platelet inhibition in STEMI patients, and the results support further research on clinical benefit.”

The double-blind, randomized phase 2b CELEBRATE trial is underway, evaluating 1,668 STEMI patients treated with a 0.110 mg/kg or 0.130 mg/kg dose of RUC-4 or placebo in the ambulance. The coprimary outcomes are restoration of coronary artery blood flow and resolution of ST-segment deviation post-PCI/angiography. Primary completion is set for March 2023.

MDedge News

Marco Valgimigli, MD, who was not involved in the study, said in an interview that RUC-4 has “some theoretical advantages, compared with conventional IIb/IIIa inhibitors, namely the absence of thrombocytopenia which is, however, relatively rare, especially with tirofiban or eptifibatide.”

The subcutaneous approach may also offer an advantage. Yet, if the administration of RUC-4 is “to happen in the ambulance – a setting where an IV line is usually established – whether the subcutaneous versus IV administration of the treatment proves to be advantageous remains to be seen,” said Dr. Valgimigli, from Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.

“We would need to see the results of large randomized trials embracing this treatment option before a clinical decision can be made, especially considering that IIb/IIa inhibitors in the ambulance have been tested in the past but ultimately abandoned,” he said.

Limitations of the study are its open-label design, the fact that iso-TRAP channel assay data were not reported by the VeryifyNow instrument and had to be calculated from the raw data, and the fact that the timing of the RUC-4 injection immediately before PCI does not fully resemble the expected use of RUC-4 in clinical practice, where RUC-4 would be administered at the same time as the aspirin, ticagrelor, and heparin, and about an hour before PCI, ten Berg and colleagues wrote.

CeleCor Therapeutics sponsored the study and provided study materials. Dr. ten Berg reported receiving lecture or consultancy fees from AstraZeneca, Eli Lilly, Daiichi Sankyo, The Medicines Company, AccuMetrics, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, Ferrer, and Idorsia, and institutional research grants from ZonMw and AstraZeneca. Coauthor Barry S. Coller is an inventor of RUC-4 and a founder, equity holder, and consultant to CeleCor. He also receives royalties from Centocor/Janssen and the VerifyNow assays. Dr. Valgimigli has received grants from Abbott, Terumo, Medicure, and AstraZeneca, and personal fees from Abbott, Chiesi, Bayer, Daiichi Sankyo, Amgen, Terumo, Alvimedica, AstraZeneca, Biosensors, and Idorsia.

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

A subcutaneous dose of the second-generation glycoprotein IIb/IIIa inhibitor RUC-4 achieved rapid dose-dependent platelet inhibition in patients with ST-segment elevation MI (STEMI) undergoing stenting in the CEL-02 study.

Platelet inhibition occurred within 15 minutes among the 27 patients, and wore off rapidly, with almost 50% of platelet function recovered within 122 minutes.

The drug was well tolerated, with no thrombocytopenia in the first 72 hours after administration, one injection-site reaction, and two major bleeds likely caused by catheter-based trauma to the proximal radial artery, reported Jurrien ten Berg, MD, PhD, St. Antonius Hospital, Nieuwegein, the Netherlands.

The results were reported during the annual meeting of the European Association of Percutaneous Cardiovascular Interventions (EuroPCR 2021) and published simultaneously in EuroIntervention.

Dr. ten Berg noted that there is a need for drugs like RUC-4 in the early treatment of STEMI because oral P2Y12 inhibitors have a “seriously delayed” onset by about 2-4 hours. Prehospital use of the glycoprotein inhibitor (GPI) tirofiban was shown to improve reperfusion and late outcomes in the ON-TIME 2 trial, but GPIs require continuous intravenous administration and are associated with thrombocytopenia.

“Since RUC-4 is unique among small-molecule GPI in not inducing the receptor to undergo a major conformational change that has been implicated in the development of thrombocytopenia, it is possible that RUC-4 may be associated with fewer episodes of thrombocytopenia than current GPI,” the authors wrote.

RUC-4, also called zalunfiban, can be delivered with a single subcutaneous dose and, in a phase 1 study, demonstrated platelet inhibition within 15 minutes and was well tolerated up to a dose of 0.075 mg/kg among healthy volunteers and patients with stable coronary artery disease on aspirin.

In the CEL-02 study, 27 STEMI patients received a weight-adjusted subcutaneous injection of RUC-4 before primary percutaneous coronary intervention (PCI) in escalating doses of 0.075 mg/kg, 0.090 mg/kg, and 0.110 mg/kg. Patients were given standard treatment in the ambulance, which included aspirin (93%), ticagrelor (93%), and unfractionated heparin (96%). The activated clotting time was less than 200 seconds in 92% of patients who received additional heparin during cardiac catheterization.

The patients’ mean age was 62 years, 26% were women, and 96% were White. Pharmacodynamic data were available for 24 patients.

The average platelet inhibition 15 minutes after the injection was 77.5%, 87.5%, and 91.7%, respectively, for the three escalating doses (P = .002 for trend).

The primary endpoint of at least 77% inhibition of the iso-TRAP channel – which corresponds to 80% inhibition of light transmission aggregometry stimulated by 20 mcM adenosine diphosphate within 15 minutes – was achieved in three of eight patients at the lowest dose and in seven of eight patients at the middle and highest doses.

“Single-dose subcutaneous RUC-4 induces a fast, potent dose-dependent response of platelet inhibition in patients with STEMI presenting for primary PCI,” Dr. ten Berg concluded. “It is therefore promising for prehospital platelet inhibition in STEMI patients, and the results support further research on clinical benefit.”

The double-blind, randomized phase 2b CELEBRATE trial is underway, evaluating 1,668 STEMI patients treated with a 0.110 mg/kg or 0.130 mg/kg dose of RUC-4 or placebo in the ambulance. The coprimary outcomes are restoration of coronary artery blood flow and resolution of ST-segment deviation post-PCI/angiography. Primary completion is set for March 2023.

MDedge News

Marco Valgimigli, MD, who was not involved in the study, said in an interview that RUC-4 has “some theoretical advantages, compared with conventional IIb/IIIa inhibitors, namely the absence of thrombocytopenia which is, however, relatively rare, especially with tirofiban or eptifibatide.”

The subcutaneous approach may also offer an advantage. Yet, if the administration of RUC-4 is “to happen in the ambulance – a setting where an IV line is usually established – whether the subcutaneous versus IV administration of the treatment proves to be advantageous remains to be seen,” said Dr. Valgimigli, from Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland.

“We would need to see the results of large randomized trials embracing this treatment option before a clinical decision can be made, especially considering that IIb/IIa inhibitors in the ambulance have been tested in the past but ultimately abandoned,” he said.

Limitations of the study are its open-label design, the fact that iso-TRAP channel assay data were not reported by the VeryifyNow instrument and had to be calculated from the raw data, and the fact that the timing of the RUC-4 injection immediately before PCI does not fully resemble the expected use of RUC-4 in clinical practice, where RUC-4 would be administered at the same time as the aspirin, ticagrelor, and heparin, and about an hour before PCI, ten Berg and colleagues wrote.

CeleCor Therapeutics sponsored the study and provided study materials. Dr. ten Berg reported receiving lecture or consultancy fees from AstraZeneca, Eli Lilly, Daiichi Sankyo, The Medicines Company, AccuMetrics, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Bayer, Ferrer, and Idorsia, and institutional research grants from ZonMw and AstraZeneca. Coauthor Barry S. Coller is an inventor of RUC-4 and a founder, equity holder, and consultant to CeleCor. He also receives royalties from Centocor/Janssen and the VerifyNow assays. Dr. Valgimigli has received grants from Abbott, Terumo, Medicure, and AstraZeneca, and personal fees from Abbott, Chiesi, Bayer, Daiichi Sankyo, Amgen, Terumo, Alvimedica, AstraZeneca, Biosensors, and Idorsia.

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

Background: Prior observational studies have suggested that a dose-dependent effect may exist between alcohol intake and incident AFib, recurrence after ablation, and cardiac structural changes.

Dr. Cool is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: Prior observational studies have suggested that a dose-dependent effect may exist between alcohol intake and incident AFib, recurrence after ablation, and cardiac structural changes.

Dr. Cool is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: Prior observational studies have suggested that a dose-dependent effect may exist between alcohol intake and incident AFib, recurrence after ablation, and cardiac structural changes.

Dr. Cool is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.