MDedge Emergency Medicine

People infected multiple times with COVID-19 are more likely to develop long COVID, and most never fully recover from the condition. Those are two of the most striking findings of a comprehensive new research study of 138,000 veterans.

Lead researcher Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care and clinical epidemiologist at Washington University in St. Louis, spoke with this news organization about his team’s findings, what we know – and don’t – about long COVID, and what it means for physicians treating patients with the condition.

Excerpts of the interview follow.

Your research concluded that for those infected early in the pandemic, some long COVID symptoms declined over 2 years, but some did not. You have also concluded that long COVID is a chronic disease. Why?

We’ve been in this journey a little bit more than three and a half years. Some patients do experience some recovery. But that’s not the norm. Most people do not really fully recover. The health trajectory for people with long COVID is really very heterogeneous. There is no one-size-fits-all. There’s really no one line that I could give you that could cover all your patients. But it is very, very, very clear that a bunch of them experienced long COVID for sure; that’s really happening.

It happened in the pre-Delta era and in the Delta era, and with Omicron subvariants, even now. There are people who think, “This is a nothing-burger anymore,” or “It’s not an issue anymore.” It’s still happening with the current variants. Vaccines do reduce risk for long COVID, but do not completely eliminate the risk for long COVID.

You work with patients with long COVID in the clinic and also analyze data from thousands more. If long COVID does not go away, what should doctors look for in everyday practice that will help them recognize and help patients with long COVID?

Long COVID is not uncommon. We see it in the clinic in large numbers. Whatever clinic you’re running – if you’re running a cardiology clinic, or a nephrology clinic, or diabetes, or primary care – probably some of your people have it. You may not know about it. They may not tell you about it. You may not recognize it.

Not all long COVID is the same, and that’s really what makes it complex and makes it really hard to deal with in the clinic. But that’s the reality that we’re all dealing with. And it’s multisystemic; it’s not like it affects the heart only, the brain only, or the autonomic nervous system only. It does not behave in the same way in different individuals – they may have different manifestations, various health trajectories, and different outcomes. It’s important for doctors to get up to speed on long COVID as a multisystem illness.

Management at this point is really managing the symptoms. We don’t have a treatment for it; we don’t have a cure for it.

Some patients experience what you’ve described as partial recovery. What does that look like?

Some individuals do experience some recovery over time, but for most individuals, the recovery is long and arduous. Long COVID can last with them for many years. Some people may come back to the clinic and say, “I’m doing better,” but if you really flesh it out and dig deeper, they didn’t do better; they adjusted to a new baseline. They used to walk the dog three to four blocks, and now they walk the dog only half a block. They used to do an activity with their partner every Saturday or Sunday, and now they do half of that.

If you’re a physician, a primary care provider, or any other provider who is dealing with a patient with long COVID, know that this is really happening. It can happen even in vaccinated individuals. The presentation is heterogeneous. Some people may present to you with and say. “Well, before I had COVID I was mentally sharp and now having I’m having difficulty with memory, etc.” It can sometimes present as fatigue or postexertional malaise.

In some instances, it can present as sleep problems. It can present as what we call postural orthostatic tachycardia syndrome (POTS). Those people get a significant increase in heart rate with postural changes.

What the most important thing we can we learn from the emergence of long COVID?

This whole thing taught us that infections can cause chronic disease. That’s really the No. 1 lesson that I take from this pandemic – that infections can cause chronic disease.

Looking at only acute illness from COVID is really only looking at the tip of the iceberg. Beneath that tip of the iceberg lies this hidden toll of disease that we don’t really talk about that much.

This pandemic shone a very, very good light on the idea that there is really an intimate connection between infections and chronic disease. It was really hardwired into our medical training as doctors that most infections, when people get over the hump of the acute phase of the disease, it’s all behind them. I think long COVID has humbled us in many, many ways, but chief among those is the realization – the stark realization – that infections can cause chronic disease.

That’s really going back to your [first] question: What does it mean that some people are not recovering? They actually have chronic illness. I’m hoping that we will find a treatment, that we’ll start finding things that would help them get back to baseline. But at this point in time, what we’re dealing with is people with chronic illness or chronic disease that may continue to affect them for many years to come in the absence of a treatment or a cure.

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

People infected multiple times with COVID-19 are more likely to develop long COVID, and most never fully recover from the condition. Those are two of the most striking findings of a comprehensive new research study of 138,000 veterans.

Lead researcher Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care and clinical epidemiologist at Washington University in St. Louis, spoke with this news organization about his team’s findings, what we know – and don’t – about long COVID, and what it means for physicians treating patients with the condition.

Excerpts of the interview follow.

Your research concluded that for those infected early in the pandemic, some long COVID symptoms declined over 2 years, but some did not. You have also concluded that long COVID is a chronic disease. Why?

We’ve been in this journey a little bit more than three and a half years. Some patients do experience some recovery. But that’s not the norm. Most people do not really fully recover. The health trajectory for people with long COVID is really very heterogeneous. There is no one-size-fits-all. There’s really no one line that I could give you that could cover all your patients. But it is very, very, very clear that a bunch of them experienced long COVID for sure; that’s really happening.

It happened in the pre-Delta era and in the Delta era, and with Omicron subvariants, even now. There are people who think, “This is a nothing-burger anymore,” or “It’s not an issue anymore.” It’s still happening with the current variants. Vaccines do reduce risk for long COVID, but do not completely eliminate the risk for long COVID.

You work with patients with long COVID in the clinic and also analyze data from thousands more. If long COVID does not go away, what should doctors look for in everyday practice that will help them recognize and help patients with long COVID?

Long COVID is not uncommon. We see it in the clinic in large numbers. Whatever clinic you’re running – if you’re running a cardiology clinic, or a nephrology clinic, or diabetes, or primary care – probably some of your people have it. You may not know about it. They may not tell you about it. You may not recognize it.

Not all long COVID is the same, and that’s really what makes it complex and makes it really hard to deal with in the clinic. But that’s the reality that we’re all dealing with. And it’s multisystemic; it’s not like it affects the heart only, the brain only, or the autonomic nervous system only. It does not behave in the same way in different individuals – they may have different manifestations, various health trajectories, and different outcomes. It’s important for doctors to get up to speed on long COVID as a multisystem illness.

Management at this point is really managing the symptoms. We don’t have a treatment for it; we don’t have a cure for it.

Some patients experience what you’ve described as partial recovery. What does that look like?

Some individuals do experience some recovery over time, but for most individuals, the recovery is long and arduous. Long COVID can last with them for many years. Some people may come back to the clinic and say, “I’m doing better,” but if you really flesh it out and dig deeper, they didn’t do better; they adjusted to a new baseline. They used to walk the dog three to four blocks, and now they walk the dog only half a block. They used to do an activity with their partner every Saturday or Sunday, and now they do half of that.

If you’re a physician, a primary care provider, or any other provider who is dealing with a patient with long COVID, know that this is really happening. It can happen even in vaccinated individuals. The presentation is heterogeneous. Some people may present to you with and say. “Well, before I had COVID I was mentally sharp and now having I’m having difficulty with memory, etc.” It can sometimes present as fatigue or postexertional malaise.

In some instances, it can present as sleep problems. It can present as what we call postural orthostatic tachycardia syndrome (POTS). Those people get a significant increase in heart rate with postural changes.

What the most important thing we can we learn from the emergence of long COVID?

This whole thing taught us that infections can cause chronic disease. That’s really the No. 1 lesson that I take from this pandemic – that infections can cause chronic disease.

Looking at only acute illness from COVID is really only looking at the tip of the iceberg. Beneath that tip of the iceberg lies this hidden toll of disease that we don’t really talk about that much.

This pandemic shone a very, very good light on the idea that there is really an intimate connection between infections and chronic disease. It was really hardwired into our medical training as doctors that most infections, when people get over the hump of the acute phase of the disease, it’s all behind them. I think long COVID has humbled us in many, many ways, but chief among those is the realization – the stark realization – that infections can cause chronic disease.

That’s really going back to your [first] question: What does it mean that some people are not recovering? They actually have chronic illness. I’m hoping that we will find a treatment, that we’ll start finding things that would help them get back to baseline. But at this point in time, what we’re dealing with is people with chronic illness or chronic disease that may continue to affect them for many years to come in the absence of a treatment or a cure.

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

People infected multiple times with COVID-19 are more likely to develop long COVID, and most never fully recover from the condition. Those are two of the most striking findings of a comprehensive new research study of 138,000 veterans.

Lead researcher Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care and clinical epidemiologist at Washington University in St. Louis, spoke with this news organization about his team’s findings, what we know – and don’t – about long COVID, and what it means for physicians treating patients with the condition.

Excerpts of the interview follow.

Your research concluded that for those infected early in the pandemic, some long COVID symptoms declined over 2 years, but some did not. You have also concluded that long COVID is a chronic disease. Why?

We’ve been in this journey a little bit more than three and a half years. Some patients do experience some recovery. But that’s not the norm. Most people do not really fully recover. The health trajectory for people with long COVID is really very heterogeneous. There is no one-size-fits-all. There’s really no one line that I could give you that could cover all your patients. But it is very, very, very clear that a bunch of them experienced long COVID for sure; that’s really happening.

It happened in the pre-Delta era and in the Delta era, and with Omicron subvariants, even now. There are people who think, “This is a nothing-burger anymore,” or “It’s not an issue anymore.” It’s still happening with the current variants. Vaccines do reduce risk for long COVID, but do not completely eliminate the risk for long COVID.

You work with patients with long COVID in the clinic and also analyze data from thousands more. If long COVID does not go away, what should doctors look for in everyday practice that will help them recognize and help patients with long COVID?

Long COVID is not uncommon. We see it in the clinic in large numbers. Whatever clinic you’re running – if you’re running a cardiology clinic, or a nephrology clinic, or diabetes, or primary care – probably some of your people have it. You may not know about it. They may not tell you about it. You may not recognize it.

Not all long COVID is the same, and that’s really what makes it complex and makes it really hard to deal with in the clinic. But that’s the reality that we’re all dealing with. And it’s multisystemic; it’s not like it affects the heart only, the brain only, or the autonomic nervous system only. It does not behave in the same way in different individuals – they may have different manifestations, various health trajectories, and different outcomes. It’s important for doctors to get up to speed on long COVID as a multisystem illness.

Management at this point is really managing the symptoms. We don’t have a treatment for it; we don’t have a cure for it.

Some patients experience what you’ve described as partial recovery. What does that look like?

Some individuals do experience some recovery over time, but for most individuals, the recovery is long and arduous. Long COVID can last with them for many years. Some people may come back to the clinic and say, “I’m doing better,” but if you really flesh it out and dig deeper, they didn’t do better; they adjusted to a new baseline. They used to walk the dog three to four blocks, and now they walk the dog only half a block. They used to do an activity with their partner every Saturday or Sunday, and now they do half of that.

If you’re a physician, a primary care provider, or any other provider who is dealing with a patient with long COVID, know that this is really happening. It can happen even in vaccinated individuals. The presentation is heterogeneous. Some people may present to you with and say. “Well, before I had COVID I was mentally sharp and now having I’m having difficulty with memory, etc.” It can sometimes present as fatigue or postexertional malaise.

In some instances, it can present as sleep problems. It can present as what we call postural orthostatic tachycardia syndrome (POTS). Those people get a significant increase in heart rate with postural changes.

What the most important thing we can we learn from the emergence of long COVID?

This whole thing taught us that infections can cause chronic disease. That’s really the No. 1 lesson that I take from this pandemic – that infections can cause chronic disease.

Looking at only acute illness from COVID is really only looking at the tip of the iceberg. Beneath that tip of the iceberg lies this hidden toll of disease that we don’t really talk about that much.

This pandemic shone a very, very good light on the idea that there is really an intimate connection between infections and chronic disease. It was really hardwired into our medical training as doctors that most infections, when people get over the hump of the acute phase of the disease, it’s all behind them. I think long COVID has humbled us in many, many ways, but chief among those is the realization – the stark realization – that infections can cause chronic disease.

That’s really going back to your [first] question: What does it mean that some people are not recovering? They actually have chronic illness. I’m hoping that we will find a treatment, that we’ll start finding things that would help them get back to baseline. But at this point in time, what we’re dealing with is people with chronic illness or chronic disease that may continue to affect them for many years to come in the absence of a treatment or a cure.

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

TOPLINE:

The addition of early and empirical high-dose cryoprecipitate to usual care does not improve clinical outcomes in patients with trauma and bleeding who required activation of a major hemorrhage protocol (MHP).

METHODOLOGY:

• CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study.
• A total of 1,604 patients were enrolled from 25 major trauma centers in the United Kingdom (n = 1,555) and 1 in the United States (n = 49) between August 2017 and November 2021.
• A total of 805 patients were randomly assigned to receive the standard MHP (standard care), and 799 were randomly assigned to receive an additional three pools of cryoprecipitate.
• The primary outcome was all-cause mortality at 28 days.

TAKEAWAY:

• Addition of early cryoprecipitate versus standard care did not improve all-cause 28-day mortality in the intent-to-treat population (25.3% vs. 26.1%; P = .74).
• In patient subgroup with penetrating trauma, 28-day mortality was significantly higher in the cryoprecipitate group than in the standard care group (16.2% vs. 10.0%; odds ratio, 1.74; P = .006).
• Massive transfusion (RBC ≥ 10 U) was similar between the cryoprecipitate and standard care groups.

IN PRACTICE:

According to the authors, it is possible that certain patients may have benefited from cryoprecipitate, but they did not receive it promptly or in adequate doses to restore functional fibrinogen levels. Despite the study’s goal of early cryoprecipitate administration, the median time to the first transfusion exceeded 1 hour after the patient’s arrival, which highlights the logistical challenges of preparing and delivering a frozen blood component from a distant blood laboratory to the patient.

SOURCE:

The study, with first author Ross Davenport, PhD, of Queen Mary University of London and colleagues, was published in JAMA).

LIMITATIONS:

There was variability of timing of cryoprecipitate administration and an overlap with patients in the standard care group receiving the intervention as part of their usual MHP treatment.

DISCLOSURES:

The study was funded by the U.K. National Institute for Health and Care Research: Health Technology Assessment and Barts Charity, U.K.

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

TOPLINE:

The addition of early and empirical high-dose cryoprecipitate to usual care does not improve clinical outcomes in patients with trauma and bleeding who required activation of a major hemorrhage protocol (MHP).

METHODOLOGY:

• CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study.
• A total of 1,604 patients were enrolled from 25 major trauma centers in the United Kingdom (n = 1,555) and 1 in the United States (n = 49) between August 2017 and November 2021.
• A total of 805 patients were randomly assigned to receive the standard MHP (standard care), and 799 were randomly assigned to receive an additional three pools of cryoprecipitate.
• The primary outcome was all-cause mortality at 28 days.

TAKEAWAY:

• Addition of early cryoprecipitate versus standard care did not improve all-cause 28-day mortality in the intent-to-treat population (25.3% vs. 26.1%; P = .74).
• In patient subgroup with penetrating trauma, 28-day mortality was significantly higher in the cryoprecipitate group than in the standard care group (16.2% vs. 10.0%; odds ratio, 1.74; P = .006).
• Massive transfusion (RBC ≥ 10 U) was similar between the cryoprecipitate and standard care groups.

IN PRACTICE:

According to the authors, it is possible that certain patients may have benefited from cryoprecipitate, but they did not receive it promptly or in adequate doses to restore functional fibrinogen levels. Despite the study’s goal of early cryoprecipitate administration, the median time to the first transfusion exceeded 1 hour after the patient’s arrival, which highlights the logistical challenges of preparing and delivering a frozen blood component from a distant blood laboratory to the patient.

SOURCE:

The study, with first author Ross Davenport, PhD, of Queen Mary University of London and colleagues, was published in JAMA).

LIMITATIONS:

There was variability of timing of cryoprecipitate administration and an overlap with patients in the standard care group receiving the intervention as part of their usual MHP treatment.

DISCLOSURES:

The study was funded by the U.K. National Institute for Health and Care Research: Health Technology Assessment and Barts Charity, U.K.

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

TOPLINE:

The addition of early and empirical high-dose cryoprecipitate to usual care does not improve clinical outcomes in patients with trauma and bleeding who required activation of a major hemorrhage protocol (MHP).

METHODOLOGY:

• CRYOSTAT-2 was an interventional, randomized, open-label, parallel-group controlled, international, multicenter study.
• A total of 1,604 patients were enrolled from 25 major trauma centers in the United Kingdom (n = 1,555) and 1 in the United States (n = 49) between August 2017 and November 2021.
• A total of 805 patients were randomly assigned to receive the standard MHP (standard care), and 799 were randomly assigned to receive an additional three pools of cryoprecipitate.
• The primary outcome was all-cause mortality at 28 days.

TAKEAWAY:

• Addition of early cryoprecipitate versus standard care did not improve all-cause 28-day mortality in the intent-to-treat population (25.3% vs. 26.1%; P = .74).
• In patient subgroup with penetrating trauma, 28-day mortality was significantly higher in the cryoprecipitate group than in the standard care group (16.2% vs. 10.0%; odds ratio, 1.74; P = .006).
• Massive transfusion (RBC ≥ 10 U) was similar between the cryoprecipitate and standard care groups.

IN PRACTICE:

According to the authors, it is possible that certain patients may have benefited from cryoprecipitate, but they did not receive it promptly or in adequate doses to restore functional fibrinogen levels. Despite the study’s goal of early cryoprecipitate administration, the median time to the first transfusion exceeded 1 hour after the patient’s arrival, which highlights the logistical challenges of preparing and delivering a frozen blood component from a distant blood laboratory to the patient.

SOURCE:

The study, with first author Ross Davenport, PhD, of Queen Mary University of London and colleagues, was published in JAMA).

LIMITATIONS:

There was variability of timing of cryoprecipitate administration and an overlap with patients in the standard care group receiving the intervention as part of their usual MHP treatment.

DISCLOSURES:

The study was funded by the U.K. National Institute for Health and Care Research: Health Technology Assessment and Barts Charity, U.K.

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

WASHINGTON – Transgender and other gender-diverse youth who visited the emergency department (ED) at a single institution had more than five times greater odds of a positive suicide screening compared with their cisgender peers, according to a study presented at the annual meeting of the American Academy of Pediatrics.

“The take-home message here is this study emphasizes the importance of universal screening to identify gender-diverse youth at risk,” Amanda Burnside, PhD, assistant professor of psychiatry and behavioral sciences at Ann and Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, told attendees. “We really need to develop robust strategies and systems to link better mental health services.”

Ann and Robert H. Lurie Children’s Hospital of Chicago

Suicide rates in transgender and gender-diverse youth are exceptionally high among youth in the U.S., Dr. Burnside said during her presentation. For example, the 2022 LGBTQ health survey from the Trevor Project found that much higher percentages of transgender and gender nonconforming youth had considered suicide in the past year compared with cisgender youth, even within the LGBTQ umbrella. Among nearly 34,000 LGBTQ youth aged 13-24, nearly half of trans females (48%) and more than half of trans males (59%) had considered suicide, compared with 28% of cisgender males and 37% of cisgender females. The rate among nonbinary/genderqueer individuals was 53%, and it was 48% for those questioning their gender.

Current methods of identifying trans and gender-diverse (TGD) youth in the hospital, however, may not actually be capturing the entire population.

“In health care settings, research involving TGD individuals has historically been limited to specialized clinic populations or youth with gender-specific diagnostic codes documented in the electronic medical record,” an approach that “likely significantly underestimates the prevalence of TGD youth in health care settings.” While at least one study has attempted to bridge this gap by searching the EMR for keywords, that study only tried to identify trans youth and not other youth on the gender diversity spectrum, such as nonbinary youth or those questioning their gender identity. Dr. Burnside and her colleagues therefore designed a study that used keywords to identify both trans youth and other gender-diverse youth who visited the ED so they could assess the rate of positive suicide screens in this population.
 

Underestimating the population at risk?

The researchers conducted a retrospective cross-sectional study of EMR data for all ED visits during which the patient underwent suicide screening. For the period of November 2019 to August 2022, they collected data on the screening results and the patient’s gender identity, age, race/ethnicity, insurance status, chief complaint in the ED and child opportunity index, which assess a youth’s access to resources based on geography. The suicide screener used was the Ask Suicide–Screening Questions (ASQ) tool.

The keywords they looked for in the EMR to identify trans and gender-diverse youth included transgender, pronouns, agender, gender dysphoria, male-to-female, female-to-male, nonbinary, preferred name, and they/them (captured as a complete term, not as “they” and “them” separately).

“If a keyword was present, the surrounding text was extracted and reviewed by two members of our team,” Dr. Burnside explained in her presentation. “We categorized keywords into either indicative of gender-diverse identity or not, and if it wasn’t clear based on the text extracted, we would conduct a manual chart review,” though that only occurred in about 3% of cases, she added.

Among 15,413 ED encounters with a suicide screen, the researchers identified 1,126 of these keywords in the EMR, among which 91.2% were classified as referring to a gender-diverse patient. Nearly all of the words were at least 90% effective in identify a gender-diverse youth, Dr. Burnside said, and all of the 197 instances of “they/them” were classified as gender diverse.

The accuracy was a little lower for the two keywords that appeared most frequently: For “pronouns,” 86.3% of 306 instances were classified as gender diverse, and for “transgender,” 83.1% of 207 instances were classified as gender diverse. Since some providers ask all patients their pronouns, the presence of “pronouns” in the EMR alone did not necessarily indicate the patient was gender diverse, Dr. Burnside said. A common reason the term “transgender” occurred in the EMR of non–gender diverse patients is that the department’s list of crisis resources includes transgender hotlines.

After identifying all the keywords, the researchers determined how many of these occurred in unique ED encounters and removed those with incomplete screening. Overall, they found 565 encounters by 399 gender-diverse individuals who had a suicide screening, representing 4.6% of total visits. This percentage is slightly lower than recent population-based estimates of gender-diverse youth, the researchers noted.

This population ranged from 8 to 23 years old, and 43% were publicly insured. The chief complaint for most of the patients (77.5%) was a mental health one. They were predominantly White (43%) or Hispanic (35%), with 10% Black youth, 4% Asian youth, and 8% youth who were “other” or two or more races. About half (52%) lived in a neighborhood with a “low” or “very low” child opportunity index.

Within this population, 81% of the patients screened positive on the suicide screening, compared with 23% positive screens across all ED visits. One in ten (10%) gender-diverse youth had active suicidal ideation, compared with 3.4% of the rest of the ED patient population. The researchers calculated that gender-diverse youth had 5.35 times greater odds of screening positive than cisgender youth in the ED (95% confidence interval [CI] 8.7-15.92). Further, a quarter (25%) of the trans and gender-diverse youth who screened positive for suicide risk had come to the ED for a primary complaint unrelated to mental health.

“We had a kid who came in because he broke his arm who had active suicidal ideation,” study coauthor Jennifer A. Hoffmann, MD, assistant professor of pediatrics at the Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, mentioned after the presentation. That particular patient even had a suicide plan, but was identified as actively suicidal only because of the screening. In other cases, she said, a youth may come in with self-inflicted injuries, and while those are the primary complaint, they are linked with suicidal ideation.

Ann & Robert H. Lurie Children's Hospital of Chicago

Uncovering valuable information

Jason Rafferty, MD, MPH, EdM, clinical assistant professor of pediatrics and of psychiatry and human behavior at Brown University, Providence, R.I., who attended the presentation, noted that the study provides information on a population that’s often difficult to get through traditional EMR research methods.

Brown University

“A lot of medical record systems don’t have uniform ways of capturing [gender diversity], but what we know as providers is that kids are really struggling and that it’s not a surprise that we’re seeing these disparities with suicidality,” Dr. Rafferty said.

The study also provides more discrete estimates by age than what most other current research measures, which tends to be lifetime suicidality as opposed to suicidal thoughts or attempts within the past year, Dr. Rafferty added.

”What this shows is, for adolescents, the risk of suicide is something we need to be paying attention to. Because it’s not that it’s something that only happens in adults, this really dispels a lot of the misquoting of the data that’s out there.” That kind of information is valuable for determining resource allocation, he said. “A disparity like this really underlies the importance of mental health resources in this field,” he said.

Dr. Burnside, Dr. Hoffmann, and Dr. Rafferty had no disclosures, and no external funding sources were noted.

WASHINGTON – Transgender and other gender-diverse youth who visited the emergency department (ED) at a single institution had more than five times greater odds of a positive suicide screening compared with their cisgender peers, according to a study presented at the annual meeting of the American Academy of Pediatrics.

“The take-home message here is this study emphasizes the importance of universal screening to identify gender-diverse youth at risk,” Amanda Burnside, PhD, assistant professor of psychiatry and behavioral sciences at Ann and Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, told attendees. “We really need to develop robust strategies and systems to link better mental health services.”

Ann and Robert H. Lurie Children’s Hospital of Chicago

Suicide rates in transgender and gender-diverse youth are exceptionally high among youth in the U.S., Dr. Burnside said during her presentation. For example, the 2022 LGBTQ health survey from the Trevor Project found that much higher percentages of transgender and gender nonconforming youth had considered suicide in the past year compared with cisgender youth, even within the LGBTQ umbrella. Among nearly 34,000 LGBTQ youth aged 13-24, nearly half of trans females (48%) and more than half of trans males (59%) had considered suicide, compared with 28% of cisgender males and 37% of cisgender females. The rate among nonbinary/genderqueer individuals was 53%, and it was 48% for those questioning their gender.

Current methods of identifying trans and gender-diverse (TGD) youth in the hospital, however, may not actually be capturing the entire population.

“In health care settings, research involving TGD individuals has historically been limited to specialized clinic populations or youth with gender-specific diagnostic codes documented in the electronic medical record,” an approach that “likely significantly underestimates the prevalence of TGD youth in health care settings.” While at least one study has attempted to bridge this gap by searching the EMR for keywords, that study only tried to identify trans youth and not other youth on the gender diversity spectrum, such as nonbinary youth or those questioning their gender identity. Dr. Burnside and her colleagues therefore designed a study that used keywords to identify both trans youth and other gender-diverse youth who visited the ED so they could assess the rate of positive suicide screens in this population.
 

Underestimating the population at risk?

The researchers conducted a retrospective cross-sectional study of EMR data for all ED visits during which the patient underwent suicide screening. For the period of November 2019 to August 2022, they collected data on the screening results and the patient’s gender identity, age, race/ethnicity, insurance status, chief complaint in the ED and child opportunity index, which assess a youth’s access to resources based on geography. The suicide screener used was the Ask Suicide–Screening Questions (ASQ) tool.

The keywords they looked for in the EMR to identify trans and gender-diverse youth included transgender, pronouns, agender, gender dysphoria, male-to-female, female-to-male, nonbinary, preferred name, and they/them (captured as a complete term, not as “they” and “them” separately).

“If a keyword was present, the surrounding text was extracted and reviewed by two members of our team,” Dr. Burnside explained in her presentation. “We categorized keywords into either indicative of gender-diverse identity or not, and if it wasn’t clear based on the text extracted, we would conduct a manual chart review,” though that only occurred in about 3% of cases, she added.

Among 15,413 ED encounters with a suicide screen, the researchers identified 1,126 of these keywords in the EMR, among which 91.2% were classified as referring to a gender-diverse patient. Nearly all of the words were at least 90% effective in identify a gender-diverse youth, Dr. Burnside said, and all of the 197 instances of “they/them” were classified as gender diverse.

The accuracy was a little lower for the two keywords that appeared most frequently: For “pronouns,” 86.3% of 306 instances were classified as gender diverse, and for “transgender,” 83.1% of 207 instances were classified as gender diverse. Since some providers ask all patients their pronouns, the presence of “pronouns” in the EMR alone did not necessarily indicate the patient was gender diverse, Dr. Burnside said. A common reason the term “transgender” occurred in the EMR of non–gender diverse patients is that the department’s list of crisis resources includes transgender hotlines.

After identifying all the keywords, the researchers determined how many of these occurred in unique ED encounters and removed those with incomplete screening. Overall, they found 565 encounters by 399 gender-diverse individuals who had a suicide screening, representing 4.6% of total visits. This percentage is slightly lower than recent population-based estimates of gender-diverse youth, the researchers noted.

This population ranged from 8 to 23 years old, and 43% were publicly insured. The chief complaint for most of the patients (77.5%) was a mental health one. They were predominantly White (43%) or Hispanic (35%), with 10% Black youth, 4% Asian youth, and 8% youth who were “other” or two or more races. About half (52%) lived in a neighborhood with a “low” or “very low” child opportunity index.

Within this population, 81% of the patients screened positive on the suicide screening, compared with 23% positive screens across all ED visits. One in ten (10%) gender-diverse youth had active suicidal ideation, compared with 3.4% of the rest of the ED patient population. The researchers calculated that gender-diverse youth had 5.35 times greater odds of screening positive than cisgender youth in the ED (95% confidence interval [CI] 8.7-15.92). Further, a quarter (25%) of the trans and gender-diverse youth who screened positive for suicide risk had come to the ED for a primary complaint unrelated to mental health.

“We had a kid who came in because he broke his arm who had active suicidal ideation,” study coauthor Jennifer A. Hoffmann, MD, assistant professor of pediatrics at the Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, mentioned after the presentation. That particular patient even had a suicide plan, but was identified as actively suicidal only because of the screening. In other cases, she said, a youth may come in with self-inflicted injuries, and while those are the primary complaint, they are linked with suicidal ideation.

Ann & Robert H. Lurie Children's Hospital of Chicago

Uncovering valuable information

Jason Rafferty, MD, MPH, EdM, clinical assistant professor of pediatrics and of psychiatry and human behavior at Brown University, Providence, R.I., who attended the presentation, noted that the study provides information on a population that’s often difficult to get through traditional EMR research methods.

Brown University

“A lot of medical record systems don’t have uniform ways of capturing [gender diversity], but what we know as providers is that kids are really struggling and that it’s not a surprise that we’re seeing these disparities with suicidality,” Dr. Rafferty said.

The study also provides more discrete estimates by age than what most other current research measures, which tends to be lifetime suicidality as opposed to suicidal thoughts or attempts within the past year, Dr. Rafferty added.

”What this shows is, for adolescents, the risk of suicide is something we need to be paying attention to. Because it’s not that it’s something that only happens in adults, this really dispels a lot of the misquoting of the data that’s out there.” That kind of information is valuable for determining resource allocation, he said. “A disparity like this really underlies the importance of mental health resources in this field,” he said.

Dr. Burnside, Dr. Hoffmann, and Dr. Rafferty had no disclosures, and no external funding sources were noted.

WASHINGTON – Transgender and other gender-diverse youth who visited the emergency department (ED) at a single institution had more than five times greater odds of a positive suicide screening compared with their cisgender peers, according to a study presented at the annual meeting of the American Academy of Pediatrics.

“The take-home message here is this study emphasizes the importance of universal screening to identify gender-diverse youth at risk,” Amanda Burnside, PhD, assistant professor of psychiatry and behavioral sciences at Ann and Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, told attendees. “We really need to develop robust strategies and systems to link better mental health services.”

Ann and Robert H. Lurie Children’s Hospital of Chicago

Suicide rates in transgender and gender-diverse youth are exceptionally high among youth in the U.S., Dr. Burnside said during her presentation. For example, the 2022 LGBTQ health survey from the Trevor Project found that much higher percentages of transgender and gender nonconforming youth had considered suicide in the past year compared with cisgender youth, even within the LGBTQ umbrella. Among nearly 34,000 LGBTQ youth aged 13-24, nearly half of trans females (48%) and more than half of trans males (59%) had considered suicide, compared with 28% of cisgender males and 37% of cisgender females. The rate among nonbinary/genderqueer individuals was 53%, and it was 48% for those questioning their gender.

Current methods of identifying trans and gender-diverse (TGD) youth in the hospital, however, may not actually be capturing the entire population.

“In health care settings, research involving TGD individuals has historically been limited to specialized clinic populations or youth with gender-specific diagnostic codes documented in the electronic medical record,” an approach that “likely significantly underestimates the prevalence of TGD youth in health care settings.” While at least one study has attempted to bridge this gap by searching the EMR for keywords, that study only tried to identify trans youth and not other youth on the gender diversity spectrum, such as nonbinary youth or those questioning their gender identity. Dr. Burnside and her colleagues therefore designed a study that used keywords to identify both trans youth and other gender-diverse youth who visited the ED so they could assess the rate of positive suicide screens in this population.
 

Underestimating the population at risk?

The researchers conducted a retrospective cross-sectional study of EMR data for all ED visits during which the patient underwent suicide screening. For the period of November 2019 to August 2022, they collected data on the screening results and the patient’s gender identity, age, race/ethnicity, insurance status, chief complaint in the ED and child opportunity index, which assess a youth’s access to resources based on geography. The suicide screener used was the Ask Suicide–Screening Questions (ASQ) tool.

The keywords they looked for in the EMR to identify trans and gender-diverse youth included transgender, pronouns, agender, gender dysphoria, male-to-female, female-to-male, nonbinary, preferred name, and they/them (captured as a complete term, not as “they” and “them” separately).

“If a keyword was present, the surrounding text was extracted and reviewed by two members of our team,” Dr. Burnside explained in her presentation. “We categorized keywords into either indicative of gender-diverse identity or not, and if it wasn’t clear based on the text extracted, we would conduct a manual chart review,” though that only occurred in about 3% of cases, she added.

Among 15,413 ED encounters with a suicide screen, the researchers identified 1,126 of these keywords in the EMR, among which 91.2% were classified as referring to a gender-diverse patient. Nearly all of the words were at least 90% effective in identify a gender-diverse youth, Dr. Burnside said, and all of the 197 instances of “they/them” were classified as gender diverse.

The accuracy was a little lower for the two keywords that appeared most frequently: For “pronouns,” 86.3% of 306 instances were classified as gender diverse, and for “transgender,” 83.1% of 207 instances were classified as gender diverse. Since some providers ask all patients their pronouns, the presence of “pronouns” in the EMR alone did not necessarily indicate the patient was gender diverse, Dr. Burnside said. A common reason the term “transgender” occurred in the EMR of non–gender diverse patients is that the department’s list of crisis resources includes transgender hotlines.

After identifying all the keywords, the researchers determined how many of these occurred in unique ED encounters and removed those with incomplete screening. Overall, they found 565 encounters by 399 gender-diverse individuals who had a suicide screening, representing 4.6% of total visits. This percentage is slightly lower than recent population-based estimates of gender-diverse youth, the researchers noted.

This population ranged from 8 to 23 years old, and 43% were publicly insured. The chief complaint for most of the patients (77.5%) was a mental health one. They were predominantly White (43%) or Hispanic (35%), with 10% Black youth, 4% Asian youth, and 8% youth who were “other” or two or more races. About half (52%) lived in a neighborhood with a “low” or “very low” child opportunity index.

Within this population, 81% of the patients screened positive on the suicide screening, compared with 23% positive screens across all ED visits. One in ten (10%) gender-diverse youth had active suicidal ideation, compared with 3.4% of the rest of the ED patient population. The researchers calculated that gender-diverse youth had 5.35 times greater odds of screening positive than cisgender youth in the ED (95% confidence interval [CI] 8.7-15.92). Further, a quarter (25%) of the trans and gender-diverse youth who screened positive for suicide risk had come to the ED for a primary complaint unrelated to mental health.

“We had a kid who came in because he broke his arm who had active suicidal ideation,” study coauthor Jennifer A. Hoffmann, MD, assistant professor of pediatrics at the Ann & Robert H. Lurie Children’s Hospital of Chicago and Northwestern University, mentioned after the presentation. That particular patient even had a suicide plan, but was identified as actively suicidal only because of the screening. In other cases, she said, a youth may come in with self-inflicted injuries, and while those are the primary complaint, they are linked with suicidal ideation.

Ann & Robert H. Lurie Children's Hospital of Chicago

Uncovering valuable information

Jason Rafferty, MD, MPH, EdM, clinical assistant professor of pediatrics and of psychiatry and human behavior at Brown University, Providence, R.I., who attended the presentation, noted that the study provides information on a population that’s often difficult to get through traditional EMR research methods.

Brown University

“A lot of medical record systems don’t have uniform ways of capturing [gender diversity], but what we know as providers is that kids are really struggling and that it’s not a surprise that we’re seeing these disparities with suicidality,” Dr. Rafferty said.

The study also provides more discrete estimates by age than what most other current research measures, which tends to be lifetime suicidality as opposed to suicidal thoughts or attempts within the past year, Dr. Rafferty added.

”What this shows is, for adolescents, the risk of suicide is something we need to be paying attention to. Because it’s not that it’s something that only happens in adults, this really dispels a lot of the misquoting of the data that’s out there.” That kind of information is valuable for determining resource allocation, he said. “A disparity like this really underlies the importance of mental health resources in this field,” he said.

Dr. Burnside, Dr. Hoffmann, and Dr. Rafferty had no disclosures, and no external funding sources were noted.

TOPLINE: 

A new study shows that piperacillin-tazobactam and cefepime are equally safe for acute kidney injury (AKI) in acute infection, with cefepime linked to more neurological issues.

METHODOLOGY:

The coadministration of piperacillin-tazobactam and vancomycin may raise the risk for AKI, according to a warning from the Food and Drug Administration.

The ACORN trial included 2,511 adults presenting to emergency department or intensive care unit with suspected infection.

Within 12 hours of presentation, these individuals were prescribed either cefepime (n = 1,214) or piperacillin-tazobactam (n = 1,297).

The primary outcome was the risk for the highest stage of AKI or death within 14 days of randomization.
 

TAKEAWAY:

The highest stage of AKI or death within 14 days did not differ significantly between the cefepime and piperacillin-tazobactam groups (odds ratio, 0.95; P = .56).

The incidence of major adverse kidney events by day 14 was not significantly different between the two groups (absolute risk difference, 1.4%; 95% confidence interval, −1.0% to 3.8%).

Patients in the cefepime versus piperacillin-tazobactam group had fewer days alive and free of delirium and coma within 14 days (OR, 0.79; 95% CI, 0.65-0.95).
 

IN PRACTICE:

In an accompanying editorial, Steven Y. C. Tong, department of infectious diseases, University of Melbourne, and colleagues wrote: “Because institutions must make decisions about which antibiotics to position on medical wards for rapid administration in patients meeting sepsis criteria, these data should offer solace that if the choice is made to use piperacillin-tazobactam, there is not an increased risk of AKI.”

SOURCE:

The study was led by Edward T. Qian, MD, of Vanderbilt University Medical Center, Nashville, Tenn. It was published online in JAMA with an accompanying editorial.

LIMITATIONS:

The study was conducted at a single academic center, which may limit the generalizability of findings.

Both patients and clinicians were not blinded to group assignment, which may have influenced clinical assessments like Richmond Agitation-Sedation Scale and CAM-ICU or the frequency of laboratory measurements like creatinine.
 

DISCLOSURES:

The project was supported by the Vanderbilt Institute for Clinical and Translational Research and several other sources, including grants from the National Center for Advancing Translational Sciences. Some authors declared receiving travel grant, personal fees, honoraria, and unrelated research support from various sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

A new study shows that piperacillin-tazobactam and cefepime are equally safe for acute kidney injury (AKI) in acute infection, with cefepime linked to more neurological issues.

METHODOLOGY:

The coadministration of piperacillin-tazobactam and vancomycin may raise the risk for AKI, according to a warning from the Food and Drug Administration.

The ACORN trial included 2,511 adults presenting to emergency department or intensive care unit with suspected infection.

Within 12 hours of presentation, these individuals were prescribed either cefepime (n = 1,214) or piperacillin-tazobactam (n = 1,297).

The primary outcome was the risk for the highest stage of AKI or death within 14 days of randomization.
 

TAKEAWAY:

The highest stage of AKI or death within 14 days did not differ significantly between the cefepime and piperacillin-tazobactam groups (odds ratio, 0.95; P = .56).

The incidence of major adverse kidney events by day 14 was not significantly different between the two groups (absolute risk difference, 1.4%; 95% confidence interval, −1.0% to 3.8%).

Patients in the cefepime versus piperacillin-tazobactam group had fewer days alive and free of delirium and coma within 14 days (OR, 0.79; 95% CI, 0.65-0.95).
 

IN PRACTICE:

In an accompanying editorial, Steven Y. C. Tong, department of infectious diseases, University of Melbourne, and colleagues wrote: “Because institutions must make decisions about which antibiotics to position on medical wards for rapid administration in patients meeting sepsis criteria, these data should offer solace that if the choice is made to use piperacillin-tazobactam, there is not an increased risk of AKI.”

SOURCE:

The study was led by Edward T. Qian, MD, of Vanderbilt University Medical Center, Nashville, Tenn. It was published online in JAMA with an accompanying editorial.

LIMITATIONS:

The study was conducted at a single academic center, which may limit the generalizability of findings.

Both patients and clinicians were not blinded to group assignment, which may have influenced clinical assessments like Richmond Agitation-Sedation Scale and CAM-ICU or the frequency of laboratory measurements like creatinine.
 

DISCLOSURES:

The project was supported by the Vanderbilt Institute for Clinical and Translational Research and several other sources, including grants from the National Center for Advancing Translational Sciences. Some authors declared receiving travel grant, personal fees, honoraria, and unrelated research support from various sources.

A version of this article appeared on Medscape.com.

TOPLINE: 

A new study shows that piperacillin-tazobactam and cefepime are equally safe for acute kidney injury (AKI) in acute infection, with cefepime linked to more neurological issues.

METHODOLOGY:

The coadministration of piperacillin-tazobactam and vancomycin may raise the risk for AKI, according to a warning from the Food and Drug Administration.

The ACORN trial included 2,511 adults presenting to emergency department or intensive care unit with suspected infection.

Within 12 hours of presentation, these individuals were prescribed either cefepime (n = 1,214) or piperacillin-tazobactam (n = 1,297).

The primary outcome was the risk for the highest stage of AKI or death within 14 days of randomization.
 

TAKEAWAY:

The highest stage of AKI or death within 14 days did not differ significantly between the cefepime and piperacillin-tazobactam groups (odds ratio, 0.95; P = .56).

The incidence of major adverse kidney events by day 14 was not significantly different between the two groups (absolute risk difference, 1.4%; 95% confidence interval, −1.0% to 3.8%).

Patients in the cefepime versus piperacillin-tazobactam group had fewer days alive and free of delirium and coma within 14 days (OR, 0.79; 95% CI, 0.65-0.95).
 

IN PRACTICE:

In an accompanying editorial, Steven Y. C. Tong, department of infectious diseases, University of Melbourne, and colleagues wrote: “Because institutions must make decisions about which antibiotics to position on medical wards for rapid administration in patients meeting sepsis criteria, these data should offer solace that if the choice is made to use piperacillin-tazobactam, there is not an increased risk of AKI.”

SOURCE:

The study was led by Edward T. Qian, MD, of Vanderbilt University Medical Center, Nashville, Tenn. It was published online in JAMA with an accompanying editorial.

LIMITATIONS:

The study was conducted at a single academic center, which may limit the generalizability of findings.

Both patients and clinicians were not blinded to group assignment, which may have influenced clinical assessments like Richmond Agitation-Sedation Scale and CAM-ICU or the frequency of laboratory measurements like creatinine.
 

DISCLOSURES:

The project was supported by the Vanderbilt Institute for Clinical and Translational Research and several other sources, including grants from the National Center for Advancing Translational Sciences. Some authors declared receiving travel grant, personal fees, honoraria, and unrelated research support from various sources.

A version of this article appeared on Medscape.com.

TOPLINE:

Severe mental illness (SMI) has been linked to a 50% increased risk for all-cause mortality risk after COVID-19, a large population-based study suggests.

METHODOLOGY:

• Investigators analyzed data from the Clinical Practice Research Datalink database, which contains health information on 13.5 million patients receiving care from family practices in England and Northern Ireland.
• The study included participants with SMI, including schizophrenia, schizoaffective disorder, and bipolar disorder.
• Participants were aged 5 years or older with a SARS-CoV-2 infection recorded between Feb. 1, 2020, and March 31, 2021, spanning two waves of the pandemic.
• Death rates among participants with SMI and COVID-19 (n = 7,150; 56% female) were compared with those in a control group of participants without SMI who had been diagnosed with COVID-19 (n = 650,000; 55% female).

TAKEAWAY:

• Participants with SMI and COVID-19 had a 53% higher risk for death than those in the non-SMI control group (adjusted hazard ratio, 1.53; 95% confidence interval, 1.39-1.68).
• Black Caribbean/Black African participants were more likely than White participants to die of COVID-19 (aHR, 1.22; 95% CI, 1.12-1.34), although ethnicity was not recorded in 30% of participants.
• After SARS-CoV-2 infection, for every additional multimorbid condition, the aHR for death increased by 6% in the SMI group and 16% in the non-SMI group (P = .001). Some of these conditions included hypertension, heart disease, diabetes, kidney disease, depression, and anxiety.

IN PRACTICE:

“From a public health perspective, our study has emphasized the need for early and timely preventative interventions (e.g. vaccination) for the SMI population. Future studies are needed to disentangle the complex biological and psychosocial factors, and health care pathways, that have led to the greater mortality rates in the SMI population,” the authors write.

SOURCE:

Jayati Das-Munshi, MD, of Kings College London, led the study, which was published online in the British Journal of Psychiatry. The study was funded by the Health Foundation.

LIMITATIONS:

COVID-19 may have been underdiagnosed or underreported in the records studied. Also, investigators did not have information about cause of death.

DISCLOSURES:

One author received funding from Janssen, GSK, and Takeda. All other authors declared no conflicts of interest.

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

TOPLINE:

Severe mental illness (SMI) has been linked to a 50% increased risk for all-cause mortality risk after COVID-19, a large population-based study suggests.

METHODOLOGY:

• Investigators analyzed data from the Clinical Practice Research Datalink database, which contains health information on 13.5 million patients receiving care from family practices in England and Northern Ireland.
• The study included participants with SMI, including schizophrenia, schizoaffective disorder, and bipolar disorder.
• Participants were aged 5 years or older with a SARS-CoV-2 infection recorded between Feb. 1, 2020, and March 31, 2021, spanning two waves of the pandemic.
• Death rates among participants with SMI and COVID-19 (n = 7,150; 56% female) were compared with those in a control group of participants without SMI who had been diagnosed with COVID-19 (n = 650,000; 55% female).

TAKEAWAY:

• Participants with SMI and COVID-19 had a 53% higher risk for death than those in the non-SMI control group (adjusted hazard ratio, 1.53; 95% confidence interval, 1.39-1.68).
• Black Caribbean/Black African participants were more likely than White participants to die of COVID-19 (aHR, 1.22; 95% CI, 1.12-1.34), although ethnicity was not recorded in 30% of participants.
• After SARS-CoV-2 infection, for every additional multimorbid condition, the aHR for death increased by 6% in the SMI group and 16% in the non-SMI group (P = .001). Some of these conditions included hypertension, heart disease, diabetes, kidney disease, depression, and anxiety.

IN PRACTICE:

“From a public health perspective, our study has emphasized the need for early and timely preventative interventions (e.g. vaccination) for the SMI population. Future studies are needed to disentangle the complex biological and psychosocial factors, and health care pathways, that have led to the greater mortality rates in the SMI population,” the authors write.

SOURCE:

Jayati Das-Munshi, MD, of Kings College London, led the study, which was published online in the British Journal of Psychiatry. The study was funded by the Health Foundation.

LIMITATIONS:

COVID-19 may have been underdiagnosed or underreported in the records studied. Also, investigators did not have information about cause of death.

DISCLOSURES:

One author received funding from Janssen, GSK, and Takeda. All other authors declared no conflicts of interest.

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

TOPLINE:

Severe mental illness (SMI) has been linked to a 50% increased risk for all-cause mortality risk after COVID-19, a large population-based study suggests.

METHODOLOGY:

• Investigators analyzed data from the Clinical Practice Research Datalink database, which contains health information on 13.5 million patients receiving care from family practices in England and Northern Ireland.
• The study included participants with SMI, including schizophrenia, schizoaffective disorder, and bipolar disorder.
• Participants were aged 5 years or older with a SARS-CoV-2 infection recorded between Feb. 1, 2020, and March 31, 2021, spanning two waves of the pandemic.
• Death rates among participants with SMI and COVID-19 (n = 7,150; 56% female) were compared with those in a control group of participants without SMI who had been diagnosed with COVID-19 (n = 650,000; 55% female).

TAKEAWAY:

• Participants with SMI and COVID-19 had a 53% higher risk for death than those in the non-SMI control group (adjusted hazard ratio, 1.53; 95% confidence interval, 1.39-1.68).
• Black Caribbean/Black African participants were more likely than White participants to die of COVID-19 (aHR, 1.22; 95% CI, 1.12-1.34), although ethnicity was not recorded in 30% of participants.
• After SARS-CoV-2 infection, for every additional multimorbid condition, the aHR for death increased by 6% in the SMI group and 16% in the non-SMI group (P = .001). Some of these conditions included hypertension, heart disease, diabetes, kidney disease, depression, and anxiety.

IN PRACTICE:

“From a public health perspective, our study has emphasized the need for early and timely preventative interventions (e.g. vaccination) for the SMI population. Future studies are needed to disentangle the complex biological and psychosocial factors, and health care pathways, that have led to the greater mortality rates in the SMI population,” the authors write.

SOURCE:

Jayati Das-Munshi, MD, of Kings College London, led the study, which was published online in the British Journal of Psychiatry. The study was funded by the Health Foundation.

LIMITATIONS:

COVID-19 may have been underdiagnosed or underreported in the records studied. Also, investigators did not have information about cause of death.

DISCLOSURES:

One author received funding from Janssen, GSK, and Takeda. All other authors declared no conflicts of interest.

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

TOPLINE:

Nirmatrelvir-ritonavir doesn’t reduce the incidence of most post-COVID conditions, according to a new study. Thromboembolic events are the exception.
 

METHODOLOGY:

• A retrospective study of 9,593 veterans older than 65 years examined the impact of nirmatrelvir-ritonavir in comparison with no treatment on post–COVID-19 conditions (PCCs).
• Researchers coded 31 conditions, including those that fell into cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, and endocrine categories.
• The incidence of PCCs was analyzed 31-180 days after treatment.

TAKEAWAY:

• The combined incidence of venous thromboembolism and pulmonary embolism was reduced among patients given nirmatrelvir-ritonavir.
• No statistically significant reduction of other conditions was found.
• Results differ from the conclusions of a smaller study that found that the incidence of 10 of 13 PCCs was lower.

IN PRACTICE:

“Our results suggest that considerations about PCCs may not be an important factor in COVID-19 treatment decisions,” the authors write.

SOURCE:

The study was funded by the Department of Veterans Affairs and was published online in Annals of Internal Medicine. George Ioannou, MD, director of hepatology at the VA Puget Sound Health Care System in Seattle, led the study.

LIMITATIONS:

A large number of outcomes were observed, so it’s possible that the association between treatment with nirmatrelvir-ritonavir and reduced incidence of thromboembolic events occurred by chance.

Data on COVID-19 treatments and PCCs may be incomplete. The long-term effects of PCCs may not have been fully captured by the ICD-10, which was used for diagnosis codes.

Electronic health records did not accurately capture the symptom burden or the date symptoms began. Patients in the treatment arm may have had more symptoms than matched control persons who were not treated.
 

DISCLOSURES:

The authors reported relationships with the Korean Diabetes Association, the American Diabetes Association, the International Society for the Diabetic Foot, Quality Insights, Brown University, and the Society for Women in Urology, among others.

A version of this article appeared on Medscape.com.

TOPLINE:

Nirmatrelvir-ritonavir doesn’t reduce the incidence of most post-COVID conditions, according to a new study. Thromboembolic events are the exception.
 

METHODOLOGY:

• A retrospective study of 9,593 veterans older than 65 years examined the impact of nirmatrelvir-ritonavir in comparison with no treatment on post–COVID-19 conditions (PCCs).
• Researchers coded 31 conditions, including those that fell into cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, and endocrine categories.
• The incidence of PCCs was analyzed 31-180 days after treatment.

TAKEAWAY:

• The combined incidence of venous thromboembolism and pulmonary embolism was reduced among patients given nirmatrelvir-ritonavir.
• No statistically significant reduction of other conditions was found.
• Results differ from the conclusions of a smaller study that found that the incidence of 10 of 13 PCCs was lower.

IN PRACTICE:

“Our results suggest that considerations about PCCs may not be an important factor in COVID-19 treatment decisions,” the authors write.

SOURCE:

The study was funded by the Department of Veterans Affairs and was published online in Annals of Internal Medicine. George Ioannou, MD, director of hepatology at the VA Puget Sound Health Care System in Seattle, led the study.

LIMITATIONS:

A large number of outcomes were observed, so it’s possible that the association between treatment with nirmatrelvir-ritonavir and reduced incidence of thromboembolic events occurred by chance.

Data on COVID-19 treatments and PCCs may be incomplete. The long-term effects of PCCs may not have been fully captured by the ICD-10, which was used for diagnosis codes.

Electronic health records did not accurately capture the symptom burden or the date symptoms began. Patients in the treatment arm may have had more symptoms than matched control persons who were not treated.
 

DISCLOSURES:

The authors reported relationships with the Korean Diabetes Association, the American Diabetes Association, the International Society for the Diabetic Foot, Quality Insights, Brown University, and the Society for Women in Urology, among others.

A version of this article appeared on Medscape.com.

TOPLINE:

Nirmatrelvir-ritonavir doesn’t reduce the incidence of most post-COVID conditions, according to a new study. Thromboembolic events are the exception.
 

METHODOLOGY:

• A retrospective study of 9,593 veterans older than 65 years examined the impact of nirmatrelvir-ritonavir in comparison with no treatment on post–COVID-19 conditions (PCCs).
• Researchers coded 31 conditions, including those that fell into cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, and endocrine categories.
• The incidence of PCCs was analyzed 31-180 days after treatment.

TAKEAWAY:

• The combined incidence of venous thromboembolism and pulmonary embolism was reduced among patients given nirmatrelvir-ritonavir.
• No statistically significant reduction of other conditions was found.
• Results differ from the conclusions of a smaller study that found that the incidence of 10 of 13 PCCs was lower.

IN PRACTICE:

“Our results suggest that considerations about PCCs may not be an important factor in COVID-19 treatment decisions,” the authors write.

SOURCE:

The study was funded by the Department of Veterans Affairs and was published online in Annals of Internal Medicine. George Ioannou, MD, director of hepatology at the VA Puget Sound Health Care System in Seattle, led the study.

LIMITATIONS:

A large number of outcomes were observed, so it’s possible that the association between treatment with nirmatrelvir-ritonavir and reduced incidence of thromboembolic events occurred by chance.

Data on COVID-19 treatments and PCCs may be incomplete. The long-term effects of PCCs may not have been fully captured by the ICD-10, which was used for diagnosis codes.

Electronic health records did not accurately capture the symptom burden or the date symptoms began. Patients in the treatment arm may have had more symptoms than matched control persons who were not treated.
 

DISCLOSURES:

The authors reported relationships with the Korean Diabetes Association, the American Diabetes Association, the International Society for the Diabetic Foot, Quality Insights, Brown University, and the Society for Women in Urology, among others.

A version of this article appeared on Medscape.com.

The anti-inflammatory agent colchicine, started within 24 hours of acute ischemic stroke or a transient ischemic attack (TIA), was not associated with a reduction in subsequent strokes or other vascular events at 90 days in the CHANCE-3 trial.

The results were presented by Yongjun Wang, MD, Beijing Tiantan Hospital, Capital Medical University, at the annual World Stroke Congress, sponsored by the World Stroke Organization.

Dr. Wang noted that inflammation may be a key factor involved in the residual risk for recurrent stroke, with data from previous CHANCE trials suggesting a higher stroke recurrence rate in patients with higher levels of high-sensitivity C-reactive protein (hsCRP), a key marker of inflammation.

Low-dose colchicine, which acts as an anti-inflammatory agent, has recently been approved in many countries for patients with established atherosclerotic disease or multiple risk factors for cardiovascular disease to reduce the risk for future cardiovascular events. This follows benefits seen in those populations in the LoDoCo-2 and COLCOT trials.

The CHANCE-3 study was conducted to evaluate whether similar benefits could be found in patients with acute ischemic stroke.

The trial involved 8,369 Chinese patients with minor to moderate ischemic stroke (National Institutes of Health Stroke Scale score ≤ 5) or high-risk TIA (ABCD2 score ≥ 4) who had an hsCRP level of at least 2 mg/L.

Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive colchicine (1 mg daily on days 1-3, followed by 0.5 mg daily for a total of 90 days) or placebo, on a background of optimal medical therapy.

The primary outcome was any stroke within 90 days. The key secondary outcomes included a composite of stroke, TIA, myocardial infarction, and vascular death within 90 days, and Modified Rankin Scale score greater than 1 at 90 days.

Results showed that the primary outcome of any stroke at 90 days occurred in 6.3% of the colchicine group versus 6.5% of the placebo group, a nonsignificant difference (P = .79).

All secondary outcomes were also neutral, with no differences between the two groups.

Addressing the different results in CHANCE-3, compared with those of the cardiovascular trials of colchicine, Dr. Wang pointed out that the cardiovascular trials had a much longer treatment and follow-up time (an average of 22 months), compared with just 3 months in CHANCE-3.

“Clinical trials with longer treatment times are needed to further assess the effects of colchicine after cerebrovascular events, but it may be that ischemic cerebrovascular disease and ischemic heart disease respond differently to colchicine treatment,” he concluded.

Commenting on the study, cochair of the WSC session at which it was presented, Ashkan Shoamanesh, MD, associate professor of medicine at McMaster University, Hamilton, Ont., said CHANCE-3 was a well-designed large phase 3 randomized trial and the first such trial to test colchicine for secondary stroke prevention. 

He agreed with Dr. Wang that the follow-up duration for this initial analysis of 3-month outcomes may have been too short to see an effect.

“So, we require randomized trials with longer follow-up prior to abandoning this potential treatment,” he added. 

Dr. Shoamanesh noted that several additional trials are currently ongoing testing colchicine for secondary prevention in patients with stroke. These include the CONVINCE, CASPER, CoVasc-ICH, and RIISC-THETIS trials.

He also pointed out that, in contrast to ischemic heart disease, which results from atherosclerosis, the mechanisms underlying ischemic stroke are more heterogeneous and include various vascular and cardioembolic pathologies.

The CHANCE-3 study was funded by grants from the National Natural Science Foundation of China, the Ministry of Science and Technology of China, the Chinese Academy of Medical Sciences, and the Beijing Municipal Health Commission.

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

The anti-inflammatory agent colchicine, started within 24 hours of acute ischemic stroke or a transient ischemic attack (TIA), was not associated with a reduction in subsequent strokes or other vascular events at 90 days in the CHANCE-3 trial.

The results were presented by Yongjun Wang, MD, Beijing Tiantan Hospital, Capital Medical University, at the annual World Stroke Congress, sponsored by the World Stroke Organization.

Dr. Wang noted that inflammation may be a key factor involved in the residual risk for recurrent stroke, with data from previous CHANCE trials suggesting a higher stroke recurrence rate in patients with higher levels of high-sensitivity C-reactive protein (hsCRP), a key marker of inflammation.

Low-dose colchicine, which acts as an anti-inflammatory agent, has recently been approved in many countries for patients with established atherosclerotic disease or multiple risk factors for cardiovascular disease to reduce the risk for future cardiovascular events. This follows benefits seen in those populations in the LoDoCo-2 and COLCOT trials.

The CHANCE-3 study was conducted to evaluate whether similar benefits could be found in patients with acute ischemic stroke.

The trial involved 8,369 Chinese patients with minor to moderate ischemic stroke (National Institutes of Health Stroke Scale score ≤ 5) or high-risk TIA (ABCD2 score ≥ 4) who had an hsCRP level of at least 2 mg/L.

Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive colchicine (1 mg daily on days 1-3, followed by 0.5 mg daily for a total of 90 days) or placebo, on a background of optimal medical therapy.

The primary outcome was any stroke within 90 days. The key secondary outcomes included a composite of stroke, TIA, myocardial infarction, and vascular death within 90 days, and Modified Rankin Scale score greater than 1 at 90 days.

Results showed that the primary outcome of any stroke at 90 days occurred in 6.3% of the colchicine group versus 6.5% of the placebo group, a nonsignificant difference (P = .79).

All secondary outcomes were also neutral, with no differences between the two groups.

Addressing the different results in CHANCE-3, compared with those of the cardiovascular trials of colchicine, Dr. Wang pointed out that the cardiovascular trials had a much longer treatment and follow-up time (an average of 22 months), compared with just 3 months in CHANCE-3.

“Clinical trials with longer treatment times are needed to further assess the effects of colchicine after cerebrovascular events, but it may be that ischemic cerebrovascular disease and ischemic heart disease respond differently to colchicine treatment,” he concluded.

Commenting on the study, cochair of the WSC session at which it was presented, Ashkan Shoamanesh, MD, associate professor of medicine at McMaster University, Hamilton, Ont., said CHANCE-3 was a well-designed large phase 3 randomized trial and the first such trial to test colchicine for secondary stroke prevention. 

He agreed with Dr. Wang that the follow-up duration for this initial analysis of 3-month outcomes may have been too short to see an effect.

“So, we require randomized trials with longer follow-up prior to abandoning this potential treatment,” he added. 

Dr. Shoamanesh noted that several additional trials are currently ongoing testing colchicine for secondary prevention in patients with stroke. These include the CONVINCE, CASPER, CoVasc-ICH, and RIISC-THETIS trials.

He also pointed out that, in contrast to ischemic heart disease, which results from atherosclerosis, the mechanisms underlying ischemic stroke are more heterogeneous and include various vascular and cardioembolic pathologies.

The CHANCE-3 study was funded by grants from the National Natural Science Foundation of China, the Ministry of Science and Technology of China, the Chinese Academy of Medical Sciences, and the Beijing Municipal Health Commission.

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

The anti-inflammatory agent colchicine, started within 24 hours of acute ischemic stroke or a transient ischemic attack (TIA), was not associated with a reduction in subsequent strokes or other vascular events at 90 days in the CHANCE-3 trial.

The results were presented by Yongjun Wang, MD, Beijing Tiantan Hospital, Capital Medical University, at the annual World Stroke Congress, sponsored by the World Stroke Organization.

Dr. Wang noted that inflammation may be a key factor involved in the residual risk for recurrent stroke, with data from previous CHANCE trials suggesting a higher stroke recurrence rate in patients with higher levels of high-sensitivity C-reactive protein (hsCRP), a key marker of inflammation.

Low-dose colchicine, which acts as an anti-inflammatory agent, has recently been approved in many countries for patients with established atherosclerotic disease or multiple risk factors for cardiovascular disease to reduce the risk for future cardiovascular events. This follows benefits seen in those populations in the LoDoCo-2 and COLCOT trials.

The CHANCE-3 study was conducted to evaluate whether similar benefits could be found in patients with acute ischemic stroke.

The trial involved 8,369 Chinese patients with minor to moderate ischemic stroke (National Institutes of Health Stroke Scale score ≤ 5) or high-risk TIA (ABCD2 score ≥ 4) who had an hsCRP level of at least 2 mg/L.

Patients were assigned within 24 hours after symptom onset, in a 1:1 ratio, to receive colchicine (1 mg daily on days 1-3, followed by 0.5 mg daily for a total of 90 days) or placebo, on a background of optimal medical therapy.

The primary outcome was any stroke within 90 days. The key secondary outcomes included a composite of stroke, TIA, myocardial infarction, and vascular death within 90 days, and Modified Rankin Scale score greater than 1 at 90 days.

Results showed that the primary outcome of any stroke at 90 days occurred in 6.3% of the colchicine group versus 6.5% of the placebo group, a nonsignificant difference (P = .79).

All secondary outcomes were also neutral, with no differences between the two groups.

Addressing the different results in CHANCE-3, compared with those of the cardiovascular trials of colchicine, Dr. Wang pointed out that the cardiovascular trials had a much longer treatment and follow-up time (an average of 22 months), compared with just 3 months in CHANCE-3.

“Clinical trials with longer treatment times are needed to further assess the effects of colchicine after cerebrovascular events, but it may be that ischemic cerebrovascular disease and ischemic heart disease respond differently to colchicine treatment,” he concluded.

Commenting on the study, cochair of the WSC session at which it was presented, Ashkan Shoamanesh, MD, associate professor of medicine at McMaster University, Hamilton, Ont., said CHANCE-3 was a well-designed large phase 3 randomized trial and the first such trial to test colchicine for secondary stroke prevention. 

He agreed with Dr. Wang that the follow-up duration for this initial analysis of 3-month outcomes may have been too short to see an effect.

“So, we require randomized trials with longer follow-up prior to abandoning this potential treatment,” he added. 

Dr. Shoamanesh noted that several additional trials are currently ongoing testing colchicine for secondary prevention in patients with stroke. These include the CONVINCE, CASPER, CoVasc-ICH, and RIISC-THETIS trials.

He also pointed out that, in contrast to ischemic heart disease, which results from atherosclerosis, the mechanisms underlying ischemic stroke are more heterogeneous and include various vascular and cardioembolic pathologies.

The CHANCE-3 study was funded by grants from the National Natural Science Foundation of China, the Ministry of Science and Technology of China, the Chinese Academy of Medical Sciences, and the Beijing Municipal Health Commission.

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

TOPLINE:

The risk for Guillain-Barré syndrome (GBS) is six times higher in people with COVID-19 in the 6 weeks following infection, according to a new study that also showed receipt of the Pfizer-BioNTech mRNA vaccine reduced GSB risk by 59%.

METHODOLOGY:

• The nested-case control study analyzed data from the largest healthcare provider in Israel for 3.2 million patients aged 16 years and older, with no history of GBS.
• GBS cases (n = 76) were identified based on hospital discharge data from January 2021 to June 2022.
• For every GBS case, investigators chose 10 controls at random, matched for age, gender, and follow-up duration (n = 760).
• Investigators examined the association between GBS and SARS-CoV-2 infection, established through documentation of prior positive SARS-CoV-2 test (PCR or antigen), and any COVID-19 vaccine administration.

TAKEAWAY:

• Among those diagnosed with GBS, 8 were exposed to SARS-CoV-2 infection only, 7 were exposed to COVID-19 vaccination only, and 1 patient was exposed to both SARS-CoV-2 infection and COVID-19 vaccination in the prior 6 weeks, leaving 60 GBS patients without exposure to either infection or vaccination.
• All COVID-19 vaccine doses administered in GBS cases within 6 weeks of the index date, and all but two doses administered in controls in the same timeframe, were Pfizer-BioNTech vaccines.
• Compared with people without GBS, those with the condition were more than six times as likely to have had SARS-CoV-2 infection within 6 weeks of GBS diagnosis (adjusted odds ratio, 6.30; 95% confidence interval, 2.55-15.56).
• People who received the COVID-19 vaccine were 59% less likely to develop GBS than those who did not get the vaccine (aOR, 0.41; 95% CI, 0.17-0.96).

IN PRACTICE:

“While Guillain-Barré is extremely rare, people should be aware that having a COVID infection can increase their risk of developing the disorder, and receiving an mRNA vaccine can decrease their risk,” study author Anat Arbel, MD, of Lady Davis Carmel Medical Center and the Technion-Israel Institute of Technology, Haifa, Israel, said in a press release.

SOURCE:

In addition to Dr. Arbel, the other lead author is Haya Bishara, MD, of Lady Davis Carmel Medical Center. The research was published online  in the journal Neurology.

LIMITATIONS:

There is a possibility of misclassification of SARS-CoV-2 infection, which could lead to an overestimation of the magnitude of association between infection and GBS. The diagnosis of GBS relied solely on ICD-9 coding, which has been shown in prior studies to contain errors.

DISCLOSURES:

The study was unfunded. Dr. Bishara and Dr. Arbel report no relevant financial relationships. One co-author, Eitan Auriel, MD, has received lecturer fees from Novo Nordisk, Pfizer, Boehringer Ingelheim, and Medison.

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

TOPLINE:

The risk for Guillain-Barré syndrome (GBS) is six times higher in people with COVID-19 in the 6 weeks following infection, according to a new study that also showed receipt of the Pfizer-BioNTech mRNA vaccine reduced GSB risk by 59%.

METHODOLOGY:

• The nested-case control study analyzed data from the largest healthcare provider in Israel for 3.2 million patients aged 16 years and older, with no history of GBS.
• GBS cases (n = 76) were identified based on hospital discharge data from January 2021 to June 2022.
• For every GBS case, investigators chose 10 controls at random, matched for age, gender, and follow-up duration (n = 760).
• Investigators examined the association between GBS and SARS-CoV-2 infection, established through documentation of prior positive SARS-CoV-2 test (PCR or antigen), and any COVID-19 vaccine administration.

TAKEAWAY:

• Among those diagnosed with GBS, 8 were exposed to SARS-CoV-2 infection only, 7 were exposed to COVID-19 vaccination only, and 1 patient was exposed to both SARS-CoV-2 infection and COVID-19 vaccination in the prior 6 weeks, leaving 60 GBS patients without exposure to either infection or vaccination.
• All COVID-19 vaccine doses administered in GBS cases within 6 weeks of the index date, and all but two doses administered in controls in the same timeframe, were Pfizer-BioNTech vaccines.
• Compared with people without GBS, those with the condition were more than six times as likely to have had SARS-CoV-2 infection within 6 weeks of GBS diagnosis (adjusted odds ratio, 6.30; 95% confidence interval, 2.55-15.56).
• People who received the COVID-19 vaccine were 59% less likely to develop GBS than those who did not get the vaccine (aOR, 0.41; 95% CI, 0.17-0.96).

IN PRACTICE:

“While Guillain-Barré is extremely rare, people should be aware that having a COVID infection can increase their risk of developing the disorder, and receiving an mRNA vaccine can decrease their risk,” study author Anat Arbel, MD, of Lady Davis Carmel Medical Center and the Technion-Israel Institute of Technology, Haifa, Israel, said in a press release.

SOURCE:

In addition to Dr. Arbel, the other lead author is Haya Bishara, MD, of Lady Davis Carmel Medical Center. The research was published online  in the journal Neurology.

LIMITATIONS:

There is a possibility of misclassification of SARS-CoV-2 infection, which could lead to an overestimation of the magnitude of association between infection and GBS. The diagnosis of GBS relied solely on ICD-9 coding, which has been shown in prior studies to contain errors.

DISCLOSURES:

The study was unfunded. Dr. Bishara and Dr. Arbel report no relevant financial relationships. One co-author, Eitan Auriel, MD, has received lecturer fees from Novo Nordisk, Pfizer, Boehringer Ingelheim, and Medison.

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

TOPLINE:

The risk for Guillain-Barré syndrome (GBS) is six times higher in people with COVID-19 in the 6 weeks following infection, according to a new study that also showed receipt of the Pfizer-BioNTech mRNA vaccine reduced GSB risk by 59%.

METHODOLOGY:

• The nested-case control study analyzed data from the largest healthcare provider in Israel for 3.2 million patients aged 16 years and older, with no history of GBS.
• GBS cases (n = 76) were identified based on hospital discharge data from January 2021 to June 2022.
• For every GBS case, investigators chose 10 controls at random, matched for age, gender, and follow-up duration (n = 760).
• Investigators examined the association between GBS and SARS-CoV-2 infection, established through documentation of prior positive SARS-CoV-2 test (PCR or antigen), and any COVID-19 vaccine administration.

TAKEAWAY:

• Among those diagnosed with GBS, 8 were exposed to SARS-CoV-2 infection only, 7 were exposed to COVID-19 vaccination only, and 1 patient was exposed to both SARS-CoV-2 infection and COVID-19 vaccination in the prior 6 weeks, leaving 60 GBS patients without exposure to either infection or vaccination.
• All COVID-19 vaccine doses administered in GBS cases within 6 weeks of the index date, and all but two doses administered in controls in the same timeframe, were Pfizer-BioNTech vaccines.
• Compared with people without GBS, those with the condition were more than six times as likely to have had SARS-CoV-2 infection within 6 weeks of GBS diagnosis (adjusted odds ratio, 6.30; 95% confidence interval, 2.55-15.56).
• People who received the COVID-19 vaccine were 59% less likely to develop GBS than those who did not get the vaccine (aOR, 0.41; 95% CI, 0.17-0.96).

IN PRACTICE:

“While Guillain-Barré is extremely rare, people should be aware that having a COVID infection can increase their risk of developing the disorder, and receiving an mRNA vaccine can decrease their risk,” study author Anat Arbel, MD, of Lady Davis Carmel Medical Center and the Technion-Israel Institute of Technology, Haifa, Israel, said in a press release.

SOURCE:

In addition to Dr. Arbel, the other lead author is Haya Bishara, MD, of Lady Davis Carmel Medical Center. The research was published online  in the journal Neurology.

LIMITATIONS:

There is a possibility of misclassification of SARS-CoV-2 infection, which could lead to an overestimation of the magnitude of association between infection and GBS. The diagnosis of GBS relied solely on ICD-9 coding, which has been shown in prior studies to contain errors.

DISCLOSURES:

The study was unfunded. Dr. Bishara and Dr. Arbel report no relevant financial relationships. One co-author, Eitan Auriel, MD, has received lecturer fees from Novo Nordisk, Pfizer, Boehringer Ingelheim, and Medison.

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

New evidence shows for the first time that the virus that causes COVID directly infects atherosclerotic plaques in the coronary arteries, producing a persistent inflammatory response.

The findings may not only explain the link between COVID and the increased risk of cardiovascular events but mark a starting point for new therapeutic approaches.

“Our study shows there is persistence of viral debris in the artery,” senior investigator Chiara Giannarelli, MD, associate professor of medicine and pathology at NYU Langone Health, New York, said in an interview. “There is an important inflammatory response. We can now look at ways to control this inflammation,” she said.

Dr. Giannarelli says COVID is more than a respiratory virus and that it can affect the whole body. “Our study shows a remarkable ability of the virus to hijack the immune system,” she points out. “Our findings may explain how that happens.”

Dr. Giannarelli says it’s important for doctors and patients to be aware of an increased cardiovascular risk after a SARS-CoV-2 infection and to pay extra attention to traditional risk factors, such as blood pressure and cholesterol.

“This study showing that severe acute respiratory syndrome coronavirus directly infects coronary artery plaques, producing inflammatory substances, really joins the dots and helps our understanding on why we’re seeing so much heart disease in COVID patients,” Peter Hotez, MD, professor of molecular virology and microbiology at Baylor College of Medicine, Houston, said in an interview.

Asked whether this direct infection of vascular plaques was unique to SARS-CoV-2 or whether this may also occur with other viruses, both Dr. Giannarelli and Dr. Hotez said they believe this may be a specific COVID effect.

“I wouldn’t say it is likely that other viruses infect coronary arteries in this way, but I suppose it is possible,” Dr. Giannarelli said.

Dr. Hotez pointed out that other viruses can cause inflammation in the heart, such as myocarditis. “But I can’t think of another virus that stimulates the sequence of events in coronary artery inflammation like we’re seeing here.”

Dr. Giannarelli noted that influenza is also associated with an increased risk of cardiovascular events, but there has been no evidence to date that it directly affects coronary arteries.

Dr. Hotez added that the increased risk of cardiovascular events with influenza has also been reported to be prolonged after the acute infection. “These new findings with SARS-CoV-2 could stimulate a redoubling of efforts to look at this possibility with influenza,” he suggested.
 

Heart disease after COVID

In a recent article published online in Nature Cardiovascular Research, Dr. Giannarelli and colleagues analyzed human autopsy tissue samples from coronary arterial walls of patients who had died from COVID in the early stages of the pandemic in New York.

They found an accumulation of viral RNA in atherosclerotic plaques in the coronary arteries, which was particularly concentrated in lipid-rich macrophage foam cells present within the plaques.

“Our data conclusively demonstrate that severe acute respiratory syndrome coronavirus is capable of infecting and replicating in macrophages within the coronary vasculature,” the researchers report.

The virus preferentially replicates in foam cells, in comparison with other macrophages, they add, suggesting that these cells might act as a reservoir of viral debris in atherosclerotic plaque.

“We have shown that the virus is targeting lipid-rich macrophages in atherosclerotic lesions. This is the first time this has been shown, and we think this is a very important finding,” Dr. Giannarelli said in an interview.

“We also found that the virus persists in these foam cells that could be responsible for long-term, low-grade inflammation in the vasculature that could contribute to the long-term cardiovascular manifestations in patients who have recovered from COVID,” she said.
 

Viral reservoirs

Macrophages residing in vascular tissue can undergo self-renewal and can remain in the tissue for many years, the investigators point out. They suggest that these macrophages may act as viral reservoirs of SARS-CoV-2 RNA in atherosclerotic plaques.

Using an ex vivo model, the researchers also found that atherosclerotic tissue could be directly infected by the virus. And just as was seen in cultured macrophages and foam cells, infection of vascular tissue triggered an inflammatory response. That response induced the secretion of key proatherogenic cytokines, such as interleukin-6 and interleukin-1 beta, which have been implicated in the pathogenesis of atherosclerosis and in an increased risk of cardiovascular events.

“Considering that plaque inflammation promotes disease progression and contributes to plaque rupture, our results provide a molecular basis for how infection of coronary lesions can contribute to the acute cardiovascular manifestations of COVID-19, such as myocardial infarction,” the researchers report.

Another interesting finding was a higher accumulation of viral RNA in the coronary vasculature of the three patients with acute ischemic cardiovascular manifestations, which they say adds to evidence that infection may increase cardiovascular risk.

Dr. Giannarelli points out that the patients in their study died in New York early in the pandemic, before vaccines were available. “They were unvaccinated and likely had little immunity against initial viral strains.”

Dr. Hotez says that when COVID-19 first emerged, many in the medical and scientific communities thought it would closely resemble the original SARS viral infection, which was primarily a respiratory pathogen.

“But it became pretty clear early on this virus was causing a lot of cardiovascular and thromboembolic disease,” he says. “This study provides an insight into the mechanisms involved here.”
 

Affecting more than lungs

Dr. Hotez pointed out that a recent study reported a 5% increase in cardiovascular deaths during the years 2020-2022, compared with before the pandemic.

“Those peaks of cardiovascular deaths corresponded with specific waves of COVID – the first happening at the time of the initial wave with the original virus and second during the Delta wave. So, there’s no question that this virus is contributing to excess cardiovascular mortality, and this paper appears to explain the mechanism.”

Dr. Hotez pointed out that the new findings suggest the cardiovascular risk may be prolonged well after the acute infection resolves.

“In long COVID, a lot of people focus on the neurological effects – brain fog and depression. But cardiac insufficiency and other cardiovascular events can also be considered another element of long COVID,” he said.

Dr. Giannarelli says her group is now studying whether patients with long COVID have virus in their coronary arteries. She points out that the current studies were a result of a team effort between experts in cardiovascular disease and virology and infectious disease. “We need to collaborate more like this to understand better the impact of viral infection in patients and the clinical manifestations,” she said.

Dr. Hotez says he believes these new findings will have implications for the future.

“COVID hasn’t gone away. The numbers have been going up again steadily in the U.S. in the last few months. There are still a significant number of hospitalizations,” he said.

While it would be unwieldy to ask for a cardiology consult for every COVID patient, he acknowledged, “there is probably a subset of people – possibly those of older age and who have had a severe case of COVID – who we suspect are now going to be more prone to cardiovascular disease because of having COVID.

“We should be vigilant in looking for cardiovascular disease in these patients,” Dr. Hotez said, “and perhaps be a bit more aggressive about controlling their cardiovascular risk factors.”

The study was funded by the U.S. National Institutes of Health, the American Heart Association, and the Chan Zuckerberg Initiative.

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

New evidence shows for the first time that the virus that causes COVID directly infects atherosclerotic plaques in the coronary arteries, producing a persistent inflammatory response.

The findings may not only explain the link between COVID and the increased risk of cardiovascular events but mark a starting point for new therapeutic approaches.

“Our study shows there is persistence of viral debris in the artery,” senior investigator Chiara Giannarelli, MD, associate professor of medicine and pathology at NYU Langone Health, New York, said in an interview. “There is an important inflammatory response. We can now look at ways to control this inflammation,” she said.

Dr. Giannarelli says COVID is more than a respiratory virus and that it can affect the whole body. “Our study shows a remarkable ability of the virus to hijack the immune system,” she points out. “Our findings may explain how that happens.”

Dr. Giannarelli says it’s important for doctors and patients to be aware of an increased cardiovascular risk after a SARS-CoV-2 infection and to pay extra attention to traditional risk factors, such as blood pressure and cholesterol.

“This study showing that severe acute respiratory syndrome coronavirus directly infects coronary artery plaques, producing inflammatory substances, really joins the dots and helps our understanding on why we’re seeing so much heart disease in COVID patients,” Peter Hotez, MD, professor of molecular virology and microbiology at Baylor College of Medicine, Houston, said in an interview.

Asked whether this direct infection of vascular plaques was unique to SARS-CoV-2 or whether this may also occur with other viruses, both Dr. Giannarelli and Dr. Hotez said they believe this may be a specific COVID effect.

“I wouldn’t say it is likely that other viruses infect coronary arteries in this way, but I suppose it is possible,” Dr. Giannarelli said.

Dr. Hotez pointed out that other viruses can cause inflammation in the heart, such as myocarditis. “But I can’t think of another virus that stimulates the sequence of events in coronary artery inflammation like we’re seeing here.”

Dr. Giannarelli noted that influenza is also associated with an increased risk of cardiovascular events, but there has been no evidence to date that it directly affects coronary arteries.

Dr. Hotez added that the increased risk of cardiovascular events with influenza has also been reported to be prolonged after the acute infection. “These new findings with SARS-CoV-2 could stimulate a redoubling of efforts to look at this possibility with influenza,” he suggested.
 

Heart disease after COVID

In a recent article published online in Nature Cardiovascular Research, Dr. Giannarelli and colleagues analyzed human autopsy tissue samples from coronary arterial walls of patients who had died from COVID in the early stages of the pandemic in New York.

They found an accumulation of viral RNA in atherosclerotic plaques in the coronary arteries, which was particularly concentrated in lipid-rich macrophage foam cells present within the plaques.

“Our data conclusively demonstrate that severe acute respiratory syndrome coronavirus is capable of infecting and replicating in macrophages within the coronary vasculature,” the researchers report.

The virus preferentially replicates in foam cells, in comparison with other macrophages, they add, suggesting that these cells might act as a reservoir of viral debris in atherosclerotic plaque.

“We have shown that the virus is targeting lipid-rich macrophages in atherosclerotic lesions. This is the first time this has been shown, and we think this is a very important finding,” Dr. Giannarelli said in an interview.

“We also found that the virus persists in these foam cells that could be responsible for long-term, low-grade inflammation in the vasculature that could contribute to the long-term cardiovascular manifestations in patients who have recovered from COVID,” she said.
 

Viral reservoirs

Macrophages residing in vascular tissue can undergo self-renewal and can remain in the tissue for many years, the investigators point out. They suggest that these macrophages may act as viral reservoirs of SARS-CoV-2 RNA in atherosclerotic plaques.

Using an ex vivo model, the researchers also found that atherosclerotic tissue could be directly infected by the virus. And just as was seen in cultured macrophages and foam cells, infection of vascular tissue triggered an inflammatory response. That response induced the secretion of key proatherogenic cytokines, such as interleukin-6 and interleukin-1 beta, which have been implicated in the pathogenesis of atherosclerosis and in an increased risk of cardiovascular events.

“Considering that plaque inflammation promotes disease progression and contributes to plaque rupture, our results provide a molecular basis for how infection of coronary lesions can contribute to the acute cardiovascular manifestations of COVID-19, such as myocardial infarction,” the researchers report.

Another interesting finding was a higher accumulation of viral RNA in the coronary vasculature of the three patients with acute ischemic cardiovascular manifestations, which they say adds to evidence that infection may increase cardiovascular risk.

Dr. Giannarelli points out that the patients in their study died in New York early in the pandemic, before vaccines were available. “They were unvaccinated and likely had little immunity against initial viral strains.”

Dr. Hotez says that when COVID-19 first emerged, many in the medical and scientific communities thought it would closely resemble the original SARS viral infection, which was primarily a respiratory pathogen.

“But it became pretty clear early on this virus was causing a lot of cardiovascular and thromboembolic disease,” he says. “This study provides an insight into the mechanisms involved here.”
 

Affecting more than lungs

Dr. Hotez pointed out that a recent study reported a 5% increase in cardiovascular deaths during the years 2020-2022, compared with before the pandemic.

“Those peaks of cardiovascular deaths corresponded with specific waves of COVID – the first happening at the time of the initial wave with the original virus and second during the Delta wave. So, there’s no question that this virus is contributing to excess cardiovascular mortality, and this paper appears to explain the mechanism.”

Dr. Hotez pointed out that the new findings suggest the cardiovascular risk may be prolonged well after the acute infection resolves.

“In long COVID, a lot of people focus on the neurological effects – brain fog and depression. But cardiac insufficiency and other cardiovascular events can also be considered another element of long COVID,” he said.

Dr. Giannarelli says her group is now studying whether patients with long COVID have virus in their coronary arteries. She points out that the current studies were a result of a team effort between experts in cardiovascular disease and virology and infectious disease. “We need to collaborate more like this to understand better the impact of viral infection in patients and the clinical manifestations,” she said.

Dr. Hotez says he believes these new findings will have implications for the future.

“COVID hasn’t gone away. The numbers have been going up again steadily in the U.S. in the last few months. There are still a significant number of hospitalizations,” he said.

While it would be unwieldy to ask for a cardiology consult for every COVID patient, he acknowledged, “there is probably a subset of people – possibly those of older age and who have had a severe case of COVID – who we suspect are now going to be more prone to cardiovascular disease because of having COVID.

“We should be vigilant in looking for cardiovascular disease in these patients,” Dr. Hotez said, “and perhaps be a bit more aggressive about controlling their cardiovascular risk factors.”

The study was funded by the U.S. National Institutes of Health, the American Heart Association, and the Chan Zuckerberg Initiative.

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

New evidence shows for the first time that the virus that causes COVID directly infects atherosclerotic plaques in the coronary arteries, producing a persistent inflammatory response.

The findings may not only explain the link between COVID and the increased risk of cardiovascular events but mark a starting point for new therapeutic approaches.

“Our study shows there is persistence of viral debris in the artery,” senior investigator Chiara Giannarelli, MD, associate professor of medicine and pathology at NYU Langone Health, New York, said in an interview. “There is an important inflammatory response. We can now look at ways to control this inflammation,” she said.

Dr. Giannarelli says COVID is more than a respiratory virus and that it can affect the whole body. “Our study shows a remarkable ability of the virus to hijack the immune system,” she points out. “Our findings may explain how that happens.”

Dr. Giannarelli says it’s important for doctors and patients to be aware of an increased cardiovascular risk after a SARS-CoV-2 infection and to pay extra attention to traditional risk factors, such as blood pressure and cholesterol.

“This study showing that severe acute respiratory syndrome coronavirus directly infects coronary artery plaques, producing inflammatory substances, really joins the dots and helps our understanding on why we’re seeing so much heart disease in COVID patients,” Peter Hotez, MD, professor of molecular virology and microbiology at Baylor College of Medicine, Houston, said in an interview.

Asked whether this direct infection of vascular plaques was unique to SARS-CoV-2 or whether this may also occur with other viruses, both Dr. Giannarelli and Dr. Hotez said they believe this may be a specific COVID effect.

“I wouldn’t say it is likely that other viruses infect coronary arteries in this way, but I suppose it is possible,” Dr. Giannarelli said.

Dr. Hotez pointed out that other viruses can cause inflammation in the heart, such as myocarditis. “But I can’t think of another virus that stimulates the sequence of events in coronary artery inflammation like we’re seeing here.”

Dr. Giannarelli noted that influenza is also associated with an increased risk of cardiovascular events, but there has been no evidence to date that it directly affects coronary arteries.

Dr. Hotez added that the increased risk of cardiovascular events with influenza has also been reported to be prolonged after the acute infection. “These new findings with SARS-CoV-2 could stimulate a redoubling of efforts to look at this possibility with influenza,” he suggested.
 

Heart disease after COVID

In a recent article published online in Nature Cardiovascular Research, Dr. Giannarelli and colleagues analyzed human autopsy tissue samples from coronary arterial walls of patients who had died from COVID in the early stages of the pandemic in New York.

They found an accumulation of viral RNA in atherosclerotic plaques in the coronary arteries, which was particularly concentrated in lipid-rich macrophage foam cells present within the plaques.

“Our data conclusively demonstrate that severe acute respiratory syndrome coronavirus is capable of infecting and replicating in macrophages within the coronary vasculature,” the researchers report.

The virus preferentially replicates in foam cells, in comparison with other macrophages, they add, suggesting that these cells might act as a reservoir of viral debris in atherosclerotic plaque.

“We have shown that the virus is targeting lipid-rich macrophages in atherosclerotic lesions. This is the first time this has been shown, and we think this is a very important finding,” Dr. Giannarelli said in an interview.

“We also found that the virus persists in these foam cells that could be responsible for long-term, low-grade inflammation in the vasculature that could contribute to the long-term cardiovascular manifestations in patients who have recovered from COVID,” she said.
 

Viral reservoirs

Macrophages residing in vascular tissue can undergo self-renewal and can remain in the tissue for many years, the investigators point out. They suggest that these macrophages may act as viral reservoirs of SARS-CoV-2 RNA in atherosclerotic plaques.

Using an ex vivo model, the researchers also found that atherosclerotic tissue could be directly infected by the virus. And just as was seen in cultured macrophages and foam cells, infection of vascular tissue triggered an inflammatory response. That response induced the secretion of key proatherogenic cytokines, such as interleukin-6 and interleukin-1 beta, which have been implicated in the pathogenesis of atherosclerosis and in an increased risk of cardiovascular events.

“Considering that plaque inflammation promotes disease progression and contributes to plaque rupture, our results provide a molecular basis for how infection of coronary lesions can contribute to the acute cardiovascular manifestations of COVID-19, such as myocardial infarction,” the researchers report.

Another interesting finding was a higher accumulation of viral RNA in the coronary vasculature of the three patients with acute ischemic cardiovascular manifestations, which they say adds to evidence that infection may increase cardiovascular risk.

Dr. Giannarelli points out that the patients in their study died in New York early in the pandemic, before vaccines were available. “They were unvaccinated and likely had little immunity against initial viral strains.”

Dr. Hotez says that when COVID-19 first emerged, many in the medical and scientific communities thought it would closely resemble the original SARS viral infection, which was primarily a respiratory pathogen.

“But it became pretty clear early on this virus was causing a lot of cardiovascular and thromboembolic disease,” he says. “This study provides an insight into the mechanisms involved here.”
 

Affecting more than lungs

Dr. Hotez pointed out that a recent study reported a 5% increase in cardiovascular deaths during the years 2020-2022, compared with before the pandemic.

“Those peaks of cardiovascular deaths corresponded with specific waves of COVID – the first happening at the time of the initial wave with the original virus and second during the Delta wave. So, there’s no question that this virus is contributing to excess cardiovascular mortality, and this paper appears to explain the mechanism.”

Dr. Hotez pointed out that the new findings suggest the cardiovascular risk may be prolonged well after the acute infection resolves.

“In long COVID, a lot of people focus on the neurological effects – brain fog and depression. But cardiac insufficiency and other cardiovascular events can also be considered another element of long COVID,” he said.

Dr. Giannarelli says her group is now studying whether patients with long COVID have virus in their coronary arteries. She points out that the current studies were a result of a team effort between experts in cardiovascular disease and virology and infectious disease. “We need to collaborate more like this to understand better the impact of viral infection in patients and the clinical manifestations,” she said.

Dr. Hotez says he believes these new findings will have implications for the future.

“COVID hasn’t gone away. The numbers have been going up again steadily in the U.S. in the last few months. There are still a significant number of hospitalizations,” he said.

While it would be unwieldy to ask for a cardiology consult for every COVID patient, he acknowledged, “there is probably a subset of people – possibly those of older age and who have had a severe case of COVID – who we suspect are now going to be more prone to cardiovascular disease because of having COVID.

“We should be vigilant in looking for cardiovascular disease in these patients,” Dr. Hotez said, “and perhaps be a bit more aggressive about controlling their cardiovascular risk factors.”

The study was funded by the U.S. National Institutes of Health, the American Heart Association, and the Chan Zuckerberg Initiative.

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

HAMBURG, Germany – Use of some antibiotic and antipsychotic drugs increases the risk of sudden cardiac arrest (SCA) among people with type 2 diabetes who do not have a history of cardiovascular disease (CVD), shows the first such analysis of real-world, primary care data.

People with type 2 diabetes who do not have a history of CVD have almost three times the risk of SCA if they take antipsychotic medications and nearly double the risk if they take certain antibiotics that prolong the QT interval, notably, macrolides and fluoroquinolones.

“These data show that commonly prescribed drugs - antipsychotic medications, used by about 3% of people with type 2 diabetes, and antibiotics, taken by 5% to 10%, convey an increased risk of sudden cardiac arrest in those without a history of cardiovascular disease,” said Peter Harms, MSc, who presented the study at the annual meeting of the European Association for the Study of Diabetes. Another drug associated with an increase in SCA among patients with diabetes was domperidone, an antinausea medication.

“Perhaps these drugs could be avoided in some cases, and GPs should be more aware of the possible consequences of their use,” he added. “If the patient has type 2 diabetes, then maybe it’s better to avoid some of these medications and try and cope without them, or at least find an alternative antibiotic.”

Mr. Harms, an epidemiologist from Amsterdam University Medical Centers, highlighted that their study was unique because the investigators drew upon primary care data. “These data are extensive, and we find a lot of associations which are very real.”

SCA is associated with 50% of all cardiac deaths and accounts for 20% of all mortality in high-income countries. Of those people who experience SCA, 80% of cases prove fatal.

“As the name suggests, it is difficult to predict because it is sudden, especially in people without a cardiovascular disease history,” Mr. Harms pointed out in an interview with this news organization. He highlighted that “around half of those who experience SCA, often between the ages of 40 and 60 years, have never seen a cardiologist, but many do have type 2 diabetes.

“We need to better understand how to recognize people at risk of SCA, know who to watch and how to prevent these events,” he emphasized.

Vladimira Fejfarova, MD, comoderated the session and commented on the study. “From the clinical point of view, it’s necessary to evaluate risk factors that can contribute to sudden cardiac arrest.”

Overall, the researchers found that, among people with type 2 diabetes who do not have a history of CVD, hypoglycemia, severe hypertension, dyslipidemia, and use of QTc-prolonging medications are associated with SCA risk. Among people with type 2 diabetes and CVD, albuminuria and heart failure are associated with SCA risk.

Dr. Fejfarova added: “With type 2 diabetes and also type 1, we need to look more at adverse events, especially when treating infections with macrolides, but also mycotic infections, because antimycotic drugs are known to influence QT intervals that could contribute to sudden cardiac arrest.

“We need to be more cautious with prescribing certain antibiotics that have these side effects in our patients with diabetes,” asserted Dr. Fejfarova, from the Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague.
 

Type 2 diabetes doubles the risk of SCA

The researcher decided to investigate the population of people with type 2 diabetes because their risk of SCD is around twice that of those without type 2 diabetes. Because these patients have relatively frequent checkups with general practitioners, Mr. Harms turned to primary care databases that contained comprehensive and relatively routine information on risk indicators.

Longitudinal associations between clinical characteristics of 3,919 patients with type 2 diabetes – both those with and those without a history of CVD – and SCA (a total of 689 patients) were determined.

Cases were found in the AmsteRdam REsuscitation STtudies (ARREST) registry of out-of-hospital resuscitation attempts by emergency medical services in the Dutch region of Noord-Holland from 2010 to 2019. Case patients were matched with up to five control patients. The control group comprised people with type 2 diabetes who had not experienced an SCA. Control patients were sourced from the same primary care practices who were of similar age and sex. Clinical measurements, including blood pressure and blood glucose readings, medication use, and medical history for the 5 years leading up to an SCA, were obtained from general practice records. A multivariable analysis was performed, and results were stratified for people with and for those without a history of CVD.

Of particular interest were drugs that interfere with cardiac function, including some prokinetic, antibiotic, and antipsychotic medications. All of the drugs are known to be associated with a change in QTc prolongation. Examples include domperidone (QTc-prolonging prokinetic), macrolides and fluoroquinolones (QTc-prolonging antibiotics), and haloperidol (a QTc-prolonging antipsychotic).
 

Antibiotic and antipsychotic use might contribute to SCA in T2D

Case patients and control patients were similar in age, hemoglobin A1c level, and other characteristics with the exception that more patients with SCA had a history of CVD (40.0% vs. 29.4%).

“Looking at the associations in the overall population, insulin use was strongly associated with SCA risk [hazard ratio, 2.38] and perhaps this was an indicator of severity of type 2 diabetes,” remarked Mr. Harms. “Also, unsurprisingly, a history of arrhythmia [HR, 1.68] and, more surprisingly, prokinetic drug use [HR, 1.66; 95% confidence interval, 1.20-2.31], specifically those known for QTc-prolongation, were associated with SCA.”

Among people who had experienced an SCA and who did not have a history of CVD (337 case patients/2,023 control patients), QTc-prolonging antipsychotic medication use was associated with SCA at an HR of 2.87, and antibiotic medication use was associated with SCA at an HR of 1.66. A low fasting glucose level (< 4.5 mmol/mol) was associated with SCA at an HR of 2.5; severely high systolic blood pressure (> 180 mm Hg) was associated with SCA at an HR of 2.21; low HDL cholesterol level, with an HR of 1.35; and high LDL cholesterol level (> 2.6 mmol/L), with an HR of 1.64.

Among people with a history of CVD (352 case patients/1,207 control patients), associations between albuminuria and SCA were moderate (HR, 1.54) and severe (HR, 1.55); heart failure was associated with SCA at an HR of 1.85 (95% CI, 1.50-2.29).

Comoderator Dr. Fejfarova added that, in addition to the findings from Dr. Harms’ study, other research presented in the same session highlighted the importance of checking patients for the presence of arrhythmias that could lead to the development of atrioventricular blocks, sinus node diseases, and SCA.

Mr. Harms and Dr. Fejfarova have disclosed no relevant financial relationships.

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

HAMBURG, Germany – Use of some antibiotic and antipsychotic drugs increases the risk of sudden cardiac arrest (SCA) among people with type 2 diabetes who do not have a history of cardiovascular disease (CVD), shows the first such analysis of real-world, primary care data.

People with type 2 diabetes who do not have a history of CVD have almost three times the risk of SCA if they take antipsychotic medications and nearly double the risk if they take certain antibiotics that prolong the QT interval, notably, macrolides and fluoroquinolones.

“These data show that commonly prescribed drugs - antipsychotic medications, used by about 3% of people with type 2 diabetes, and antibiotics, taken by 5% to 10%, convey an increased risk of sudden cardiac arrest in those without a history of cardiovascular disease,” said Peter Harms, MSc, who presented the study at the annual meeting of the European Association for the Study of Diabetes. Another drug associated with an increase in SCA among patients with diabetes was domperidone, an antinausea medication.

“Perhaps these drugs could be avoided in some cases, and GPs should be more aware of the possible consequences of their use,” he added. “If the patient has type 2 diabetes, then maybe it’s better to avoid some of these medications and try and cope without them, or at least find an alternative antibiotic.”

Mr. Harms, an epidemiologist from Amsterdam University Medical Centers, highlighted that their study was unique because the investigators drew upon primary care data. “These data are extensive, and we find a lot of associations which are very real.”

SCA is associated with 50% of all cardiac deaths and accounts for 20% of all mortality in high-income countries. Of those people who experience SCA, 80% of cases prove fatal.

“As the name suggests, it is difficult to predict because it is sudden, especially in people without a cardiovascular disease history,” Mr. Harms pointed out in an interview with this news organization. He highlighted that “around half of those who experience SCA, often between the ages of 40 and 60 years, have never seen a cardiologist, but many do have type 2 diabetes.

“We need to better understand how to recognize people at risk of SCA, know who to watch and how to prevent these events,” he emphasized.

Vladimira Fejfarova, MD, comoderated the session and commented on the study. “From the clinical point of view, it’s necessary to evaluate risk factors that can contribute to sudden cardiac arrest.”

Overall, the researchers found that, among people with type 2 diabetes who do not have a history of CVD, hypoglycemia, severe hypertension, dyslipidemia, and use of QTc-prolonging medications are associated with SCA risk. Among people with type 2 diabetes and CVD, albuminuria and heart failure are associated with SCA risk.

Dr. Fejfarova added: “With type 2 diabetes and also type 1, we need to look more at adverse events, especially when treating infections with macrolides, but also mycotic infections, because antimycotic drugs are known to influence QT intervals that could contribute to sudden cardiac arrest.

“We need to be more cautious with prescribing certain antibiotics that have these side effects in our patients with diabetes,” asserted Dr. Fejfarova, from the Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague.
 

Type 2 diabetes doubles the risk of SCA

The researcher decided to investigate the population of people with type 2 diabetes because their risk of SCD is around twice that of those without type 2 diabetes. Because these patients have relatively frequent checkups with general practitioners, Mr. Harms turned to primary care databases that contained comprehensive and relatively routine information on risk indicators.

Longitudinal associations between clinical characteristics of 3,919 patients with type 2 diabetes – both those with and those without a history of CVD – and SCA (a total of 689 patients) were determined.

Cases were found in the AmsteRdam REsuscitation STtudies (ARREST) registry of out-of-hospital resuscitation attempts by emergency medical services in the Dutch region of Noord-Holland from 2010 to 2019. Case patients were matched with up to five control patients. The control group comprised people with type 2 diabetes who had not experienced an SCA. Control patients were sourced from the same primary care practices who were of similar age and sex. Clinical measurements, including blood pressure and blood glucose readings, medication use, and medical history for the 5 years leading up to an SCA, were obtained from general practice records. A multivariable analysis was performed, and results were stratified for people with and for those without a history of CVD.

Of particular interest were drugs that interfere with cardiac function, including some prokinetic, antibiotic, and antipsychotic medications. All of the drugs are known to be associated with a change in QTc prolongation. Examples include domperidone (QTc-prolonging prokinetic), macrolides and fluoroquinolones (QTc-prolonging antibiotics), and haloperidol (a QTc-prolonging antipsychotic).
 

Antibiotic and antipsychotic use might contribute to SCA in T2D

Case patients and control patients were similar in age, hemoglobin A1c level, and other characteristics with the exception that more patients with SCA had a history of CVD (40.0% vs. 29.4%).

“Looking at the associations in the overall population, insulin use was strongly associated with SCA risk [hazard ratio, 2.38] and perhaps this was an indicator of severity of type 2 diabetes,” remarked Mr. Harms. “Also, unsurprisingly, a history of arrhythmia [HR, 1.68] and, more surprisingly, prokinetic drug use [HR, 1.66; 95% confidence interval, 1.20-2.31], specifically those known for QTc-prolongation, were associated with SCA.”

Among people who had experienced an SCA and who did not have a history of CVD (337 case patients/2,023 control patients), QTc-prolonging antipsychotic medication use was associated with SCA at an HR of 2.87, and antibiotic medication use was associated with SCA at an HR of 1.66. A low fasting glucose level (< 4.5 mmol/mol) was associated with SCA at an HR of 2.5; severely high systolic blood pressure (> 180 mm Hg) was associated with SCA at an HR of 2.21; low HDL cholesterol level, with an HR of 1.35; and high LDL cholesterol level (> 2.6 mmol/L), with an HR of 1.64.

Among people with a history of CVD (352 case patients/1,207 control patients), associations between albuminuria and SCA were moderate (HR, 1.54) and severe (HR, 1.55); heart failure was associated with SCA at an HR of 1.85 (95% CI, 1.50-2.29).

Comoderator Dr. Fejfarova added that, in addition to the findings from Dr. Harms’ study, other research presented in the same session highlighted the importance of checking patients for the presence of arrhythmias that could lead to the development of atrioventricular blocks, sinus node diseases, and SCA.

Mr. Harms and Dr. Fejfarova have disclosed no relevant financial relationships.

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

HAMBURG, Germany – Use of some antibiotic and antipsychotic drugs increases the risk of sudden cardiac arrest (SCA) among people with type 2 diabetes who do not have a history of cardiovascular disease (CVD), shows the first such analysis of real-world, primary care data.

People with type 2 diabetes who do not have a history of CVD have almost three times the risk of SCA if they take antipsychotic medications and nearly double the risk if they take certain antibiotics that prolong the QT interval, notably, macrolides and fluoroquinolones.

“These data show that commonly prescribed drugs - antipsychotic medications, used by about 3% of people with type 2 diabetes, and antibiotics, taken by 5% to 10%, convey an increased risk of sudden cardiac arrest in those without a history of cardiovascular disease,” said Peter Harms, MSc, who presented the study at the annual meeting of the European Association for the Study of Diabetes. Another drug associated with an increase in SCA among patients with diabetes was domperidone, an antinausea medication.

“Perhaps these drugs could be avoided in some cases, and GPs should be more aware of the possible consequences of their use,” he added. “If the patient has type 2 diabetes, then maybe it’s better to avoid some of these medications and try and cope without them, or at least find an alternative antibiotic.”

Mr. Harms, an epidemiologist from Amsterdam University Medical Centers, highlighted that their study was unique because the investigators drew upon primary care data. “These data are extensive, and we find a lot of associations which are very real.”

SCA is associated with 50% of all cardiac deaths and accounts for 20% of all mortality in high-income countries. Of those people who experience SCA, 80% of cases prove fatal.

“As the name suggests, it is difficult to predict because it is sudden, especially in people without a cardiovascular disease history,” Mr. Harms pointed out in an interview with this news organization. He highlighted that “around half of those who experience SCA, often between the ages of 40 and 60 years, have never seen a cardiologist, but many do have type 2 diabetes.

“We need to better understand how to recognize people at risk of SCA, know who to watch and how to prevent these events,” he emphasized.

Vladimira Fejfarova, MD, comoderated the session and commented on the study. “From the clinical point of view, it’s necessary to evaluate risk factors that can contribute to sudden cardiac arrest.”

Overall, the researchers found that, among people with type 2 diabetes who do not have a history of CVD, hypoglycemia, severe hypertension, dyslipidemia, and use of QTc-prolonging medications are associated with SCA risk. Among people with type 2 diabetes and CVD, albuminuria and heart failure are associated with SCA risk.

Dr. Fejfarova added: “With type 2 diabetes and also type 1, we need to look more at adverse events, especially when treating infections with macrolides, but also mycotic infections, because antimycotic drugs are known to influence QT intervals that could contribute to sudden cardiac arrest.

“We need to be more cautious with prescribing certain antibiotics that have these side effects in our patients with diabetes,” asserted Dr. Fejfarova, from the Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague.
 

Type 2 diabetes doubles the risk of SCA

The researcher decided to investigate the population of people with type 2 diabetes because their risk of SCD is around twice that of those without type 2 diabetes. Because these patients have relatively frequent checkups with general practitioners, Mr. Harms turned to primary care databases that contained comprehensive and relatively routine information on risk indicators.

Longitudinal associations between clinical characteristics of 3,919 patients with type 2 diabetes – both those with and those without a history of CVD – and SCA (a total of 689 patients) were determined.

Cases were found in the AmsteRdam REsuscitation STtudies (ARREST) registry of out-of-hospital resuscitation attempts by emergency medical services in the Dutch region of Noord-Holland from 2010 to 2019. Case patients were matched with up to five control patients. The control group comprised people with type 2 diabetes who had not experienced an SCA. Control patients were sourced from the same primary care practices who were of similar age and sex. Clinical measurements, including blood pressure and blood glucose readings, medication use, and medical history for the 5 years leading up to an SCA, were obtained from general practice records. A multivariable analysis was performed, and results were stratified for people with and for those without a history of CVD.

Of particular interest were drugs that interfere with cardiac function, including some prokinetic, antibiotic, and antipsychotic medications. All of the drugs are known to be associated with a change in QTc prolongation. Examples include domperidone (QTc-prolonging prokinetic), macrolides and fluoroquinolones (QTc-prolonging antibiotics), and haloperidol (a QTc-prolonging antipsychotic).
 

Antibiotic and antipsychotic use might contribute to SCA in T2D

Case patients and control patients were similar in age, hemoglobin A1c level, and other characteristics with the exception that more patients with SCA had a history of CVD (40.0% vs. 29.4%).

“Looking at the associations in the overall population, insulin use was strongly associated with SCA risk [hazard ratio, 2.38] and perhaps this was an indicator of severity of type 2 diabetes,” remarked Mr. Harms. “Also, unsurprisingly, a history of arrhythmia [HR, 1.68] and, more surprisingly, prokinetic drug use [HR, 1.66; 95% confidence interval, 1.20-2.31], specifically those known for QTc-prolongation, were associated with SCA.”

Among people who had experienced an SCA and who did not have a history of CVD (337 case patients/2,023 control patients), QTc-prolonging antipsychotic medication use was associated with SCA at an HR of 2.87, and antibiotic medication use was associated with SCA at an HR of 1.66. A low fasting glucose level (< 4.5 mmol/mol) was associated with SCA at an HR of 2.5; severely high systolic blood pressure (> 180 mm Hg) was associated with SCA at an HR of 2.21; low HDL cholesterol level, with an HR of 1.35; and high LDL cholesterol level (> 2.6 mmol/L), with an HR of 1.64.

Among people with a history of CVD (352 case patients/1,207 control patients), associations between albuminuria and SCA were moderate (HR, 1.54) and severe (HR, 1.55); heart failure was associated with SCA at an HR of 1.85 (95% CI, 1.50-2.29).

Comoderator Dr. Fejfarova added that, in addition to the findings from Dr. Harms’ study, other research presented in the same session highlighted the importance of checking patients for the presence of arrhythmias that could lead to the development of atrioventricular blocks, sinus node diseases, and SCA.

Mr. Harms and Dr. Fejfarova have disclosed no relevant financial relationships.

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