Emergency Medicine

The COVID-19 pandemic has created unique and unprecedented challenges for the clinical research world, with potentially long-lasting consequences.

A new analysis of the extent of disruption shows that the average rate of stopped trials nearly doubled during the first 5 months of 2020, compared with the 2 previous years.

“Typically, clinical research precedes clinical practice by several years, so this disruption we’re seeing now will be felt for many years to come,” said Mario Guadino, MD, of Weill Cornell Medicine, New York.

The analysis was published online July 31 in the Journal of the American College of Cardiology.

The researchers used Python software to query meta-data from all trials reported on ClinicalTrials.gov. Of 321,218 non-COVID-19 trials queried, 28,672 (8.9%) were reported as stopped, defined as a switch in trial status from “recruiting” to “active and not recruiting,” “completed,” “suspended,” “terminated,” or “withdrawn.”

The average rate of discontinuation was 638 trials/month from January 2017 to December 2019, rising to 1,147 trials/month between January 2020 and May 2020 (P < .001 for trend).

Once stopped (as opposed to paused), restarting a trial is a tricky prospect, said Dr. Guadino. “You can’t stop and restart a trial because it creates a lot of issues, so we should expect many of these stopped trials to never be completed.”

He said these figures likely represent an underestimate of the true impact of the pandemic because there is typically a delay in the updating of the status of a trial on ClinicalTrials.gov.

“We are likely looking only at the tip of the iceberg,” he added. “My impression is that the number of trials that will be affected and even canceled will be very high.”

As for cardiology trials, one of the report’s authors, Deepak Bhatt, MD, Brigham and Women’s Hospital, Boston, without naming specific trials, had this to say: “Several cardiovascular trials were paused, and some were permanently discontinued. It may be a while before we fully appreciate just how much information was lost and how much might be salvaged.”

He’s not worried, however, that upcoming cardiology meetings, which have moved online for the foreseeable future, might get a bit boring. “Fortunately, there is enough good work going on in the cardiovascular and cardiometabolic space that I believe there will still be ample randomized and observational data of high quality to present at the major meetings,” Dr. Bhatt said in an email.

The researchers found a weak correlation between the national population-adjusted numbers of COVID-19 cases and the proportion of non-COVID-19 trials stopped by country.

Even for trials that stopped recruiting for a period of time but are continuing, there are myriad issues involving compliance, data integrity, statistical interpretability, etc.

“Even if there is just a temporary disruption, that will most likely lead to reduced enrollment, missing follow-up visits, and protocol deviations, all things that would be red flags during normal times and impact the quality of the clinical trial,” said Dr. Guadino.

“And if your outcome of interest is mortality, well, how exactly do you measure that during a pandemic?” he added.
 

Stopped for lack of funding

Besides the logistical issues, another reason trials may be in jeopardy is funding. A warning early in the pandemic from the research community in Canada that funding was quickly drying up, leaving both jobs and data at risk, led to an aid package from the government to keep the lights on.

The National Institutes of Health (NIH), the Canadian Institutes of Health Research, and similar groups “have devoted large sums of money to research in COVID, which is of course very appropriate, but that clearly reduces the amount of funding that is available for other researchers,” said Dr. Guadino.

Some funding agencies around the world have canceled or put on hold all non-COVID-19 clinical trials still at the design state, Dr. Guadino said in an interview.

The NIH, he stressed, has not canceled funding and has been “extremely open and cooperative” in trying to help trialists navigate the many COVID-generated issues. They’ve even issued guidance on how to manage trials during COVID-19.

Of note, in the survey, the majority of the trials stopped (95.4%) had nongovernmental funding.

“The data are not very granular, so we’re only able to make some very simple, descriptive comments, but it does seem like the more fragile trials – those that are smaller and industry-funded – are the ones more likely to be disrupted,” said Dr. Guadino.

In some cases, he said, priorities have shifted to COVID-19. “If a small company is sponsoring a trial and they decide they want to sponsor something related to COVID, or they realize that because of the slow enrollment, the trial becomes too expensive to complete, they may opt to just abandon it,” said Dr. Guadino.

At what cost? It will take years to sort that out, he said.

This study received no funding. Dr. Guadino and Dr. Bhatt are both active trialists, participating in both industry- and government-sponsored clinical research.
 

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

The COVID-19 pandemic has created unique and unprecedented challenges for the clinical research world, with potentially long-lasting consequences.

A new analysis of the extent of disruption shows that the average rate of stopped trials nearly doubled during the first 5 months of 2020, compared with the 2 previous years.

“Typically, clinical research precedes clinical practice by several years, so this disruption we’re seeing now will be felt for many years to come,” said Mario Guadino, MD, of Weill Cornell Medicine, New York.

The analysis was published online July 31 in the Journal of the American College of Cardiology.

The researchers used Python software to query meta-data from all trials reported on ClinicalTrials.gov. Of 321,218 non-COVID-19 trials queried, 28,672 (8.9%) were reported as stopped, defined as a switch in trial status from “recruiting” to “active and not recruiting,” “completed,” “suspended,” “terminated,” or “withdrawn.”

The average rate of discontinuation was 638 trials/month from January 2017 to December 2019, rising to 1,147 trials/month between January 2020 and May 2020 (P < .001 for trend).

Once stopped (as opposed to paused), restarting a trial is a tricky prospect, said Dr. Guadino. “You can’t stop and restart a trial because it creates a lot of issues, so we should expect many of these stopped trials to never be completed.”

He said these figures likely represent an underestimate of the true impact of the pandemic because there is typically a delay in the updating of the status of a trial on ClinicalTrials.gov.

“We are likely looking only at the tip of the iceberg,” he added. “My impression is that the number of trials that will be affected and even canceled will be very high.”

As for cardiology trials, one of the report’s authors, Deepak Bhatt, MD, Brigham and Women’s Hospital, Boston, without naming specific trials, had this to say: “Several cardiovascular trials were paused, and some were permanently discontinued. It may be a while before we fully appreciate just how much information was lost and how much might be salvaged.”

He’s not worried, however, that upcoming cardiology meetings, which have moved online for the foreseeable future, might get a bit boring. “Fortunately, there is enough good work going on in the cardiovascular and cardiometabolic space that I believe there will still be ample randomized and observational data of high quality to present at the major meetings,” Dr. Bhatt said in an email.

The researchers found a weak correlation between the national population-adjusted numbers of COVID-19 cases and the proportion of non-COVID-19 trials stopped by country.

Even for trials that stopped recruiting for a period of time but are continuing, there are myriad issues involving compliance, data integrity, statistical interpretability, etc.

“Even if there is just a temporary disruption, that will most likely lead to reduced enrollment, missing follow-up visits, and protocol deviations, all things that would be red flags during normal times and impact the quality of the clinical trial,” said Dr. Guadino.

“And if your outcome of interest is mortality, well, how exactly do you measure that during a pandemic?” he added.
 

Stopped for lack of funding

Besides the logistical issues, another reason trials may be in jeopardy is funding. A warning early in the pandemic from the research community in Canada that funding was quickly drying up, leaving both jobs and data at risk, led to an aid package from the government to keep the lights on.

The National Institutes of Health (NIH), the Canadian Institutes of Health Research, and similar groups “have devoted large sums of money to research in COVID, which is of course very appropriate, but that clearly reduces the amount of funding that is available for other researchers,” said Dr. Guadino.

Some funding agencies around the world have canceled or put on hold all non-COVID-19 clinical trials still at the design state, Dr. Guadino said in an interview.

The NIH, he stressed, has not canceled funding and has been “extremely open and cooperative” in trying to help trialists navigate the many COVID-generated issues. They’ve even issued guidance on how to manage trials during COVID-19.

Of note, in the survey, the majority of the trials stopped (95.4%) had nongovernmental funding.

“The data are not very granular, so we’re only able to make some very simple, descriptive comments, but it does seem like the more fragile trials – those that are smaller and industry-funded – are the ones more likely to be disrupted,” said Dr. Guadino.

In some cases, he said, priorities have shifted to COVID-19. “If a small company is sponsoring a trial and they decide they want to sponsor something related to COVID, or they realize that because of the slow enrollment, the trial becomes too expensive to complete, they may opt to just abandon it,” said Dr. Guadino.

At what cost? It will take years to sort that out, he said.

This study received no funding. Dr. Guadino and Dr. Bhatt are both active trialists, participating in both industry- and government-sponsored clinical research.
 

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

The COVID-19 pandemic has created unique and unprecedented challenges for the clinical research world, with potentially long-lasting consequences.

A new analysis of the extent of disruption shows that the average rate of stopped trials nearly doubled during the first 5 months of 2020, compared with the 2 previous years.

“Typically, clinical research precedes clinical practice by several years, so this disruption we’re seeing now will be felt for many years to come,” said Mario Guadino, MD, of Weill Cornell Medicine, New York.

The analysis was published online July 31 in the Journal of the American College of Cardiology.

The researchers used Python software to query meta-data from all trials reported on ClinicalTrials.gov. Of 321,218 non-COVID-19 trials queried, 28,672 (8.9%) were reported as stopped, defined as a switch in trial status from “recruiting” to “active and not recruiting,” “completed,” “suspended,” “terminated,” or “withdrawn.”

The average rate of discontinuation was 638 trials/month from January 2017 to December 2019, rising to 1,147 trials/month between January 2020 and May 2020 (P < .001 for trend).

Once stopped (as opposed to paused), restarting a trial is a tricky prospect, said Dr. Guadino. “You can’t stop and restart a trial because it creates a lot of issues, so we should expect many of these stopped trials to never be completed.”

He said these figures likely represent an underestimate of the true impact of the pandemic because there is typically a delay in the updating of the status of a trial on ClinicalTrials.gov.

“We are likely looking only at the tip of the iceberg,” he added. “My impression is that the number of trials that will be affected and even canceled will be very high.”

As for cardiology trials, one of the report’s authors, Deepak Bhatt, MD, Brigham and Women’s Hospital, Boston, without naming specific trials, had this to say: “Several cardiovascular trials were paused, and some were permanently discontinued. It may be a while before we fully appreciate just how much information was lost and how much might be salvaged.”

He’s not worried, however, that upcoming cardiology meetings, which have moved online for the foreseeable future, might get a bit boring. “Fortunately, there is enough good work going on in the cardiovascular and cardiometabolic space that I believe there will still be ample randomized and observational data of high quality to present at the major meetings,” Dr. Bhatt said in an email.

The researchers found a weak correlation between the national population-adjusted numbers of COVID-19 cases and the proportion of non-COVID-19 trials stopped by country.

Even for trials that stopped recruiting for a period of time but are continuing, there are myriad issues involving compliance, data integrity, statistical interpretability, etc.

“Even if there is just a temporary disruption, that will most likely lead to reduced enrollment, missing follow-up visits, and protocol deviations, all things that would be red flags during normal times and impact the quality of the clinical trial,” said Dr. Guadino.

“And if your outcome of interest is mortality, well, how exactly do you measure that during a pandemic?” he added.
 

Stopped for lack of funding

Besides the logistical issues, another reason trials may be in jeopardy is funding. A warning early in the pandemic from the research community in Canada that funding was quickly drying up, leaving both jobs and data at risk, led to an aid package from the government to keep the lights on.

The National Institutes of Health (NIH), the Canadian Institutes of Health Research, and similar groups “have devoted large sums of money to research in COVID, which is of course very appropriate, but that clearly reduces the amount of funding that is available for other researchers,” said Dr. Guadino.

Some funding agencies around the world have canceled or put on hold all non-COVID-19 clinical trials still at the design state, Dr. Guadino said in an interview.

The NIH, he stressed, has not canceled funding and has been “extremely open and cooperative” in trying to help trialists navigate the many COVID-generated issues. They’ve even issued guidance on how to manage trials during COVID-19.

Of note, in the survey, the majority of the trials stopped (95.4%) had nongovernmental funding.

“The data are not very granular, so we’re only able to make some very simple, descriptive comments, but it does seem like the more fragile trials – those that are smaller and industry-funded – are the ones more likely to be disrupted,” said Dr. Guadino.

In some cases, he said, priorities have shifted to COVID-19. “If a small company is sponsoring a trial and they decide they want to sponsor something related to COVID, or they realize that because of the slow enrollment, the trial becomes too expensive to complete, they may opt to just abandon it,” said Dr. Guadino.

At what cost? It will take years to sort that out, he said.

This study received no funding. Dr. Guadino and Dr. Bhatt are both active trialists, participating in both industry- and government-sponsored clinical research.
 

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

Let us begin with a thought exercise. Close your eyes and picture the word, “hero.” What comes to mind? A relative, a teacher, a fictional character wielding a hammer or flying gracefully through the air?

© Maridav / iStockphoto.com

Several months ago, our country was introduced to a foe that brought us to our knees. Before that time, the idea of a hero had fluctuated with circumstance and had been guided by aging and maturity; however, since the moment COVID-19 struck, a new image has emerged. Not all heroes wear capes, but some wield stethoscopes.

Over these past months the phrase, “Health Care Heroes” has spread throughout our collective consciousness, highlighted everywhere from talk shows and news media to billboards and journals. Doctors, nurses, and other health care professionals are lauded for their strength, dedication, resilience, and compassion. Citizens line up to clap, honk horns, and shower praise in recognition of those who have risked their health, sacrificed their personal lives, and committed themselves to the greater good. Yet, what does it mean to be a hero, and what is the cost of hero worship?

The focus of medical training has gradually shifted to include the physical as well as mental well-being of future physicians, but the remnants of traditional doctrine linger. Hours of focused training through study and direct clinical interaction reinforce dedication to patient care. Rewards are given for time spent and compassion lent, and research is lauded, but family time is rarely applauded. We are encouraged to do our greatest, work our hardest, be the best, rise and defeat every test. Failure (or the perception thereof) is not an option.

According to Rikinkumar S. Patel, MD, MPH, and associates, physicians have nearly twice the burnout rate of other professionals (Behav Sci. [Basel]. 2018 Nov;8[11]:98). The dedication to our craft propels excellence as well as sacrifice. When COVID-19 entered our lives, many of my colleagues did not hesitate to heed to the call for action. They immersed themselves in the ICU, led triage units, and extended work hours in the service of the sick and dying. Several were years removed from emergency/intensive care, while others were allocated from their chosen residency programs and voluntarily thrust into an environment they had never before traversed.

These individuals are praised as “brave,” “dedicated,” “selfless.” A few even provided insight into their experiences through various publications highlighting their appreciation and gratitude toward such a treacherous, albeit, tremendous experience. Even though their words are an honest perspective of life through one of the worst health care crises in 100 years, in effect, they perpetuate the noble hero; the myth of the super doctor.

In a profession that has borne witness to multiple suicides over the past few months, why do we not encourage open dialogue of our victories as well as our defeats? Our wins as much as our losses? Why does an esteemed veteran physician feel guilt over declining to provide emergency services to patients whom they have long forgotten how to manage? What drives the guilt and the self-doubt? Are we ashamed of what others will think? Is it that the fear of not living up to our cherished medical oath outweighs our own boundaries and acknowledgment of our limitations?

A hero is an entity, a person encompassing a state of being, yet health care professionals are bestowed this title and this burden on a near-daily basis. Physicians are people. We love, we fear, we hesitate, we fight, we deem to overcome. We are perfectly imperfect. The more in tune we are to vulnerability, the more honest we can become with ourselves and one another.
 

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

Let us begin with a thought exercise. Close your eyes and picture the word, “hero.” What comes to mind? A relative, a teacher, a fictional character wielding a hammer or flying gracefully through the air?

© Maridav / iStockphoto.com

Several months ago, our country was introduced to a foe that brought us to our knees. Before that time, the idea of a hero had fluctuated with circumstance and had been guided by aging and maturity; however, since the moment COVID-19 struck, a new image has emerged. Not all heroes wear capes, but some wield stethoscopes.

Over these past months the phrase, “Health Care Heroes” has spread throughout our collective consciousness, highlighted everywhere from talk shows and news media to billboards and journals. Doctors, nurses, and other health care professionals are lauded for their strength, dedication, resilience, and compassion. Citizens line up to clap, honk horns, and shower praise in recognition of those who have risked their health, sacrificed their personal lives, and committed themselves to the greater good. Yet, what does it mean to be a hero, and what is the cost of hero worship?

The focus of medical training has gradually shifted to include the physical as well as mental well-being of future physicians, but the remnants of traditional doctrine linger. Hours of focused training through study and direct clinical interaction reinforce dedication to patient care. Rewards are given for time spent and compassion lent, and research is lauded, but family time is rarely applauded. We are encouraged to do our greatest, work our hardest, be the best, rise and defeat every test. Failure (or the perception thereof) is not an option.

According to Rikinkumar S. Patel, MD, MPH, and associates, physicians have nearly twice the burnout rate of other professionals (Behav Sci. [Basel]. 2018 Nov;8[11]:98). The dedication to our craft propels excellence as well as sacrifice. When COVID-19 entered our lives, many of my colleagues did not hesitate to heed to the call for action. They immersed themselves in the ICU, led triage units, and extended work hours in the service of the sick and dying. Several were years removed from emergency/intensive care, while others were allocated from their chosen residency programs and voluntarily thrust into an environment they had never before traversed.

These individuals are praised as “brave,” “dedicated,” “selfless.” A few even provided insight into their experiences through various publications highlighting their appreciation and gratitude toward such a treacherous, albeit, tremendous experience. Even though their words are an honest perspective of life through one of the worst health care crises in 100 years, in effect, they perpetuate the noble hero; the myth of the super doctor.

In a profession that has borne witness to multiple suicides over the past few months, why do we not encourage open dialogue of our victories as well as our defeats? Our wins as much as our losses? Why does an esteemed veteran physician feel guilt over declining to provide emergency services to patients whom they have long forgotten how to manage? What drives the guilt and the self-doubt? Are we ashamed of what others will think? Is it that the fear of not living up to our cherished medical oath outweighs our own boundaries and acknowledgment of our limitations?

A hero is an entity, a person encompassing a state of being, yet health care professionals are bestowed this title and this burden on a near-daily basis. Physicians are people. We love, we fear, we hesitate, we fight, we deem to overcome. We are perfectly imperfect. The more in tune we are to vulnerability, the more honest we can become with ourselves and one another.
 

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

Let us begin with a thought exercise. Close your eyes and picture the word, “hero.” What comes to mind? A relative, a teacher, a fictional character wielding a hammer or flying gracefully through the air?

© Maridav / iStockphoto.com

Several months ago, our country was introduced to a foe that brought us to our knees. Before that time, the idea of a hero had fluctuated with circumstance and had been guided by aging and maturity; however, since the moment COVID-19 struck, a new image has emerged. Not all heroes wear capes, but some wield stethoscopes.

Over these past months the phrase, “Health Care Heroes” has spread throughout our collective consciousness, highlighted everywhere from talk shows and news media to billboards and journals. Doctors, nurses, and other health care professionals are lauded for their strength, dedication, resilience, and compassion. Citizens line up to clap, honk horns, and shower praise in recognition of those who have risked their health, sacrificed their personal lives, and committed themselves to the greater good. Yet, what does it mean to be a hero, and what is the cost of hero worship?

The focus of medical training has gradually shifted to include the physical as well as mental well-being of future physicians, but the remnants of traditional doctrine linger. Hours of focused training through study and direct clinical interaction reinforce dedication to patient care. Rewards are given for time spent and compassion lent, and research is lauded, but family time is rarely applauded. We are encouraged to do our greatest, work our hardest, be the best, rise and defeat every test. Failure (or the perception thereof) is not an option.

According to Rikinkumar S. Patel, MD, MPH, and associates, physicians have nearly twice the burnout rate of other professionals (Behav Sci. [Basel]. 2018 Nov;8[11]:98). The dedication to our craft propels excellence as well as sacrifice. When COVID-19 entered our lives, many of my colleagues did not hesitate to heed to the call for action. They immersed themselves in the ICU, led triage units, and extended work hours in the service of the sick and dying. Several were years removed from emergency/intensive care, while others were allocated from their chosen residency programs and voluntarily thrust into an environment they had never before traversed.

These individuals are praised as “brave,” “dedicated,” “selfless.” A few even provided insight into their experiences through various publications highlighting their appreciation and gratitude toward such a treacherous, albeit, tremendous experience. Even though their words are an honest perspective of life through one of the worst health care crises in 100 years, in effect, they perpetuate the noble hero; the myth of the super doctor.

In a profession that has borne witness to multiple suicides over the past few months, why do we not encourage open dialogue of our victories as well as our defeats? Our wins as much as our losses? Why does an esteemed veteran physician feel guilt over declining to provide emergency services to patients whom they have long forgotten how to manage? What drives the guilt and the self-doubt? Are we ashamed of what others will think? Is it that the fear of not living up to our cherished medical oath outweighs our own boundaries and acknowledgment of our limitations?

A hero is an entity, a person encompassing a state of being, yet health care professionals are bestowed this title and this burden on a near-daily basis. Physicians are people. We love, we fear, we hesitate, we fight, we deem to overcome. We are perfectly imperfect. The more in tune we are to vulnerability, the more honest we can become with ourselves and one another.
 

Dr. Thomas is a board-certified adult psychiatrist with an interest in chronic illness, women’s behavioral health, and minority mental health. She currently practices in North Kingstown and East Providence, R.I. She has no conflicts of interest.

A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.

Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.

The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.

When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.

The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.

The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
 

Differences in mortality, patients, treatment

In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).

The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).

The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.

Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
 

More than fear of COVID-19?

One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.

“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.

In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.

“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”

Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.

More data gathered by other centers might provide information about what it all means.

“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”

The investigators reported having no financial conflicts of interest.

SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.

A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.

Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.

The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.

When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.

The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.

The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
 

Differences in mortality, patients, treatment

In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).

The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).

The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.

Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
 

More than fear of COVID-19?

One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.

“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.

In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.

“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”

Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.

More data gathered by other centers might provide information about what it all means.

“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”

The investigators reported having no financial conflicts of interest.

SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.

A substantial decrease in hospital admissions for acute MI was accompanied by a rise in mortality, particularly for ST-segment elevation MI (STEMI), following the onset of the COVID-19 pandemic, according to a cross-sectional retrospective study.

Although it can’t be confirmed from these results that the observed increase in in-hospital acute MI (AMI) mortality are related to delays in seeking treatment, this is a reasonable working hypothesis until more is known, commented Harlan Krumholz, MD, who was not involved in the study.

The analysis, derived from data collected at 49 centers in a hospital system spread across six states, supports previous reports that patients with AMI were avoiding hospitalization, according to the investigators, who were led by Tyler J. Gluckman, MD, medical director of the Center for Cardiovascular Analytics, Providence Heart Institute, Portland, Ore.

When compared with a nearly 14-month period that preceded the COVID-19 pandemic, the rate of AMI-associated hospitalization fell by 19 cases per week (95% confidence interval, –29.0 to –9.0 cases) in the early COVID-19 period, which was defined by the investigators as spanning from Feb. 23, 2020 to March 28, 2020.

The case rate per week then increased by 10.5 (95% CI, 4.6-16.5 cases) in a subsequent 8-week period spanning between March 29, 2020, and May 16, 2020. Although a substantial increase from the early COVID-19 period, the case rate remained below the baseline established before COVID-19.

The analysis looked at 15,244 AMI hospitalizations among 14,724 patients treated in the Providence St. Joseph Hospital System, which has facilities in Alaska, California, Montana, Oregon, Texas, and Washington. The 1,915 AMI cases captured from Feb. 23, 2020, represented 13% of the total.
 

Differences in mortality, patients, treatment

In the early period, the ratio of observed-to-expected (O/E) mortality relative to the pre–COVID-19 baseline increased by 27% (odds ratio, 1.27; 95% CI, 1.07-1.48). When STEMI was analyzed separately, the O/E mortality was nearly double that of the baseline period (OR, 1.96; 95% CI, 1.22-2.70). In the latter post–COVID-19 period of observation, the overall increase in AMI-associated mortality on the basis of an O/E ratio was no longer significant relative to the baseline period (OR, 1.23; 95% CI, 0.98-1.47). However, the relative increase in STEMI-associated mortality on an O/E basis was even greater (OR, 2.40; 95% CI, 1.65-3.16) in the second COVID-19 period analyzed. Even after risk adjustment, the OR for STEMI mortality remained significantly elevated relative to baseline (1.52; 95% CI, 1.02-2.26).

The differences in AMI patients treated before the onset of the COVID-19 pandemic and those treated afterwards might be relevant, according to the investigators. Specifically, patients hospitalized after Feb. 23, 2020 were 1-3 years younger (P < .001) depending on type of AMI, and more likely to be Asian (P = .01).

The length of stay was 6 hours shorter in the early COVID-19 period and 7 hours shorter in the latter period relative to baseline, but an analysis of treatment approaches to non-STEMI and STEMI during the COVID-19 pandemic were not found to be significantly different from baseline.

Prior to the COVID-19 pandemic, 79% of STEMI patients and 77% of non-STEMI patients were discharged home, which was significantly lower than in the early COVID-19 period, when 83% (P = .02) of STEMI and 81% (P = .006) of non-STEMI patients were discharged home. In the latter period, discharge to home care was also significantly higher than in the baseline period.
 

More than fear of COVID-19?

One theory to account for the reduction in AMI hospitalizations and the increase in AMI-related mortality is the possibility that patients were slow to seek care at acute care hospitals because of concern about COVID-19 infection, according to Dr. Gluckman and coinvestigators.

“Given the time-sensitive nature of STEMI, any delay by patients, emergency medical services, the emergency department, or cardiac catheterization laboratory may have played a role,” they suggested.

In an interview, Dr. Gluckman said that further effort to identify the reasons for the increased AMI-related mortality is planned. Pulling data from the electronic medical records of the patients included in this retrospective analysis might be a “challenge,” but Dr. Gluckman reported that he and his coinvestigators plan to look at a different set of registry data that might provide information on sources of delay, particularly in the STEMI population.

“This includes looking at a number of time factors, such as symptom onset to first medical contact, first medical contact to device, and door-in-door-out times,” Dr. Gluckman said. The goal is to “better understand if delays [in treatment] occurred during the pandemic and, if so, how they may have contributed to increases in risk adjusted mortality.”

Dr. Krumholz, director of the Yale Center for Outcomes Research and Evaluation, New Haven, Conn., called this study a “useful” confirmation of changes in AMI-related care with the onset of the COVID-19 pandemic. As reported anecdotally, the study “indicates marked decreases in hospitalizations of patients with AMI even in areas that were not experiencing big outbreaks but did have some restrictions to limit spread,” he noted.

More data gathered by other centers might provide information about what it all means.

“There remain so many questions about what happened and what consequences accrued,” Dr. Krumholz observed. “In the meantime, we need to continue to send the message that people with symptoms that suggest a heart attack need to rapidly seek care.”

The investigators reported having no financial conflicts of interest.

SOURCE: Gluckman TJ et al. JAMA Cardiol. 2020 Aug 7. doi: 10.1001/jamacardio.2020.3629.

A new analysis from Michigan’s largest health system provides sobering verification of the risks for QT interval prolongation in COVID-19 patients treated with hydroxychloroquine and azithromycin (HCQ/AZM).

One in five patients (21%) had a corrected QT (QTc) interval of at least 500 msec, a value that increases the risk for torsade de pointes in the general population and at which cardiovascular leaders have suggested withholding HCQ/AZM in COVID-19 patients.

“One of the most striking findings was when we looked at the other drugs being administered to these patients; 61% were being administered drugs that had QT-prolonging effects concomitantly with the HCQ and AZM therapy. So they were inadvertently doubling down on the QT-prolonging effects of these drugs,” senior author David E. Haines, MD, director of the Heart Rhythm Center at William Beaumont Hospital, Royal Oak, Mich., said in an interview.

A total of 34 medications overlapped with HCQ/AZM therapy are known or suspected to increase the risk for torsade de pointes, a potentially life-threatening ventricular tachycardia. The most common of these were propofol coadministered in 123 patients, ondansetron in 114, dexmedetomidine in 54, haloperidol in 44, amiodarone in 43, and tramadol in 26.

“This speaks to the medical complexity of this patient population, but also suggests inadequate awareness of the QT-prolonging effects of many common medications,” the researchers say.

The study was published Aug. 5 in JACC Clinical Electrophysiology.

Both hydroxychloroquine and azithromycin increase the risk for QTc-interval prolongation by blocking the KCHN2-encoded hERG potassium channel. Several reports have linked the drugs to a triggering of QT prolongation in patients with COVID-19.

For the present study, Dr. Haines and colleagues examined data from 586 consecutive patients admitted with COVID-19 to the Beaumont Hospitals in Royal Oak and Troy, Mich., between March 13 and April 6. A baseline QTc interval was measured with 12-lead ECG prior to treatment initiation with hydroxychloroquine 400 mg twice daily for two doses, then 200 mg twice daily for 4 days, and azithromycin 500 mg once followed by 250 mg daily for 4 days.

Because of limited availability at the time, lead II ECG telemetry monitoring over the 5-day course of HCQ/AZM was recommended only in patients with baseline QTc intervals of at least 440 msec.

Patients without an interpretable baseline ECG or available telemetry/ECG monitoring for at least 1 day were also excluded, leaving 415 patients (mean age, 64 years; 45% female) in the study population. More than half (52%) were Black, 52% had hypertension, 30% had diabetes, and 14% had cancer.

As seen in previous studies, the QTc interval increased progressively and significantly after the administration of HCQ/AZM, from 443 msec to 473 msec.

The average time to maximum QTc was 2.9 days in a subset of 135 patients with QTc measurements prior to starting therapy and on days 1 through 5.

In multivariate analysis, independent predictors of a potentially hazardous QTc interval of at least 500 msec were:

• Age older than 65 years (odds ratio, 3.0; 95% confidence interval, 1.62-5.54).
• History of  (OR, 4.65; 95% CI, 2.01-10.74).
• Admission  of at least 1.5 mg/dL (OR, 2.22; 95% CI, 1.28-3.84).
• Peak troponin I level above 0.04 mg/mL (OR, 3.89; 95% CI, 2.22-6.83).
• Body mass index below 30 kg/m² (OR for a BMI of 30 kg/m² or higher, 0.45; 95% CI, 0.26-0.78).

Concomitant use of drugs with known risk for torsade de pointes was a significant risk factor in univariate analysis (OR, 1.73; P = .036), but fell out in the multivariate model.

No patients experienced high-grade arrhythmias during the study. In all, 112 of the 586 patients died during hospitalization, including 85 (21%) of the 415 study patients.

The change in QTc interval from baseline was greater in patients who died. Despite this, the only independent predictor of mortality was older age. One possible explanation is that the decision to monitor patients with baseline QTc intervals of at least 440 msec may have skewed the study population toward people with moderate or slightly long QTc intervals prior to the initiation of HCQ/AZM, Dr. Haines suggested. Monitoring and treatment duration were short, and clinicians also likely adjusted medications when excess QTc prolongation was observed.

Although it’s been months since data collection was completed in April, and the paper was written in record-breaking time, the study “is still very relevant because the drug is still out there,” observed Dr. Haines. “Even though it may not be used in as widespread a fashion as it had been when we first submitted the paper, it is still being used routinely by many hospitals and many practitioners.”

The use of hydroxychloroquine is “going through the roof” because of COVID-19, commented Dhanunjaya Lakkireddy, MD, medical director for the Kansas City Heart Rhythm Institute, HCA Midwest Health, Overland Park, Kan., who was not involved in the study.

“This study is very relevant, and I’m glad they shared their experience, and it’s pretty consistent with the data presented by other people. The question of whether hydroxychloroquine helps people with COVID is up for debate, but there is more evidence today that it is not as helpful as it was 3 months ago,” said Dr. Lakkireddy, who is also chair of the American College of Cardiology Electrophysiology Council.

He expressed concern for patients who may be taking HCQ with other medications that have QT-prolonging effects, and for the lack of long-term protocols in place for the drug.

In the coming weeks, however, the ACC and rheumatology leaders will be publishing an expert consensus statement that addresses key issues, such as how to best to use HCQ, maintenance HCQ, electrolyte monitoring, the optimal timing of electrocardiography and cardiac magnetic imaging, and symptoms to look for if cardiac involvement is suspected, Dr. Lakkireddy said.

Asked whether HCQ and AZM should be used in COVID-19 patients, Dr. Haines said in an interview that the “QT-prolonging effects are real, the arrhythmogenic potential is real, and the benefit to patients is nil or marginal. So I think that use of these drugs is appropriate and reasonable if it is done in a setting of a controlled trial, and I support that. But the routine use of these drugs probably is not warranted based on the data that we have available.”

Still, hydroxychloroquine continues to be dragged into the spotlight in recent days as an effective treatment for COVID-19, despite discredited research and the U.S. Food and Drug Administration’s June 15 revocation of its emergency-use authorization to allow use of HCQ and chloroquine to treat certain hospitalized COVID-19 patients.

“The unfortunate politicization of this issue has really muddied the waters because the general public doesn’t know what to believe or who to believe. The fact that treatment for a disease as serious as COVID should be modulated by political affiliation is just crazy to me,” said Dr. Haines. “We should be using the best science and taking careful observations, and whatever the recommendations derived from that should be uniformly adopted by everybody, irrespective of your political affiliation.”

Dr. Haines has received honoraria from Biosense Webster, Farapulse, and Sagentia, and is a consultant for Affera, Boston Scientific, Integer, Medtronic, Philips Healthcare, and Zoll. Dr. Lakkireddy has served as a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, and Medtronic. 

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

A new analysis from Michigan’s largest health system provides sobering verification of the risks for QT interval prolongation in COVID-19 patients treated with hydroxychloroquine and azithromycin (HCQ/AZM).

One in five patients (21%) had a corrected QT (QTc) interval of at least 500 msec, a value that increases the risk for torsade de pointes in the general population and at which cardiovascular leaders have suggested withholding HCQ/AZM in COVID-19 patients.

“One of the most striking findings was when we looked at the other drugs being administered to these patients; 61% were being administered drugs that had QT-prolonging effects concomitantly with the HCQ and AZM therapy. So they were inadvertently doubling down on the QT-prolonging effects of these drugs,” senior author David E. Haines, MD, director of the Heart Rhythm Center at William Beaumont Hospital, Royal Oak, Mich., said in an interview.

A total of 34 medications overlapped with HCQ/AZM therapy are known or suspected to increase the risk for torsade de pointes, a potentially life-threatening ventricular tachycardia. The most common of these were propofol coadministered in 123 patients, ondansetron in 114, dexmedetomidine in 54, haloperidol in 44, amiodarone in 43, and tramadol in 26.

“This speaks to the medical complexity of this patient population, but also suggests inadequate awareness of the QT-prolonging effects of many common medications,” the researchers say.

The study was published Aug. 5 in JACC Clinical Electrophysiology.

Both hydroxychloroquine and azithromycin increase the risk for QTc-interval prolongation by blocking the KCHN2-encoded hERG potassium channel. Several reports have linked the drugs to a triggering of QT prolongation in patients with COVID-19.

For the present study, Dr. Haines and colleagues examined data from 586 consecutive patients admitted with COVID-19 to the Beaumont Hospitals in Royal Oak and Troy, Mich., between March 13 and April 6. A baseline QTc interval was measured with 12-lead ECG prior to treatment initiation with hydroxychloroquine 400 mg twice daily for two doses, then 200 mg twice daily for 4 days, and azithromycin 500 mg once followed by 250 mg daily for 4 days.

Because of limited availability at the time, lead II ECG telemetry monitoring over the 5-day course of HCQ/AZM was recommended only in patients with baseline QTc intervals of at least 440 msec.

Patients without an interpretable baseline ECG or available telemetry/ECG monitoring for at least 1 day were also excluded, leaving 415 patients (mean age, 64 years; 45% female) in the study population. More than half (52%) were Black, 52% had hypertension, 30% had diabetes, and 14% had cancer.

As seen in previous studies, the QTc interval increased progressively and significantly after the administration of HCQ/AZM, from 443 msec to 473 msec.

The average time to maximum QTc was 2.9 days in a subset of 135 patients with QTc measurements prior to starting therapy and on days 1 through 5.

In multivariate analysis, independent predictors of a potentially hazardous QTc interval of at least 500 msec were:

• Age older than 65 years (odds ratio, 3.0; 95% confidence interval, 1.62-5.54).
• History of  (OR, 4.65; 95% CI, 2.01-10.74).
• Admission  of at least 1.5 mg/dL (OR, 2.22; 95% CI, 1.28-3.84).
• Peak troponin I level above 0.04 mg/mL (OR, 3.89; 95% CI, 2.22-6.83).
• Body mass index below 30 kg/m² (OR for a BMI of 30 kg/m² or higher, 0.45; 95% CI, 0.26-0.78).

Concomitant use of drugs with known risk for torsade de pointes was a significant risk factor in univariate analysis (OR, 1.73; P = .036), but fell out in the multivariate model.

No patients experienced high-grade arrhythmias during the study. In all, 112 of the 586 patients died during hospitalization, including 85 (21%) of the 415 study patients.

The change in QTc interval from baseline was greater in patients who died. Despite this, the only independent predictor of mortality was older age. One possible explanation is that the decision to monitor patients with baseline QTc intervals of at least 440 msec may have skewed the study population toward people with moderate or slightly long QTc intervals prior to the initiation of HCQ/AZM, Dr. Haines suggested. Monitoring and treatment duration were short, and clinicians also likely adjusted medications when excess QTc prolongation was observed.

Although it’s been months since data collection was completed in April, and the paper was written in record-breaking time, the study “is still very relevant because the drug is still out there,” observed Dr. Haines. “Even though it may not be used in as widespread a fashion as it had been when we first submitted the paper, it is still being used routinely by many hospitals and many practitioners.”

The use of hydroxychloroquine is “going through the roof” because of COVID-19, commented Dhanunjaya Lakkireddy, MD, medical director for the Kansas City Heart Rhythm Institute, HCA Midwest Health, Overland Park, Kan., who was not involved in the study.

“This study is very relevant, and I’m glad they shared their experience, and it’s pretty consistent with the data presented by other people. The question of whether hydroxychloroquine helps people with COVID is up for debate, but there is more evidence today that it is not as helpful as it was 3 months ago,” said Dr. Lakkireddy, who is also chair of the American College of Cardiology Electrophysiology Council.

He expressed concern for patients who may be taking HCQ with other medications that have QT-prolonging effects, and for the lack of long-term protocols in place for the drug.

In the coming weeks, however, the ACC and rheumatology leaders will be publishing an expert consensus statement that addresses key issues, such as how to best to use HCQ, maintenance HCQ, electrolyte monitoring, the optimal timing of electrocardiography and cardiac magnetic imaging, and symptoms to look for if cardiac involvement is suspected, Dr. Lakkireddy said.

Asked whether HCQ and AZM should be used in COVID-19 patients, Dr. Haines said in an interview that the “QT-prolonging effects are real, the arrhythmogenic potential is real, and the benefit to patients is nil or marginal. So I think that use of these drugs is appropriate and reasonable if it is done in a setting of a controlled trial, and I support that. But the routine use of these drugs probably is not warranted based on the data that we have available.”

Still, hydroxychloroquine continues to be dragged into the spotlight in recent days as an effective treatment for COVID-19, despite discredited research and the U.S. Food and Drug Administration’s June 15 revocation of its emergency-use authorization to allow use of HCQ and chloroquine to treat certain hospitalized COVID-19 patients.

“The unfortunate politicization of this issue has really muddied the waters because the general public doesn’t know what to believe or who to believe. The fact that treatment for a disease as serious as COVID should be modulated by political affiliation is just crazy to me,” said Dr. Haines. “We should be using the best science and taking careful observations, and whatever the recommendations derived from that should be uniformly adopted by everybody, irrespective of your political affiliation.”

Dr. Haines has received honoraria from Biosense Webster, Farapulse, and Sagentia, and is a consultant for Affera, Boston Scientific, Integer, Medtronic, Philips Healthcare, and Zoll. Dr. Lakkireddy has served as a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, and Medtronic. 

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

A new analysis from Michigan’s largest health system provides sobering verification of the risks for QT interval prolongation in COVID-19 patients treated with hydroxychloroquine and azithromycin (HCQ/AZM).

One in five patients (21%) had a corrected QT (QTc) interval of at least 500 msec, a value that increases the risk for torsade de pointes in the general population and at which cardiovascular leaders have suggested withholding HCQ/AZM in COVID-19 patients.

“One of the most striking findings was when we looked at the other drugs being administered to these patients; 61% were being administered drugs that had QT-prolonging effects concomitantly with the HCQ and AZM therapy. So they were inadvertently doubling down on the QT-prolonging effects of these drugs,” senior author David E. Haines, MD, director of the Heart Rhythm Center at William Beaumont Hospital, Royal Oak, Mich., said in an interview.

A total of 34 medications overlapped with HCQ/AZM therapy are known or suspected to increase the risk for torsade de pointes, a potentially life-threatening ventricular tachycardia. The most common of these were propofol coadministered in 123 patients, ondansetron in 114, dexmedetomidine in 54, haloperidol in 44, amiodarone in 43, and tramadol in 26.

“This speaks to the medical complexity of this patient population, but also suggests inadequate awareness of the QT-prolonging effects of many common medications,” the researchers say.

The study was published Aug. 5 in JACC Clinical Electrophysiology.

Both hydroxychloroquine and azithromycin increase the risk for QTc-interval prolongation by blocking the KCHN2-encoded hERG potassium channel. Several reports have linked the drugs to a triggering of QT prolongation in patients with COVID-19.

For the present study, Dr. Haines and colleagues examined data from 586 consecutive patients admitted with COVID-19 to the Beaumont Hospitals in Royal Oak and Troy, Mich., between March 13 and April 6. A baseline QTc interval was measured with 12-lead ECG prior to treatment initiation with hydroxychloroquine 400 mg twice daily for two doses, then 200 mg twice daily for 4 days, and azithromycin 500 mg once followed by 250 mg daily for 4 days.

Because of limited availability at the time, lead II ECG telemetry monitoring over the 5-day course of HCQ/AZM was recommended only in patients with baseline QTc intervals of at least 440 msec.

Patients without an interpretable baseline ECG or available telemetry/ECG monitoring for at least 1 day were also excluded, leaving 415 patients (mean age, 64 years; 45% female) in the study population. More than half (52%) were Black, 52% had hypertension, 30% had diabetes, and 14% had cancer.

As seen in previous studies, the QTc interval increased progressively and significantly after the administration of HCQ/AZM, from 443 msec to 473 msec.

The average time to maximum QTc was 2.9 days in a subset of 135 patients with QTc measurements prior to starting therapy and on days 1 through 5.

In multivariate analysis, independent predictors of a potentially hazardous QTc interval of at least 500 msec were:

• Age older than 65 years (odds ratio, 3.0; 95% confidence interval, 1.62-5.54).
• History of  (OR, 4.65; 95% CI, 2.01-10.74).
• Admission  of at least 1.5 mg/dL (OR, 2.22; 95% CI, 1.28-3.84).
• Peak troponin I level above 0.04 mg/mL (OR, 3.89; 95% CI, 2.22-6.83).
• Body mass index below 30 kg/m² (OR for a BMI of 30 kg/m² or higher, 0.45; 95% CI, 0.26-0.78).

Concomitant use of drugs with known risk for torsade de pointes was a significant risk factor in univariate analysis (OR, 1.73; P = .036), but fell out in the multivariate model.

No patients experienced high-grade arrhythmias during the study. In all, 112 of the 586 patients died during hospitalization, including 85 (21%) of the 415 study patients.

The change in QTc interval from baseline was greater in patients who died. Despite this, the only independent predictor of mortality was older age. One possible explanation is that the decision to monitor patients with baseline QTc intervals of at least 440 msec may have skewed the study population toward people with moderate or slightly long QTc intervals prior to the initiation of HCQ/AZM, Dr. Haines suggested. Monitoring and treatment duration were short, and clinicians also likely adjusted medications when excess QTc prolongation was observed.

Although it’s been months since data collection was completed in April, and the paper was written in record-breaking time, the study “is still very relevant because the drug is still out there,” observed Dr. Haines. “Even though it may not be used in as widespread a fashion as it had been when we first submitted the paper, it is still being used routinely by many hospitals and many practitioners.”

The use of hydroxychloroquine is “going through the roof” because of COVID-19, commented Dhanunjaya Lakkireddy, MD, medical director for the Kansas City Heart Rhythm Institute, HCA Midwest Health, Overland Park, Kan., who was not involved in the study.

“This study is very relevant, and I’m glad they shared their experience, and it’s pretty consistent with the data presented by other people. The question of whether hydroxychloroquine helps people with COVID is up for debate, but there is more evidence today that it is not as helpful as it was 3 months ago,” said Dr. Lakkireddy, who is also chair of the American College of Cardiology Electrophysiology Council.

He expressed concern for patients who may be taking HCQ with other medications that have QT-prolonging effects, and for the lack of long-term protocols in place for the drug.

In the coming weeks, however, the ACC and rheumatology leaders will be publishing an expert consensus statement that addresses key issues, such as how to best to use HCQ, maintenance HCQ, electrolyte monitoring, the optimal timing of electrocardiography and cardiac magnetic imaging, and symptoms to look for if cardiac involvement is suspected, Dr. Lakkireddy said.

Asked whether HCQ and AZM should be used in COVID-19 patients, Dr. Haines said in an interview that the “QT-prolonging effects are real, the arrhythmogenic potential is real, and the benefit to patients is nil or marginal. So I think that use of these drugs is appropriate and reasonable if it is done in a setting of a controlled trial, and I support that. But the routine use of these drugs probably is not warranted based on the data that we have available.”

Still, hydroxychloroquine continues to be dragged into the spotlight in recent days as an effective treatment for COVID-19, despite discredited research and the U.S. Food and Drug Administration’s June 15 revocation of its emergency-use authorization to allow use of HCQ and chloroquine to treat certain hospitalized COVID-19 patients.

“The unfortunate politicization of this issue has really muddied the waters because the general public doesn’t know what to believe or who to believe. The fact that treatment for a disease as serious as COVID should be modulated by political affiliation is just crazy to me,” said Dr. Haines. “We should be using the best science and taking careful observations, and whatever the recommendations derived from that should be uniformly adopted by everybody, irrespective of your political affiliation.”

Dr. Haines has received honoraria from Biosense Webster, Farapulse, and Sagentia, and is a consultant for Affera, Boston Scientific, Integer, Medtronic, Philips Healthcare, and Zoll. Dr. Lakkireddy has served as a consultant to Abbott, Biosense Webster, Biotronik, Boston Scientific, and Medtronic. 

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

Fractional flow reserve derived noninvasively from coronary CT angiography is a safe and accurate method for assessing the significance of coronary artery disease in patients with severe aortic stenosis who are headed for transcatheter aortic valve replacement (TAVR), according to results of the CAST-FFR prospective study.

Indeed, utilization of coronary CT angiography–derived fractional flow reserve (CT-FFR) for this purpose offers the advantage of using a single noninvasive imaging method to replace two invasive procedures: coronary angiography to assess the anatomy of coronary lesions, and conventional FFR using a pressure wire to determine the functional significance of a given coronary stenosis as a cause of ischemia, Michael Michail, MBBS, explained in reporting the results at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

“Because up to 50% of patients with severe aortic stenosis undergoing TAVR have coexisting coronary artery disease, it remains common practice to perform prior invasive coronary angiography. However, this is associated with inherent risks, particularly in an elderly cohort with comorbidities. Additionally, coronary angiography provides no information on the functional impact of coronary stenoses, which may be important in guiding revascularization decisions prior to TAVR,” noted Dr. Michail, a cardiologist at Monash University, Melbourne.
 

Simulating FFR: ‘A one-stop shop cardiac CT’

Dr. Michail presented the results of the prospective CAST-FFR study, the first evaluation of CT-FFR for assessment of coronary arteries in patients with severe symptomatic aortic stenosis. This method uses computational fluid dynamics to transform data obtained noninvasively from a standard coronary CT angiography acquisition into a simulated FFR. And it offers the potential to streamline patient care.

“In current practice we see elderly patients with a long pre-TAVR assessment period, with numerous appointments and invasive procedures. Our vision is a one-stop shop cardiac CT that will provide the cardiologist with a complete assessment of the annular measurements, peripheral vasculature, and the coronary arteries ahead of their procedure,” according to Dr. Michail.

“We believe the ability to perform the requisite coronary assessment using CT-FFR will translate to improved patient care in several ways,” he continued. “Firstly, this will shorten the number of tests and overall diagnostic journey for patients. It will reduce the risk from unnecessary invasive procedures, and this will also reduce discomfort for the patient. Based on emerging evidence on the adverse prognostic impact of functionally significant coronary disease in aortic stenosis, this data has the potential to improve procedural risk stratification. And finally, contingent on further data, this may improve lesion selection for upfront revascularization.”

The CAST-FFR study was a small, single-center, proof-of-concept study in which 42 patients with severe aortic stenosis underwent both coronary CT angiography and conventional FFR with a pressure wire. The CT data was sent to a core laboratory for conversion into CT-FFR by evaluators blinded to the conventional FFR values.

Of the 42 participants, 39 (93%) had usable CT-FFR data on 60 coronary vessels. Dr. Michail and coinvestigators found a strong correlation between the conventional pressure wire FFR and CT-FFR findings, with a receiver operating characteristic area under the curve of 0.83 per vessel. CT-FFR had a diagnostic sensitivity and specificity of 73.9% and 78.4%, respectively, with a positive predictive value of 68%, a negative predictive value of 82.9%, and a diagnostic accuracy of 76.7%.

He cited as study limitations the small size, the fact that patients with previous revascularization or significant left ventricular impairment were excluded, and the study cohort’s relative youth.

“With a mean age of 76.2 years, it’s unclear whether these results can be extrapolated to very elderly patients with more calcified arteries undergoing TAVR. Encouragingly, though, a subgroup analysis based on calcium score showed no effect on accuracy,” according to the cardiologist.

CT-FFR may ‘shorten the diagnostic journey’ for fragile patients

Discussant Daniele Andreini, MD, PhD, praised the investigators’ concept of integrating the functional assessment provided by CT-FFR into a one-stop shop examination by cardiac CT angiography for TAVR planning.

“I would like to underline one of Dr. Michail’s messages: It’s really important to shorten the diagnostic journey for these fragile, older patients with aortic stenosis in order to improve safety, use less contrast, and avoid complications,” said Dr. Andreini, a cardiologist at the University of Milan and director of the cardiovascular CT and radiology unit at Monzino Cardiology Center, also in Milan.

Both Dr. Michail and Dr. Andreini reported having no financial conflicts of interest.

[email protected]

Fractional flow reserve derived noninvasively from coronary CT angiography is a safe and accurate method for assessing the significance of coronary artery disease in patients with severe aortic stenosis who are headed for transcatheter aortic valve replacement (TAVR), according to results of the CAST-FFR prospective study.

Indeed, utilization of coronary CT angiography–derived fractional flow reserve (CT-FFR) for this purpose offers the advantage of using a single noninvasive imaging method to replace two invasive procedures: coronary angiography to assess the anatomy of coronary lesions, and conventional FFR using a pressure wire to determine the functional significance of a given coronary stenosis as a cause of ischemia, Michael Michail, MBBS, explained in reporting the results at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

“Because up to 50% of patients with severe aortic stenosis undergoing TAVR have coexisting coronary artery disease, it remains common practice to perform prior invasive coronary angiography. However, this is associated with inherent risks, particularly in an elderly cohort with comorbidities. Additionally, coronary angiography provides no information on the functional impact of coronary stenoses, which may be important in guiding revascularization decisions prior to TAVR,” noted Dr. Michail, a cardiologist at Monash University, Melbourne.
 

Simulating FFR: ‘A one-stop shop cardiac CT’

Dr. Michail presented the results of the prospective CAST-FFR study, the first evaluation of CT-FFR for assessment of coronary arteries in patients with severe symptomatic aortic stenosis. This method uses computational fluid dynamics to transform data obtained noninvasively from a standard coronary CT angiography acquisition into a simulated FFR. And it offers the potential to streamline patient care.

“In current practice we see elderly patients with a long pre-TAVR assessment period, with numerous appointments and invasive procedures. Our vision is a one-stop shop cardiac CT that will provide the cardiologist with a complete assessment of the annular measurements, peripheral vasculature, and the coronary arteries ahead of their procedure,” according to Dr. Michail.

“We believe the ability to perform the requisite coronary assessment using CT-FFR will translate to improved patient care in several ways,” he continued. “Firstly, this will shorten the number of tests and overall diagnostic journey for patients. It will reduce the risk from unnecessary invasive procedures, and this will also reduce discomfort for the patient. Based on emerging evidence on the adverse prognostic impact of functionally significant coronary disease in aortic stenosis, this data has the potential to improve procedural risk stratification. And finally, contingent on further data, this may improve lesion selection for upfront revascularization.”

The CAST-FFR study was a small, single-center, proof-of-concept study in which 42 patients with severe aortic stenosis underwent both coronary CT angiography and conventional FFR with a pressure wire. The CT data was sent to a core laboratory for conversion into CT-FFR by evaluators blinded to the conventional FFR values.

Of the 42 participants, 39 (93%) had usable CT-FFR data on 60 coronary vessels. Dr. Michail and coinvestigators found a strong correlation between the conventional pressure wire FFR and CT-FFR findings, with a receiver operating characteristic area under the curve of 0.83 per vessel. CT-FFR had a diagnostic sensitivity and specificity of 73.9% and 78.4%, respectively, with a positive predictive value of 68%, a negative predictive value of 82.9%, and a diagnostic accuracy of 76.7%.

He cited as study limitations the small size, the fact that patients with previous revascularization or significant left ventricular impairment were excluded, and the study cohort’s relative youth.

“With a mean age of 76.2 years, it’s unclear whether these results can be extrapolated to very elderly patients with more calcified arteries undergoing TAVR. Encouragingly, though, a subgroup analysis based on calcium score showed no effect on accuracy,” according to the cardiologist.

CT-FFR may ‘shorten the diagnostic journey’ for fragile patients

Discussant Daniele Andreini, MD, PhD, praised the investigators’ concept of integrating the functional assessment provided by CT-FFR into a one-stop shop examination by cardiac CT angiography for TAVR planning.

“I would like to underline one of Dr. Michail’s messages: It’s really important to shorten the diagnostic journey for these fragile, older patients with aortic stenosis in order to improve safety, use less contrast, and avoid complications,” said Dr. Andreini, a cardiologist at the University of Milan and director of the cardiovascular CT and radiology unit at Monzino Cardiology Center, also in Milan.

Both Dr. Michail and Dr. Andreini reported having no financial conflicts of interest.

[email protected]

Fractional flow reserve derived noninvasively from coronary CT angiography is a safe and accurate method for assessing the significance of coronary artery disease in patients with severe aortic stenosis who are headed for transcatheter aortic valve replacement (TAVR), according to results of the CAST-FFR prospective study.

Indeed, utilization of coronary CT angiography–derived fractional flow reserve (CT-FFR) for this purpose offers the advantage of using a single noninvasive imaging method to replace two invasive procedures: coronary angiography to assess the anatomy of coronary lesions, and conventional FFR using a pressure wire to determine the functional significance of a given coronary stenosis as a cause of ischemia, Michael Michail, MBBS, explained in reporting the results at the virtual annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

“Because up to 50% of patients with severe aortic stenosis undergoing TAVR have coexisting coronary artery disease, it remains common practice to perform prior invasive coronary angiography. However, this is associated with inherent risks, particularly in an elderly cohort with comorbidities. Additionally, coronary angiography provides no information on the functional impact of coronary stenoses, which may be important in guiding revascularization decisions prior to TAVR,” noted Dr. Michail, a cardiologist at Monash University, Melbourne.
 

Simulating FFR: ‘A one-stop shop cardiac CT’

Dr. Michail presented the results of the prospective CAST-FFR study, the first evaluation of CT-FFR for assessment of coronary arteries in patients with severe symptomatic aortic stenosis. This method uses computational fluid dynamics to transform data obtained noninvasively from a standard coronary CT angiography acquisition into a simulated FFR. And it offers the potential to streamline patient care.

“In current practice we see elderly patients with a long pre-TAVR assessment period, with numerous appointments and invasive procedures. Our vision is a one-stop shop cardiac CT that will provide the cardiologist with a complete assessment of the annular measurements, peripheral vasculature, and the coronary arteries ahead of their procedure,” according to Dr. Michail.

“We believe the ability to perform the requisite coronary assessment using CT-FFR will translate to improved patient care in several ways,” he continued. “Firstly, this will shorten the number of tests and overall diagnostic journey for patients. It will reduce the risk from unnecessary invasive procedures, and this will also reduce discomfort for the patient. Based on emerging evidence on the adverse prognostic impact of functionally significant coronary disease in aortic stenosis, this data has the potential to improve procedural risk stratification. And finally, contingent on further data, this may improve lesion selection for upfront revascularization.”

The CAST-FFR study was a small, single-center, proof-of-concept study in which 42 patients with severe aortic stenosis underwent both coronary CT angiography and conventional FFR with a pressure wire. The CT data was sent to a core laboratory for conversion into CT-FFR by evaluators blinded to the conventional FFR values.

Of the 42 participants, 39 (93%) had usable CT-FFR data on 60 coronary vessels. Dr. Michail and coinvestigators found a strong correlation between the conventional pressure wire FFR and CT-FFR findings, with a receiver operating characteristic area under the curve of 0.83 per vessel. CT-FFR had a diagnostic sensitivity and specificity of 73.9% and 78.4%, respectively, with a positive predictive value of 68%, a negative predictive value of 82.9%, and a diagnostic accuracy of 76.7%.

He cited as study limitations the small size, the fact that patients with previous revascularization or significant left ventricular impairment were excluded, and the study cohort’s relative youth.

“With a mean age of 76.2 years, it’s unclear whether these results can be extrapolated to very elderly patients with more calcified arteries undergoing TAVR. Encouragingly, though, a subgroup analysis based on calcium score showed no effect on accuracy,” according to the cardiologist.

CT-FFR may ‘shorten the diagnostic journey’ for fragile patients

Discussant Daniele Andreini, MD, PhD, praised the investigators’ concept of integrating the functional assessment provided by CT-FFR into a one-stop shop examination by cardiac CT angiography for TAVR planning.

“I would like to underline one of Dr. Michail’s messages: It’s really important to shorten the diagnostic journey for these fragile, older patients with aortic stenosis in order to improve safety, use less contrast, and avoid complications,” said Dr. Andreini, a cardiologist at the University of Milan and director of the cardiovascular CT and radiology unit at Monzino Cardiology Center, also in Milan.

Both Dr. Michail and Dr. Andreini reported having no financial conflicts of interest.

[email protected]

Monogenic disorders with heart and vascular effects are each pretty rare in clinical practice but collectively can make up a fair proportion of the patients cardiologists see. Still, the diagnosis is missed more often than not, even when the clinical signs are there, suggests an observational study, supporting broader genetic testing in cardiovascular patients.

In a cohort of more than 8,000 patients referred for cardiac catheterization, diagnosis of such a monogenic cardiovascular disease (MCVD) was made in only 35% of those with one related gene variant and signs of phenotypic expression in the electronic health record.

The findings are novel for measuring the field’s “burden of missed diagnoses” in patients with MCVD, which “represent a missed opportunity that could be addressed by genetic screening,” contended the study report, published in the Aug. 18 issue of the Journal of the American College of Cardiology.

“The underrecognition of these diseases underscores the importance of including monogenic diseases in the treating physician’s differential diagnosis,” say the authors, led by Jawan W. Abdulrahim, MD, Duke University, Durham, N.C.

Diagnosis of MCVDs can be important, the group wrote, because many, including familial transthyretin amyloidosis (TTR) and other disorders that pose an increased risk for sudden death, have evidence-based treatment modalities available or are clinically actionable. “Identification of patients with MCVD variants” is also “important for cascade screening of family members who are at risk of inheriting the pathogenic mutations.”

“We tend to ignore these monogenic diseases because they are so rare individually but, in aggregate, monogenic diseases are actually quite common,” senior author Svati H. Shah, MD, MHS, also of Duke University, said in an interview.

The results “support that the cardiology community over time adopt a genotype-forward approach,” one in which every patient presenting to a cardiovascular clinic is genotyped, she said.

One implication of such an approach, Dr. Shah agreed, is that “we would be able to pick these people up earlier in their disease, especially in the context of therapies that could improve certainly their progression, but even their survival.”

For now, she said, the study suggests that “these disorders are more frequent than perhaps all cardiologists are aware of, and we just need to keep our eyes open and know when to refer patients to a cardiovascular genetics clinic, which maybe has more time and can deal with all the nuances that go along with genetic testing.”

In the total cohort, 4.5% were found to carry a gene variant known or believed to cause such diseases. The most frequently represented conditions were familial TTR, hereditary hemochromatosis, heterozygous familial hypercholesterolemia, and various cardiomyopathies.

Of those patients, 52 received a clinical diagnosis of the monogenic disorder after an EHR review. Of the 290 without such a diagnosis, two-thirds showed no evidence in their EHR of the variant’s phenotypic signs. But the records of the other third featured at least some signs that the disease had manifested clinically.

“These data serve as a reminder that monogenic Mendelian disease, including heart and vascular disease, varies in penetrance from individual to individual and may not always present with clinically detectable phenotypes,” noted an editorial accompanying the report.

They also “provide a compelling basis for expanding the role of targeted genetic testing in patients with more traditional forms of heart and vascular disease,” wrote Scott M. Damrauer, MD, University of Pennsylvania, Philadelphia, and William S. Weintraub, MD, Medstar Washington Hospital Center and Georgetown University, Washington.

“Based on the current report, the number needed to screen in a complex cardiovascular patient population to detect 1 case of undiagnosed monogenic cardiovascular disease is 85,” they wrote. “This places targeted genetic testing well within what is considered to be efficacious for most screening programs and in the range of that of other common cardiovascular diseases and cancers.”

Among the 342 patients with a variant predicting a single MCVD – in addition to the 52 who received a diagnosis – 193 had records with no indication of phenotypic expression and so did not receive a diagnosis.

But the 97 patients without a diagnosis who nevertheless had documented signs of some phenotypic expression were deemed, on the basis of extent of expression, to represent a possibly, probably, or definitely missed diagnosis.

Familial TTR made up about 45% of such potentially missed diagnoses, the report noted.

Broader screening of patients with cardiovascular disease, Dr. Shah speculated, “might actually be not only a clinically useful endeavor, but – when we think about the aggregate burden of these monogenic disorders – potentially even cost-effective.”

As the price of genetic sequencing drops, she said, “I think we’ll start to see even more health systems wanting to incorporate the genotype-forward approach.”

Dr. Shah reports serving as primary investigator for research sponsored by Verily Life Sciences and AstraZeneca. Dr. Abdulrahim reports no relevant relationships. Disclosures for the other authors are in the report. Dr. Damrauer discloses receiving research support from RenalytixAI and consulting fees from Calico Labs. Dr. Weintraub had no relevant disclosures.

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

Monogenic disorders with heart and vascular effects are each pretty rare in clinical practice but collectively can make up a fair proportion of the patients cardiologists see. Still, the diagnosis is missed more often than not, even when the clinical signs are there, suggests an observational study, supporting broader genetic testing in cardiovascular patients.

In a cohort of more than 8,000 patients referred for cardiac catheterization, diagnosis of such a monogenic cardiovascular disease (MCVD) was made in only 35% of those with one related gene variant and signs of phenotypic expression in the electronic health record.

The findings are novel for measuring the field’s “burden of missed diagnoses” in patients with MCVD, which “represent a missed opportunity that could be addressed by genetic screening,” contended the study report, published in the Aug. 18 issue of the Journal of the American College of Cardiology.

“The underrecognition of these diseases underscores the importance of including monogenic diseases in the treating physician’s differential diagnosis,” say the authors, led by Jawan W. Abdulrahim, MD, Duke University, Durham, N.C.

Diagnosis of MCVDs can be important, the group wrote, because many, including familial transthyretin amyloidosis (TTR) and other disorders that pose an increased risk for sudden death, have evidence-based treatment modalities available or are clinically actionable. “Identification of patients with MCVD variants” is also “important for cascade screening of family members who are at risk of inheriting the pathogenic mutations.”

“We tend to ignore these monogenic diseases because they are so rare individually but, in aggregate, monogenic diseases are actually quite common,” senior author Svati H. Shah, MD, MHS, also of Duke University, said in an interview.

The results “support that the cardiology community over time adopt a genotype-forward approach,” one in which every patient presenting to a cardiovascular clinic is genotyped, she said.

One implication of such an approach, Dr. Shah agreed, is that “we would be able to pick these people up earlier in their disease, especially in the context of therapies that could improve certainly their progression, but even their survival.”

For now, she said, the study suggests that “these disorders are more frequent than perhaps all cardiologists are aware of, and we just need to keep our eyes open and know when to refer patients to a cardiovascular genetics clinic, which maybe has more time and can deal with all the nuances that go along with genetic testing.”

In the total cohort, 4.5% were found to carry a gene variant known or believed to cause such diseases. The most frequently represented conditions were familial TTR, hereditary hemochromatosis, heterozygous familial hypercholesterolemia, and various cardiomyopathies.

Of those patients, 52 received a clinical diagnosis of the monogenic disorder after an EHR review. Of the 290 without such a diagnosis, two-thirds showed no evidence in their EHR of the variant’s phenotypic signs. But the records of the other third featured at least some signs that the disease had manifested clinically.

“These data serve as a reminder that monogenic Mendelian disease, including heart and vascular disease, varies in penetrance from individual to individual and may not always present with clinically detectable phenotypes,” noted an editorial accompanying the report.

They also “provide a compelling basis for expanding the role of targeted genetic testing in patients with more traditional forms of heart and vascular disease,” wrote Scott M. Damrauer, MD, University of Pennsylvania, Philadelphia, and William S. Weintraub, MD, Medstar Washington Hospital Center and Georgetown University, Washington.

“Based on the current report, the number needed to screen in a complex cardiovascular patient population to detect 1 case of undiagnosed monogenic cardiovascular disease is 85,” they wrote. “This places targeted genetic testing well within what is considered to be efficacious for most screening programs and in the range of that of other common cardiovascular diseases and cancers.”

Among the 342 patients with a variant predicting a single MCVD – in addition to the 52 who received a diagnosis – 193 had records with no indication of phenotypic expression and so did not receive a diagnosis.

But the 97 patients without a diagnosis who nevertheless had documented signs of some phenotypic expression were deemed, on the basis of extent of expression, to represent a possibly, probably, or definitely missed diagnosis.

Familial TTR made up about 45% of such potentially missed diagnoses, the report noted.

Broader screening of patients with cardiovascular disease, Dr. Shah speculated, “might actually be not only a clinically useful endeavor, but – when we think about the aggregate burden of these monogenic disorders – potentially even cost-effective.”

As the price of genetic sequencing drops, she said, “I think we’ll start to see even more health systems wanting to incorporate the genotype-forward approach.”

Dr. Shah reports serving as primary investigator for research sponsored by Verily Life Sciences and AstraZeneca. Dr. Abdulrahim reports no relevant relationships. Disclosures for the other authors are in the report. Dr. Damrauer discloses receiving research support from RenalytixAI and consulting fees from Calico Labs. Dr. Weintraub had no relevant disclosures.

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

Monogenic disorders with heart and vascular effects are each pretty rare in clinical practice but collectively can make up a fair proportion of the patients cardiologists see. Still, the diagnosis is missed more often than not, even when the clinical signs are there, suggests an observational study, supporting broader genetic testing in cardiovascular patients.

In a cohort of more than 8,000 patients referred for cardiac catheterization, diagnosis of such a monogenic cardiovascular disease (MCVD) was made in only 35% of those with one related gene variant and signs of phenotypic expression in the electronic health record.

The findings are novel for measuring the field’s “burden of missed diagnoses” in patients with MCVD, which “represent a missed opportunity that could be addressed by genetic screening,” contended the study report, published in the Aug. 18 issue of the Journal of the American College of Cardiology.

“The underrecognition of these diseases underscores the importance of including monogenic diseases in the treating physician’s differential diagnosis,” say the authors, led by Jawan W. Abdulrahim, MD, Duke University, Durham, N.C.

Diagnosis of MCVDs can be important, the group wrote, because many, including familial transthyretin amyloidosis (TTR) and other disorders that pose an increased risk for sudden death, have evidence-based treatment modalities available or are clinically actionable. “Identification of patients with MCVD variants” is also “important for cascade screening of family members who are at risk of inheriting the pathogenic mutations.”

“We tend to ignore these monogenic diseases because they are so rare individually but, in aggregate, monogenic diseases are actually quite common,” senior author Svati H. Shah, MD, MHS, also of Duke University, said in an interview.

The results “support that the cardiology community over time adopt a genotype-forward approach,” one in which every patient presenting to a cardiovascular clinic is genotyped, she said.

One implication of such an approach, Dr. Shah agreed, is that “we would be able to pick these people up earlier in their disease, especially in the context of therapies that could improve certainly their progression, but even their survival.”

For now, she said, the study suggests that “these disorders are more frequent than perhaps all cardiologists are aware of, and we just need to keep our eyes open and know when to refer patients to a cardiovascular genetics clinic, which maybe has more time and can deal with all the nuances that go along with genetic testing.”

In the total cohort, 4.5% were found to carry a gene variant known or believed to cause such diseases. The most frequently represented conditions were familial TTR, hereditary hemochromatosis, heterozygous familial hypercholesterolemia, and various cardiomyopathies.

Of those patients, 52 received a clinical diagnosis of the monogenic disorder after an EHR review. Of the 290 without such a diagnosis, two-thirds showed no evidence in their EHR of the variant’s phenotypic signs. But the records of the other third featured at least some signs that the disease had manifested clinically.

“These data serve as a reminder that monogenic Mendelian disease, including heart and vascular disease, varies in penetrance from individual to individual and may not always present with clinically detectable phenotypes,” noted an editorial accompanying the report.

They also “provide a compelling basis for expanding the role of targeted genetic testing in patients with more traditional forms of heart and vascular disease,” wrote Scott M. Damrauer, MD, University of Pennsylvania, Philadelphia, and William S. Weintraub, MD, Medstar Washington Hospital Center and Georgetown University, Washington.

“Based on the current report, the number needed to screen in a complex cardiovascular patient population to detect 1 case of undiagnosed monogenic cardiovascular disease is 85,” they wrote. “This places targeted genetic testing well within what is considered to be efficacious for most screening programs and in the range of that of other common cardiovascular diseases and cancers.”

Among the 342 patients with a variant predicting a single MCVD – in addition to the 52 who received a diagnosis – 193 had records with no indication of phenotypic expression and so did not receive a diagnosis.

But the 97 patients without a diagnosis who nevertheless had documented signs of some phenotypic expression were deemed, on the basis of extent of expression, to represent a possibly, probably, or definitely missed diagnosis.

Familial TTR made up about 45% of such potentially missed diagnoses, the report noted.

Broader screening of patients with cardiovascular disease, Dr. Shah speculated, “might actually be not only a clinically useful endeavor, but – when we think about the aggregate burden of these monogenic disorders – potentially even cost-effective.”

As the price of genetic sequencing drops, she said, “I think we’ll start to see even more health systems wanting to incorporate the genotype-forward approach.”

Dr. Shah reports serving as primary investigator for research sponsored by Verily Life Sciences and AstraZeneca. Dr. Abdulrahim reports no relevant relationships. Disclosures for the other authors are in the report. Dr. Damrauer discloses receiving research support from RenalytixAI and consulting fees from Calico Labs. Dr. Weintraub had no relevant disclosures.

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

A group of experts representing various international professional societies has drafted a consensus statement on the determination of brain death or death by neurologic criteria (BD/DNC). The document, a result of the World Brain Death Project, surveys the clinical aspects of this determination, such as clinical testing, apnea testing, and the number of examinations required, as well as its social and legal aspects, including documentation, qualifications for making the determination, and religious attitudes toward BD/DNC.

The recommendations are the minimum criteria for BD/DNC, and countries and professional societies may choose to adopt stricter criteria, the authors noted. Seventeen supplements to the consensus statement contain detailed reports on topics the statement examines, including focuses on both adults and children.

“Perhaps the most important points of this project are, first, to show the worldwide acceptance of the concept of BD/DNC and what the minimum requirements are for BD/DNC,” said corresponding author Gene Sung, MD, MPH, director of the neurocritical care and stroke division at the University of Southern California, Los Angeles. Second, “this standard is centered around a clinical determination without the need for other testing.”

The consensus document and supplements were published online Aug. 3 in JAMA.

Comprehensive review

A lack of rigor has led to many differences in the determination of BD/DNC, said Dr. Sung. “Some of the variance that is common are the numbers of exams and examiners that are required and whether ancillary tests are required for determination of BD/DNC. In addition, a lot of guidelines and protocols that are in use are not thorough in detailing how to do the examinations and what to do in different circumstances.”

Professional societies such as the World Federation of Intensive and Critical Care recruited experts in BD/DNC to develop recommendations, which were based on relevant articles that they identified during a literature search. “We wanted to develop a fairly comprehensive document that, along with the 17 supplements, builds a foundation to show how to determine BD/DNC – what the minimum clinical criteria needed are and what to do in special circumstances,” Dr. Sung said.

Major sections of the statement include recommendations for the minimum clinical standards for the determination of BD/DNC in adults and children.

Determination must begin by establishing that the patient has sustained an irreversible brain injury that resulted in the loss of all brain function, according to the authors. Confounders such as pharmacologic paralysis and the effect of CNS depressant medications should be ruled out.

In addition, clinical evaluation must include an assessment for coma and an evaluation for brain stem areflexia. Among other criteria, the pupils should be fixed and nonresponsive to light, the face should not move in response to noxious cranial stimulation, and the gag and cough reflexes should be absent. Apnea testing is recommended to evaluate the responsiveness of respiratory centers in the medulla.

Although the definition of BD/DNC is the same in children as in adults, less evidence is available for the determination of BD/DNC in the very young. The authors thus advised a cautious approach to the evaluation of infants and younger children.

Recommendations vary by age and often require serial examinations, including apnea testing, they noted.

Ancillary testing

The consensus statement also reviews ancillary testing, which the authors recommend be required when the minimum clinical examination, including the apnea test, cannot be completed and when it is in the presence of confounding conditions that cannot be resolved.

The authors recommended digital subtraction angiography, radionuclide studies, and transcranial Doppler ultrasonography as ancillary tests based on blood flow in the brain. However, CT angiography and magnetic resonance angiography not be used.

A lack of guidance makes performing an apnea test in patients receiving extracorporeal membrane oxygenation (ECMO) challenging, according to the authors. Nevertheless, they recommended that the same principles of BD/DNC be applied to adults and children receiving ECMO.

They further recommended a period of preoxygenation before the apnea test, and the document describes in detail the method for administering this test to people receiving ECMO.

Another potentially challenging situation pointed out in the consensus document is the determination of BD/DNC in patients who have been treated with targeted temperature management. Therapeutic hypothermia, particularly if it is preceded or accompanied by sedation, can temporarily impair brain stem reflexes, thus mimicking BD/DNC.

The new document includes a flowchart and step-by-step recommendations as well as suggestions for determining BD/DNC under these circumstances.

Among document limitations acknowledged by the authors is the lack of high-quality data from randomized, controlled trials on which to base their recommendations.

In addition, economic, technological, or personnel limitations may reduce the available options for ancillary testing, they added. Also, the recommendations do not incorporate contributions from patients or social or religious groups, although the authors were mindful of their concerns.

To promote the national and international harmonization of BD/DNC criteria, “medical societies and countries can evaluate their own policies in relation to this document and fix any deficiencies,” Dr. Sung said.

“Many countries do not have any BD/DNC policies and can use the documents from this project to create their own. There may need to be discussions with legal, governmental, religious, and societal leaders to help understand and accept BD/DNC and to help enact policies in different communities,” he added.

Divergent definitions

The determination of death is not simply a scientific question, but also a philosophical, religious, and cultural question, wrote Robert D. Truog, MD, director of the Harvard Center for Bioethics, Boston, and colleagues in an accompanying editorial. Future research should consider cultural differences over these questions.

“Most important is that there be a clear and logical consistency between the definition of death and the tests that are used to diagnose it,” Dr. Truog said.

The concept of whole brain death was advanced as an equivalent to biological death, “such that, when the brain dies, the body literally disintegrates, just as it does after cardiac arrest,” but evidence indicates that this claim is untrue, Dr. Truog said. Current tests also do not diagnose the death of the whole brain.

Another hypothesis is that brain stem death represents the irreversible loss of consciousness and the capacity for spontaneous respiration.

“Instead of focusing on biology, [this definition] focuses on values and is based on the claim that when a person is in a state of irreversible apneic unconsciousness, we may consider them to be dead,” said Dr. Truog. He and his coeditorialists argued that the concept of whole brain death should be replaced with that of brain stem death.

“This report should be a call for our profession, as well as for federal and state lawmakers, to reform our laws so that they are consistent with our diagnostic criteria,” Dr. Truog said.

“The most straightforward way of doing this would be to change U.S. law and adopt the British standard of brain stem death, and then refine our testing to make the diagnosis of irreversible apneic unconsciousness as reliable and safe as possible,” he concluded.

The drafting of the consensus statement was not supported by outside funding. Dr. Sung reported no relevant financial relationships. Dr. Truog reported receiving compensation from Sanofi and Covance for participating in data and safety monitoring boards unrelated to the consensus document.

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

A group of experts representing various international professional societies has drafted a consensus statement on the determination of brain death or death by neurologic criteria (BD/DNC). The document, a result of the World Brain Death Project, surveys the clinical aspects of this determination, such as clinical testing, apnea testing, and the number of examinations required, as well as its social and legal aspects, including documentation, qualifications for making the determination, and religious attitudes toward BD/DNC.

The recommendations are the minimum criteria for BD/DNC, and countries and professional societies may choose to adopt stricter criteria, the authors noted. Seventeen supplements to the consensus statement contain detailed reports on topics the statement examines, including focuses on both adults and children.

“Perhaps the most important points of this project are, first, to show the worldwide acceptance of the concept of BD/DNC and what the minimum requirements are for BD/DNC,” said corresponding author Gene Sung, MD, MPH, director of the neurocritical care and stroke division at the University of Southern California, Los Angeles. Second, “this standard is centered around a clinical determination without the need for other testing.”

The consensus document and supplements were published online Aug. 3 in JAMA.

Comprehensive review

A lack of rigor has led to many differences in the determination of BD/DNC, said Dr. Sung. “Some of the variance that is common are the numbers of exams and examiners that are required and whether ancillary tests are required for determination of BD/DNC. In addition, a lot of guidelines and protocols that are in use are not thorough in detailing how to do the examinations and what to do in different circumstances.”

Professional societies such as the World Federation of Intensive and Critical Care recruited experts in BD/DNC to develop recommendations, which were based on relevant articles that they identified during a literature search. “We wanted to develop a fairly comprehensive document that, along with the 17 supplements, builds a foundation to show how to determine BD/DNC – what the minimum clinical criteria needed are and what to do in special circumstances,” Dr. Sung said.

Major sections of the statement include recommendations for the minimum clinical standards for the determination of BD/DNC in adults and children.

Determination must begin by establishing that the patient has sustained an irreversible brain injury that resulted in the loss of all brain function, according to the authors. Confounders such as pharmacologic paralysis and the effect of CNS depressant medications should be ruled out.

In addition, clinical evaluation must include an assessment for coma and an evaluation for brain stem areflexia. Among other criteria, the pupils should be fixed and nonresponsive to light, the face should not move in response to noxious cranial stimulation, and the gag and cough reflexes should be absent. Apnea testing is recommended to evaluate the responsiveness of respiratory centers in the medulla.

Although the definition of BD/DNC is the same in children as in adults, less evidence is available for the determination of BD/DNC in the very young. The authors thus advised a cautious approach to the evaluation of infants and younger children.

Recommendations vary by age and often require serial examinations, including apnea testing, they noted.

Ancillary testing

The consensus statement also reviews ancillary testing, which the authors recommend be required when the minimum clinical examination, including the apnea test, cannot be completed and when it is in the presence of confounding conditions that cannot be resolved.

The authors recommended digital subtraction angiography, radionuclide studies, and transcranial Doppler ultrasonography as ancillary tests based on blood flow in the brain. However, CT angiography and magnetic resonance angiography not be used.

A lack of guidance makes performing an apnea test in patients receiving extracorporeal membrane oxygenation (ECMO) challenging, according to the authors. Nevertheless, they recommended that the same principles of BD/DNC be applied to adults and children receiving ECMO.

They further recommended a period of preoxygenation before the apnea test, and the document describes in detail the method for administering this test to people receiving ECMO.

Another potentially challenging situation pointed out in the consensus document is the determination of BD/DNC in patients who have been treated with targeted temperature management. Therapeutic hypothermia, particularly if it is preceded or accompanied by sedation, can temporarily impair brain stem reflexes, thus mimicking BD/DNC.

The new document includes a flowchart and step-by-step recommendations as well as suggestions for determining BD/DNC under these circumstances.

Among document limitations acknowledged by the authors is the lack of high-quality data from randomized, controlled trials on which to base their recommendations.

In addition, economic, technological, or personnel limitations may reduce the available options for ancillary testing, they added. Also, the recommendations do not incorporate contributions from patients or social or religious groups, although the authors were mindful of their concerns.

To promote the national and international harmonization of BD/DNC criteria, “medical societies and countries can evaluate their own policies in relation to this document and fix any deficiencies,” Dr. Sung said.

“Many countries do not have any BD/DNC policies and can use the documents from this project to create their own. There may need to be discussions with legal, governmental, religious, and societal leaders to help understand and accept BD/DNC and to help enact policies in different communities,” he added.

Divergent definitions

The determination of death is not simply a scientific question, but also a philosophical, religious, and cultural question, wrote Robert D. Truog, MD, director of the Harvard Center for Bioethics, Boston, and colleagues in an accompanying editorial. Future research should consider cultural differences over these questions.

“Most important is that there be a clear and logical consistency between the definition of death and the tests that are used to diagnose it,” Dr. Truog said.

The concept of whole brain death was advanced as an equivalent to biological death, “such that, when the brain dies, the body literally disintegrates, just as it does after cardiac arrest,” but evidence indicates that this claim is untrue, Dr. Truog said. Current tests also do not diagnose the death of the whole brain.

Another hypothesis is that brain stem death represents the irreversible loss of consciousness and the capacity for spontaneous respiration.

“Instead of focusing on biology, [this definition] focuses on values and is based on the claim that when a person is in a state of irreversible apneic unconsciousness, we may consider them to be dead,” said Dr. Truog. He and his coeditorialists argued that the concept of whole brain death should be replaced with that of brain stem death.

“This report should be a call for our profession, as well as for federal and state lawmakers, to reform our laws so that they are consistent with our diagnostic criteria,” Dr. Truog said.

“The most straightforward way of doing this would be to change U.S. law and adopt the British standard of brain stem death, and then refine our testing to make the diagnosis of irreversible apneic unconsciousness as reliable and safe as possible,” he concluded.

The drafting of the consensus statement was not supported by outside funding. Dr. Sung reported no relevant financial relationships. Dr. Truog reported receiving compensation from Sanofi and Covance for participating in data and safety monitoring boards unrelated to the consensus document.

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

A group of experts representing various international professional societies has drafted a consensus statement on the determination of brain death or death by neurologic criteria (BD/DNC). The document, a result of the World Brain Death Project, surveys the clinical aspects of this determination, such as clinical testing, apnea testing, and the number of examinations required, as well as its social and legal aspects, including documentation, qualifications for making the determination, and religious attitudes toward BD/DNC.

The recommendations are the minimum criteria for BD/DNC, and countries and professional societies may choose to adopt stricter criteria, the authors noted. Seventeen supplements to the consensus statement contain detailed reports on topics the statement examines, including focuses on both adults and children.

“Perhaps the most important points of this project are, first, to show the worldwide acceptance of the concept of BD/DNC and what the minimum requirements are for BD/DNC,” said corresponding author Gene Sung, MD, MPH, director of the neurocritical care and stroke division at the University of Southern California, Los Angeles. Second, “this standard is centered around a clinical determination without the need for other testing.”

The consensus document and supplements were published online Aug. 3 in JAMA.

Comprehensive review

A lack of rigor has led to many differences in the determination of BD/DNC, said Dr. Sung. “Some of the variance that is common are the numbers of exams and examiners that are required and whether ancillary tests are required for determination of BD/DNC. In addition, a lot of guidelines and protocols that are in use are not thorough in detailing how to do the examinations and what to do in different circumstances.”

Professional societies such as the World Federation of Intensive and Critical Care recruited experts in BD/DNC to develop recommendations, which were based on relevant articles that they identified during a literature search. “We wanted to develop a fairly comprehensive document that, along with the 17 supplements, builds a foundation to show how to determine BD/DNC – what the minimum clinical criteria needed are and what to do in special circumstances,” Dr. Sung said.

Major sections of the statement include recommendations for the minimum clinical standards for the determination of BD/DNC in adults and children.

Determination must begin by establishing that the patient has sustained an irreversible brain injury that resulted in the loss of all brain function, according to the authors. Confounders such as pharmacologic paralysis and the effect of CNS depressant medications should be ruled out.

In addition, clinical evaluation must include an assessment for coma and an evaluation for brain stem areflexia. Among other criteria, the pupils should be fixed and nonresponsive to light, the face should not move in response to noxious cranial stimulation, and the gag and cough reflexes should be absent. Apnea testing is recommended to evaluate the responsiveness of respiratory centers in the medulla.

Although the definition of BD/DNC is the same in children as in adults, less evidence is available for the determination of BD/DNC in the very young. The authors thus advised a cautious approach to the evaluation of infants and younger children.

Recommendations vary by age and often require serial examinations, including apnea testing, they noted.

Ancillary testing

The consensus statement also reviews ancillary testing, which the authors recommend be required when the minimum clinical examination, including the apnea test, cannot be completed and when it is in the presence of confounding conditions that cannot be resolved.

The authors recommended digital subtraction angiography, radionuclide studies, and transcranial Doppler ultrasonography as ancillary tests based on blood flow in the brain. However, CT angiography and magnetic resonance angiography not be used.

A lack of guidance makes performing an apnea test in patients receiving extracorporeal membrane oxygenation (ECMO) challenging, according to the authors. Nevertheless, they recommended that the same principles of BD/DNC be applied to adults and children receiving ECMO.

They further recommended a period of preoxygenation before the apnea test, and the document describes in detail the method for administering this test to people receiving ECMO.

Another potentially challenging situation pointed out in the consensus document is the determination of BD/DNC in patients who have been treated with targeted temperature management. Therapeutic hypothermia, particularly if it is preceded or accompanied by sedation, can temporarily impair brain stem reflexes, thus mimicking BD/DNC.

The new document includes a flowchart and step-by-step recommendations as well as suggestions for determining BD/DNC under these circumstances.

Among document limitations acknowledged by the authors is the lack of high-quality data from randomized, controlled trials on which to base their recommendations.

In addition, economic, technological, or personnel limitations may reduce the available options for ancillary testing, they added. Also, the recommendations do not incorporate contributions from patients or social or religious groups, although the authors were mindful of their concerns.

To promote the national and international harmonization of BD/DNC criteria, “medical societies and countries can evaluate their own policies in relation to this document and fix any deficiencies,” Dr. Sung said.

“Many countries do not have any BD/DNC policies and can use the documents from this project to create their own. There may need to be discussions with legal, governmental, religious, and societal leaders to help understand and accept BD/DNC and to help enact policies in different communities,” he added.

Divergent definitions

The determination of death is not simply a scientific question, but also a philosophical, religious, and cultural question, wrote Robert D. Truog, MD, director of the Harvard Center for Bioethics, Boston, and colleagues in an accompanying editorial. Future research should consider cultural differences over these questions.

“Most important is that there be a clear and logical consistency between the definition of death and the tests that are used to diagnose it,” Dr. Truog said.

The concept of whole brain death was advanced as an equivalent to biological death, “such that, when the brain dies, the body literally disintegrates, just as it does after cardiac arrest,” but evidence indicates that this claim is untrue, Dr. Truog said. Current tests also do not diagnose the death of the whole brain.

Another hypothesis is that brain stem death represents the irreversible loss of consciousness and the capacity for spontaneous respiration.

“Instead of focusing on biology, [this definition] focuses on values and is based on the claim that when a person is in a state of irreversible apneic unconsciousness, we may consider them to be dead,” said Dr. Truog. He and his coeditorialists argued that the concept of whole brain death should be replaced with that of brain stem death.

“This report should be a call for our profession, as well as for federal and state lawmakers, to reform our laws so that they are consistent with our diagnostic criteria,” Dr. Truog said.

“The most straightforward way of doing this would be to change U.S. law and adopt the British standard of brain stem death, and then refine our testing to make the diagnosis of irreversible apneic unconsciousness as reliable and safe as possible,” he concluded.

The drafting of the consensus statement was not supported by outside funding. Dr. Sung reported no relevant financial relationships. Dr. Truog reported receiving compensation from Sanofi and Covance for participating in data and safety monitoring boards unrelated to the consensus document.

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

New guidance from the U.K. National Diabetes COVID-19 Response Group addresses glucose management in patients with COVID-19 who are receiving dexamethasone therapy.

Although there are already guidelines that address inpatient management of steroid-induced hyperglycemia, the authors of the new document wrote that this new expert opinion paper was needed “given the ‘triple insult’ of dexamethasone-induced–impaired glucose metabolism, COVID-19–induced insulin resistance, and COVID-19–impaired insulin production.”

RECOVERY trial spurs response

The document, which is the latest in a series from the Association of British Clinical Diabetologists, was published online Aug. 2 in Diabetic Medicine. The group is chaired by Gerry Rayman, MD, consultant physician at the diabetes centre and diabetes research unit, East Suffolk (England) and North East NHS Foundation Trust.

The guidance was developed in response to the recent “breakthrough” Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, which showed that dexamethasone reduced deaths in patients with COVID-19 on ventilators or receiving oxygen therapy. The advice is not intended for critical care units but can be adapted for that use.

The dose used in RECOVERY – 6 mg daily for 10 days – is 400%-500% greater than the therapeutic glucocorticoid replacement dose. High glucocorticoid doses can exacerbate hyperglycemia in people with established diabetes, unmask undiagnosed diabetes, precipitate hyperglycemia or new-onset diabetes, and can also cause hyperglycemic hyperosmolar state (HHS), the authors explained.

They recommended a target glucose of 6.0-10.0 mmol/L (108-180 mg/dL), although they say up to 12 mmol/L (216 mg/dL) is “acceptable.” They then gave advice on frequency of monitoring for people with and without known diabetes, exclusion of diabetic ketoacidosis and HHS, correction of initial hyperglycemia and maintenance of glycemic control using subcutaneous insulin, and prevention of hypoglycemia at the end of dexamethasone therapy (day 10) with insulin down-titration, discharge, and follow-up.

The detailed insulin guidance covers dose escalation for both insulin-treated and insulin-naive patients. A table suggests increasing correction doses of rapid-acting insulin based on prior total daily dose or weight.

Use of once- or twice-daily NPH insulin is recommended for patients whose glucose has risen above 12 mmol/L, in some cases with the addition of a long-acting analog. A second chart gives dose adjustments for those insulins. Additional guidance addresses patients on insulin pumps.

Guidance useful for U.S. physicians

Francisco Pasquel, MD, assistant professor of medicine in the division of endocrinology at Emory University, Atlanta, said in an interview that he believes the guidance is “acceptable” for worldwide use, and that “it’s coherent and consistent with what we typically do.”

However, Dr. Pasquel, who founded COVID-in-Diabetes, an online repository of published guidance and shared experience – to which this new document has now been added – did take issue with one piece of advice. The guidance says that patients already taking premixed insulin formulations can continue using them while increasing the dose by 20%-40%. Given the risk of hypoglycemia associated with those formulations, Dr. Pasquel said he would switch those patients to NPH during the time that they’re on dexamethasone.

He also noted that the rapid-acting insulin dose range of 2-10 units provided in the first table, for correction of initial hyperglycemia, are more conservative than those used at his hospital, where correction doses of up to 14-16 units are sometimes necessary.

But Dr. Pasquel praised the group’s overall efforts since the pandemic began, noting that “they’re very organized and constantly updating their recommendations. They have a unified system in the [National Health Service], so it’s easier to standardize. They have a unique [electronic health record] which is far superior to what we do from a public health perspective.”

Dr. Rayman reported no relevant financial relationships. Dr. Pasquel reported receiving research funding from Dexcom, Merck, and the National Institutes of Health, and consulting for AstraZeneca, Eli Lilly, Merck, and Boehringer Ingelheim.

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

New guidance from the U.K. National Diabetes COVID-19 Response Group addresses glucose management in patients with COVID-19 who are receiving dexamethasone therapy.

Although there are already guidelines that address inpatient management of steroid-induced hyperglycemia, the authors of the new document wrote that this new expert opinion paper was needed “given the ‘triple insult’ of dexamethasone-induced–impaired glucose metabolism, COVID-19–induced insulin resistance, and COVID-19–impaired insulin production.”

RECOVERY trial spurs response

The document, which is the latest in a series from the Association of British Clinical Diabetologists, was published online Aug. 2 in Diabetic Medicine. The group is chaired by Gerry Rayman, MD, consultant physician at the diabetes centre and diabetes research unit, East Suffolk (England) and North East NHS Foundation Trust.

The guidance was developed in response to the recent “breakthrough” Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, which showed that dexamethasone reduced deaths in patients with COVID-19 on ventilators or receiving oxygen therapy. The advice is not intended for critical care units but can be adapted for that use.

The dose used in RECOVERY – 6 mg daily for 10 days – is 400%-500% greater than the therapeutic glucocorticoid replacement dose. High glucocorticoid doses can exacerbate hyperglycemia in people with established diabetes, unmask undiagnosed diabetes, precipitate hyperglycemia or new-onset diabetes, and can also cause hyperglycemic hyperosmolar state (HHS), the authors explained.

They recommended a target glucose of 6.0-10.0 mmol/L (108-180 mg/dL), although they say up to 12 mmol/L (216 mg/dL) is “acceptable.” They then gave advice on frequency of monitoring for people with and without known diabetes, exclusion of diabetic ketoacidosis and HHS, correction of initial hyperglycemia and maintenance of glycemic control using subcutaneous insulin, and prevention of hypoglycemia at the end of dexamethasone therapy (day 10) with insulin down-titration, discharge, and follow-up.

The detailed insulin guidance covers dose escalation for both insulin-treated and insulin-naive patients. A table suggests increasing correction doses of rapid-acting insulin based on prior total daily dose or weight.

Use of once- or twice-daily NPH insulin is recommended for patients whose glucose has risen above 12 mmol/L, in some cases with the addition of a long-acting analog. A second chart gives dose adjustments for those insulins. Additional guidance addresses patients on insulin pumps.

Guidance useful for U.S. physicians

Francisco Pasquel, MD, assistant professor of medicine in the division of endocrinology at Emory University, Atlanta, said in an interview that he believes the guidance is “acceptable” for worldwide use, and that “it’s coherent and consistent with what we typically do.”

However, Dr. Pasquel, who founded COVID-in-Diabetes, an online repository of published guidance and shared experience – to which this new document has now been added – did take issue with one piece of advice. The guidance says that patients already taking premixed insulin formulations can continue using them while increasing the dose by 20%-40%. Given the risk of hypoglycemia associated with those formulations, Dr. Pasquel said he would switch those patients to NPH during the time that they’re on dexamethasone.

He also noted that the rapid-acting insulin dose range of 2-10 units provided in the first table, for correction of initial hyperglycemia, are more conservative than those used at his hospital, where correction doses of up to 14-16 units are sometimes necessary.

But Dr. Pasquel praised the group’s overall efforts since the pandemic began, noting that “they’re very organized and constantly updating their recommendations. They have a unified system in the [National Health Service], so it’s easier to standardize. They have a unique [electronic health record] which is far superior to what we do from a public health perspective.”

Dr. Rayman reported no relevant financial relationships. Dr. Pasquel reported receiving research funding from Dexcom, Merck, and the National Institutes of Health, and consulting for AstraZeneca, Eli Lilly, Merck, and Boehringer Ingelheim.

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

New guidance from the U.K. National Diabetes COVID-19 Response Group addresses glucose management in patients with COVID-19 who are receiving dexamethasone therapy.

Although there are already guidelines that address inpatient management of steroid-induced hyperglycemia, the authors of the new document wrote that this new expert opinion paper was needed “given the ‘triple insult’ of dexamethasone-induced–impaired glucose metabolism, COVID-19–induced insulin resistance, and COVID-19–impaired insulin production.”

RECOVERY trial spurs response

The document, which is the latest in a series from the Association of British Clinical Diabetologists, was published online Aug. 2 in Diabetic Medicine. The group is chaired by Gerry Rayman, MD, consultant physician at the diabetes centre and diabetes research unit, East Suffolk (England) and North East NHS Foundation Trust.

The guidance was developed in response to the recent “breakthrough” Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, which showed that dexamethasone reduced deaths in patients with COVID-19 on ventilators or receiving oxygen therapy. The advice is not intended for critical care units but can be adapted for that use.

The dose used in RECOVERY – 6 mg daily for 10 days – is 400%-500% greater than the therapeutic glucocorticoid replacement dose. High glucocorticoid doses can exacerbate hyperglycemia in people with established diabetes, unmask undiagnosed diabetes, precipitate hyperglycemia or new-onset diabetes, and can also cause hyperglycemic hyperosmolar state (HHS), the authors explained.

They recommended a target glucose of 6.0-10.0 mmol/L (108-180 mg/dL), although they say up to 12 mmol/L (216 mg/dL) is “acceptable.” They then gave advice on frequency of monitoring for people with and without known diabetes, exclusion of diabetic ketoacidosis and HHS, correction of initial hyperglycemia and maintenance of glycemic control using subcutaneous insulin, and prevention of hypoglycemia at the end of dexamethasone therapy (day 10) with insulin down-titration, discharge, and follow-up.

The detailed insulin guidance covers dose escalation for both insulin-treated and insulin-naive patients. A table suggests increasing correction doses of rapid-acting insulin based on prior total daily dose or weight.

Use of once- or twice-daily NPH insulin is recommended for patients whose glucose has risen above 12 mmol/L, in some cases with the addition of a long-acting analog. A second chart gives dose adjustments for those insulins. Additional guidance addresses patients on insulin pumps.

Guidance useful for U.S. physicians

Francisco Pasquel, MD, assistant professor of medicine in the division of endocrinology at Emory University, Atlanta, said in an interview that he believes the guidance is “acceptable” for worldwide use, and that “it’s coherent and consistent with what we typically do.”

However, Dr. Pasquel, who founded COVID-in-Diabetes, an online repository of published guidance and shared experience – to which this new document has now been added – did take issue with one piece of advice. The guidance says that patients already taking premixed insulin formulations can continue using them while increasing the dose by 20%-40%. Given the risk of hypoglycemia associated with those formulations, Dr. Pasquel said he would switch those patients to NPH during the time that they’re on dexamethasone.

He also noted that the rapid-acting insulin dose range of 2-10 units provided in the first table, for correction of initial hyperglycemia, are more conservative than those used at his hospital, where correction doses of up to 14-16 units are sometimes necessary.

But Dr. Pasquel praised the group’s overall efforts since the pandemic began, noting that “they’re very organized and constantly updating their recommendations. They have a unified system in the [National Health Service], so it’s easier to standardize. They have a unique [electronic health record] which is far superior to what we do from a public health perspective.”

Dr. Rayman reported no relevant financial relationships. Dr. Pasquel reported receiving research funding from Dexcom, Merck, and the National Institutes of Health, and consulting for AstraZeneca, Eli Lilly, Merck, and Boehringer Ingelheim.

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

ED visits related to mental health conditions increased nearly twofold from 2007-2008 to 2015-2016, new research suggests.

Data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) showed that, over the 10-year study period, the proportion of ED visits for mental health diagnoses increased from 6.6% to 10.9%, with substance use accounting for much of the increase.

Although there have been policy efforts, such as expanding access to mental health care as part of the Affordable Care Act (ACA) of 2011, the “increasing use of the ED for mental health reasons is concerning,” senior author Taeho Greg Rhee, PhD, MSW, said in an interview.

“Treating mental health conditions in EDs is often considered suboptimal” because of limited time for full psychiatric assessment, lack of trained providers, and limited privacy in EDs, said Dr. Rhee of Yale University, New Haven, Conn.

The findings were published online July 28 in The Journal of Clinical Psychiatry.
 

“Outdated” research

Roughly one-fifth of U.S. adults experience some type of mental, behavioral, or emotional disorder annually. Moreover, the suicide rate has been steadily increasing, and there continues to be a “raging opioid epidemic,” the researchers wrote.

Despite these alarming figures, 57.4% of adults with mental illness reported in 2017 that they had not received any mental health treatment in the past year, reported the investigators.

Previous research has suggested that many adults have difficulty seeking outpatient mental health treatment and may turn to EDs instead. However, most studies of mental health ED use “are by now outdated, as they used data from years prior to the full implementation of the ACA,” the researchers noted.

“More Americans are suffering from mental illness, and given the recent policy efforts of expanding access to mental health care, we were questioning if ED visits due to mental health has changed or not,” Dr. Rhee said.

To investigate the question, the researchers conducted a cross-sectional analysis of data from the NHAMCS, a publicly available dataset provided by the National Center for Health Statistics of the Centers for Disease Control and Prevention.

They grouped psychiatric diagnoses into five categories: mood disorders, anxiety disorders, psychosis or schizophrenia, suicide attempt or ideation, or other/unspecified. Substance use diagnoses were grouped into six categories: alcohol, amphetamine, cannabis, cocaine, opioid, or other/unspecified.

These categories were used to determine the type of disorder a patient had, whether the patient had both psychiatric and substance-related diagnoses, and whether the patient received multiple mental health diagnoses at the time of the ED visit.

Sociodemographic covariates included age, sex, race/ethnicity, and insurance coverage.
 

Twofold and fourfold increases

Of 100.9 million outpatient ED visits that took place between 2007 and 2016, approximately 8.4 million (8.3%) were for psychiatric or substance use–related diagnoses. Also, the visits were more likely from adults who were younger than 45 years, male, non-Hispanic White, and covered by Medicaid or other public insurance types (58.5%, 52.5%, 65.2%, and 58.6%, respectively).

The overall rate of ED visits for any mental health diagnosis nearly doubled between 2007-2008 and 2015-2016. The rate of visits in which both psychiatric and substance use–related diagnoses increased fourfold during that time span. ED visits involving at least two mental health diagnoses increased twofold.

Additional changes in the number of visits are listed below (for each, P < .001).

When these comparisons were adjusted for age, sex, and race/ethnicity, “linearly increasing trends of mental health–related ED visits were consistently found in all categories,” the authors reported. No trends were found regarding age, sex, or race/ethnicity. By contrast, mental health–related ED visits in which Medicaid was identified as the primary source of insurance nearly doubled between 2007–2008 and 2015–2016 (from 27.2% to 42.8%).

Other/unspecified psychiatric diagnoses, such as adjustment disorder and personality disorders, almost tripled between 2007-2008 and 2015-2016 (from 1,040 to 2,961 per 100,000 ED visits). ED visits for mood disorders and anxiety disorders also increased over time.

Alcohol-related ED visits were the most common substance use visits, increasing from 1,669 in 2007-2008 to 3,007 per 100,000 visits in 2015-2016. Amphetamine- and opioid-related ED visits more than doubled, and other/unspecified–related ED visits more than tripled during that time.

“One explanation why ED visits for mental health conditions have increased is that substance-related problems, which include overdose/self-injury issues, have increased over time,” Dr. Rhee noted, which “makes sense,” inasmuch as opioid, cannabis, and amphetamine use has increased across the country.

Another explanation is that, although mental health care access has been expanded through the ACA, “people, especially those with lower socioeconomic backgrounds, do not know how to get access to care and are still underserved,” he said.

“If mental health–related ED visits continue to increase in the future, there are several steps to be made. ED providers need to be better equipped with mental health care, and behavioral health should be better integrated as part of the care coordination,” said Dr. Rhee.

He added that reimbursement models across different insurance types, such as Medicare, Medicaid, and private insurance, “should consider expanding their coverage of mental health treatment in ED settings.”
 

“Canary in the coal mine”

Commenting on the study in an interview, Benjamin Druss, MD, MPH, professor and Rosalynn Carter Chair in Mental Health, Rollins School of Public Health, Emory University, Atlanta, called EDs the “canaries in the coal mine” for the broader health system.

The growing number of ED visits for behavioral problems “could represent both a rise in acute conditions such as substance use and lack of access to outpatient treatment,” said Dr. Druss, who was not involved with the research.

The findings “suggest the importance of strategies to effectively manage patients with behavioral conditions in ED settings and to effectively link them with high-quality outpatient care,” he noted.

Dr. Rhee has received funding from the National Institute on Aging and the American Foundation for Suicide Prevention. The other study authors and Dr. Druss report no relevant financial relationships.

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

ED visits related to mental health conditions increased nearly twofold from 2007-2008 to 2015-2016, new research suggests.

Data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) showed that, over the 10-year study period, the proportion of ED visits for mental health diagnoses increased from 6.6% to 10.9%, with substance use accounting for much of the increase.

Although there have been policy efforts, such as expanding access to mental health care as part of the Affordable Care Act (ACA) of 2011, the “increasing use of the ED for mental health reasons is concerning,” senior author Taeho Greg Rhee, PhD, MSW, said in an interview.

“Treating mental health conditions in EDs is often considered suboptimal” because of limited time for full psychiatric assessment, lack of trained providers, and limited privacy in EDs, said Dr. Rhee of Yale University, New Haven, Conn.

The findings were published online July 28 in The Journal of Clinical Psychiatry.
 

“Outdated” research

Roughly one-fifth of U.S. adults experience some type of mental, behavioral, or emotional disorder annually. Moreover, the suicide rate has been steadily increasing, and there continues to be a “raging opioid epidemic,” the researchers wrote.

Despite these alarming figures, 57.4% of adults with mental illness reported in 2017 that they had not received any mental health treatment in the past year, reported the investigators.

Previous research has suggested that many adults have difficulty seeking outpatient mental health treatment and may turn to EDs instead. However, most studies of mental health ED use “are by now outdated, as they used data from years prior to the full implementation of the ACA,” the researchers noted.

“More Americans are suffering from mental illness, and given the recent policy efforts of expanding access to mental health care, we were questioning if ED visits due to mental health has changed or not,” Dr. Rhee said.

To investigate the question, the researchers conducted a cross-sectional analysis of data from the NHAMCS, a publicly available dataset provided by the National Center for Health Statistics of the Centers for Disease Control and Prevention.

They grouped psychiatric diagnoses into five categories: mood disorders, anxiety disorders, psychosis or schizophrenia, suicide attempt or ideation, or other/unspecified. Substance use diagnoses were grouped into six categories: alcohol, amphetamine, cannabis, cocaine, opioid, or other/unspecified.

These categories were used to determine the type of disorder a patient had, whether the patient had both psychiatric and substance-related diagnoses, and whether the patient received multiple mental health diagnoses at the time of the ED visit.

Sociodemographic covariates included age, sex, race/ethnicity, and insurance coverage.
 

Twofold and fourfold increases

Of 100.9 million outpatient ED visits that took place between 2007 and 2016, approximately 8.4 million (8.3%) were for psychiatric or substance use–related diagnoses. Also, the visits were more likely from adults who were younger than 45 years, male, non-Hispanic White, and covered by Medicaid or other public insurance types (58.5%, 52.5%, 65.2%, and 58.6%, respectively).

The overall rate of ED visits for any mental health diagnosis nearly doubled between 2007-2008 and 2015-2016. The rate of visits in which both psychiatric and substance use–related diagnoses increased fourfold during that time span. ED visits involving at least two mental health diagnoses increased twofold.

Additional changes in the number of visits are listed below (for each, P < .001).

When these comparisons were adjusted for age, sex, and race/ethnicity, “linearly increasing trends of mental health–related ED visits were consistently found in all categories,” the authors reported. No trends were found regarding age, sex, or race/ethnicity. By contrast, mental health–related ED visits in which Medicaid was identified as the primary source of insurance nearly doubled between 2007–2008 and 2015–2016 (from 27.2% to 42.8%).

Other/unspecified psychiatric diagnoses, such as adjustment disorder and personality disorders, almost tripled between 2007-2008 and 2015-2016 (from 1,040 to 2,961 per 100,000 ED visits). ED visits for mood disorders and anxiety disorders also increased over time.

Alcohol-related ED visits were the most common substance use visits, increasing from 1,669 in 2007-2008 to 3,007 per 100,000 visits in 2015-2016. Amphetamine- and opioid-related ED visits more than doubled, and other/unspecified–related ED visits more than tripled during that time.

“One explanation why ED visits for mental health conditions have increased is that substance-related problems, which include overdose/self-injury issues, have increased over time,” Dr. Rhee noted, which “makes sense,” inasmuch as opioid, cannabis, and amphetamine use has increased across the country.

Another explanation is that, although mental health care access has been expanded through the ACA, “people, especially those with lower socioeconomic backgrounds, do not know how to get access to care and are still underserved,” he said.

“If mental health–related ED visits continue to increase in the future, there are several steps to be made. ED providers need to be better equipped with mental health care, and behavioral health should be better integrated as part of the care coordination,” said Dr. Rhee.

He added that reimbursement models across different insurance types, such as Medicare, Medicaid, and private insurance, “should consider expanding their coverage of mental health treatment in ED settings.”
 

“Canary in the coal mine”

Commenting on the study in an interview, Benjamin Druss, MD, MPH, professor and Rosalynn Carter Chair in Mental Health, Rollins School of Public Health, Emory University, Atlanta, called EDs the “canaries in the coal mine” for the broader health system.

The growing number of ED visits for behavioral problems “could represent both a rise in acute conditions such as substance use and lack of access to outpatient treatment,” said Dr. Druss, who was not involved with the research.

The findings “suggest the importance of strategies to effectively manage patients with behavioral conditions in ED settings and to effectively link them with high-quality outpatient care,” he noted.

Dr. Rhee has received funding from the National Institute on Aging and the American Foundation for Suicide Prevention. The other study authors and Dr. Druss report no relevant financial relationships.

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

ED visits related to mental health conditions increased nearly twofold from 2007-2008 to 2015-2016, new research suggests.

Data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) showed that, over the 10-year study period, the proportion of ED visits for mental health diagnoses increased from 6.6% to 10.9%, with substance use accounting for much of the increase.

Although there have been policy efforts, such as expanding access to mental health care as part of the Affordable Care Act (ACA) of 2011, the “increasing use of the ED for mental health reasons is concerning,” senior author Taeho Greg Rhee, PhD, MSW, said in an interview.

“Treating mental health conditions in EDs is often considered suboptimal” because of limited time for full psychiatric assessment, lack of trained providers, and limited privacy in EDs, said Dr. Rhee of Yale University, New Haven, Conn.

The findings were published online July 28 in The Journal of Clinical Psychiatry.
 

“Outdated” research

Roughly one-fifth of U.S. adults experience some type of mental, behavioral, or emotional disorder annually. Moreover, the suicide rate has been steadily increasing, and there continues to be a “raging opioid epidemic,” the researchers wrote.

Despite these alarming figures, 57.4% of adults with mental illness reported in 2017 that they had not received any mental health treatment in the past year, reported the investigators.

Previous research has suggested that many adults have difficulty seeking outpatient mental health treatment and may turn to EDs instead. However, most studies of mental health ED use “are by now outdated, as they used data from years prior to the full implementation of the ACA,” the researchers noted.

“More Americans are suffering from mental illness, and given the recent policy efforts of expanding access to mental health care, we were questioning if ED visits due to mental health has changed or not,” Dr. Rhee said.

To investigate the question, the researchers conducted a cross-sectional analysis of data from the NHAMCS, a publicly available dataset provided by the National Center for Health Statistics of the Centers for Disease Control and Prevention.

They grouped psychiatric diagnoses into five categories: mood disorders, anxiety disorders, psychosis or schizophrenia, suicide attempt or ideation, or other/unspecified. Substance use diagnoses were grouped into six categories: alcohol, amphetamine, cannabis, cocaine, opioid, or other/unspecified.

These categories were used to determine the type of disorder a patient had, whether the patient had both psychiatric and substance-related diagnoses, and whether the patient received multiple mental health diagnoses at the time of the ED visit.

Sociodemographic covariates included age, sex, race/ethnicity, and insurance coverage.
 

Twofold and fourfold increases

Of 100.9 million outpatient ED visits that took place between 2007 and 2016, approximately 8.4 million (8.3%) were for psychiatric or substance use–related diagnoses. Also, the visits were more likely from adults who were younger than 45 years, male, non-Hispanic White, and covered by Medicaid or other public insurance types (58.5%, 52.5%, 65.2%, and 58.6%, respectively).

The overall rate of ED visits for any mental health diagnosis nearly doubled between 2007-2008 and 2015-2016. The rate of visits in which both psychiatric and substance use–related diagnoses increased fourfold during that time span. ED visits involving at least two mental health diagnoses increased twofold.

Additional changes in the number of visits are listed below (for each, P < .001).

When these comparisons were adjusted for age, sex, and race/ethnicity, “linearly increasing trends of mental health–related ED visits were consistently found in all categories,” the authors reported. No trends were found regarding age, sex, or race/ethnicity. By contrast, mental health–related ED visits in which Medicaid was identified as the primary source of insurance nearly doubled between 2007–2008 and 2015–2016 (from 27.2% to 42.8%).

Other/unspecified psychiatric diagnoses, such as adjustment disorder and personality disorders, almost tripled between 2007-2008 and 2015-2016 (from 1,040 to 2,961 per 100,000 ED visits). ED visits for mood disorders and anxiety disorders also increased over time.

Alcohol-related ED visits were the most common substance use visits, increasing from 1,669 in 2007-2008 to 3,007 per 100,000 visits in 2015-2016. Amphetamine- and opioid-related ED visits more than doubled, and other/unspecified–related ED visits more than tripled during that time.

“One explanation why ED visits for mental health conditions have increased is that substance-related problems, which include overdose/self-injury issues, have increased over time,” Dr. Rhee noted, which “makes sense,” inasmuch as opioid, cannabis, and amphetamine use has increased across the country.

Another explanation is that, although mental health care access has been expanded through the ACA, “people, especially those with lower socioeconomic backgrounds, do not know how to get access to care and are still underserved,” he said.

“If mental health–related ED visits continue to increase in the future, there are several steps to be made. ED providers need to be better equipped with mental health care, and behavioral health should be better integrated as part of the care coordination,” said Dr. Rhee.

He added that reimbursement models across different insurance types, such as Medicare, Medicaid, and private insurance, “should consider expanding their coverage of mental health treatment in ED settings.”
 

“Canary in the coal mine”

Commenting on the study in an interview, Benjamin Druss, MD, MPH, professor and Rosalynn Carter Chair in Mental Health, Rollins School of Public Health, Emory University, Atlanta, called EDs the “canaries in the coal mine” for the broader health system.

The growing number of ED visits for behavioral problems “could represent both a rise in acute conditions such as substance use and lack of access to outpatient treatment,” said Dr. Druss, who was not involved with the research.

The findings “suggest the importance of strategies to effectively manage patients with behavioral conditions in ED settings and to effectively link them with high-quality outpatient care,” he noted.

Dr. Rhee has received funding from the National Institute on Aging and the American Foundation for Suicide Prevention. The other study authors and Dr. Druss report no relevant financial relationships.

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

Italian patients with diabetic foot ulceration (DFUs) suffered mightily during the height of the coronavirus pandemic in that country, according to a newly published study.

Phalinn Ooi/CC-BY-2.0

Amid a mandatory national lockdown, the rates of amputations skyrocketed at a hospital far from the hardest-hit region as many patients developed gangrene.

The findings offer critical lessons for the United States, said wound care specialist William H. Tettelbach, MD, of Western Peaks Specialty Hospital near Salt Lake City. “It’s become more obvious that outpatient wound care is a critical care need for the community because of the risk of ignoring these chronic wounds and letting them remain open. We cannot let these services be closed down like some were when the pandemic started.”

The study, led by Paola Caruso, MD, of the University of Campania Luigi Vanvitelli in Naples, appeared in Diabetes Care.

The researchers launched the study to understand how patients with diabetes and DFU fared during the height of the pandemic in Italy, where tens of thousands of people died, mainly in the northern region of the country. They focused on patients in the southern region who were admitted to the division of endocrinology and metabolic diseases at the Teaching Hospital at the University of Campania Luigi Vanvitelli.

The study compared 25 patients who were admitted from March 9 to May 18, 2020, with 38 patients who were admitted from a longer period between January and May 2019. The demographics of the groups are similar, with average ages in the early 60s and more men than women (21:4, respectively, in 2020 and 23:15, respectively, in 2019.)

The results reveal high numbers of emergent and serious cases in 2020. Compared with 2019, fewer were outpatients (16% vs. 45%, P = .028) and more were emergency patients (76% vs. 26%, P < .001).

Clinically, gangrene was much more common in the 2020 group, compared with the 2019 group (64% vs. 29%, P = .009), as was amputation (60% vs. 18%, P = .001).

The researchers determined that amputation was more than three times more likely in the 2020 versus the 2019 group (relative risk, 3.26; 95% confidence interval, 1.55-6.84) even though the 2019 period was longer. After adjustment for gender, the heightened risk in 2020 was 2.50 (95% CI, 1.18-5.29).

There was no statistically significant increase in the risk of revascularization.

“The COVID-19 lockdown may have had a detrimental impact on amputation risk because of the sudden interruption of DFU care and lower-limb preservation pathways, resulting in delayed diagnosis and treatment,” the researchers wrote. “DFU is often characterized by progressive clinical course, which can rapidly lead patients to critical worsening of their ulcers.”

They added that “the higher risk of amputation observed during COVID-19 lockdown confirms the need for proper and timely management of DFU patients to prevent dramatic outcomes responsible for a reduction of quality of life and increased morbidity and mortality.”

The study authors didn’t discuss why more patients seemed to have stayed home and not gotten proper care. It’s not clear if they were scared to get treatment or couldn’t obtain it because of the national shutdown.

Both have been factors affecting diabetic foot care in the United States during the pandemic, said Dr. Tettelbach. He called the study “timely and pertinent,” and said it highlights how wound care is “a critical need” that must remain available even when other medical services such as elective surgeries are shut down.

Infection-control protocols such as allowing patients to wait for appointments in their cars instead of waiting rooms will alleviate the fears of certain patients about seeking in-person care during the pandemic, he said. But some patients will be afraid to come in no matter what, he said, and home health may be the best solution for their care.

Several of the study authors reported various disclosures. Dr. Tettelbach reported no relevant disclosures.

SOURCE: Caruso P et al. Diabetes Care. 2020 Jul 23. doi:10.2337/dc20-1347.

Italian patients with diabetic foot ulceration (DFUs) suffered mightily during the height of the coronavirus pandemic in that country, according to a newly published study.

Phalinn Ooi/CC-BY-2.0

Amid a mandatory national lockdown, the rates of amputations skyrocketed at a hospital far from the hardest-hit region as many patients developed gangrene.

The findings offer critical lessons for the United States, said wound care specialist William H. Tettelbach, MD, of Western Peaks Specialty Hospital near Salt Lake City. “It’s become more obvious that outpatient wound care is a critical care need for the community because of the risk of ignoring these chronic wounds and letting them remain open. We cannot let these services be closed down like some were when the pandemic started.”

The study, led by Paola Caruso, MD, of the University of Campania Luigi Vanvitelli in Naples, appeared in Diabetes Care.

The researchers launched the study to understand how patients with diabetes and DFU fared during the height of the pandemic in Italy, where tens of thousands of people died, mainly in the northern region of the country. They focused on patients in the southern region who were admitted to the division of endocrinology and metabolic diseases at the Teaching Hospital at the University of Campania Luigi Vanvitelli.

The study compared 25 patients who were admitted from March 9 to May 18, 2020, with 38 patients who were admitted from a longer period between January and May 2019. The demographics of the groups are similar, with average ages in the early 60s and more men than women (21:4, respectively, in 2020 and 23:15, respectively, in 2019.)

The results reveal high numbers of emergent and serious cases in 2020. Compared with 2019, fewer were outpatients (16% vs. 45%, P = .028) and more were emergency patients (76% vs. 26%, P < .001).

Clinically, gangrene was much more common in the 2020 group, compared with the 2019 group (64% vs. 29%, P = .009), as was amputation (60% vs. 18%, P = .001).

The researchers determined that amputation was more than three times more likely in the 2020 versus the 2019 group (relative risk, 3.26; 95% confidence interval, 1.55-6.84) even though the 2019 period was longer. After adjustment for gender, the heightened risk in 2020 was 2.50 (95% CI, 1.18-5.29).

There was no statistically significant increase in the risk of revascularization.

“The COVID-19 lockdown may have had a detrimental impact on amputation risk because of the sudden interruption of DFU care and lower-limb preservation pathways, resulting in delayed diagnosis and treatment,” the researchers wrote. “DFU is often characterized by progressive clinical course, which can rapidly lead patients to critical worsening of their ulcers.”

They added that “the higher risk of amputation observed during COVID-19 lockdown confirms the need for proper and timely management of DFU patients to prevent dramatic outcomes responsible for a reduction of quality of life and increased morbidity and mortality.”

The study authors didn’t discuss why more patients seemed to have stayed home and not gotten proper care. It’s not clear if they were scared to get treatment or couldn’t obtain it because of the national shutdown.

Both have been factors affecting diabetic foot care in the United States during the pandemic, said Dr. Tettelbach. He called the study “timely and pertinent,” and said it highlights how wound care is “a critical need” that must remain available even when other medical services such as elective surgeries are shut down.

Infection-control protocols such as allowing patients to wait for appointments in their cars instead of waiting rooms will alleviate the fears of certain patients about seeking in-person care during the pandemic, he said. But some patients will be afraid to come in no matter what, he said, and home health may be the best solution for their care.

Several of the study authors reported various disclosures. Dr. Tettelbach reported no relevant disclosures.

SOURCE: Caruso P et al. Diabetes Care. 2020 Jul 23. doi:10.2337/dc20-1347.

Italian patients with diabetic foot ulceration (DFUs) suffered mightily during the height of the coronavirus pandemic in that country, according to a newly published study.

Phalinn Ooi/CC-BY-2.0

Amid a mandatory national lockdown, the rates of amputations skyrocketed at a hospital far from the hardest-hit region as many patients developed gangrene.

The findings offer critical lessons for the United States, said wound care specialist William H. Tettelbach, MD, of Western Peaks Specialty Hospital near Salt Lake City. “It’s become more obvious that outpatient wound care is a critical care need for the community because of the risk of ignoring these chronic wounds and letting them remain open. We cannot let these services be closed down like some were when the pandemic started.”

The study, led by Paola Caruso, MD, of the University of Campania Luigi Vanvitelli in Naples, appeared in Diabetes Care.

The researchers launched the study to understand how patients with diabetes and DFU fared during the height of the pandemic in Italy, where tens of thousands of people died, mainly in the northern region of the country. They focused on patients in the southern region who were admitted to the division of endocrinology and metabolic diseases at the Teaching Hospital at the University of Campania Luigi Vanvitelli.

The study compared 25 patients who were admitted from March 9 to May 18, 2020, with 38 patients who were admitted from a longer period between January and May 2019. The demographics of the groups are similar, with average ages in the early 60s and more men than women (21:4, respectively, in 2020 and 23:15, respectively, in 2019.)

The results reveal high numbers of emergent and serious cases in 2020. Compared with 2019, fewer were outpatients (16% vs. 45%, P = .028) and more were emergency patients (76% vs. 26%, P < .001).

Clinically, gangrene was much more common in the 2020 group, compared with the 2019 group (64% vs. 29%, P = .009), as was amputation (60% vs. 18%, P = .001).

The researchers determined that amputation was more than three times more likely in the 2020 versus the 2019 group (relative risk, 3.26; 95% confidence interval, 1.55-6.84) even though the 2019 period was longer. After adjustment for gender, the heightened risk in 2020 was 2.50 (95% CI, 1.18-5.29).

There was no statistically significant increase in the risk of revascularization.

“The COVID-19 lockdown may have had a detrimental impact on amputation risk because of the sudden interruption of DFU care and lower-limb preservation pathways, resulting in delayed diagnosis and treatment,” the researchers wrote. “DFU is often characterized by progressive clinical course, which can rapidly lead patients to critical worsening of their ulcers.”

They added that “the higher risk of amputation observed during COVID-19 lockdown confirms the need for proper and timely management of DFU patients to prevent dramatic outcomes responsible for a reduction of quality of life and increased morbidity and mortality.”

The study authors didn’t discuss why more patients seemed to have stayed home and not gotten proper care. It’s not clear if they were scared to get treatment or couldn’t obtain it because of the national shutdown.

Both have been factors affecting diabetic foot care in the United States during the pandemic, said Dr. Tettelbach. He called the study “timely and pertinent,” and said it highlights how wound care is “a critical need” that must remain available even when other medical services such as elective surgeries are shut down.

Infection-control protocols such as allowing patients to wait for appointments in their cars instead of waiting rooms will alleviate the fears of certain patients about seeking in-person care during the pandemic, he said. But some patients will be afraid to come in no matter what, he said, and home health may be the best solution for their care.

Several of the study authors reported various disclosures. Dr. Tettelbach reported no relevant disclosures.

SOURCE: Caruso P et al. Diabetes Care. 2020 Jul 23. doi:10.2337/dc20-1347.