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Faster testing possible for secondary ICU infections

Article Type
Changed
Fri, 11/19/2021 - 08:18

The SARS-CoV-2 pandemic has given added impetus for metagenomic testing using nanopore sequencing to progress from a research tool to routine clinical application. A study led by researchers from Guy’s and St. Thomas’ NHS Foundation Trust has shown the potential for clinical metagenomics to become a same-day test for identifying secondary infection in ventilated ICU patients. Getting results in hours rather than days would help to ensure rapid treatment with the correct antibiotic, minimize unnecessary prescriptions, and thus reduce the growing menace of antimicrobial resistance.

‘SARS-CoV-2 has put considerable strain on ICUs’

The researchers point out that the setting of an intensive care unit involves frequent staff-patient contact that imparts a risk of secondary or nosocomial infection. In addition, invasive ventilation may introduce organisms into the lungs and lead to ventilator-acquired pneumonia. This carries a high mortality and is responsible for up to 70% of antimicrobial prescribing, with current guidelines requiring empiric antibiotics pending culture results, which typically takes 2-4 days.

Many of these infection problems worsened during SARS-CoV-2. Expanded critical care capacity raised the risk of nosocomial infections, with attendant increased antimicrobial prescriptions and the threat of antimicrobial resistance. In addition, treatment of COVID-19 patients with steroid therapy potentially exacerbates bacterial or fungal infections.

The researchers, from the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London, in collaboration with the Quadram Institute in Norwich, Oxford Nanopore Technologies, and Viapath, the U.K.’s largest independent pathology service provider, noted that the pandemic thus reinforced “a need for rapid comprehensive diagnostics to improve antimicrobial stewardship and help prevent emergence and transmission of multi-drug-resistant organisms.”

“As soon as the pandemic started, our scientists realized there would be a benefit to sequencing genomes of all bacteria and fungi causing infection in COVID-19 patients while on ICU,” said Professor Jonathan Edgeworth, who led the research team.

“Within a few weeks we showed it can diagnose secondary infection, target antibiotic treatment, and detect outbreaks much earlier than current technologies – all from a single sample.”
 

Proof-of-concept study

The team performed a proof-of-concept study of nanopore metagenomics sequencing – a type of DNA sequencing that allows direct rapid unbiased detection of all organisms present in a clinical sample – on 43 surplus respiratory samples from 34 intubated COVID-19 patients with suspected secondary bacterial or fungal pneumonia. Patients were drawn from seven ICUs at St. Thomas’ Hospital, London over a 9-week period between April 11 and June 15 2020, during the first wave of COVID-19.

Their median age was 52, 70% were male, 47% White, and 44% Black or minority ethnicities. Median length of stay was 32 days and mortality 24%. Samples sent for metagenomic analysis and culture included 10 bronchoalveolar lavages, 6 tracheal aspirates, and 27 non-direct bronchoalveolar lavages.

The study, published in Genome Medicine, showed that an 8-hour metagenomics workflow was 92% sensitive (95% CI, 75% to 99%) and 82% specific (95% CI, 57% to 96%) for bacterial identification, based on culture-positive and culture-negative samples, respectively.

The main Gram-negative bacteria identified were Klebsiella spp. (53%), Citrobacter spp. (15%), and E coli (9%). The main Gram-positive bacteria were S aureus (9%), C striatum (24%) and Enterococcus spp. (12%). In addition, C albicans, other Candida spp. and Aspergillus spp. were cultured from 38%, 15%, and 9% of patients, respectively.

In every case, the initial antibiotics prescribed according to prevailing guideline recommendations would have been modified by metagenomic sequencing demonstrating the presence or absence of β-lactam-resistant genes carried by Enterobacterales.

Next day results of sequencing also detected Aspergillus fumigatus in four samples, with results 100% concordant with quantitative PCR for both the four positive and 39 negative samples. It identified two multi-drug–resistant outbreaks, one involving K pneumoniae ST307 affecting four patients and one a C striatum outbreak involving 14 patients across three ICUs.

Thus, a single sample can provide enough genetic sequence data to compare pathogen genomes with a database and accurately identify patients carrying the same strain, enabling early detection of outbreaks. This is the first time this combined benefit of a single test has been demonstrated, the team say.

Gordon Sanghera, CEO of Oxford Nanopore commented that “rapidly characterizing co-infections for precision prescribing is a vital next step for both COVID-19 patients and respiratory disease in general.”

Dr. Andrew Page of the Quadram Institute said: “We have been working on metagenomics technology for the last 7 years. It is great to see it applied to patient care during the COVID-19 pandemic.”

He said in an interview: “The pandemic has accelerated the transition from using sequencing purely in research labs to using it in the clinic to rapidly provide clinicians with information they can use to improve outcomes for patients.”
 

 

 

Potential to inform antimicrobial prescribing and infection control

“Clinical metagenomic testing provides accurate pathogen detection and antibiotic resistance prediction in a same-day laboratory workflow, with assembled genomes available the next day for genomic surveillance,” the researchers say.

The technology “could fundamentally change the multi-disciplinary team approach to managing ICU infections.” It has the potential to improve initial targeted antimicrobial treatment and infection control decisions, as well as help rapidly detect unsuspected outbreaks of multi-drug–resistant pathogens.

Professor Edgeworth told this news organization that since the study, “secondary bacterial and fungal infections have increased, perhaps due to immunomodulatory treatments or just the length of time patients spend on ICU recovering from COVID-19. This makes rapid diagnosis even more important to ensure patients get more targeted antibiotics earlier, rather than relying on generic guidelines.”

The team “are planning to move respiratory metagenomics into pilot service under our Trust’s quality improvement framework,” he revealed. This will enable them to gather data on patient benefits.  

“We also need to see how clinicians use these tests to improve antibiotic treatment, to stop antibiotics when not needed or to identify outbreaks earlier, and then how that translates into tangible benefits for individual patients and the wider NHS.”

He predicts that the technique will revolutionize the approach to prevention and treatment of serious infection in ICUs, and it is now planned to offer it as a clinical service for COVID-19 and influenza patients during the coming winter.

In addition, he said: “It can be equally applied to other samples such as tissue fluids and biopsies, including those removed at operation. It therefore has potential to impact on diagnostics for many clinical services, particularly if the progress is maintained at the current pace.”

This article first appeared on Medscape UK/Univadis.

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The SARS-CoV-2 pandemic has given added impetus for metagenomic testing using nanopore sequencing to progress from a research tool to routine clinical application. A study led by researchers from Guy’s and St. Thomas’ NHS Foundation Trust has shown the potential for clinical metagenomics to become a same-day test for identifying secondary infection in ventilated ICU patients. Getting results in hours rather than days would help to ensure rapid treatment with the correct antibiotic, minimize unnecessary prescriptions, and thus reduce the growing menace of antimicrobial resistance.

‘SARS-CoV-2 has put considerable strain on ICUs’

The researchers point out that the setting of an intensive care unit involves frequent staff-patient contact that imparts a risk of secondary or nosocomial infection. In addition, invasive ventilation may introduce organisms into the lungs and lead to ventilator-acquired pneumonia. This carries a high mortality and is responsible for up to 70% of antimicrobial prescribing, with current guidelines requiring empiric antibiotics pending culture results, which typically takes 2-4 days.

Many of these infection problems worsened during SARS-CoV-2. Expanded critical care capacity raised the risk of nosocomial infections, with attendant increased antimicrobial prescriptions and the threat of antimicrobial resistance. In addition, treatment of COVID-19 patients with steroid therapy potentially exacerbates bacterial or fungal infections.

The researchers, from the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London, in collaboration with the Quadram Institute in Norwich, Oxford Nanopore Technologies, and Viapath, the U.K.’s largest independent pathology service provider, noted that the pandemic thus reinforced “a need for rapid comprehensive diagnostics to improve antimicrobial stewardship and help prevent emergence and transmission of multi-drug-resistant organisms.”

“As soon as the pandemic started, our scientists realized there would be a benefit to sequencing genomes of all bacteria and fungi causing infection in COVID-19 patients while on ICU,” said Professor Jonathan Edgeworth, who led the research team.

“Within a few weeks we showed it can diagnose secondary infection, target antibiotic treatment, and detect outbreaks much earlier than current technologies – all from a single sample.”
 

Proof-of-concept study

The team performed a proof-of-concept study of nanopore metagenomics sequencing – a type of DNA sequencing that allows direct rapid unbiased detection of all organisms present in a clinical sample – on 43 surplus respiratory samples from 34 intubated COVID-19 patients with suspected secondary bacterial or fungal pneumonia. Patients were drawn from seven ICUs at St. Thomas’ Hospital, London over a 9-week period between April 11 and June 15 2020, during the first wave of COVID-19.

Their median age was 52, 70% were male, 47% White, and 44% Black or minority ethnicities. Median length of stay was 32 days and mortality 24%. Samples sent for metagenomic analysis and culture included 10 bronchoalveolar lavages, 6 tracheal aspirates, and 27 non-direct bronchoalveolar lavages.

The study, published in Genome Medicine, showed that an 8-hour metagenomics workflow was 92% sensitive (95% CI, 75% to 99%) and 82% specific (95% CI, 57% to 96%) for bacterial identification, based on culture-positive and culture-negative samples, respectively.

The main Gram-negative bacteria identified were Klebsiella spp. (53%), Citrobacter spp. (15%), and E coli (9%). The main Gram-positive bacteria were S aureus (9%), C striatum (24%) and Enterococcus spp. (12%). In addition, C albicans, other Candida spp. and Aspergillus spp. were cultured from 38%, 15%, and 9% of patients, respectively.

In every case, the initial antibiotics prescribed according to prevailing guideline recommendations would have been modified by metagenomic sequencing demonstrating the presence or absence of β-lactam-resistant genes carried by Enterobacterales.

Next day results of sequencing also detected Aspergillus fumigatus in four samples, with results 100% concordant with quantitative PCR for both the four positive and 39 negative samples. It identified two multi-drug–resistant outbreaks, one involving K pneumoniae ST307 affecting four patients and one a C striatum outbreak involving 14 patients across three ICUs.

Thus, a single sample can provide enough genetic sequence data to compare pathogen genomes with a database and accurately identify patients carrying the same strain, enabling early detection of outbreaks. This is the first time this combined benefit of a single test has been demonstrated, the team say.

Gordon Sanghera, CEO of Oxford Nanopore commented that “rapidly characterizing co-infections for precision prescribing is a vital next step for both COVID-19 patients and respiratory disease in general.”

Dr. Andrew Page of the Quadram Institute said: “We have been working on metagenomics technology for the last 7 years. It is great to see it applied to patient care during the COVID-19 pandemic.”

He said in an interview: “The pandemic has accelerated the transition from using sequencing purely in research labs to using it in the clinic to rapidly provide clinicians with information they can use to improve outcomes for patients.”
 

 

 

Potential to inform antimicrobial prescribing and infection control

“Clinical metagenomic testing provides accurate pathogen detection and antibiotic resistance prediction in a same-day laboratory workflow, with assembled genomes available the next day for genomic surveillance,” the researchers say.

The technology “could fundamentally change the multi-disciplinary team approach to managing ICU infections.” It has the potential to improve initial targeted antimicrobial treatment and infection control decisions, as well as help rapidly detect unsuspected outbreaks of multi-drug–resistant pathogens.

Professor Edgeworth told this news organization that since the study, “secondary bacterial and fungal infections have increased, perhaps due to immunomodulatory treatments or just the length of time patients spend on ICU recovering from COVID-19. This makes rapid diagnosis even more important to ensure patients get more targeted antibiotics earlier, rather than relying on generic guidelines.”

The team “are planning to move respiratory metagenomics into pilot service under our Trust’s quality improvement framework,” he revealed. This will enable them to gather data on patient benefits.  

“We also need to see how clinicians use these tests to improve antibiotic treatment, to stop antibiotics when not needed or to identify outbreaks earlier, and then how that translates into tangible benefits for individual patients and the wider NHS.”

He predicts that the technique will revolutionize the approach to prevention and treatment of serious infection in ICUs, and it is now planned to offer it as a clinical service for COVID-19 and influenza patients during the coming winter.

In addition, he said: “It can be equally applied to other samples such as tissue fluids and biopsies, including those removed at operation. It therefore has potential to impact on diagnostics for many clinical services, particularly if the progress is maintained at the current pace.”

This article first appeared on Medscape UK/Univadis.

The SARS-CoV-2 pandemic has given added impetus for metagenomic testing using nanopore sequencing to progress from a research tool to routine clinical application. A study led by researchers from Guy’s and St. Thomas’ NHS Foundation Trust has shown the potential for clinical metagenomics to become a same-day test for identifying secondary infection in ventilated ICU patients. Getting results in hours rather than days would help to ensure rapid treatment with the correct antibiotic, minimize unnecessary prescriptions, and thus reduce the growing menace of antimicrobial resistance.

‘SARS-CoV-2 has put considerable strain on ICUs’

The researchers point out that the setting of an intensive care unit involves frequent staff-patient contact that imparts a risk of secondary or nosocomial infection. In addition, invasive ventilation may introduce organisms into the lungs and lead to ventilator-acquired pneumonia. This carries a high mortality and is responsible for up to 70% of antimicrobial prescribing, with current guidelines requiring empiric antibiotics pending culture results, which typically takes 2-4 days.

Many of these infection problems worsened during SARS-CoV-2. Expanded critical care capacity raised the risk of nosocomial infections, with attendant increased antimicrobial prescriptions and the threat of antimicrobial resistance. In addition, treatment of COVID-19 patients with steroid therapy potentially exacerbates bacterial or fungal infections.

The researchers, from the National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London, in collaboration with the Quadram Institute in Norwich, Oxford Nanopore Technologies, and Viapath, the U.K.’s largest independent pathology service provider, noted that the pandemic thus reinforced “a need for rapid comprehensive diagnostics to improve antimicrobial stewardship and help prevent emergence and transmission of multi-drug-resistant organisms.”

“As soon as the pandemic started, our scientists realized there would be a benefit to sequencing genomes of all bacteria and fungi causing infection in COVID-19 patients while on ICU,” said Professor Jonathan Edgeworth, who led the research team.

“Within a few weeks we showed it can diagnose secondary infection, target antibiotic treatment, and detect outbreaks much earlier than current technologies – all from a single sample.”
 

Proof-of-concept study

The team performed a proof-of-concept study of nanopore metagenomics sequencing – a type of DNA sequencing that allows direct rapid unbiased detection of all organisms present in a clinical sample – on 43 surplus respiratory samples from 34 intubated COVID-19 patients with suspected secondary bacterial or fungal pneumonia. Patients were drawn from seven ICUs at St. Thomas’ Hospital, London over a 9-week period between April 11 and June 15 2020, during the first wave of COVID-19.

Their median age was 52, 70% were male, 47% White, and 44% Black or minority ethnicities. Median length of stay was 32 days and mortality 24%. Samples sent for metagenomic analysis and culture included 10 bronchoalveolar lavages, 6 tracheal aspirates, and 27 non-direct bronchoalveolar lavages.

The study, published in Genome Medicine, showed that an 8-hour metagenomics workflow was 92% sensitive (95% CI, 75% to 99%) and 82% specific (95% CI, 57% to 96%) for bacterial identification, based on culture-positive and culture-negative samples, respectively.

The main Gram-negative bacteria identified were Klebsiella spp. (53%), Citrobacter spp. (15%), and E coli (9%). The main Gram-positive bacteria were S aureus (9%), C striatum (24%) and Enterococcus spp. (12%). In addition, C albicans, other Candida spp. and Aspergillus spp. were cultured from 38%, 15%, and 9% of patients, respectively.

In every case, the initial antibiotics prescribed according to prevailing guideline recommendations would have been modified by metagenomic sequencing demonstrating the presence or absence of β-lactam-resistant genes carried by Enterobacterales.

Next day results of sequencing also detected Aspergillus fumigatus in four samples, with results 100% concordant with quantitative PCR for both the four positive and 39 negative samples. It identified two multi-drug–resistant outbreaks, one involving K pneumoniae ST307 affecting four patients and one a C striatum outbreak involving 14 patients across three ICUs.

Thus, a single sample can provide enough genetic sequence data to compare pathogen genomes with a database and accurately identify patients carrying the same strain, enabling early detection of outbreaks. This is the first time this combined benefit of a single test has been demonstrated, the team say.

Gordon Sanghera, CEO of Oxford Nanopore commented that “rapidly characterizing co-infections for precision prescribing is a vital next step for both COVID-19 patients and respiratory disease in general.”

Dr. Andrew Page of the Quadram Institute said: “We have been working on metagenomics technology for the last 7 years. It is great to see it applied to patient care during the COVID-19 pandemic.”

He said in an interview: “The pandemic has accelerated the transition from using sequencing purely in research labs to using it in the clinic to rapidly provide clinicians with information they can use to improve outcomes for patients.”
 

 

 

Potential to inform antimicrobial prescribing and infection control

“Clinical metagenomic testing provides accurate pathogen detection and antibiotic resistance prediction in a same-day laboratory workflow, with assembled genomes available the next day for genomic surveillance,” the researchers say.

The technology “could fundamentally change the multi-disciplinary team approach to managing ICU infections.” It has the potential to improve initial targeted antimicrobial treatment and infection control decisions, as well as help rapidly detect unsuspected outbreaks of multi-drug–resistant pathogens.

Professor Edgeworth told this news organization that since the study, “secondary bacterial and fungal infections have increased, perhaps due to immunomodulatory treatments or just the length of time patients spend on ICU recovering from COVID-19. This makes rapid diagnosis even more important to ensure patients get more targeted antibiotics earlier, rather than relying on generic guidelines.”

The team “are planning to move respiratory metagenomics into pilot service under our Trust’s quality improvement framework,” he revealed. This will enable them to gather data on patient benefits.  

“We also need to see how clinicians use these tests to improve antibiotic treatment, to stop antibiotics when not needed or to identify outbreaks earlier, and then how that translates into tangible benefits for individual patients and the wider NHS.”

He predicts that the technique will revolutionize the approach to prevention and treatment of serious infection in ICUs, and it is now planned to offer it as a clinical service for COVID-19 and influenza patients during the coming winter.

In addition, he said: “It can be equally applied to other samples such as tissue fluids and biopsies, including those removed at operation. It therefore has potential to impact on diagnostics for many clinical services, particularly if the progress is maintained at the current pace.”

This article first appeared on Medscape UK/Univadis.

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Hospitalists helped plan COVID-19 field hospitals

Article Type
Changed
Thu, 11/18/2021 - 14:42

‘It’s a great thing to be overprepared’

At the height of the COVID-19 pandemic’s terrifying first wave in the spring of 2020, dozens of hospitals in high-incidence areas either planned or opened temporary, emergency field hospitals to cover anticipated demand for beds beyond the capacity of local permanent hospitals.

Chastened by images of overwhelmed health care systems in Northern Italy and other hard-hit areas,1 the planners used available modeling tools and estimates for projecting maximum potential need in worst-case scenarios. Some of these temporary hospitals never opened. Others opened in convention centers, parking garages, or parking lot tents, and ended up being used to a lesser degree than the worst-case scenarios.

But those who participated in the planning – including, in many cases, hospitalists – believe they created alternate care site manuals that could be quickly revived in the event of future COVID surges or other, similar crises. Better to plan for too much, they say, than not plan for enough.

Field hospitals or alternate care sites are defined in a recent journal article in Prehospital Disaster Medicine as “locations that can be converted to provide either inpatient and/or outpatient health services when existing facilities are compromised by a hazard impact or the volume of patients exceeds available capacity and/or capabilities.”2

University of Michigan Institute for Healthcare Policy and Innovation
Dr. Sue Anne Bell

The lead author of that report, Sue Anne Bell, PhD, FNP-BC, a disaster expert and assistant professor of nursing at the University of Michigan (UM), was one of five members of the leadership team for planning UM’s field hospital. They used an organizational unit structure based on the U.S. military’s staffing structure, with their work organized around six units of planning: personnel and labor, security, clinical operations, logistics and supply, planning and training, and communications. This team planned a 519-bed step-down care facility, the Michigan Medicine Field Hospital, for a 73,000-foot indoor track and performance facility at the university, three miles from UM’s main hospital. The aim was to provide safe care in a resource-limited environment.

“We were prepared, but the need never materialized as the peak of COVID cases started to subside,” Dr. Bell said. The team was ready to open within days using a “T-Minus” framework of days remaining on an official countdown clock. But when the need and deadlines kept getting pushed back, that gave them more time to develop clearer procedures.

Two Michigan Medicine hospitalists, Christopher Smith, MD, and David Paje, MD, MPH, both professors at UM’s medical school, were intimately involved in the process. “I was the medical director for the respiratory care unit that was opened for COVID patients, so I was pulled in to assist in the field hospital planning,” said Dr. Smith.

Dr. Christopher Smith


Dr. Paje was director of the short-stay unit and had been a medical officer in the U.S. Army, with training in how to set up military field hospitals. He credits that background as helpful for UM’s COVID field hospital planning, along with his experience in hospital medicine operations.

“We expected that these patients would need the expertise of hospitalists, who had quickly become familiar with the peculiarities of the new disease. That played a role in the decisions we made. Hospitalists were at the front lines of COVID care and had unique clinical insights about managing those with severe disease,” Dr. Paje added.

“When we started, the projections were dire. You don’t want to believe something like that is going to happen. When COVID started to cool off, it was more of a relief to us than anything else,” Dr. Smith said. “Still, it was a very worthwhile exercise. At the end of the day, we put together a comprehensive guide, which is ready for the next crisis.”
 

 

 

Baltimore builds a convention center hospital

A COVID-19 field hospital was planned and executed at an exhibit hall in the Baltimore Convention Center, starting in March 2020 under the leadership of Johns Hopkins Bayview hospitalist Eric Howell, MD, MHM, who eventually handed over responsibilities as chief medical officer when he assumed the position of CEO for the Society of Hospital Medicine in July of that year.

Courtesy Dr. Eric Howell
Dr. Eric Howell was chief medical officer for the Joint Commission-accredited Baltimore Civic Center Field Hospital for COVID-19 patients, opened in March 2020.

Hopkins collaborated with the University of Maryland health system and state leaders, including the Secretary of Health, to open a 252-bed temporary facility, which at its peak carried a census of 48 patients, with no on-site mortality or cardiac arrests, before it was closed in June 2021 – ready to reopen if necessary. It also served as Baltimore’s major site for polymerase chain reaction COVID-19 testing, vaccinations, and monoclonal antibody infusions, along with medical research.

“My belief at the time we started was that my entire 20-year career as a hospitalist had prepared me for the challenge of opening a COVID field hospital,” Dr. Howell said. “I had learned how to build clinical programs. The difference was that instead of months and years to build a program, we only had a few weeks.”

His first request was to bring on an associate medical director for the field hospital, Melinda E. Kantsiper, MD, a hospitalist and director of clinical operations in the Division of Hospital Medicine at Johns Hopkins Bayview. She became the field hospital’s CMO when Dr. Howell moved to SHM. “As hospitalists, we are trained to care for the patient in front of us while at the same time creating systems that can adjust to rapidly changing circumstances,” Dr. Kantsiper said. “We did what was asked and set up a field hospital that cared for a total of 1,500 COVID patients.”

Courtesy Johns Hopkins Medicine
Dr. Melinda E. Kantsiper


Hospitalists have the tools that are needed for this work, and shouldn’t be reluctant to contribute to field hospital planning, she said. “This was a real eye-opener for me. Eric explained to me that hospitalists really practice acute care medicine, which doesn’t have to be within the four walls of a hospital.”

The Baltimore field hospital has been a fantastic experience, Dr. Kantsiper added. “But it’s not a building designed for health care delivery.” For the right group of providers, the experience of working in a temporary facility such as this can be positive and exhilarating. “But we need to make sure we take care of our staff. It takes a toll. How we keep them safe – physically and emotionally – has to be top of mind,” she said.

The leaders at Hopkins Medicine and their collaborators truly engaged with the field hospital’s mission, Dr. Howell added.

Dr. Eric E. Howell

“They gave us a lot of autonomy and helped us break down barriers. They gave us the political capital to say proper PPE was absolutely essential. As hard and devastating as the pandemic has been, one take-away is that we showed that we can be more flexible and elastic in response to actual needs than we used to think.”

 

 

Range of challenges

Among the questions that need to be answered by a field hospital’s planners, the first is ‘where to put it?’ The answer is, hopefully, someplace not too far away, large enough, with ready access to supplies and intake. The next question is ‘who is the patient?’ Clinicians must determine who goes to the field hospital versus who stays at the standing hospital. How sick should these patients be? And when do they need to go back to the permanent hospital? Can staff be trained to recognize when patients in the field hospital are starting to decompensate? The EPIC Deterioration Index3 is a proprietary prediction model that was used by more than a hundred hospitals during the pandemic.

The hospitalist team may develop specific inclusion and exclusion criteria – for example, don’t admit patients who are receiving oxygen therapy above a certain threshold or who are hemodynamically unstable. These criteria should reflect the capacity of the field hospital and the needs of the permanent hospital. At Michigan, as at other field hospital sites, the goal was to offer a step-down or postacute setting for patients with COVID-19 who were too sick to return home but didn’t need acute or ICU-level care, thereby freeing up beds at the permanent hospital for patients who were sicker.

Other questions: What is the process for admissions and discharges? How will patients be transported? What kind of staffing is needed, and what levels of care will be provided? What about rehabilitation services, or palliative care? What about patients with substance abuse or psychiatric comorbidities?

“Are we going to do paper charting? How will that work out for long-term documentation and billing?” Dr. Bell said. A clear reporting structure and communication pathways are essential. Among the other operational processes to address, outlined in Dr. Bell’s article, are orientation and training, PPE donning and doffing procedures, the code or rapid response team, patient and staff food and nutrition, infection control protocols, pharmacy services, access to radiology, rounding procedures, staff support, and the morgue.

One other issue that shouldn’t be overlooked is health equity in the field hospital. “Providing safe and equitable care should be the focus. Thinking who goes to the field hospital should be done within a health equity framework,” Dr. Bell said.4 She also wonders if field hospital planners are sharing their experience with colleagues across the country and developing more collaborative relationships with other hospitals in their communities.

“Field hospitals can be different things,” Dr. Bell said. “The important take-home is it doesn’t have to be in a tent or a parking garage, which can be suboptimal.” In many cases, it may be better to focus on finding unused space within the hospital – whether a lobby, staff lounge, or unoccupied unit – closer to personnel, supplies, pharmacy, and the like. “I think the pandemic showed us how unprepared we were as a health care system, and how much more we need to do in preparation for future crises.”

Limits to the temporary hospital

In New York City, which had the country’s worst COVID-19 outbreak during the first surge in the spring of 2020, a 1,000-bed field hospital was opened at the Jacob Javits Center in March 2020 and closed that June. “I was in the field hospital early, in March and April, when our hospitals were temporarily overrun,” said hospitalist Mona Krouss, MD, FACP, CPPS, NYC Health + Hospitals’ director of patient safety. “My role was to figure out how to get patients on our medical floors into these field hospitals, with responsibility for helping to revise admission criteria,” she said.

“No one knew how horrible it would become. This was so unanticipated, so difficult to operationalize. What they were able to create was amazing, but there were just too many barriers to have it work smoothly,” Dr. Krouss said.

Dr. Mona Krouss


“The military stepped in, and they helped us so much. We wouldn’t have been able to survive without their help.” But there is only so much a field hospital can do to provide acute medical care. Later, military medical teams shifted to roles in temporary units inside the permanent hospitals. “They came to the hospital wanting to be deployed,” she said.

“We could only send patients [to the field hospital] who were fairly stable, and choosing the right ones was difficult.” Dr. Krouss said. In the end, not a lot of COVID-19 patients from NYC Health + Hospitals ended up going to the Javits Center, in part because the paperwork and logistics of getting someone in was a barrier, Dr. Krouss said. A process was established for referring doctors to call a phone number and speak with a New York City Department of Health employee to go through the criteria for admission to the field hospital.

“That could take up to 30 minutes before getting approval. Then you had to go through the same process all over again for sign-out to another physician, and then register the patient with a special bar code. Then you had to arrange ambulance transfer. Doctors didn’t want to go through all of that – everybody was too busy,” she explained. Hospitalists have since worked on streamlining the criteria. “Now we have a good process for the future. We made it more seamless,” she noted.

Susan Lee, DO, MBA, hospitalist and chief medical officer for Renown Regional Medical Center in Reno, Nev., helped to plan an alternate care site in anticipation of up to a thousand COVID patients in her community – far beyond the scope of the existing hospitals. Hospitalists were involved the entire time in planning, design of the unit, design of staffing models, care protocols, and the like, working through an evidence-based medical committee and a COVID-19 provider task force for the Renown Health System.

Courtesy of Renown Regional Medical Center
Renown COVID-19 field hospital under construction in Reno, Nev.


“Because of a history of fires and earthquakes in this region, we had an emergency planning infrastructure in place. We put the field hospital on the first and second floors of a parking garage, with built-in negative pressure capacity. We also built space for staff break rooms and desk space. It took 10 days to build the hospital, thanks to some very talented people in management and facility design,” Dr. Lee said.

Then, the hospital was locked up and sat empty for 7 months, until the surge in December 2020, when Reno was hit by a bigger wave – this time exceeding the hospitals’ capacity. Through mid-January of 2021, clinicians cared for approximately 240 COVID-19 patients, up to 47 at a time, in the field hospital. A third wave in the autumn of 2021 plateaued at a level lower than the previous fall, so the field hospital is not currently needed.

Dr. Susan Lee

Replicating hospital work flows

“We ensured that everybody who needed to be within the walls of the permanent hospitals was able to stay there,” said Dr. Lee’s colleague, hospitalist Adnan (Eddy) Akbar, MD. “The postacute system we ordinarily rely on was no longer accepting patients. Other hospitals in the area were able to manage within their capacity because Renown’s field hospital could admit excess patients. We tried to replicate in the field hospital, as much as possible, the work flows and systems of our main hospital.”

When the field hospital finally opened, Dr. Akbar said, “we had a good feeling. We were ready. If something more catastrophic had come down, we were ready to care for more patients. In the field hospital you have to keep monitoring your work flow – almost on a daily basis. But we felt privileged to be working for a system where you knew you can go and care for everyone who needed care.”

One upside of the field hospital experience for participating clinicians, Dr. Lee added, is the opportunity to practice creatively. “The downside is it’s extremely expensive, and has consequences for the mental health of staff. Like so many of these things, it wore on people over time – such as all the time spent donning and doffing protective equipment. And recently the patients have become a lot less gracious.”

Amy Baughman, MD, a hospitalist at Massachusetts General Hospital in Boston, was co-medical director of the postacute care section of a 1,000-bed field hospital, Boston Hope Medical Center, opened in April 2020 at the Boston Convention and Exhibition Center. The other half of the facility was dedicated to undomiciled COVID-19 patients who had no place else to go. Peak census was around 100 patients, housed on four units, each with a clinical team led by a physician.

Partners HealthCare
Boston Hope Medical Center, a 1,000-bed field hospital for patients with COVID-19, is seen from above.


Dr. Baughman’s field hospital experience has taught her the importance of “staying within your domain of expertise. Physicians are attracted to difficult problems and want to do everything themselves. Next time I won’t be the one installing hand sanitizer dispensers.” A big part of running a field hospital is logistics, she said, and physicians are trained clinicians, not necessarily logistics engineers.

“So it’s important to partner with logistics experts. A huge part of our success in building a facility in 9 days of almost continuous construction was the involvement of the National Guard,” she said. An incident command system was led by an experienced military general incident commander, with two clinical codirectors. The army also sent in full teams of health professionals.

Dr. Amy Baughman


The facility admitted a lot fewer patients than the worst-case projections before it closed in June 2020. “But at the end of the day, we provided a lot of excellent care,” Dr. Baughman said. “This was about preparing for a disaster. It was all hands on deck, and the hands were health professionals. We spent a lot of money for the patients we took care of, but we had no choice, based on what we believed could happen. At that time, so many nursing facilities and homeless shelters were closed to us. It was impossible to predict what utilization would be.”

Subsequent experience has taught that a lot of even seriously ill COVID-19 patients can be managed safely at home, for example, using accelerated home oxygen monitoring with telelinked pulse oximeters. But in the beginning, Dr. Baughman said, “it was a new situation for us. We had seen what happened in Europe and China. It’s a great thing to be overprepared.”
 

References

1. Horowitz J. Italy’s health care system groans under coronavirus – a warning to the world. New York Times. 2020 Mar 12.

2. Bell SA et al. T-Minus 10 days: The role of an academic medical institution in field hospital planning. Prehosp Disaster Med. 2021 Feb 18:1-6. doi: 10.1017/S1049023X21000224.

3. Singh K et al. Evaluating a widely implemented proprietary deterioration index model among hospitalized patients with COVID-19. Ann Am Thorac Soc. 2021 Jul;18(7):1129-37. doi: 10.1513/AnnalsATS.202006-698OC.

4. Bell SA et al. Alternate care sites during COVID-19 pandemic: Policy implications for pandemic surge planning. Disaster Med Public Health Prep. 2021 Jul 23;1-3. doi: 10.1017/dmp.2021.241.

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‘It’s a great thing to be overprepared’

‘It’s a great thing to be overprepared’

At the height of the COVID-19 pandemic’s terrifying first wave in the spring of 2020, dozens of hospitals in high-incidence areas either planned or opened temporary, emergency field hospitals to cover anticipated demand for beds beyond the capacity of local permanent hospitals.

Chastened by images of overwhelmed health care systems in Northern Italy and other hard-hit areas,1 the planners used available modeling tools and estimates for projecting maximum potential need in worst-case scenarios. Some of these temporary hospitals never opened. Others opened in convention centers, parking garages, or parking lot tents, and ended up being used to a lesser degree than the worst-case scenarios.

But those who participated in the planning – including, in many cases, hospitalists – believe they created alternate care site manuals that could be quickly revived in the event of future COVID surges or other, similar crises. Better to plan for too much, they say, than not plan for enough.

Field hospitals or alternate care sites are defined in a recent journal article in Prehospital Disaster Medicine as “locations that can be converted to provide either inpatient and/or outpatient health services when existing facilities are compromised by a hazard impact or the volume of patients exceeds available capacity and/or capabilities.”2

University of Michigan Institute for Healthcare Policy and Innovation
Dr. Sue Anne Bell

The lead author of that report, Sue Anne Bell, PhD, FNP-BC, a disaster expert and assistant professor of nursing at the University of Michigan (UM), was one of five members of the leadership team for planning UM’s field hospital. They used an organizational unit structure based on the U.S. military’s staffing structure, with their work organized around six units of planning: personnel and labor, security, clinical operations, logistics and supply, planning and training, and communications. This team planned a 519-bed step-down care facility, the Michigan Medicine Field Hospital, for a 73,000-foot indoor track and performance facility at the university, three miles from UM’s main hospital. The aim was to provide safe care in a resource-limited environment.

“We were prepared, but the need never materialized as the peak of COVID cases started to subside,” Dr. Bell said. The team was ready to open within days using a “T-Minus” framework of days remaining on an official countdown clock. But when the need and deadlines kept getting pushed back, that gave them more time to develop clearer procedures.

Two Michigan Medicine hospitalists, Christopher Smith, MD, and David Paje, MD, MPH, both professors at UM’s medical school, were intimately involved in the process. “I was the medical director for the respiratory care unit that was opened for COVID patients, so I was pulled in to assist in the field hospital planning,” said Dr. Smith.

Dr. Christopher Smith


Dr. Paje was director of the short-stay unit and had been a medical officer in the U.S. Army, with training in how to set up military field hospitals. He credits that background as helpful for UM’s COVID field hospital planning, along with his experience in hospital medicine operations.

“We expected that these patients would need the expertise of hospitalists, who had quickly become familiar with the peculiarities of the new disease. That played a role in the decisions we made. Hospitalists were at the front lines of COVID care and had unique clinical insights about managing those with severe disease,” Dr. Paje added.

“When we started, the projections were dire. You don’t want to believe something like that is going to happen. When COVID started to cool off, it was more of a relief to us than anything else,” Dr. Smith said. “Still, it was a very worthwhile exercise. At the end of the day, we put together a comprehensive guide, which is ready for the next crisis.”
 

 

 

Baltimore builds a convention center hospital

A COVID-19 field hospital was planned and executed at an exhibit hall in the Baltimore Convention Center, starting in March 2020 under the leadership of Johns Hopkins Bayview hospitalist Eric Howell, MD, MHM, who eventually handed over responsibilities as chief medical officer when he assumed the position of CEO for the Society of Hospital Medicine in July of that year.

Courtesy Dr. Eric Howell
Dr. Eric Howell was chief medical officer for the Joint Commission-accredited Baltimore Civic Center Field Hospital for COVID-19 patients, opened in March 2020.

Hopkins collaborated with the University of Maryland health system and state leaders, including the Secretary of Health, to open a 252-bed temporary facility, which at its peak carried a census of 48 patients, with no on-site mortality or cardiac arrests, before it was closed in June 2021 – ready to reopen if necessary. It also served as Baltimore’s major site for polymerase chain reaction COVID-19 testing, vaccinations, and monoclonal antibody infusions, along with medical research.

“My belief at the time we started was that my entire 20-year career as a hospitalist had prepared me for the challenge of opening a COVID field hospital,” Dr. Howell said. “I had learned how to build clinical programs. The difference was that instead of months and years to build a program, we only had a few weeks.”

His first request was to bring on an associate medical director for the field hospital, Melinda E. Kantsiper, MD, a hospitalist and director of clinical operations in the Division of Hospital Medicine at Johns Hopkins Bayview. She became the field hospital’s CMO when Dr. Howell moved to SHM. “As hospitalists, we are trained to care for the patient in front of us while at the same time creating systems that can adjust to rapidly changing circumstances,” Dr. Kantsiper said. “We did what was asked and set up a field hospital that cared for a total of 1,500 COVID patients.”

Courtesy Johns Hopkins Medicine
Dr. Melinda E. Kantsiper


Hospitalists have the tools that are needed for this work, and shouldn’t be reluctant to contribute to field hospital planning, she said. “This was a real eye-opener for me. Eric explained to me that hospitalists really practice acute care medicine, which doesn’t have to be within the four walls of a hospital.”

The Baltimore field hospital has been a fantastic experience, Dr. Kantsiper added. “But it’s not a building designed for health care delivery.” For the right group of providers, the experience of working in a temporary facility such as this can be positive and exhilarating. “But we need to make sure we take care of our staff. It takes a toll. How we keep them safe – physically and emotionally – has to be top of mind,” she said.

The leaders at Hopkins Medicine and their collaborators truly engaged with the field hospital’s mission, Dr. Howell added.

Dr. Eric E. Howell

“They gave us a lot of autonomy and helped us break down barriers. They gave us the political capital to say proper PPE was absolutely essential. As hard and devastating as the pandemic has been, one take-away is that we showed that we can be more flexible and elastic in response to actual needs than we used to think.”

 

 

Range of challenges

Among the questions that need to be answered by a field hospital’s planners, the first is ‘where to put it?’ The answer is, hopefully, someplace not too far away, large enough, with ready access to supplies and intake. The next question is ‘who is the patient?’ Clinicians must determine who goes to the field hospital versus who stays at the standing hospital. How sick should these patients be? And when do they need to go back to the permanent hospital? Can staff be trained to recognize when patients in the field hospital are starting to decompensate? The EPIC Deterioration Index3 is a proprietary prediction model that was used by more than a hundred hospitals during the pandemic.

The hospitalist team may develop specific inclusion and exclusion criteria – for example, don’t admit patients who are receiving oxygen therapy above a certain threshold or who are hemodynamically unstable. These criteria should reflect the capacity of the field hospital and the needs of the permanent hospital. At Michigan, as at other field hospital sites, the goal was to offer a step-down or postacute setting for patients with COVID-19 who were too sick to return home but didn’t need acute or ICU-level care, thereby freeing up beds at the permanent hospital for patients who were sicker.

Other questions: What is the process for admissions and discharges? How will patients be transported? What kind of staffing is needed, and what levels of care will be provided? What about rehabilitation services, or palliative care? What about patients with substance abuse or psychiatric comorbidities?

“Are we going to do paper charting? How will that work out for long-term documentation and billing?” Dr. Bell said. A clear reporting structure and communication pathways are essential. Among the other operational processes to address, outlined in Dr. Bell’s article, are orientation and training, PPE donning and doffing procedures, the code or rapid response team, patient and staff food and nutrition, infection control protocols, pharmacy services, access to radiology, rounding procedures, staff support, and the morgue.

One other issue that shouldn’t be overlooked is health equity in the field hospital. “Providing safe and equitable care should be the focus. Thinking who goes to the field hospital should be done within a health equity framework,” Dr. Bell said.4 She also wonders if field hospital planners are sharing their experience with colleagues across the country and developing more collaborative relationships with other hospitals in their communities.

“Field hospitals can be different things,” Dr. Bell said. “The important take-home is it doesn’t have to be in a tent or a parking garage, which can be suboptimal.” In many cases, it may be better to focus on finding unused space within the hospital – whether a lobby, staff lounge, or unoccupied unit – closer to personnel, supplies, pharmacy, and the like. “I think the pandemic showed us how unprepared we were as a health care system, and how much more we need to do in preparation for future crises.”

Limits to the temporary hospital

In New York City, which had the country’s worst COVID-19 outbreak during the first surge in the spring of 2020, a 1,000-bed field hospital was opened at the Jacob Javits Center in March 2020 and closed that June. “I was in the field hospital early, in March and April, when our hospitals were temporarily overrun,” said hospitalist Mona Krouss, MD, FACP, CPPS, NYC Health + Hospitals’ director of patient safety. “My role was to figure out how to get patients on our medical floors into these field hospitals, with responsibility for helping to revise admission criteria,” she said.

“No one knew how horrible it would become. This was so unanticipated, so difficult to operationalize. What they were able to create was amazing, but there were just too many barriers to have it work smoothly,” Dr. Krouss said.

Dr. Mona Krouss


“The military stepped in, and they helped us so much. We wouldn’t have been able to survive without their help.” But there is only so much a field hospital can do to provide acute medical care. Later, military medical teams shifted to roles in temporary units inside the permanent hospitals. “They came to the hospital wanting to be deployed,” she said.

“We could only send patients [to the field hospital] who were fairly stable, and choosing the right ones was difficult.” Dr. Krouss said. In the end, not a lot of COVID-19 patients from NYC Health + Hospitals ended up going to the Javits Center, in part because the paperwork and logistics of getting someone in was a barrier, Dr. Krouss said. A process was established for referring doctors to call a phone number and speak with a New York City Department of Health employee to go through the criteria for admission to the field hospital.

“That could take up to 30 minutes before getting approval. Then you had to go through the same process all over again for sign-out to another physician, and then register the patient with a special bar code. Then you had to arrange ambulance transfer. Doctors didn’t want to go through all of that – everybody was too busy,” she explained. Hospitalists have since worked on streamlining the criteria. “Now we have a good process for the future. We made it more seamless,” she noted.

Susan Lee, DO, MBA, hospitalist and chief medical officer for Renown Regional Medical Center in Reno, Nev., helped to plan an alternate care site in anticipation of up to a thousand COVID patients in her community – far beyond the scope of the existing hospitals. Hospitalists were involved the entire time in planning, design of the unit, design of staffing models, care protocols, and the like, working through an evidence-based medical committee and a COVID-19 provider task force for the Renown Health System.

Courtesy of Renown Regional Medical Center
Renown COVID-19 field hospital under construction in Reno, Nev.


“Because of a history of fires and earthquakes in this region, we had an emergency planning infrastructure in place. We put the field hospital on the first and second floors of a parking garage, with built-in negative pressure capacity. We also built space for staff break rooms and desk space. It took 10 days to build the hospital, thanks to some very talented people in management and facility design,” Dr. Lee said.

Then, the hospital was locked up and sat empty for 7 months, until the surge in December 2020, when Reno was hit by a bigger wave – this time exceeding the hospitals’ capacity. Through mid-January of 2021, clinicians cared for approximately 240 COVID-19 patients, up to 47 at a time, in the field hospital. A third wave in the autumn of 2021 plateaued at a level lower than the previous fall, so the field hospital is not currently needed.

Dr. Susan Lee

Replicating hospital work flows

“We ensured that everybody who needed to be within the walls of the permanent hospitals was able to stay there,” said Dr. Lee’s colleague, hospitalist Adnan (Eddy) Akbar, MD. “The postacute system we ordinarily rely on was no longer accepting patients. Other hospitals in the area were able to manage within their capacity because Renown’s field hospital could admit excess patients. We tried to replicate in the field hospital, as much as possible, the work flows and systems of our main hospital.”

When the field hospital finally opened, Dr. Akbar said, “we had a good feeling. We were ready. If something more catastrophic had come down, we were ready to care for more patients. In the field hospital you have to keep monitoring your work flow – almost on a daily basis. But we felt privileged to be working for a system where you knew you can go and care for everyone who needed care.”

One upside of the field hospital experience for participating clinicians, Dr. Lee added, is the opportunity to practice creatively. “The downside is it’s extremely expensive, and has consequences for the mental health of staff. Like so many of these things, it wore on people over time – such as all the time spent donning and doffing protective equipment. And recently the patients have become a lot less gracious.”

Amy Baughman, MD, a hospitalist at Massachusetts General Hospital in Boston, was co-medical director of the postacute care section of a 1,000-bed field hospital, Boston Hope Medical Center, opened in April 2020 at the Boston Convention and Exhibition Center. The other half of the facility was dedicated to undomiciled COVID-19 patients who had no place else to go. Peak census was around 100 patients, housed on four units, each with a clinical team led by a physician.

Partners HealthCare
Boston Hope Medical Center, a 1,000-bed field hospital for patients with COVID-19, is seen from above.


Dr. Baughman’s field hospital experience has taught her the importance of “staying within your domain of expertise. Physicians are attracted to difficult problems and want to do everything themselves. Next time I won’t be the one installing hand sanitizer dispensers.” A big part of running a field hospital is logistics, she said, and physicians are trained clinicians, not necessarily logistics engineers.

“So it’s important to partner with logistics experts. A huge part of our success in building a facility in 9 days of almost continuous construction was the involvement of the National Guard,” she said. An incident command system was led by an experienced military general incident commander, with two clinical codirectors. The army also sent in full teams of health professionals.

Dr. Amy Baughman


The facility admitted a lot fewer patients than the worst-case projections before it closed in June 2020. “But at the end of the day, we provided a lot of excellent care,” Dr. Baughman said. “This was about preparing for a disaster. It was all hands on deck, and the hands were health professionals. We spent a lot of money for the patients we took care of, but we had no choice, based on what we believed could happen. At that time, so many nursing facilities and homeless shelters were closed to us. It was impossible to predict what utilization would be.”

Subsequent experience has taught that a lot of even seriously ill COVID-19 patients can be managed safely at home, for example, using accelerated home oxygen monitoring with telelinked pulse oximeters. But in the beginning, Dr. Baughman said, “it was a new situation for us. We had seen what happened in Europe and China. It’s a great thing to be overprepared.”
 

References

1. Horowitz J. Italy’s health care system groans under coronavirus – a warning to the world. New York Times. 2020 Mar 12.

2. Bell SA et al. T-Minus 10 days: The role of an academic medical institution in field hospital planning. Prehosp Disaster Med. 2021 Feb 18:1-6. doi: 10.1017/S1049023X21000224.

3. Singh K et al. Evaluating a widely implemented proprietary deterioration index model among hospitalized patients with COVID-19. Ann Am Thorac Soc. 2021 Jul;18(7):1129-37. doi: 10.1513/AnnalsATS.202006-698OC.

4. Bell SA et al. Alternate care sites during COVID-19 pandemic: Policy implications for pandemic surge planning. Disaster Med Public Health Prep. 2021 Jul 23;1-3. doi: 10.1017/dmp.2021.241.

At the height of the COVID-19 pandemic’s terrifying first wave in the spring of 2020, dozens of hospitals in high-incidence areas either planned or opened temporary, emergency field hospitals to cover anticipated demand for beds beyond the capacity of local permanent hospitals.

Chastened by images of overwhelmed health care systems in Northern Italy and other hard-hit areas,1 the planners used available modeling tools and estimates for projecting maximum potential need in worst-case scenarios. Some of these temporary hospitals never opened. Others opened in convention centers, parking garages, or parking lot tents, and ended up being used to a lesser degree than the worst-case scenarios.

But those who participated in the planning – including, in many cases, hospitalists – believe they created alternate care site manuals that could be quickly revived in the event of future COVID surges or other, similar crises. Better to plan for too much, they say, than not plan for enough.

Field hospitals or alternate care sites are defined in a recent journal article in Prehospital Disaster Medicine as “locations that can be converted to provide either inpatient and/or outpatient health services when existing facilities are compromised by a hazard impact or the volume of patients exceeds available capacity and/or capabilities.”2

University of Michigan Institute for Healthcare Policy and Innovation
Dr. Sue Anne Bell

The lead author of that report, Sue Anne Bell, PhD, FNP-BC, a disaster expert and assistant professor of nursing at the University of Michigan (UM), was one of five members of the leadership team for planning UM’s field hospital. They used an organizational unit structure based on the U.S. military’s staffing structure, with their work organized around six units of planning: personnel and labor, security, clinical operations, logistics and supply, planning and training, and communications. This team planned a 519-bed step-down care facility, the Michigan Medicine Field Hospital, for a 73,000-foot indoor track and performance facility at the university, three miles from UM’s main hospital. The aim was to provide safe care in a resource-limited environment.

“We were prepared, but the need never materialized as the peak of COVID cases started to subside,” Dr. Bell said. The team was ready to open within days using a “T-Minus” framework of days remaining on an official countdown clock. But when the need and deadlines kept getting pushed back, that gave them more time to develop clearer procedures.

Two Michigan Medicine hospitalists, Christopher Smith, MD, and David Paje, MD, MPH, both professors at UM’s medical school, were intimately involved in the process. “I was the medical director for the respiratory care unit that was opened for COVID patients, so I was pulled in to assist in the field hospital planning,” said Dr. Smith.

Dr. Christopher Smith


Dr. Paje was director of the short-stay unit and had been a medical officer in the U.S. Army, with training in how to set up military field hospitals. He credits that background as helpful for UM’s COVID field hospital planning, along with his experience in hospital medicine operations.

“We expected that these patients would need the expertise of hospitalists, who had quickly become familiar with the peculiarities of the new disease. That played a role in the decisions we made. Hospitalists were at the front lines of COVID care and had unique clinical insights about managing those with severe disease,” Dr. Paje added.

“When we started, the projections were dire. You don’t want to believe something like that is going to happen. When COVID started to cool off, it was more of a relief to us than anything else,” Dr. Smith said. “Still, it was a very worthwhile exercise. At the end of the day, we put together a comprehensive guide, which is ready for the next crisis.”
 

 

 

Baltimore builds a convention center hospital

A COVID-19 field hospital was planned and executed at an exhibit hall in the Baltimore Convention Center, starting in March 2020 under the leadership of Johns Hopkins Bayview hospitalist Eric Howell, MD, MHM, who eventually handed over responsibilities as chief medical officer when he assumed the position of CEO for the Society of Hospital Medicine in July of that year.

Courtesy Dr. Eric Howell
Dr. Eric Howell was chief medical officer for the Joint Commission-accredited Baltimore Civic Center Field Hospital for COVID-19 patients, opened in March 2020.

Hopkins collaborated with the University of Maryland health system and state leaders, including the Secretary of Health, to open a 252-bed temporary facility, which at its peak carried a census of 48 patients, with no on-site mortality or cardiac arrests, before it was closed in June 2021 – ready to reopen if necessary. It also served as Baltimore’s major site for polymerase chain reaction COVID-19 testing, vaccinations, and monoclonal antibody infusions, along with medical research.

“My belief at the time we started was that my entire 20-year career as a hospitalist had prepared me for the challenge of opening a COVID field hospital,” Dr. Howell said. “I had learned how to build clinical programs. The difference was that instead of months and years to build a program, we only had a few weeks.”

His first request was to bring on an associate medical director for the field hospital, Melinda E. Kantsiper, MD, a hospitalist and director of clinical operations in the Division of Hospital Medicine at Johns Hopkins Bayview. She became the field hospital’s CMO when Dr. Howell moved to SHM. “As hospitalists, we are trained to care for the patient in front of us while at the same time creating systems that can adjust to rapidly changing circumstances,” Dr. Kantsiper said. “We did what was asked and set up a field hospital that cared for a total of 1,500 COVID patients.”

Courtesy Johns Hopkins Medicine
Dr. Melinda E. Kantsiper


Hospitalists have the tools that are needed for this work, and shouldn’t be reluctant to contribute to field hospital planning, she said. “This was a real eye-opener for me. Eric explained to me that hospitalists really practice acute care medicine, which doesn’t have to be within the four walls of a hospital.”

The Baltimore field hospital has been a fantastic experience, Dr. Kantsiper added. “But it’s not a building designed for health care delivery.” For the right group of providers, the experience of working in a temporary facility such as this can be positive and exhilarating. “But we need to make sure we take care of our staff. It takes a toll. How we keep them safe – physically and emotionally – has to be top of mind,” she said.

The leaders at Hopkins Medicine and their collaborators truly engaged with the field hospital’s mission, Dr. Howell added.

Dr. Eric E. Howell

“They gave us a lot of autonomy and helped us break down barriers. They gave us the political capital to say proper PPE was absolutely essential. As hard and devastating as the pandemic has been, one take-away is that we showed that we can be more flexible and elastic in response to actual needs than we used to think.”

 

 

Range of challenges

Among the questions that need to be answered by a field hospital’s planners, the first is ‘where to put it?’ The answer is, hopefully, someplace not too far away, large enough, with ready access to supplies and intake. The next question is ‘who is the patient?’ Clinicians must determine who goes to the field hospital versus who stays at the standing hospital. How sick should these patients be? And when do they need to go back to the permanent hospital? Can staff be trained to recognize when patients in the field hospital are starting to decompensate? The EPIC Deterioration Index3 is a proprietary prediction model that was used by more than a hundred hospitals during the pandemic.

The hospitalist team may develop specific inclusion and exclusion criteria – for example, don’t admit patients who are receiving oxygen therapy above a certain threshold or who are hemodynamically unstable. These criteria should reflect the capacity of the field hospital and the needs of the permanent hospital. At Michigan, as at other field hospital sites, the goal was to offer a step-down or postacute setting for patients with COVID-19 who were too sick to return home but didn’t need acute or ICU-level care, thereby freeing up beds at the permanent hospital for patients who were sicker.

Other questions: What is the process for admissions and discharges? How will patients be transported? What kind of staffing is needed, and what levels of care will be provided? What about rehabilitation services, or palliative care? What about patients with substance abuse or psychiatric comorbidities?

“Are we going to do paper charting? How will that work out for long-term documentation and billing?” Dr. Bell said. A clear reporting structure and communication pathways are essential. Among the other operational processes to address, outlined in Dr. Bell’s article, are orientation and training, PPE donning and doffing procedures, the code or rapid response team, patient and staff food and nutrition, infection control protocols, pharmacy services, access to radiology, rounding procedures, staff support, and the morgue.

One other issue that shouldn’t be overlooked is health equity in the field hospital. “Providing safe and equitable care should be the focus. Thinking who goes to the field hospital should be done within a health equity framework,” Dr. Bell said.4 She also wonders if field hospital planners are sharing their experience with colleagues across the country and developing more collaborative relationships with other hospitals in their communities.

“Field hospitals can be different things,” Dr. Bell said. “The important take-home is it doesn’t have to be in a tent or a parking garage, which can be suboptimal.” In many cases, it may be better to focus on finding unused space within the hospital – whether a lobby, staff lounge, or unoccupied unit – closer to personnel, supplies, pharmacy, and the like. “I think the pandemic showed us how unprepared we were as a health care system, and how much more we need to do in preparation for future crises.”

Limits to the temporary hospital

In New York City, which had the country’s worst COVID-19 outbreak during the first surge in the spring of 2020, a 1,000-bed field hospital was opened at the Jacob Javits Center in March 2020 and closed that June. “I was in the field hospital early, in March and April, when our hospitals were temporarily overrun,” said hospitalist Mona Krouss, MD, FACP, CPPS, NYC Health + Hospitals’ director of patient safety. “My role was to figure out how to get patients on our medical floors into these field hospitals, with responsibility for helping to revise admission criteria,” she said.

“No one knew how horrible it would become. This was so unanticipated, so difficult to operationalize. What they were able to create was amazing, but there were just too many barriers to have it work smoothly,” Dr. Krouss said.

Dr. Mona Krouss


“The military stepped in, and they helped us so much. We wouldn’t have been able to survive without their help.” But there is only so much a field hospital can do to provide acute medical care. Later, military medical teams shifted to roles in temporary units inside the permanent hospitals. “They came to the hospital wanting to be deployed,” she said.

“We could only send patients [to the field hospital] who were fairly stable, and choosing the right ones was difficult.” Dr. Krouss said. In the end, not a lot of COVID-19 patients from NYC Health + Hospitals ended up going to the Javits Center, in part because the paperwork and logistics of getting someone in was a barrier, Dr. Krouss said. A process was established for referring doctors to call a phone number and speak with a New York City Department of Health employee to go through the criteria for admission to the field hospital.

“That could take up to 30 minutes before getting approval. Then you had to go through the same process all over again for sign-out to another physician, and then register the patient with a special bar code. Then you had to arrange ambulance transfer. Doctors didn’t want to go through all of that – everybody was too busy,” she explained. Hospitalists have since worked on streamlining the criteria. “Now we have a good process for the future. We made it more seamless,” she noted.

Susan Lee, DO, MBA, hospitalist and chief medical officer for Renown Regional Medical Center in Reno, Nev., helped to plan an alternate care site in anticipation of up to a thousand COVID patients in her community – far beyond the scope of the existing hospitals. Hospitalists were involved the entire time in planning, design of the unit, design of staffing models, care protocols, and the like, working through an evidence-based medical committee and a COVID-19 provider task force for the Renown Health System.

Courtesy of Renown Regional Medical Center
Renown COVID-19 field hospital under construction in Reno, Nev.


“Because of a history of fires and earthquakes in this region, we had an emergency planning infrastructure in place. We put the field hospital on the first and second floors of a parking garage, with built-in negative pressure capacity. We also built space for staff break rooms and desk space. It took 10 days to build the hospital, thanks to some very talented people in management and facility design,” Dr. Lee said.

Then, the hospital was locked up and sat empty for 7 months, until the surge in December 2020, when Reno was hit by a bigger wave – this time exceeding the hospitals’ capacity. Through mid-January of 2021, clinicians cared for approximately 240 COVID-19 patients, up to 47 at a time, in the field hospital. A third wave in the autumn of 2021 plateaued at a level lower than the previous fall, so the field hospital is not currently needed.

Dr. Susan Lee

Replicating hospital work flows

“We ensured that everybody who needed to be within the walls of the permanent hospitals was able to stay there,” said Dr. Lee’s colleague, hospitalist Adnan (Eddy) Akbar, MD. “The postacute system we ordinarily rely on was no longer accepting patients. Other hospitals in the area were able to manage within their capacity because Renown’s field hospital could admit excess patients. We tried to replicate in the field hospital, as much as possible, the work flows and systems of our main hospital.”

When the field hospital finally opened, Dr. Akbar said, “we had a good feeling. We were ready. If something more catastrophic had come down, we were ready to care for more patients. In the field hospital you have to keep monitoring your work flow – almost on a daily basis. But we felt privileged to be working for a system where you knew you can go and care for everyone who needed care.”

One upside of the field hospital experience for participating clinicians, Dr. Lee added, is the opportunity to practice creatively. “The downside is it’s extremely expensive, and has consequences for the mental health of staff. Like so many of these things, it wore on people over time – such as all the time spent donning and doffing protective equipment. And recently the patients have become a lot less gracious.”

Amy Baughman, MD, a hospitalist at Massachusetts General Hospital in Boston, was co-medical director of the postacute care section of a 1,000-bed field hospital, Boston Hope Medical Center, opened in April 2020 at the Boston Convention and Exhibition Center. The other half of the facility was dedicated to undomiciled COVID-19 patients who had no place else to go. Peak census was around 100 patients, housed on four units, each with a clinical team led by a physician.

Partners HealthCare
Boston Hope Medical Center, a 1,000-bed field hospital for patients with COVID-19, is seen from above.


Dr. Baughman’s field hospital experience has taught her the importance of “staying within your domain of expertise. Physicians are attracted to difficult problems and want to do everything themselves. Next time I won’t be the one installing hand sanitizer dispensers.” A big part of running a field hospital is logistics, she said, and physicians are trained clinicians, not necessarily logistics engineers.

“So it’s important to partner with logistics experts. A huge part of our success in building a facility in 9 days of almost continuous construction was the involvement of the National Guard,” she said. An incident command system was led by an experienced military general incident commander, with two clinical codirectors. The army also sent in full teams of health professionals.

Dr. Amy Baughman


The facility admitted a lot fewer patients than the worst-case projections before it closed in June 2020. “But at the end of the day, we provided a lot of excellent care,” Dr. Baughman said. “This was about preparing for a disaster. It was all hands on deck, and the hands were health professionals. We spent a lot of money for the patients we took care of, but we had no choice, based on what we believed could happen. At that time, so many nursing facilities and homeless shelters were closed to us. It was impossible to predict what utilization would be.”

Subsequent experience has taught that a lot of even seriously ill COVID-19 patients can be managed safely at home, for example, using accelerated home oxygen monitoring with telelinked pulse oximeters. But in the beginning, Dr. Baughman said, “it was a new situation for us. We had seen what happened in Europe and China. It’s a great thing to be overprepared.”
 

References

1. Horowitz J. Italy’s health care system groans under coronavirus – a warning to the world. New York Times. 2020 Mar 12.

2. Bell SA et al. T-Minus 10 days: The role of an academic medical institution in field hospital planning. Prehosp Disaster Med. 2021 Feb 18:1-6. doi: 10.1017/S1049023X21000224.

3. Singh K et al. Evaluating a widely implemented proprietary deterioration index model among hospitalized patients with COVID-19. Ann Am Thorac Soc. 2021 Jul;18(7):1129-37. doi: 10.1513/AnnalsATS.202006-698OC.

4. Bell SA et al. Alternate care sites during COVID-19 pandemic: Policy implications for pandemic surge planning. Disaster Med Public Health Prep. 2021 Jul 23;1-3. doi: 10.1017/dmp.2021.241.

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U.S. overdose deaths hit an all-time high

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Thu, 12/09/2021 - 13:41

The Centers for Disease Control and Prevention reported that an estimated 100,306 Americans died from drug overdoses during the period from April 2020 to April 2021, a 28.5% increase from the previous year.

Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.

The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.

The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.

“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.

“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.

Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”

Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”

Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support. 

Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.

In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.

“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
 

Fake pills, fentanyl a huge issue

Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.

“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.

Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.

The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.

“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.

Dr. Nora D. Volkow

National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.

Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”

Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.

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

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The Centers for Disease Control and Prevention reported that an estimated 100,306 Americans died from drug overdoses during the period from April 2020 to April 2021, a 28.5% increase from the previous year.

Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.

The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.

The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.

“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.

“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.

Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”

Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”

Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support. 

Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.

In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.

“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
 

Fake pills, fentanyl a huge issue

Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.

“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.

Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.

The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.

“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.

Dr. Nora D. Volkow

National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.

Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”

Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.

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

The Centers for Disease Control and Prevention reported that an estimated 100,306 Americans died from drug overdoses during the period from April 2020 to April 2021, a 28.5% increase from the previous year.

Deaths in some states rose even more precipitously. Vermont saw an almost 70% increase, and drug overdose deaths in West Virginia increased by 62%. Many states, including Alabama, California, Kansas, Kentucky, Louisiana, Tennessee, and Washington, had a 45%-50% rise in overdose deaths.

The data released by the CDC was provisional, as there is generally a lag between a reported overdose and confirmation of the death to the National Vital Statistics System. The agency uses statistical models that render the counts almost 100% accurate, the CDC says.

The vast majority (73,757) of overdose deaths involved opioids – with most of those (62,338) involving synthetic opioids such as fentanyl. Federal officials said that one American died every 5 minutes from an overdose, or 265 a day.

“We have to acknowledge what this is – it is a crisis,” Department of Health & Human Services Secretary Xavier Becerra told reporters on a call.

“As much as the numbers speak so vividly, they don’t tell the whole story. We see it in the faces of grieving families and all those overworked caregivers. You hear it every time you get that panicked 911 phone call, you read it in obituaries of sons and daughters who left us way too soon,” Mr. Becerra said.

Rahul Gupta, MD, director of the White House Office of National Drug Control Policy, said that “this is unacceptable, and it requires an unprecedented response.”

Dr. Gupta, who noted that he has a waiver to treat substance use disorder patients with buprenorphine, said he’s seen “first-hand the heartbreak of the overdose epidemic,” adding that, with 23 years in practice, “I’ve learned that an overdose is a cry for help and for far too many people that cry goes unanswered.”

Both Mr. Becerra and Dr. Gupta called on Congress to pass President Joe Biden’s fiscal 2022 budget request, noting that it calls for $41 billion – a $669 million increase from fiscal year 2021 – to go to agencies working on drug interdiction and substance use prevention, treatment, and recovery support. 

Dr. Gupta also announced that the administration was releasing a model law that could be used by state legislatures to help standardize policies on making the overdose antidote naloxone more accessible. Currently, such policies are a patchwork across the nation.

In addition, the federal government is newly supporting harm reduction, Mr. Becerra said. This means federal money can be used by clinics and outreach programs to buy fentanyl test strips, which they can then distribute to drug users.

“It’s important for Americans to have the ability to make sure that they can test for fentanyl in the substance,” Dr. Gupta said.
 

Fake pills, fentanyl a huge issue

Federal officials said that both fentanyl and methamphetamine are contributing to rising numbers of fatalities.

“Drug cartels in Mexico are mass-producing fentanyl and methamphetamine largely sourced from chemicals in China and they are distributing these substances throughout the United States,” Anne Milgram, administrator of the Drug Enforcement Administration, said on the call.

Ms. Milgram said the agency had seized 12,000 pounds of fentanyl in 2021, enough to provide every American with a lethal dose. Fentanyl is also mixed in with cocaine, heroin, methamphetamine, and marijuana – often in counterfeit pills, Ms. Milgram said.

The DEA and other law enforcement agencies have seized more than 14 million such pills in 2021. “These types of pills are easily accessible today on social media and e-commerce platforms, Ms. Milgram said.

“Drug dealers are now in our homes,” she said. “Wherever there is a smart phone or a computer, a dealer is one click away,” Ms. Milgram said.

Dr. Nora D. Volkow

National Institute on Drug Abuse Director Nora D. Volkow, MD, said that dealers will continue to push both fentanyl and methamphetamine because they are among the most addictive substances. They also are more profitable because they don’t require cultivation and harvesting, she said on the call.

Dr. Volkow also noted that naloxone is not as effective in reversing fentanyl overdoses because fentanyl is more potent than heroin and other opioids, and “it gets into the brain extremely rapidly.”

Ongoing research is aimed at developing a faster delivery mechanism and a longer-lasting formulation to counter overdoses, Dr. Volkow said.

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

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Timing of endoscopy for acute upper GI bleeding

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Thu, 11/18/2021 - 13:06

Background: Prior studies have failed to show a benefit to earlier endoscopic intervention in acute GI bleeding. However, those studies were performed in all-comers without attention to the varying risk within the patient population.

Dr. Cheryl Lee


Study design: Randomized controlled trial.

Setting: Single center in Hong Kong.

Synopsis: Patients at high risk for further bleeding or death by clinical score were randomized to endoscopy within 6 hours (“urgent endoscopy”), vs. the following day (“early endoscopy”), of GI consultation. Those who required immediate endoscopic intervention because of hemodynamic instability were excluded. All were prescribed proton-pump inhibitor drip, with the addition of vasoactive drugs and antibiotics if there was a suspected variceal bleed. There was no difference in 30-day mortality between the two groups – 8.9% with urgent endoscopy and 6.6% with early endoscopy (HR, 1.35; 95% CI, 0.72-2.54). There was no difference in length of hospital stay or the number of transfusions. Earlier endoscopy within 6 hours was associated with a higher number of actively bleeding lesions requiring intervention and a nonstatistical increase in recurrent bleeding within 30 days. It is believed that more time on proton-pump inhibitor infusion prior to endoscopy allows for stabilization of bleeds, thus requiring less intervention when endoscopy does occur.

Bottom line: Early endoscopy within 6 hours was not beneficial for those at high risk for rebleeding and death from upper GI bleed.

Citation: Lau JYW et al. Timing of endoscopy for acute upper gastrointestinal bleeding. N Engl J Med. 2020;382:1299-308. doi:10.1056/NEJMoa1912484.

Dr. Lee is a hospitalist at Northwestern Memorial Hospital and Lurie Children’s Hospital and assistant professor of medicine, Feinberg School of Medicine, all in Chicago.

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Background: Prior studies have failed to show a benefit to earlier endoscopic intervention in acute GI bleeding. However, those studies were performed in all-comers without attention to the varying risk within the patient population.

Dr. Cheryl Lee


Study design: Randomized controlled trial.

Setting: Single center in Hong Kong.

Synopsis: Patients at high risk for further bleeding or death by clinical score were randomized to endoscopy within 6 hours (“urgent endoscopy”), vs. the following day (“early endoscopy”), of GI consultation. Those who required immediate endoscopic intervention because of hemodynamic instability were excluded. All were prescribed proton-pump inhibitor drip, with the addition of vasoactive drugs and antibiotics if there was a suspected variceal bleed. There was no difference in 30-day mortality between the two groups – 8.9% with urgent endoscopy and 6.6% with early endoscopy (HR, 1.35; 95% CI, 0.72-2.54). There was no difference in length of hospital stay or the number of transfusions. Earlier endoscopy within 6 hours was associated with a higher number of actively bleeding lesions requiring intervention and a nonstatistical increase in recurrent bleeding within 30 days. It is believed that more time on proton-pump inhibitor infusion prior to endoscopy allows for stabilization of bleeds, thus requiring less intervention when endoscopy does occur.

Bottom line: Early endoscopy within 6 hours was not beneficial for those at high risk for rebleeding and death from upper GI bleed.

Citation: Lau JYW et al. Timing of endoscopy for acute upper gastrointestinal bleeding. N Engl J Med. 2020;382:1299-308. doi:10.1056/NEJMoa1912484.

Dr. Lee is a hospitalist at Northwestern Memorial Hospital and Lurie Children’s Hospital and assistant professor of medicine, Feinberg School of Medicine, all in Chicago.

Background: Prior studies have failed to show a benefit to earlier endoscopic intervention in acute GI bleeding. However, those studies were performed in all-comers without attention to the varying risk within the patient population.

Dr. Cheryl Lee


Study design: Randomized controlled trial.

Setting: Single center in Hong Kong.

Synopsis: Patients at high risk for further bleeding or death by clinical score were randomized to endoscopy within 6 hours (“urgent endoscopy”), vs. the following day (“early endoscopy”), of GI consultation. Those who required immediate endoscopic intervention because of hemodynamic instability were excluded. All were prescribed proton-pump inhibitor drip, with the addition of vasoactive drugs and antibiotics if there was a suspected variceal bleed. There was no difference in 30-day mortality between the two groups – 8.9% with urgent endoscopy and 6.6% with early endoscopy (HR, 1.35; 95% CI, 0.72-2.54). There was no difference in length of hospital stay or the number of transfusions. Earlier endoscopy within 6 hours was associated with a higher number of actively bleeding lesions requiring intervention and a nonstatistical increase in recurrent bleeding within 30 days. It is believed that more time on proton-pump inhibitor infusion prior to endoscopy allows for stabilization of bleeds, thus requiring less intervention when endoscopy does occur.

Bottom line: Early endoscopy within 6 hours was not beneficial for those at high risk for rebleeding and death from upper GI bleed.

Citation: Lau JYW et al. Timing of endoscopy for acute upper gastrointestinal bleeding. N Engl J Med. 2020;382:1299-308. doi:10.1056/NEJMoa1912484.

Dr. Lee is a hospitalist at Northwestern Memorial Hospital and Lurie Children’s Hospital and assistant professor of medicine, Feinberg School of Medicine, all in Chicago.

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Text-based COVID monitoring system could reduce deaths, relieve ED in winter surge

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Changed
Wed, 11/17/2021 - 14:48

Holiday travel season is right around the corner, but coronavirus cases have already started to climb. But a new automated texting system could relieve pressure on emergency departments and reduce mortality rates if there were an uptick in COVID-19 this winter.

COVID Watch, a text message–based remote monitoring program developed by the University of Pennsylvania Health System, was associated with a 68% reduction in the risk of death, compared with those who received usual care. This was the main finding of a paper published in the Annals of Internal Medicine.

The investigators also determined that patients who enrolled in the program were more likely to seek care in the ED and when they did, they came in on average 2 days sooner than those who received usual care.

“When our clinical team designed COVID Watch the goal was to facilitate hospital care for patients who require it, while supporting access to care for patients who can safely remain at home,” study author M. Kit Delgado, MD, MS, an assistant professor of emergency medicine and epidemiology at Penn Presbyterian Medical Center in Philadelphia, said in an interview.

Researchers had initially hoped COVID Watch would relieve pressure on EDs, Dr. Delgado said.
 

Significantly lower mortality seen among COVID Watch group

For the study, Dr. Delgado and colleagues enrolled 3,488 patients in COVID Watch and 4,377 in the usual care group to compare outcomes at 30 and 60 days.

“We didn’t include patients who were diagnosed with COVID in the ER or hospital, so this is a lower-risk cohort of patients who test positive in outpatient settings,” Dr. Delgado noted. “Outpatients who received usual care and COVID Watch both had relatively low mortality, but it was significantly lower in those who were in COVID Watch.”

The researchers found that 3 patients in the COVID Watch group died within 30 days of their enrollment, compared with 12 in the control group. At 60 days after enrollment, 5 people within COVID Watch died, compared with 16 not using the system. More than one-third of the deaths in the usual care group occurred outside the hospital, compared with zero deaths among those in COVID Watch.
 

More than half of program participants were Black or Latino

The messaging system also reduced mortality rates among “all major racial and ethnic subgroups,” the researchers said, with more than 50% of the patients enrolled in COVID Watch having been Black or Latino.

“This is important because Black and Hispanic communities have experienced higher exposure and infection rates, decreased access to care, and have had higher mortality rates,” Dr. Delgado said. “Therefore, the results imply that this type of program could play a role in decreasing disparities in COVID outcomes if scaled more broadly.”
 

Outside expert: COVID Watch bring new approach to digital health monitoring

The study not only highlights the efficacy and sustainment of the COVID Watch program, but it sheds light on the possibility of using text message monitoring systems on other chronic disease conditions, said Jamie Faro, PhD, who was not involved in the study.

“It brings a new approach to health monitoring using digital means, which may lessen the burden on health care providers and be more cost effective than usual care approaches,” said Dr. Faro, who is assistant professor at the department of population and quantitative health sciences at the University of Massachusetts, Worcester. “Text messaging, which is used by over 80% of Americans, can allow us to reach a large percentage of the population for remote health care monitoring.”

Researchers of the current study said the findings “reveal a model for outpatient health system management of patients with COVID-19 and possibly other conditions where the early detection of clinical declines is critical.” Dr. Faro said that COVID Watch can have a measurable impact on an outcome that is truly life or death. However, it would be critical to understand how to reach those who either “were not offered or refused to take part in the program.”

The authors of the paper and Dr. Faro had no disclosures.

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Holiday travel season is right around the corner, but coronavirus cases have already started to climb. But a new automated texting system could relieve pressure on emergency departments and reduce mortality rates if there were an uptick in COVID-19 this winter.

COVID Watch, a text message–based remote monitoring program developed by the University of Pennsylvania Health System, was associated with a 68% reduction in the risk of death, compared with those who received usual care. This was the main finding of a paper published in the Annals of Internal Medicine.

The investigators also determined that patients who enrolled in the program were more likely to seek care in the ED and when they did, they came in on average 2 days sooner than those who received usual care.

“When our clinical team designed COVID Watch the goal was to facilitate hospital care for patients who require it, while supporting access to care for patients who can safely remain at home,” study author M. Kit Delgado, MD, MS, an assistant professor of emergency medicine and epidemiology at Penn Presbyterian Medical Center in Philadelphia, said in an interview.

Researchers had initially hoped COVID Watch would relieve pressure on EDs, Dr. Delgado said.
 

Significantly lower mortality seen among COVID Watch group

For the study, Dr. Delgado and colleagues enrolled 3,488 patients in COVID Watch and 4,377 in the usual care group to compare outcomes at 30 and 60 days.

“We didn’t include patients who were diagnosed with COVID in the ER or hospital, so this is a lower-risk cohort of patients who test positive in outpatient settings,” Dr. Delgado noted. “Outpatients who received usual care and COVID Watch both had relatively low mortality, but it was significantly lower in those who were in COVID Watch.”

The researchers found that 3 patients in the COVID Watch group died within 30 days of their enrollment, compared with 12 in the control group. At 60 days after enrollment, 5 people within COVID Watch died, compared with 16 not using the system. More than one-third of the deaths in the usual care group occurred outside the hospital, compared with zero deaths among those in COVID Watch.
 

More than half of program participants were Black or Latino

The messaging system also reduced mortality rates among “all major racial and ethnic subgroups,” the researchers said, with more than 50% of the patients enrolled in COVID Watch having been Black or Latino.

“This is important because Black and Hispanic communities have experienced higher exposure and infection rates, decreased access to care, and have had higher mortality rates,” Dr. Delgado said. “Therefore, the results imply that this type of program could play a role in decreasing disparities in COVID outcomes if scaled more broadly.”
 

Outside expert: COVID Watch bring new approach to digital health monitoring

The study not only highlights the efficacy and sustainment of the COVID Watch program, but it sheds light on the possibility of using text message monitoring systems on other chronic disease conditions, said Jamie Faro, PhD, who was not involved in the study.

“It brings a new approach to health monitoring using digital means, which may lessen the burden on health care providers and be more cost effective than usual care approaches,” said Dr. Faro, who is assistant professor at the department of population and quantitative health sciences at the University of Massachusetts, Worcester. “Text messaging, which is used by over 80% of Americans, can allow us to reach a large percentage of the population for remote health care monitoring.”

Researchers of the current study said the findings “reveal a model for outpatient health system management of patients with COVID-19 and possibly other conditions where the early detection of clinical declines is critical.” Dr. Faro said that COVID Watch can have a measurable impact on an outcome that is truly life or death. However, it would be critical to understand how to reach those who either “were not offered or refused to take part in the program.”

The authors of the paper and Dr. Faro had no disclosures.

Holiday travel season is right around the corner, but coronavirus cases have already started to climb. But a new automated texting system could relieve pressure on emergency departments and reduce mortality rates if there were an uptick in COVID-19 this winter.

COVID Watch, a text message–based remote monitoring program developed by the University of Pennsylvania Health System, was associated with a 68% reduction in the risk of death, compared with those who received usual care. This was the main finding of a paper published in the Annals of Internal Medicine.

The investigators also determined that patients who enrolled in the program were more likely to seek care in the ED and when they did, they came in on average 2 days sooner than those who received usual care.

“When our clinical team designed COVID Watch the goal was to facilitate hospital care for patients who require it, while supporting access to care for patients who can safely remain at home,” study author M. Kit Delgado, MD, MS, an assistant professor of emergency medicine and epidemiology at Penn Presbyterian Medical Center in Philadelphia, said in an interview.

Researchers had initially hoped COVID Watch would relieve pressure on EDs, Dr. Delgado said.
 

Significantly lower mortality seen among COVID Watch group

For the study, Dr. Delgado and colleagues enrolled 3,488 patients in COVID Watch and 4,377 in the usual care group to compare outcomes at 30 and 60 days.

“We didn’t include patients who were diagnosed with COVID in the ER or hospital, so this is a lower-risk cohort of patients who test positive in outpatient settings,” Dr. Delgado noted. “Outpatients who received usual care and COVID Watch both had relatively low mortality, but it was significantly lower in those who were in COVID Watch.”

The researchers found that 3 patients in the COVID Watch group died within 30 days of their enrollment, compared with 12 in the control group. At 60 days after enrollment, 5 people within COVID Watch died, compared with 16 not using the system. More than one-third of the deaths in the usual care group occurred outside the hospital, compared with zero deaths among those in COVID Watch.
 

More than half of program participants were Black or Latino

The messaging system also reduced mortality rates among “all major racial and ethnic subgroups,” the researchers said, with more than 50% of the patients enrolled in COVID Watch having been Black or Latino.

“This is important because Black and Hispanic communities have experienced higher exposure and infection rates, decreased access to care, and have had higher mortality rates,” Dr. Delgado said. “Therefore, the results imply that this type of program could play a role in decreasing disparities in COVID outcomes if scaled more broadly.”
 

Outside expert: COVID Watch bring new approach to digital health monitoring

The study not only highlights the efficacy and sustainment of the COVID Watch program, but it sheds light on the possibility of using text message monitoring systems on other chronic disease conditions, said Jamie Faro, PhD, who was not involved in the study.

“It brings a new approach to health monitoring using digital means, which may lessen the burden on health care providers and be more cost effective than usual care approaches,” said Dr. Faro, who is assistant professor at the department of population and quantitative health sciences at the University of Massachusetts, Worcester. “Text messaging, which is used by over 80% of Americans, can allow us to reach a large percentage of the population for remote health care monitoring.”

Researchers of the current study said the findings “reveal a model for outpatient health system management of patients with COVID-19 and possibly other conditions where the early detection of clinical declines is critical.” Dr. Faro said that COVID Watch can have a measurable impact on an outcome that is truly life or death. However, it would be critical to understand how to reach those who either “were not offered or refused to take part in the program.”

The authors of the paper and Dr. Faro had no disclosures.

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Early rhythm control in atrial fibrillation (EAST-AFNET trial) 

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Wed, 11/17/2021 - 12:32

Background: Despite advances in AFib management, up to 5% of patients will have a major complication each year. Current guidelines favor rate control based on prior studies that did not show mortality benefit with rhythm control. By expanding the rhythm strategy to include catheter ablation in early AFib, this trial re-examines if implementing rhythm control leads to improved clinical outcomes. 

Dr. Sophia Korovaichuk


Study design: Prospective, open blinded randomized controlled trial. 

Setting: 135 centers in 11 European countries.

Synopsis: Of patients with a new AFib diagnosis (less than 1 year, median 36 days), 2,789 were randomized 1:1 to rhythm control or usual care. Patients were 75 years old or older with prior CVA or 2 or fewer cardiovascular conditions. Both arms were continued on guideline-directed treatment, including rate control medications and anticoagulation. Rhythm control involved use of antiarrhythmics, catheter ablation (8% at enrollment, 20% by 5 years), or early cardioversion. Patients assigned to rhythm control had a lower risk for primary composite outcome of CV death, stroke, or hospitalization for worsening heart failure or acute coronary syndrome (HR, 0.79; 96% confidence interval, 0.66-0.94; P = .005) at 5 years, and the trial was stopped early for efficacy. Despite the 21% relative risk reduction, the absolute risk reduction was modest at 1.1 per 100 person-years. There were no significant differences in composite rate of all-cause mortality, although more adverse events occurred in the rhythm arm (4.9% vs. 1%). Overall rates of stroke and death were relatively low in both groups, underscoring the importance of continuing guideline-directed therapy. Hospital days were similar between the two groups, suggesting that rhythm control is not associated with higher cost burden. Limitations include its open-label design, loss of patients to follow-up (9% in control arm), and lack of generalizability to patients with long-standing AFib.

Bottom line: Early initiation of rhythm control therapy was associated with improved outcomes in patients with newly diagnosed AFib compared with usual care alone.

Citation: Kirchhof P et al. Early rhythm-control therapy in patients with atrial fibrillation. N Engl J Med. 2020 Aug 29;383:1305-1316. doi: 10.1056/NEJMoa2019422.

Dr. Korovaichuk is a hospitalist at Northwestern Memorial Hospital and assistant professor of medicine, Feinberg School of Medicine, both in Chicago.

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Background: Despite advances in AFib management, up to 5% of patients will have a major complication each year. Current guidelines favor rate control based on prior studies that did not show mortality benefit with rhythm control. By expanding the rhythm strategy to include catheter ablation in early AFib, this trial re-examines if implementing rhythm control leads to improved clinical outcomes. 

Dr. Sophia Korovaichuk


Study design: Prospective, open blinded randomized controlled trial. 

Setting: 135 centers in 11 European countries.

Synopsis: Of patients with a new AFib diagnosis (less than 1 year, median 36 days), 2,789 were randomized 1:1 to rhythm control or usual care. Patients were 75 years old or older with prior CVA or 2 or fewer cardiovascular conditions. Both arms were continued on guideline-directed treatment, including rate control medications and anticoagulation. Rhythm control involved use of antiarrhythmics, catheter ablation (8% at enrollment, 20% by 5 years), or early cardioversion. Patients assigned to rhythm control had a lower risk for primary composite outcome of CV death, stroke, or hospitalization for worsening heart failure or acute coronary syndrome (HR, 0.79; 96% confidence interval, 0.66-0.94; P = .005) at 5 years, and the trial was stopped early for efficacy. Despite the 21% relative risk reduction, the absolute risk reduction was modest at 1.1 per 100 person-years. There were no significant differences in composite rate of all-cause mortality, although more adverse events occurred in the rhythm arm (4.9% vs. 1%). Overall rates of stroke and death were relatively low in both groups, underscoring the importance of continuing guideline-directed therapy. Hospital days were similar between the two groups, suggesting that rhythm control is not associated with higher cost burden. Limitations include its open-label design, loss of patients to follow-up (9% in control arm), and lack of generalizability to patients with long-standing AFib.

Bottom line: Early initiation of rhythm control therapy was associated with improved outcomes in patients with newly diagnosed AFib compared with usual care alone.

Citation: Kirchhof P et al. Early rhythm-control therapy in patients with atrial fibrillation. N Engl J Med. 2020 Aug 29;383:1305-1316. doi: 10.1056/NEJMoa2019422.

Dr. Korovaichuk is a hospitalist at Northwestern Memorial Hospital and assistant professor of medicine, Feinberg School of Medicine, both in Chicago.

Background: Despite advances in AFib management, up to 5% of patients will have a major complication each year. Current guidelines favor rate control based on prior studies that did not show mortality benefit with rhythm control. By expanding the rhythm strategy to include catheter ablation in early AFib, this trial re-examines if implementing rhythm control leads to improved clinical outcomes. 

Dr. Sophia Korovaichuk


Study design: Prospective, open blinded randomized controlled trial. 

Setting: 135 centers in 11 European countries.

Synopsis: Of patients with a new AFib diagnosis (less than 1 year, median 36 days), 2,789 were randomized 1:1 to rhythm control or usual care. Patients were 75 years old or older with prior CVA or 2 or fewer cardiovascular conditions. Both arms were continued on guideline-directed treatment, including rate control medications and anticoagulation. Rhythm control involved use of antiarrhythmics, catheter ablation (8% at enrollment, 20% by 5 years), or early cardioversion. Patients assigned to rhythm control had a lower risk for primary composite outcome of CV death, stroke, or hospitalization for worsening heart failure or acute coronary syndrome (HR, 0.79; 96% confidence interval, 0.66-0.94; P = .005) at 5 years, and the trial was stopped early for efficacy. Despite the 21% relative risk reduction, the absolute risk reduction was modest at 1.1 per 100 person-years. There were no significant differences in composite rate of all-cause mortality, although more adverse events occurred in the rhythm arm (4.9% vs. 1%). Overall rates of stroke and death were relatively low in both groups, underscoring the importance of continuing guideline-directed therapy. Hospital days were similar between the two groups, suggesting that rhythm control is not associated with higher cost burden. Limitations include its open-label design, loss of patients to follow-up (9% in control arm), and lack of generalizability to patients with long-standing AFib.

Bottom line: Early initiation of rhythm control therapy was associated with improved outcomes in patients with newly diagnosed AFib compared with usual care alone.

Citation: Kirchhof P et al. Early rhythm-control therapy in patients with atrial fibrillation. N Engl J Med. 2020 Aug 29;383:1305-1316. doi: 10.1056/NEJMoa2019422.

Dr. Korovaichuk is a hospitalist at Northwestern Memorial Hospital and assistant professor of medicine, Feinberg School of Medicine, both in Chicago.

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EMPEROR-Preserved findings confirmed in ‘true’ HFpEF patients

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Tue, 05/03/2022 - 15:03

Main results from the landmark EMPEROR-Preserved trial, reported in August, established for the first time that treatment with a drug, the sodium-glucose cotransporter 2 inhibitor empagliflozin, could clearly benefit patients with heart failure with preserved ejection fraction (HFpEF).

Dr. Stefan Anker

The only caveat was that EMPEROR-Preserved enrolled patients with a left ventricular ejection fraction of at least 41%, while “true” HFpEF means patients with heart failure and an LVEF of at least 50%, according to recent definitions. About one-third of the 5,988 patients enrolled in EMPEROR-Preserved had an LVEF of 41%-49%, heart failure with mildly reduced ejection fraction.

Secondary analysis from the EMPEROR-Preserved trial has now resolved this ambiguity by showing that, among the 4,005 patients (67%) enrolled in the trial with an LVEF of at least 50%, treatment with empagliflozin (Jardiance) reduced the study’s primary endpoint – cardiovascular death or first hospitalization for heart failure – by a significant 17%, relative to patients who received placebo, dismissing any doubt about the relevance of the overall finding to the subgroup of patients with unmitigated HFpEF.

“This is the first large-scale trial to document meaningful and significant improvements associated with drug therapy in patients with ‘true’ HFpEF,” Stefan D. Anker, MD, said in presenting the results at the American Heart Association scientific sessions.

Streamlining heart failure treatment

The demonstration that empagliflozin is an effective – and safe – treatment for patients with HFpEF not only provides a new treatment for a disorder that until now had no evidence-based intervention, but also streamlines the management approach for treating patients with heart failure with an agent from empagliflozin’s class, the SGLT2 inhibitors, commented Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation programs at Ascension St. Vincent Heart Center in Indianapolis.

Dr. Mary N. Walsh

That’s because empagliflozin has shown significant and consistent benefit across essentially the full range of LVEFs seen in patients with heart failure based on its performance in EMPEROR-Preserved as well as in a mirror-image trial, EMPEROR-Reduced, run in patients with heart failure with reduced ejection fraction.

“Clinicians do not need to stop and assess LVEF with echocardiography or other imaging before they decide on how to treat heart failure patients” with an SGLT2 inhibitor, noted Dr. Walsh, a designated discussant for the report. “Clinicians who are busy can now refer less to LVEF than to the patient’s phenotype.”
 

Treatment prevents hospitalization for heart failure

The more-detailed data reported by Dr. Anker also strengthened the case that the benefit from empagliflozin in patients with an LVEF of at least 50% mostly came from a reduction in hospitalizations for heart failure (HHF), which dropped following start of empagliflozin treatment by a relative 22%, compared with placebo for first HHF, a significant decline, and by a relative 17% for total HHF, a reduction that missed significance in this secondary analysis. The other half of the primary endpoint, cardiovascular death, declined by a nonsignificant 11% with empagliflozin treatment, compared with placebo in patients with clear-cut HFpEF.

Dr. Clyde W. Yancy

The significant reduction in first HHF is, by itself, sufficient reason to use empagliflozin (or possibly a different SGLT2 inhibitor) in patients with HFpEF, maintained Clyde W. Yancy, MD, professor and chief of cardiology at Northwestern Medicine in Chicago.

“Attenuated HHF is a meaningful outcome,” stressed Dr. Yancy, also a discussant for the study. “This is the first time we’ve had evidence supporting that we can change the natural history of patients with HFpEF. While we still need to find interventions that save lives, we cannot overlook that this treatment can improve morbidity, and we cannot overlook that patient quality of life is better.”
 

Further benefits in patients with an LVEF of at least 50%

Dr. Anker, professor of cardiology and metabolism at Charité Medical University in Berlin, also reported results from several other analyses that further defined the effect of empagliflozin on clinical outcomes of patients with “true” HFpEF:

  • The impact of empagliflozin, compared with placebo, for reducing both the study’s combined, primary outcome as well as total HHF was statistically consistent across all strata of LVEF, from 50% to greater than 70%. However, both outcome measures also showed a puzzling loss of benefit among patients with an LVEF of 65%-69%. In prior reports, a researcher on the EMPEROR-Preserved team, Milton Packer, MD, speculated that some patients in this LVEF stratum might not actually have had heart failure but instead had a different disorder that mimicked heart failure in clinical presentation, such as atrial fibrillation.
  • Patients’ quality of life as measured by the Kansas City Cardiomyopathy Questionnaire showed a consistent benefit from empagliflozin treatment, compared with placebo, both in patients with an LVEF of at least 50% as well as in those with an LVEF of 41%-49%. In both subgroups the adjusted mean difference from placebo was significant and about 1.5 points.
  • Patients showed a significant improvement in average New York Heart Association functional class while on treatment, and a strong trend toward less deterioration in functional class while on treatment.
  • Deterioration of renal function on treatment slowed by an average 1.24 mL/min per 1.73 m2 per year in patients on empagliflozin, compared with placebo, in the subgroup with an LVEF of at least 50%.

Dr. Anker also reported the primary outcome and component results for the subgroup of patients with a baseline LVEF of 41%-49%. These patients had what looked like a “bigger magnitude” of effect from treatment, he noted, showing a significant 29% relative decline in the primary endpoint, compared with placebo-treated patients, and a significant 42% relative drop in first HHF and a significant 43% relative decline in total HHF, compared with placebo.

The primary analysis from EMPEROR-Preserved, which included all 5,988 randomized patients with heart failure and an LVEF of 41% or greater, showed a significant reduction in the combined, primary endpoint with empagliflozin treatment of 21%, compared with control patients during a median follow-up of about 26 months. The absolute rate reduction of the combined primary endpoint was 3.3% during 26-months’ follow-up. Statistical tests have shown no heterogeneity of this effect by diabetes status (49% of patients had diabetes), nor by renal function down to an estimated glomerular filtration rate at entry as low as 20 mL/min per 1.73 m2.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Lilly, the two companies that market empagliflozin (Jardiance). Dr. Anker has been a consultant to Boehringer Ingelheim as well as to Abbott Vascular, Bayer, Brahms, Cardiac Dimensions, Cordio, Novartis, Servier, and Vifor. Dr. Walsh and Dr. Yancy had no disclosures.

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Main results from the landmark EMPEROR-Preserved trial, reported in August, established for the first time that treatment with a drug, the sodium-glucose cotransporter 2 inhibitor empagliflozin, could clearly benefit patients with heart failure with preserved ejection fraction (HFpEF).

Dr. Stefan Anker

The only caveat was that EMPEROR-Preserved enrolled patients with a left ventricular ejection fraction of at least 41%, while “true” HFpEF means patients with heart failure and an LVEF of at least 50%, according to recent definitions. About one-third of the 5,988 patients enrolled in EMPEROR-Preserved had an LVEF of 41%-49%, heart failure with mildly reduced ejection fraction.

Secondary analysis from the EMPEROR-Preserved trial has now resolved this ambiguity by showing that, among the 4,005 patients (67%) enrolled in the trial with an LVEF of at least 50%, treatment with empagliflozin (Jardiance) reduced the study’s primary endpoint – cardiovascular death or first hospitalization for heart failure – by a significant 17%, relative to patients who received placebo, dismissing any doubt about the relevance of the overall finding to the subgroup of patients with unmitigated HFpEF.

“This is the first large-scale trial to document meaningful and significant improvements associated with drug therapy in patients with ‘true’ HFpEF,” Stefan D. Anker, MD, said in presenting the results at the American Heart Association scientific sessions.

Streamlining heart failure treatment

The demonstration that empagliflozin is an effective – and safe – treatment for patients with HFpEF not only provides a new treatment for a disorder that until now had no evidence-based intervention, but also streamlines the management approach for treating patients with heart failure with an agent from empagliflozin’s class, the SGLT2 inhibitors, commented Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation programs at Ascension St. Vincent Heart Center in Indianapolis.

Dr. Mary N. Walsh

That’s because empagliflozin has shown significant and consistent benefit across essentially the full range of LVEFs seen in patients with heart failure based on its performance in EMPEROR-Preserved as well as in a mirror-image trial, EMPEROR-Reduced, run in patients with heart failure with reduced ejection fraction.

“Clinicians do not need to stop and assess LVEF with echocardiography or other imaging before they decide on how to treat heart failure patients” with an SGLT2 inhibitor, noted Dr. Walsh, a designated discussant for the report. “Clinicians who are busy can now refer less to LVEF than to the patient’s phenotype.”
 

Treatment prevents hospitalization for heart failure

The more-detailed data reported by Dr. Anker also strengthened the case that the benefit from empagliflozin in patients with an LVEF of at least 50% mostly came from a reduction in hospitalizations for heart failure (HHF), which dropped following start of empagliflozin treatment by a relative 22%, compared with placebo for first HHF, a significant decline, and by a relative 17% for total HHF, a reduction that missed significance in this secondary analysis. The other half of the primary endpoint, cardiovascular death, declined by a nonsignificant 11% with empagliflozin treatment, compared with placebo in patients with clear-cut HFpEF.

Dr. Clyde W. Yancy

The significant reduction in first HHF is, by itself, sufficient reason to use empagliflozin (or possibly a different SGLT2 inhibitor) in patients with HFpEF, maintained Clyde W. Yancy, MD, professor and chief of cardiology at Northwestern Medicine in Chicago.

“Attenuated HHF is a meaningful outcome,” stressed Dr. Yancy, also a discussant for the study. “This is the first time we’ve had evidence supporting that we can change the natural history of patients with HFpEF. While we still need to find interventions that save lives, we cannot overlook that this treatment can improve morbidity, and we cannot overlook that patient quality of life is better.”
 

Further benefits in patients with an LVEF of at least 50%

Dr. Anker, professor of cardiology and metabolism at Charité Medical University in Berlin, also reported results from several other analyses that further defined the effect of empagliflozin on clinical outcomes of patients with “true” HFpEF:

  • The impact of empagliflozin, compared with placebo, for reducing both the study’s combined, primary outcome as well as total HHF was statistically consistent across all strata of LVEF, from 50% to greater than 70%. However, both outcome measures also showed a puzzling loss of benefit among patients with an LVEF of 65%-69%. In prior reports, a researcher on the EMPEROR-Preserved team, Milton Packer, MD, speculated that some patients in this LVEF stratum might not actually have had heart failure but instead had a different disorder that mimicked heart failure in clinical presentation, such as atrial fibrillation.
  • Patients’ quality of life as measured by the Kansas City Cardiomyopathy Questionnaire showed a consistent benefit from empagliflozin treatment, compared with placebo, both in patients with an LVEF of at least 50% as well as in those with an LVEF of 41%-49%. In both subgroups the adjusted mean difference from placebo was significant and about 1.5 points.
  • Patients showed a significant improvement in average New York Heart Association functional class while on treatment, and a strong trend toward less deterioration in functional class while on treatment.
  • Deterioration of renal function on treatment slowed by an average 1.24 mL/min per 1.73 m2 per year in patients on empagliflozin, compared with placebo, in the subgroup with an LVEF of at least 50%.

Dr. Anker also reported the primary outcome and component results for the subgroup of patients with a baseline LVEF of 41%-49%. These patients had what looked like a “bigger magnitude” of effect from treatment, he noted, showing a significant 29% relative decline in the primary endpoint, compared with placebo-treated patients, and a significant 42% relative drop in first HHF and a significant 43% relative decline in total HHF, compared with placebo.

The primary analysis from EMPEROR-Preserved, which included all 5,988 randomized patients with heart failure and an LVEF of 41% or greater, showed a significant reduction in the combined, primary endpoint with empagliflozin treatment of 21%, compared with control patients during a median follow-up of about 26 months. The absolute rate reduction of the combined primary endpoint was 3.3% during 26-months’ follow-up. Statistical tests have shown no heterogeneity of this effect by diabetes status (49% of patients had diabetes), nor by renal function down to an estimated glomerular filtration rate at entry as low as 20 mL/min per 1.73 m2.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Lilly, the two companies that market empagliflozin (Jardiance). Dr. Anker has been a consultant to Boehringer Ingelheim as well as to Abbott Vascular, Bayer, Brahms, Cardiac Dimensions, Cordio, Novartis, Servier, and Vifor. Dr. Walsh and Dr. Yancy had no disclosures.

Main results from the landmark EMPEROR-Preserved trial, reported in August, established for the first time that treatment with a drug, the sodium-glucose cotransporter 2 inhibitor empagliflozin, could clearly benefit patients with heart failure with preserved ejection fraction (HFpEF).

Dr. Stefan Anker

The only caveat was that EMPEROR-Preserved enrolled patients with a left ventricular ejection fraction of at least 41%, while “true” HFpEF means patients with heart failure and an LVEF of at least 50%, according to recent definitions. About one-third of the 5,988 patients enrolled in EMPEROR-Preserved had an LVEF of 41%-49%, heart failure with mildly reduced ejection fraction.

Secondary analysis from the EMPEROR-Preserved trial has now resolved this ambiguity by showing that, among the 4,005 patients (67%) enrolled in the trial with an LVEF of at least 50%, treatment with empagliflozin (Jardiance) reduced the study’s primary endpoint – cardiovascular death or first hospitalization for heart failure – by a significant 17%, relative to patients who received placebo, dismissing any doubt about the relevance of the overall finding to the subgroup of patients with unmitigated HFpEF.

“This is the first large-scale trial to document meaningful and significant improvements associated with drug therapy in patients with ‘true’ HFpEF,” Stefan D. Anker, MD, said in presenting the results at the American Heart Association scientific sessions.

Streamlining heart failure treatment

The demonstration that empagliflozin is an effective – and safe – treatment for patients with HFpEF not only provides a new treatment for a disorder that until now had no evidence-based intervention, but also streamlines the management approach for treating patients with heart failure with an agent from empagliflozin’s class, the SGLT2 inhibitors, commented Mary Norine Walsh, MD, medical director of the heart failure and cardiac transplantation programs at Ascension St. Vincent Heart Center in Indianapolis.

Dr. Mary N. Walsh

That’s because empagliflozin has shown significant and consistent benefit across essentially the full range of LVEFs seen in patients with heart failure based on its performance in EMPEROR-Preserved as well as in a mirror-image trial, EMPEROR-Reduced, run in patients with heart failure with reduced ejection fraction.

“Clinicians do not need to stop and assess LVEF with echocardiography or other imaging before they decide on how to treat heart failure patients” with an SGLT2 inhibitor, noted Dr. Walsh, a designated discussant for the report. “Clinicians who are busy can now refer less to LVEF than to the patient’s phenotype.”
 

Treatment prevents hospitalization for heart failure

The more-detailed data reported by Dr. Anker also strengthened the case that the benefit from empagliflozin in patients with an LVEF of at least 50% mostly came from a reduction in hospitalizations for heart failure (HHF), which dropped following start of empagliflozin treatment by a relative 22%, compared with placebo for first HHF, a significant decline, and by a relative 17% for total HHF, a reduction that missed significance in this secondary analysis. The other half of the primary endpoint, cardiovascular death, declined by a nonsignificant 11% with empagliflozin treatment, compared with placebo in patients with clear-cut HFpEF.

Dr. Clyde W. Yancy

The significant reduction in first HHF is, by itself, sufficient reason to use empagliflozin (or possibly a different SGLT2 inhibitor) in patients with HFpEF, maintained Clyde W. Yancy, MD, professor and chief of cardiology at Northwestern Medicine in Chicago.

“Attenuated HHF is a meaningful outcome,” stressed Dr. Yancy, also a discussant for the study. “This is the first time we’ve had evidence supporting that we can change the natural history of patients with HFpEF. While we still need to find interventions that save lives, we cannot overlook that this treatment can improve morbidity, and we cannot overlook that patient quality of life is better.”
 

Further benefits in patients with an LVEF of at least 50%

Dr. Anker, professor of cardiology and metabolism at Charité Medical University in Berlin, also reported results from several other analyses that further defined the effect of empagliflozin on clinical outcomes of patients with “true” HFpEF:

  • The impact of empagliflozin, compared with placebo, for reducing both the study’s combined, primary outcome as well as total HHF was statistically consistent across all strata of LVEF, from 50% to greater than 70%. However, both outcome measures also showed a puzzling loss of benefit among patients with an LVEF of 65%-69%. In prior reports, a researcher on the EMPEROR-Preserved team, Milton Packer, MD, speculated that some patients in this LVEF stratum might not actually have had heart failure but instead had a different disorder that mimicked heart failure in clinical presentation, such as atrial fibrillation.
  • Patients’ quality of life as measured by the Kansas City Cardiomyopathy Questionnaire showed a consistent benefit from empagliflozin treatment, compared with placebo, both in patients with an LVEF of at least 50% as well as in those with an LVEF of 41%-49%. In both subgroups the adjusted mean difference from placebo was significant and about 1.5 points.
  • Patients showed a significant improvement in average New York Heart Association functional class while on treatment, and a strong trend toward less deterioration in functional class while on treatment.
  • Deterioration of renal function on treatment slowed by an average 1.24 mL/min per 1.73 m2 per year in patients on empagliflozin, compared with placebo, in the subgroup with an LVEF of at least 50%.

Dr. Anker also reported the primary outcome and component results for the subgroup of patients with a baseline LVEF of 41%-49%. These patients had what looked like a “bigger magnitude” of effect from treatment, he noted, showing a significant 29% relative decline in the primary endpoint, compared with placebo-treated patients, and a significant 42% relative drop in first HHF and a significant 43% relative decline in total HHF, compared with placebo.

The primary analysis from EMPEROR-Preserved, which included all 5,988 randomized patients with heart failure and an LVEF of 41% or greater, showed a significant reduction in the combined, primary endpoint with empagliflozin treatment of 21%, compared with control patients during a median follow-up of about 26 months. The absolute rate reduction of the combined primary endpoint was 3.3% during 26-months’ follow-up. Statistical tests have shown no heterogeneity of this effect by diabetes status (49% of patients had diabetes), nor by renal function down to an estimated glomerular filtration rate at entry as low as 20 mL/min per 1.73 m2.

EMPEROR-Preserved was sponsored by Boehringer Ingelheim and Lilly, the two companies that market empagliflozin (Jardiance). Dr. Anker has been a consultant to Boehringer Ingelheim as well as to Abbott Vascular, Bayer, Brahms, Cardiac Dimensions, Cordio, Novartis, Servier, and Vifor. Dr. Walsh and Dr. Yancy had no disclosures.

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Ticagrelor reversal agent achieves quick hemostasis: REVERSE-IT

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Wed, 11/17/2021 - 10:22

The experimental monoclonal antibody bentracimab, which reverses the antiplatelet effects of ticagrelor, appears to be heading toward regulatory approval, on the basis of an interim analysis of the phase 3 REVERSE-IT trial.

Dr. Deepak L. Bhatt

“Rates of effective hemostasis were adjudicated as good or excellent in more than 90% of cases with no drug-related serious adverse events or allergic or infusion-related reactions,” reported Deepak L. Bhatt, MD, at the American Heart Association scientific sessions.

The interim analysis of this nonrandomized, single-arm study was requested by the Food and Drug Administration, which is considering a conditional accelerated approval of bentracimab (formerly PB2452) if efficacy and safety are established.

Upon administration, bentracimab binds to free ticagrelor so that ticagrelor cannot bind to the P2Y12 platelet receptor. This interrupts one of the key steps in the pathway of platelet aggregation.

REVERSE-IT is still enrolling patients. This interim analysis was conducted with the first 150 patients who met eligibility criteria and were treated. Of these, 142 patients were enrolled for an urgent surgical indication and 8 for a major bleeding indication. After some exclusions for lack of urgency and reclassifications following adjudication, there were 113 surgical cases and 9 major bleeding patients evaluable for hemostasis.
 

Platelet function assays test reversal

On the primary reversal endpoint, which was restoration of activity on the proprietary platelet function assays Verify Now and PRUTest, a rapid restoration of platelet function was achieved in both surgical and major-bleeding patients. Platelet reactivity climbed to near normal levels within 10 minutes of administration, and peak effects were sustained through the first 24 hours after administration.

On the basis of the platelet function assays, the pattern of response to bentracimab was “very similar in the surgical and bleeding patients,” reported Dr. Bhatt, executive director of interventional cardiovascular programs at Brigham and Women’s Health, Boston.

The effect was also consistent across a broad array of prespecified subgroups, including stratifications by age, renal function, time from last dose of ticagrelor, race, and the presence of comorbidities, such as diabetes, renal dysfunction, hypertension, and history of MI.
 

Hemostasis documented in all but one patient

Adjudicated hemostasis was achieved in 100% of the 113 urgent surgical patients evaluated. In the nine major bleeding patients, six achieved excellent hemostasis and one achieved good hemostasis. One had poor hemostasis, and one was unevaluable.

Platelet rebound following bentracimab administration, measured by mean platelet volume, was not observed.

There were no serious adverse events, allergic reactions, or serious infusion-related reactions associated with the administration of bentracimab, Dr. Bhatt said.

While Dr. Bhatt acknowledged that the number of patients in the major-bleeding subgroup was small, he noted that the reduction in platelet reactivity relative to baseline was still significant. In addition, he characterized urgent surgery as “an excellent model of bleeding” and pointed out the consistency of results in the surgical and major-bleeding groups.

The interim results are also consistent with phase 1 data published 2 years ago, and with the subsequent phase 2 studies. All of these data are now under regulatory review both in the United States and in Europe, according to Dr. Bhatt.
 

 

 

No good current options for reversal

Evidence of efficacy and safety is encouraging, because current options for urgently reversing ticagrelor are “disappointing,” according to the invited discussant Gilles Montalescot, MD, PhD, professor of cardiology, Pitié-Salpêtrière Hôpital, Paris.

Dr. Gilles Montalescot

“Platelet transfusion has some value for clopidogrel and prasugrel, but it does not work for ticagrelor,” said Dr. Montalescot, referring to two other P2Y12 inhibitors. Substantiating the need for a reversal agent, he identified several other strategies that have proven ineffective, such as desmopressin and sorbent hemadsorption.

Overall, Dr. Montalescot acknowledged the need for a highly effective ticagrelor reversal agent, but he did have some criticisms of REVERSE-IT. For one, he was not convinced about the design.

“What was unethical in having a control group?” he asked, suggesting that it was feasible and would have addressed issues of relative efficacy and safety.

For example, the authors concluded that none of the thrombotic events were likely to be treatment related, but “four events occurred immediately after reversal without an alternate explanation,” Dr. Montalescot pointed out. “Was this a signal or background noise?”

Nevertheless, he agreed that the interim phase 3 data are consistent with the previously reported phase 2 studies, and he reiterated that a strategy to reverse ticagrelor’s effects is an important unmet need.

Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PhaseBio, which provided funding for the REVERSE-IT trial. Dr. Montalescot reported financial relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cell-Prothera, CSL-Behring, Europa, Idorsia, Servicer, Medtronic, Merck Sharpe & Dohme, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.
 

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The experimental monoclonal antibody bentracimab, which reverses the antiplatelet effects of ticagrelor, appears to be heading toward regulatory approval, on the basis of an interim analysis of the phase 3 REVERSE-IT trial.

Dr. Deepak L. Bhatt

“Rates of effective hemostasis were adjudicated as good or excellent in more than 90% of cases with no drug-related serious adverse events or allergic or infusion-related reactions,” reported Deepak L. Bhatt, MD, at the American Heart Association scientific sessions.

The interim analysis of this nonrandomized, single-arm study was requested by the Food and Drug Administration, which is considering a conditional accelerated approval of bentracimab (formerly PB2452) if efficacy and safety are established.

Upon administration, bentracimab binds to free ticagrelor so that ticagrelor cannot bind to the P2Y12 platelet receptor. This interrupts one of the key steps in the pathway of platelet aggregation.

REVERSE-IT is still enrolling patients. This interim analysis was conducted with the first 150 patients who met eligibility criteria and were treated. Of these, 142 patients were enrolled for an urgent surgical indication and 8 for a major bleeding indication. After some exclusions for lack of urgency and reclassifications following adjudication, there were 113 surgical cases and 9 major bleeding patients evaluable for hemostasis.
 

Platelet function assays test reversal

On the primary reversal endpoint, which was restoration of activity on the proprietary platelet function assays Verify Now and PRUTest, a rapid restoration of platelet function was achieved in both surgical and major-bleeding patients. Platelet reactivity climbed to near normal levels within 10 minutes of administration, and peak effects were sustained through the first 24 hours after administration.

On the basis of the platelet function assays, the pattern of response to bentracimab was “very similar in the surgical and bleeding patients,” reported Dr. Bhatt, executive director of interventional cardiovascular programs at Brigham and Women’s Health, Boston.

The effect was also consistent across a broad array of prespecified subgroups, including stratifications by age, renal function, time from last dose of ticagrelor, race, and the presence of comorbidities, such as diabetes, renal dysfunction, hypertension, and history of MI.
 

Hemostasis documented in all but one patient

Adjudicated hemostasis was achieved in 100% of the 113 urgent surgical patients evaluated. In the nine major bleeding patients, six achieved excellent hemostasis and one achieved good hemostasis. One had poor hemostasis, and one was unevaluable.

Platelet rebound following bentracimab administration, measured by mean platelet volume, was not observed.

There were no serious adverse events, allergic reactions, or serious infusion-related reactions associated with the administration of bentracimab, Dr. Bhatt said.

While Dr. Bhatt acknowledged that the number of patients in the major-bleeding subgroup was small, he noted that the reduction in platelet reactivity relative to baseline was still significant. In addition, he characterized urgent surgery as “an excellent model of bleeding” and pointed out the consistency of results in the surgical and major-bleeding groups.

The interim results are also consistent with phase 1 data published 2 years ago, and with the subsequent phase 2 studies. All of these data are now under regulatory review both in the United States and in Europe, according to Dr. Bhatt.
 

 

 

No good current options for reversal

Evidence of efficacy and safety is encouraging, because current options for urgently reversing ticagrelor are “disappointing,” according to the invited discussant Gilles Montalescot, MD, PhD, professor of cardiology, Pitié-Salpêtrière Hôpital, Paris.

Dr. Gilles Montalescot

“Platelet transfusion has some value for clopidogrel and prasugrel, but it does not work for ticagrelor,” said Dr. Montalescot, referring to two other P2Y12 inhibitors. Substantiating the need for a reversal agent, he identified several other strategies that have proven ineffective, such as desmopressin and sorbent hemadsorption.

Overall, Dr. Montalescot acknowledged the need for a highly effective ticagrelor reversal agent, but he did have some criticisms of REVERSE-IT. For one, he was not convinced about the design.

“What was unethical in having a control group?” he asked, suggesting that it was feasible and would have addressed issues of relative efficacy and safety.

For example, the authors concluded that none of the thrombotic events were likely to be treatment related, but “four events occurred immediately after reversal without an alternate explanation,” Dr. Montalescot pointed out. “Was this a signal or background noise?”

Nevertheless, he agreed that the interim phase 3 data are consistent with the previously reported phase 2 studies, and he reiterated that a strategy to reverse ticagrelor’s effects is an important unmet need.

Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PhaseBio, which provided funding for the REVERSE-IT trial. Dr. Montalescot reported financial relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cell-Prothera, CSL-Behring, Europa, Idorsia, Servicer, Medtronic, Merck Sharpe & Dohme, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.
 

The experimental monoclonal antibody bentracimab, which reverses the antiplatelet effects of ticagrelor, appears to be heading toward regulatory approval, on the basis of an interim analysis of the phase 3 REVERSE-IT trial.

Dr. Deepak L. Bhatt

“Rates of effective hemostasis were adjudicated as good or excellent in more than 90% of cases with no drug-related serious adverse events or allergic or infusion-related reactions,” reported Deepak L. Bhatt, MD, at the American Heart Association scientific sessions.

The interim analysis of this nonrandomized, single-arm study was requested by the Food and Drug Administration, which is considering a conditional accelerated approval of bentracimab (formerly PB2452) if efficacy and safety are established.

Upon administration, bentracimab binds to free ticagrelor so that ticagrelor cannot bind to the P2Y12 platelet receptor. This interrupts one of the key steps in the pathway of platelet aggregation.

REVERSE-IT is still enrolling patients. This interim analysis was conducted with the first 150 patients who met eligibility criteria and were treated. Of these, 142 patients were enrolled for an urgent surgical indication and 8 for a major bleeding indication. After some exclusions for lack of urgency and reclassifications following adjudication, there were 113 surgical cases and 9 major bleeding patients evaluable for hemostasis.
 

Platelet function assays test reversal

On the primary reversal endpoint, which was restoration of activity on the proprietary platelet function assays Verify Now and PRUTest, a rapid restoration of platelet function was achieved in both surgical and major-bleeding patients. Platelet reactivity climbed to near normal levels within 10 minutes of administration, and peak effects were sustained through the first 24 hours after administration.

On the basis of the platelet function assays, the pattern of response to bentracimab was “very similar in the surgical and bleeding patients,” reported Dr. Bhatt, executive director of interventional cardiovascular programs at Brigham and Women’s Health, Boston.

The effect was also consistent across a broad array of prespecified subgroups, including stratifications by age, renal function, time from last dose of ticagrelor, race, and the presence of comorbidities, such as diabetes, renal dysfunction, hypertension, and history of MI.
 

Hemostasis documented in all but one patient

Adjudicated hemostasis was achieved in 100% of the 113 urgent surgical patients evaluated. In the nine major bleeding patients, six achieved excellent hemostasis and one achieved good hemostasis. One had poor hemostasis, and one was unevaluable.

Platelet rebound following bentracimab administration, measured by mean platelet volume, was not observed.

There were no serious adverse events, allergic reactions, or serious infusion-related reactions associated with the administration of bentracimab, Dr. Bhatt said.

While Dr. Bhatt acknowledged that the number of patients in the major-bleeding subgroup was small, he noted that the reduction in platelet reactivity relative to baseline was still significant. In addition, he characterized urgent surgery as “an excellent model of bleeding” and pointed out the consistency of results in the surgical and major-bleeding groups.

The interim results are also consistent with phase 1 data published 2 years ago, and with the subsequent phase 2 studies. All of these data are now under regulatory review both in the United States and in Europe, according to Dr. Bhatt.
 

 

 

No good current options for reversal

Evidence of efficacy and safety is encouraging, because current options for urgently reversing ticagrelor are “disappointing,” according to the invited discussant Gilles Montalescot, MD, PhD, professor of cardiology, Pitié-Salpêtrière Hôpital, Paris.

Dr. Gilles Montalescot

“Platelet transfusion has some value for clopidogrel and prasugrel, but it does not work for ticagrelor,” said Dr. Montalescot, referring to two other P2Y12 inhibitors. Substantiating the need for a reversal agent, he identified several other strategies that have proven ineffective, such as desmopressin and sorbent hemadsorption.

Overall, Dr. Montalescot acknowledged the need for a highly effective ticagrelor reversal agent, but he did have some criticisms of REVERSE-IT. For one, he was not convinced about the design.

“What was unethical in having a control group?” he asked, suggesting that it was feasible and would have addressed issues of relative efficacy and safety.

For example, the authors concluded that none of the thrombotic events were likely to be treatment related, but “four events occurred immediately after reversal without an alternate explanation,” Dr. Montalescot pointed out. “Was this a signal or background noise?”

Nevertheless, he agreed that the interim phase 3 data are consistent with the previously reported phase 2 studies, and he reiterated that a strategy to reverse ticagrelor’s effects is an important unmet need.

Dr. Bhatt has a financial relationship with a large number of pharmaceutical companies, including PhaseBio, which provided funding for the REVERSE-IT trial. Dr. Montalescot reported financial relationships with Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cell-Prothera, CSL-Behring, Europa, Idorsia, Servicer, Medtronic, Merck Sharpe & Dohme, Novartis, Pfizer, Quantum Genomics, and Sanofi-Aventis.
 

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Comparing pulmonary embolism mortality risk scores 

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Changed
Tue, 11/16/2021 - 16:02

Background: Though most PEs do not have significant complications, 15% may be associated with risk of death or hemodynamic compromise. Retrospectively derived risk scores are used to risk-stratify patients and guide acute treatment strategies. It is unclear how well existing risk scores estimate mortality outcomes in patients with acute PE. 

Dr. Sophia Korovaichuk


Study design: Multicenter cohort study.

Setting: Eight hospitals participating in Pulmonary Embolism Response Team (PERT) consortium registry.

Synopsis: The study included 416 patients with radiographically confirmed acute PE, baseline data for risk calculations, and PERT consultation to consider advanced therapies. Four risk scores (PESI, simplified PESI, BOVA, and European Society of Cardiology) were calculated for each patient independently of clinical care. Patients were assigned into lower- and higher-­risk groups. All-cause mortality was assessed on days 7 and 30. The discrimination of each risk score was measured using area under the curve (AUC). Seven-day mortality ranged 1.3%-3.1% in the lower-risk group, and 7%-16.3% in the high-risk group. Thirty-day mortality in the low-risk group ranged 2.6%-10.2% and 14.4%-26.3% in the high-risk group. PE risk scores have only moderate discrimination for mortality at 7 days (AUC range, 0.616-0.666) and less discrimination at 30 days (AUC range, 0.550-0.694) with little association among the risk scores. Limitations include failure to capture all presenting PEs and inability to differentiate between all-cause and specific PE-related mortality. 

Bottom line: While helpful in predicting shorter-term mortality, acute PE risk scores are not highly accurate at predicting longer-term mortality and should be integrated with broad clinical information when making management decisions.

Citation: Barnes GD et al. Comparison of 4 acute pulmonary embolism mortality risk scores in patients evaluated by pulmonary embolism response teams. JAMA Netw Open. 2020 Aug 3;3(8):e2010779. doi: 10.1001/jamanetworkopen.2020.10779.

Dr. Korovaichuk is a hospitalist at Northwestern Memorial Hospital and assistant professor of medicine, Feinberg School of Medicine, both in Chicago.

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Background: Though most PEs do not have significant complications, 15% may be associated with risk of death or hemodynamic compromise. Retrospectively derived risk scores are used to risk-stratify patients and guide acute treatment strategies. It is unclear how well existing risk scores estimate mortality outcomes in patients with acute PE. 

Dr. Sophia Korovaichuk


Study design: Multicenter cohort study.

Setting: Eight hospitals participating in Pulmonary Embolism Response Team (PERT) consortium registry.

Synopsis: The study included 416 patients with radiographically confirmed acute PE, baseline data for risk calculations, and PERT consultation to consider advanced therapies. Four risk scores (PESI, simplified PESI, BOVA, and European Society of Cardiology) were calculated for each patient independently of clinical care. Patients were assigned into lower- and higher-­risk groups. All-cause mortality was assessed on days 7 and 30. The discrimination of each risk score was measured using area under the curve (AUC). Seven-day mortality ranged 1.3%-3.1% in the lower-risk group, and 7%-16.3% in the high-risk group. Thirty-day mortality in the low-risk group ranged 2.6%-10.2% and 14.4%-26.3% in the high-risk group. PE risk scores have only moderate discrimination for mortality at 7 days (AUC range, 0.616-0.666) and less discrimination at 30 days (AUC range, 0.550-0.694) with little association among the risk scores. Limitations include failure to capture all presenting PEs and inability to differentiate between all-cause and specific PE-related mortality. 

Bottom line: While helpful in predicting shorter-term mortality, acute PE risk scores are not highly accurate at predicting longer-term mortality and should be integrated with broad clinical information when making management decisions.

Citation: Barnes GD et al. Comparison of 4 acute pulmonary embolism mortality risk scores in patients evaluated by pulmonary embolism response teams. JAMA Netw Open. 2020 Aug 3;3(8):e2010779. doi: 10.1001/jamanetworkopen.2020.10779.

Dr. Korovaichuk is a hospitalist at Northwestern Memorial Hospital and assistant professor of medicine, Feinberg School of Medicine, both in Chicago.

Background: Though most PEs do not have significant complications, 15% may be associated with risk of death or hemodynamic compromise. Retrospectively derived risk scores are used to risk-stratify patients and guide acute treatment strategies. It is unclear how well existing risk scores estimate mortality outcomes in patients with acute PE. 

Dr. Sophia Korovaichuk


Study design: Multicenter cohort study.

Setting: Eight hospitals participating in Pulmonary Embolism Response Team (PERT) consortium registry.

Synopsis: The study included 416 patients with radiographically confirmed acute PE, baseline data for risk calculations, and PERT consultation to consider advanced therapies. Four risk scores (PESI, simplified PESI, BOVA, and European Society of Cardiology) were calculated for each patient independently of clinical care. Patients were assigned into lower- and higher-­risk groups. All-cause mortality was assessed on days 7 and 30. The discrimination of each risk score was measured using area under the curve (AUC). Seven-day mortality ranged 1.3%-3.1% in the lower-risk group, and 7%-16.3% in the high-risk group. Thirty-day mortality in the low-risk group ranged 2.6%-10.2% and 14.4%-26.3% in the high-risk group. PE risk scores have only moderate discrimination for mortality at 7 days (AUC range, 0.616-0.666) and less discrimination at 30 days (AUC range, 0.550-0.694) with little association among the risk scores. Limitations include failure to capture all presenting PEs and inability to differentiate between all-cause and specific PE-related mortality. 

Bottom line: While helpful in predicting shorter-term mortality, acute PE risk scores are not highly accurate at predicting longer-term mortality and should be integrated with broad clinical information when making management decisions.

Citation: Barnes GD et al. Comparison of 4 acute pulmonary embolism mortality risk scores in patients evaluated by pulmonary embolism response teams. JAMA Netw Open. 2020 Aug 3;3(8):e2010779. doi: 10.1001/jamanetworkopen.2020.10779.

Dr. Korovaichuk is a hospitalist at Northwestern Memorial Hospital and assistant professor of medicine, Feinberg School of Medicine, both in Chicago.

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EHRs have no impact on inpatient heart failure clinical choices or outcomes

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Changed
Tue, 11/16/2021 - 07:52

When provided at the bedside of patients hospitalized for heart failure, an electronic health record (EHR) alert with prognostic information did not improve outcomes or appear to have any impact on what treatments were offered.

There was no signal that the EHR prognostic alerts, which identified the 12-month risk of mortality, had any impact on any of a variety of clinical-decision-making metrics or on any of the primary or secondary outcomes, according to Tariq Ahmad, MD, who reported results of the randomized REVEAL-HF trial, presented at the American Heart Association scientific sessions.

“These results call into question the hypothesis that accurate prognostic information alone will lead to better clinical decision-making,” said Dr. Ahmad, medical director of the Heart Transplant and Mechanical Circulatory Support Program at Yale University, New Haven, Conn., and principal investigator of REVEAL-HF.

He acknowledged that the possibility that many clinicians pay little or no attention to EHR alert might have played a role in the negative results.

At four participating Yale-affiliated clinical centers, all patients hospitalized for acute heart failure were randomized as long as they were over the age of 18, had an N-terminal pro-brain natriuretic peptide (NT-proBNP) level above 500 pg/mL, and had been placed on IV diuretics within 24 hours of admission. In the experimental arm, the provider at the time of entering orders received an EHR alert with an estimate of the risk of all-cause mortality at 12 months. There was no such alert for patients managed in the control arm.
 

Twelve-month mortality estimates calculated

The all-cause mortality risk was calculated on a sizeable list of variables that included laboratory results, such as cell counts, and patient characteristics, such as weight and age. The risk estimate was displayed along with a five-category color-coded bar to provide context for the risk in the spectrum of very low, low, medium, high, and very high likelihood of death within 12 months.

The 1,590 patients randomized to the experimental arm and the 1,534 patients randomized to the usual care arm did not differ significantly in any baseline characteristics. The median age was about 77 years, the mean left ventricular ejection fraction (LVEF) was 55%. About 29% had an LVEF below 40%, about 40% had chronic kidney disease, and about 30% had chronic obstructive pulmonary disease (COPD).

The composite primary outcome of all-cause mortality or rehospitalization within 12 months was reached by 38.9% and 39.3% (P = 0.82) of the intervention and control arms, respectively. The components of the primary outcome were also nearly identical, as was inpatient mortality (8.4% vs. 8.8%; P = 0.72).

There were no significant differences in any of the secondary outcomes, which included rates of 30-day rehospitalizations, discharge on guideline-recommended heart failure therapies, implantation of a cardioverter defibrillator, use of a left ventricular assist device, or heart transplant.

The proportion of patients referred for palliative care was almost identical in the very low, low, and medium risk groups. In the high (23.4 vs. 15.6; P = 0.19) and very high (50% vs. 40%; P = 0.92) groups, there were numerically more referrals in the group randomized to usual care, but these rates did not reach significance.
 

 

 

No differences seen in discharge meds

There was essentially no difference between groups in the rates at which patients were discharged on beta-blockers, renin-angiotensin system inhibitors, sodium-glucose co-transporter type 2 (SGLT2) inhibitors, or mineralocorticoid antagonists.

When prespecified subgroups, such as those older than age 75 years relative to those younger, males relative to females, Black versus White participants, patients with reduced ejection fraction (HFrEF) relative to preserved ejection fraction (HFpEF), and intensive care unit versus non-ICU patients, were compared, there were no indications that the EHR alert improved outcomes.

Invited discussant Harriette G. C. Van Spall, MD, director of digital health and virtual care and associate professor of cardiology at McMaster University, Hamilton, Ont., did not dispute the conclusions, but she pointed out several potential explanations for the neutral result.

Dr. Harriette G.C. Van Spall

Not least, nearly 75% of those enrolled had low risk or very low risk for adverse outcomes within 1 year, so the opportunity to show a reduction in events, including all-cause mortality, was limited.

“This was largely a HFpEF population, for which there are no treatments for which a risk score would change therapy,” she said.
 

EHR alert efficacy questioned

There is considerable evidence that risk prediction tools “are common but underutilized in HF,” Dr. Van Spall added. She noted that many clinicians find alerts in the EHR more annoying than informative, and it remains unknown what proportion of clinicians pay attention to them, particularly in the absence of evidence that they lead to meaningful improvements in care over their own clinical judgment.

Dr. Ahmad agreed.

“I think that we need to study these alerts in a clinical trial format,” he said. Acknowledging that alerts have been poorly received by many clinicians, Dr. Ahmad said that trials to validate the impact of any specific alert are needed to improve their credibility. If a positive impact cannot be shown, he said the alert should be eliminated, leaving only the alerts with proven clinical value.

Dr. Ahmad reported financial relationships with Amgen, AstraZeneca, Boehringer Ingelheim, Cytokinetics, Novartis, and Relypsa. Dr. Van Spall reports no potential conflicts of interest.

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When provided at the bedside of patients hospitalized for heart failure, an electronic health record (EHR) alert with prognostic information did not improve outcomes or appear to have any impact on what treatments were offered.

There was no signal that the EHR prognostic alerts, which identified the 12-month risk of mortality, had any impact on any of a variety of clinical-decision-making metrics or on any of the primary or secondary outcomes, according to Tariq Ahmad, MD, who reported results of the randomized REVEAL-HF trial, presented at the American Heart Association scientific sessions.

“These results call into question the hypothesis that accurate prognostic information alone will lead to better clinical decision-making,” said Dr. Ahmad, medical director of the Heart Transplant and Mechanical Circulatory Support Program at Yale University, New Haven, Conn., and principal investigator of REVEAL-HF.

He acknowledged that the possibility that many clinicians pay little or no attention to EHR alert might have played a role in the negative results.

At four participating Yale-affiliated clinical centers, all patients hospitalized for acute heart failure were randomized as long as they were over the age of 18, had an N-terminal pro-brain natriuretic peptide (NT-proBNP) level above 500 pg/mL, and had been placed on IV diuretics within 24 hours of admission. In the experimental arm, the provider at the time of entering orders received an EHR alert with an estimate of the risk of all-cause mortality at 12 months. There was no such alert for patients managed in the control arm.
 

Twelve-month mortality estimates calculated

The all-cause mortality risk was calculated on a sizeable list of variables that included laboratory results, such as cell counts, and patient characteristics, such as weight and age. The risk estimate was displayed along with a five-category color-coded bar to provide context for the risk in the spectrum of very low, low, medium, high, and very high likelihood of death within 12 months.

The 1,590 patients randomized to the experimental arm and the 1,534 patients randomized to the usual care arm did not differ significantly in any baseline characteristics. The median age was about 77 years, the mean left ventricular ejection fraction (LVEF) was 55%. About 29% had an LVEF below 40%, about 40% had chronic kidney disease, and about 30% had chronic obstructive pulmonary disease (COPD).

The composite primary outcome of all-cause mortality or rehospitalization within 12 months was reached by 38.9% and 39.3% (P = 0.82) of the intervention and control arms, respectively. The components of the primary outcome were also nearly identical, as was inpatient mortality (8.4% vs. 8.8%; P = 0.72).

There were no significant differences in any of the secondary outcomes, which included rates of 30-day rehospitalizations, discharge on guideline-recommended heart failure therapies, implantation of a cardioverter defibrillator, use of a left ventricular assist device, or heart transplant.

The proportion of patients referred for palliative care was almost identical in the very low, low, and medium risk groups. In the high (23.4 vs. 15.6; P = 0.19) and very high (50% vs. 40%; P = 0.92) groups, there were numerically more referrals in the group randomized to usual care, but these rates did not reach significance.
 

 

 

No differences seen in discharge meds

There was essentially no difference between groups in the rates at which patients were discharged on beta-blockers, renin-angiotensin system inhibitors, sodium-glucose co-transporter type 2 (SGLT2) inhibitors, or mineralocorticoid antagonists.

When prespecified subgroups, such as those older than age 75 years relative to those younger, males relative to females, Black versus White participants, patients with reduced ejection fraction (HFrEF) relative to preserved ejection fraction (HFpEF), and intensive care unit versus non-ICU patients, were compared, there were no indications that the EHR alert improved outcomes.

Invited discussant Harriette G. C. Van Spall, MD, director of digital health and virtual care and associate professor of cardiology at McMaster University, Hamilton, Ont., did not dispute the conclusions, but she pointed out several potential explanations for the neutral result.

Dr. Harriette G.C. Van Spall

Not least, nearly 75% of those enrolled had low risk or very low risk for adverse outcomes within 1 year, so the opportunity to show a reduction in events, including all-cause mortality, was limited.

“This was largely a HFpEF population, for which there are no treatments for which a risk score would change therapy,” she said.
 

EHR alert efficacy questioned

There is considerable evidence that risk prediction tools “are common but underutilized in HF,” Dr. Van Spall added. She noted that many clinicians find alerts in the EHR more annoying than informative, and it remains unknown what proportion of clinicians pay attention to them, particularly in the absence of evidence that they lead to meaningful improvements in care over their own clinical judgment.

Dr. Ahmad agreed.

“I think that we need to study these alerts in a clinical trial format,” he said. Acknowledging that alerts have been poorly received by many clinicians, Dr. Ahmad said that trials to validate the impact of any specific alert are needed to improve their credibility. If a positive impact cannot be shown, he said the alert should be eliminated, leaving only the alerts with proven clinical value.

Dr. Ahmad reported financial relationships with Amgen, AstraZeneca, Boehringer Ingelheim, Cytokinetics, Novartis, and Relypsa. Dr. Van Spall reports no potential conflicts of interest.

When provided at the bedside of patients hospitalized for heart failure, an electronic health record (EHR) alert with prognostic information did not improve outcomes or appear to have any impact on what treatments were offered.

There was no signal that the EHR prognostic alerts, which identified the 12-month risk of mortality, had any impact on any of a variety of clinical-decision-making metrics or on any of the primary or secondary outcomes, according to Tariq Ahmad, MD, who reported results of the randomized REVEAL-HF trial, presented at the American Heart Association scientific sessions.

“These results call into question the hypothesis that accurate prognostic information alone will lead to better clinical decision-making,” said Dr. Ahmad, medical director of the Heart Transplant and Mechanical Circulatory Support Program at Yale University, New Haven, Conn., and principal investigator of REVEAL-HF.

He acknowledged that the possibility that many clinicians pay little or no attention to EHR alert might have played a role in the negative results.

At four participating Yale-affiliated clinical centers, all patients hospitalized for acute heart failure were randomized as long as they were over the age of 18, had an N-terminal pro-brain natriuretic peptide (NT-proBNP) level above 500 pg/mL, and had been placed on IV diuretics within 24 hours of admission. In the experimental arm, the provider at the time of entering orders received an EHR alert with an estimate of the risk of all-cause mortality at 12 months. There was no such alert for patients managed in the control arm.
 

Twelve-month mortality estimates calculated

The all-cause mortality risk was calculated on a sizeable list of variables that included laboratory results, such as cell counts, and patient characteristics, such as weight and age. The risk estimate was displayed along with a five-category color-coded bar to provide context for the risk in the spectrum of very low, low, medium, high, and very high likelihood of death within 12 months.

The 1,590 patients randomized to the experimental arm and the 1,534 patients randomized to the usual care arm did not differ significantly in any baseline characteristics. The median age was about 77 years, the mean left ventricular ejection fraction (LVEF) was 55%. About 29% had an LVEF below 40%, about 40% had chronic kidney disease, and about 30% had chronic obstructive pulmonary disease (COPD).

The composite primary outcome of all-cause mortality or rehospitalization within 12 months was reached by 38.9% and 39.3% (P = 0.82) of the intervention and control arms, respectively. The components of the primary outcome were also nearly identical, as was inpatient mortality (8.4% vs. 8.8%; P = 0.72).

There were no significant differences in any of the secondary outcomes, which included rates of 30-day rehospitalizations, discharge on guideline-recommended heart failure therapies, implantation of a cardioverter defibrillator, use of a left ventricular assist device, or heart transplant.

The proportion of patients referred for palliative care was almost identical in the very low, low, and medium risk groups. In the high (23.4 vs. 15.6; P = 0.19) and very high (50% vs. 40%; P = 0.92) groups, there were numerically more referrals in the group randomized to usual care, but these rates did not reach significance.
 

 

 

No differences seen in discharge meds

There was essentially no difference between groups in the rates at which patients were discharged on beta-blockers, renin-angiotensin system inhibitors, sodium-glucose co-transporter type 2 (SGLT2) inhibitors, or mineralocorticoid antagonists.

When prespecified subgroups, such as those older than age 75 years relative to those younger, males relative to females, Black versus White participants, patients with reduced ejection fraction (HFrEF) relative to preserved ejection fraction (HFpEF), and intensive care unit versus non-ICU patients, were compared, there were no indications that the EHR alert improved outcomes.

Invited discussant Harriette G. C. Van Spall, MD, director of digital health and virtual care and associate professor of cardiology at McMaster University, Hamilton, Ont., did not dispute the conclusions, but she pointed out several potential explanations for the neutral result.

Dr. Harriette G.C. Van Spall

Not least, nearly 75% of those enrolled had low risk or very low risk for adverse outcomes within 1 year, so the opportunity to show a reduction in events, including all-cause mortality, was limited.

“This was largely a HFpEF population, for which there are no treatments for which a risk score would change therapy,” she said.
 

EHR alert efficacy questioned

There is considerable evidence that risk prediction tools “are common but underutilized in HF,” Dr. Van Spall added. She noted that many clinicians find alerts in the EHR more annoying than informative, and it remains unknown what proportion of clinicians pay attention to them, particularly in the absence of evidence that they lead to meaningful improvements in care over their own clinical judgment.

Dr. Ahmad agreed.

“I think that we need to study these alerts in a clinical trial format,” he said. Acknowledging that alerts have been poorly received by many clinicians, Dr. Ahmad said that trials to validate the impact of any specific alert are needed to improve their credibility. If a positive impact cannot be shown, he said the alert should be eliminated, leaving only the alerts with proven clinical value.

Dr. Ahmad reported financial relationships with Amgen, AstraZeneca, Boehringer Ingelheim, Cytokinetics, Novartis, and Relypsa. Dr. Van Spall reports no potential conflicts of interest.

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