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Eliminating hepatitis by 2030: HHS releases new strategic plan
In an effort to counteract alarming trends in rising hepatitis infections, the U.S. Department of Health and Human Services has developed and released its Viral Hepatitis National Strategic Plan 2021-2025, which aims to eliminate viral hepatitis infection in the United States by 2030.
An estimated 3.3 million people in the United States were chronically infected with hepatitis B (HBV) and hepatitis C (HCV) as of 2016. In addition, the country “is currently facing unprecedented hepatitis A (HAV) outbreaks, while progress in preventing hepatitis B has stalled, and hepatitis C rates nearly tripled from 2011 to 2018,” according to the HHS.
The new plan, “A Roadmap to Elimination for the United States,” builds upon previous initiatives the HHS has made to tackle the diseases and was coordinated by the Office of the Assistant Secretary for Health through the Office of Infectious Disease and HIV/AIDS Policy.
The plan focuses on HAV, HBV, and HCV, which have the largest impact on the health of the nation, according to the HHS. The plan addresses populations with the highest burden of viral hepatitis based on nationwide data so that resources can be focused there to achieve the greatest impact. Persons who inject drugs are a priority population for all three hepatitis viruses. HAV efforts will also include a focus on the homeless population. HBV efforts will also focus on Asian and Pacific Islander and the Black, non-Hispanic populations, while HCV efforts will include a focus on Black, non-Hispanic people, people born during 1945-1965, people with HIV, and the American Indian/Alaska Native population.
Goal-setting
There are five main goals outlined in the plan, according to the HHS:
- Prevent new hepatitis infections.
- Improve hepatitis-related health outcomes of people with viral hepatitis.
- Reduce hepatitis-related disparities and health inequities.
- Improve hepatitis surveillance and data use.
- Achieve integrated, coordinated efforts that address the viral hepatitis epidemics among all partners and stakeholders.
“The United States will be a place where new viral hepatitis infections are prevented, every person knows their status, and every person with viral hepatitis has high-quality health care and treatment and lives free from stigma and discrimination. This vision includes all people, regardless of age, sex, gender identity, sexual orientation, race, ethnicity, religion, disability, geographic location, or socioeconomic circumstance,” according to the HHS vision statement.
In an effort to counteract alarming trends in rising hepatitis infections, the U.S. Department of Health and Human Services has developed and released its Viral Hepatitis National Strategic Plan 2021-2025, which aims to eliminate viral hepatitis infection in the United States by 2030.
An estimated 3.3 million people in the United States were chronically infected with hepatitis B (HBV) and hepatitis C (HCV) as of 2016. In addition, the country “is currently facing unprecedented hepatitis A (HAV) outbreaks, while progress in preventing hepatitis B has stalled, and hepatitis C rates nearly tripled from 2011 to 2018,” according to the HHS.
The new plan, “A Roadmap to Elimination for the United States,” builds upon previous initiatives the HHS has made to tackle the diseases and was coordinated by the Office of the Assistant Secretary for Health through the Office of Infectious Disease and HIV/AIDS Policy.
The plan focuses on HAV, HBV, and HCV, which have the largest impact on the health of the nation, according to the HHS. The plan addresses populations with the highest burden of viral hepatitis based on nationwide data so that resources can be focused there to achieve the greatest impact. Persons who inject drugs are a priority population for all three hepatitis viruses. HAV efforts will also include a focus on the homeless population. HBV efforts will also focus on Asian and Pacific Islander and the Black, non-Hispanic populations, while HCV efforts will include a focus on Black, non-Hispanic people, people born during 1945-1965, people with HIV, and the American Indian/Alaska Native population.
Goal-setting
There are five main goals outlined in the plan, according to the HHS:
- Prevent new hepatitis infections.
- Improve hepatitis-related health outcomes of people with viral hepatitis.
- Reduce hepatitis-related disparities and health inequities.
- Improve hepatitis surveillance and data use.
- Achieve integrated, coordinated efforts that address the viral hepatitis epidemics among all partners and stakeholders.
“The United States will be a place where new viral hepatitis infections are prevented, every person knows their status, and every person with viral hepatitis has high-quality health care and treatment and lives free from stigma and discrimination. This vision includes all people, regardless of age, sex, gender identity, sexual orientation, race, ethnicity, religion, disability, geographic location, or socioeconomic circumstance,” according to the HHS vision statement.
In an effort to counteract alarming trends in rising hepatitis infections, the U.S. Department of Health and Human Services has developed and released its Viral Hepatitis National Strategic Plan 2021-2025, which aims to eliminate viral hepatitis infection in the United States by 2030.
An estimated 3.3 million people in the United States were chronically infected with hepatitis B (HBV) and hepatitis C (HCV) as of 2016. In addition, the country “is currently facing unprecedented hepatitis A (HAV) outbreaks, while progress in preventing hepatitis B has stalled, and hepatitis C rates nearly tripled from 2011 to 2018,” according to the HHS.
The new plan, “A Roadmap to Elimination for the United States,” builds upon previous initiatives the HHS has made to tackle the diseases and was coordinated by the Office of the Assistant Secretary for Health through the Office of Infectious Disease and HIV/AIDS Policy.
The plan focuses on HAV, HBV, and HCV, which have the largest impact on the health of the nation, according to the HHS. The plan addresses populations with the highest burden of viral hepatitis based on nationwide data so that resources can be focused there to achieve the greatest impact. Persons who inject drugs are a priority population for all three hepatitis viruses. HAV efforts will also include a focus on the homeless population. HBV efforts will also focus on Asian and Pacific Islander and the Black, non-Hispanic populations, while HCV efforts will include a focus on Black, non-Hispanic people, people born during 1945-1965, people with HIV, and the American Indian/Alaska Native population.
Goal-setting
There are five main goals outlined in the plan, according to the HHS:
- Prevent new hepatitis infections.
- Improve hepatitis-related health outcomes of people with viral hepatitis.
- Reduce hepatitis-related disparities and health inequities.
- Improve hepatitis surveillance and data use.
- Achieve integrated, coordinated efforts that address the viral hepatitis epidemics among all partners and stakeholders.
“The United States will be a place where new viral hepatitis infections are prevented, every person knows their status, and every person with viral hepatitis has high-quality health care and treatment and lives free from stigma and discrimination. This vision includes all people, regardless of age, sex, gender identity, sexual orientation, race, ethnicity, religion, disability, geographic location, or socioeconomic circumstance,” according to the HHS vision statement.
NEWS FROM HHS
Childhood smoking and depression contribute to young adult opioid use
Depression and tobacco use in childhood significantly increased the risk for opioid use in young adults, according to data from a prospective study of approximately 1,000 individuals.
Previous research, including the annual Monitoring the Future study, documents opioid use among adolescents in the United States, but childhood risk factors for opioid use in young adults have not been well studied, wrote Lilly Shanahan, PhD, of the University of Zürich, and colleagues.
In a prospective cohort study published in JAMA Pediatrics, the researchers identified 1,252 non-Hispanic White and American Indian opioid-naive individuals aged 9-16 years in rural North Carolina. They interviewed participants and parents up to 7 times between January 1993 and December 2000, and interviewed participants only at ages 19, 21, 25, and 30 years between January 1999 and December 2015.
Overall, 24.2% of study participants had used a nonheroin opioid by age 30 years, and both chronic depression and dysthymia were significantly associated with this use (odds ratios 5.43 and 7.13, respectively).
In addition, 155 participants (8.8%) reported weekly use of a nonheroin opioid, and 95 (6.6%) reported weekly heroin use by age 30 years. Chronic depression and dysthymia also were strongly associated with weekly nonheroin opioid use (OR 8.89 and 11.51, respectively).
In a multivariate analysis, depression, tobacco use, and cannabis use at ages 9-16 years were strongly associated with overall opioid use at ages 19-30 years.
“One possible reason childhood chronic depression increases the risk of later opioid use is self-medication, including the use of psychoactive substances, to alleviate depression,” the researchers noted. In addition, the mood-altering properties of opioids may increase their appeal to depressed youth as a way to relieve impaired reward system function, they said.
Potential mechanisms for the association between early tobacco use and later opioid use include the alterations to neurodevelopment caused by nicotine exposure in adolescence, as well as increased risk for depression, reduced pain thresholds, and use of nicotine as a gateway to harder drugs, the researchers added.
Several childhood risk factors were not associated with young adult opioid use in multivariate analysis in this study, including alcohol use, sociodemographic status, maltreatment, family dysfunction, and anxiety, the researchers wrote. “Previous studies typically measured these risk factors retrospectively or in late adolescence and young adulthood, and most did not consider depressive disorders, which may mediate associations between select childhood risk factors and later opioid use,” they said.
The study findings were limited by several factors, including the inability to distinguish between medical and nonmedical opioid use, the incomplete list of available opioids, and the exclusion of Black participants because of low sample size, the researchers noted. However, the results were strengthened by the longitudinal, community-representative design and the inclusion of up to 11 assessments of opioid use, they said.
“Our findings suggest strong opportunities for early prevention and intervention, including in primary care settings,” using known evidence-based strategies, they concluded.
More screening is needed
“Children in the United States are at high risk of serious adult health issues as a result of childhood factors such as ACEs (adverse childhood experiences),” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “This study looks prospectively at other factors in childhood over a long period of time leading to opioid usage, with its serious risks and health consequences including overdose death,” she said. “It is unclear what the effects of COVID-19 will be on the population of children growing up now and how opioid usage might change as a result,” she noted.
“Some of the links to adult usage are predictable, such as depression, tobacco use, and cannabis use in early adolescence,” said Dr. Boulter. “Surprising was the lack of correlation between anxiety, early alcohol use, child mistreatment, and sociodemographic factors with future opioid use,” she said.
The take-home message for clinicians is to screen children and adolescents for factors leading to opioid usage in young adults “with preventive strategies including avoidance of pain medication prescriptions and early referral and treatment for depression and use of cannabis and tobacco products using tools like SBIRT (Screening, Brief Intervention, and Referral to Treatment),” Dr. Boulter emphasized.
As for additional research, “It would be interesting to study e-cigarette usage and see if the correlation with future opioid usage is similar to older tobacco products,” she said. “Also helpful would be to delve deeper into connections between medical or dental diagnoses when opioids were first prescribed and later usage of those products,” Dr. Boulter noted.
The study was supported in part by the by the National Institute of Mental Health and the National Institute on Drug Abuse. The researchers had no financial conflicts to disclose. Dr. Boulter had no disclosures but serves on the Pediatric News Editorial Advisory Board.
Depression and tobacco use in childhood significantly increased the risk for opioid use in young adults, according to data from a prospective study of approximately 1,000 individuals.
Previous research, including the annual Monitoring the Future study, documents opioid use among adolescents in the United States, but childhood risk factors for opioid use in young adults have not been well studied, wrote Lilly Shanahan, PhD, of the University of Zürich, and colleagues.
In a prospective cohort study published in JAMA Pediatrics, the researchers identified 1,252 non-Hispanic White and American Indian opioid-naive individuals aged 9-16 years in rural North Carolina. They interviewed participants and parents up to 7 times between January 1993 and December 2000, and interviewed participants only at ages 19, 21, 25, and 30 years between January 1999 and December 2015.
Overall, 24.2% of study participants had used a nonheroin opioid by age 30 years, and both chronic depression and dysthymia were significantly associated with this use (odds ratios 5.43 and 7.13, respectively).
In addition, 155 participants (8.8%) reported weekly use of a nonheroin opioid, and 95 (6.6%) reported weekly heroin use by age 30 years. Chronic depression and dysthymia also were strongly associated with weekly nonheroin opioid use (OR 8.89 and 11.51, respectively).
In a multivariate analysis, depression, tobacco use, and cannabis use at ages 9-16 years were strongly associated with overall opioid use at ages 19-30 years.
“One possible reason childhood chronic depression increases the risk of later opioid use is self-medication, including the use of psychoactive substances, to alleviate depression,” the researchers noted. In addition, the mood-altering properties of opioids may increase their appeal to depressed youth as a way to relieve impaired reward system function, they said.
Potential mechanisms for the association between early tobacco use and later opioid use include the alterations to neurodevelopment caused by nicotine exposure in adolescence, as well as increased risk for depression, reduced pain thresholds, and use of nicotine as a gateway to harder drugs, the researchers added.
Several childhood risk factors were not associated with young adult opioid use in multivariate analysis in this study, including alcohol use, sociodemographic status, maltreatment, family dysfunction, and anxiety, the researchers wrote. “Previous studies typically measured these risk factors retrospectively or in late adolescence and young adulthood, and most did not consider depressive disorders, which may mediate associations between select childhood risk factors and later opioid use,” they said.
The study findings were limited by several factors, including the inability to distinguish between medical and nonmedical opioid use, the incomplete list of available opioids, and the exclusion of Black participants because of low sample size, the researchers noted. However, the results were strengthened by the longitudinal, community-representative design and the inclusion of up to 11 assessments of opioid use, they said.
“Our findings suggest strong opportunities for early prevention and intervention, including in primary care settings,” using known evidence-based strategies, they concluded.
More screening is needed
“Children in the United States are at high risk of serious adult health issues as a result of childhood factors such as ACEs (adverse childhood experiences),” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “This study looks prospectively at other factors in childhood over a long period of time leading to opioid usage, with its serious risks and health consequences including overdose death,” she said. “It is unclear what the effects of COVID-19 will be on the population of children growing up now and how opioid usage might change as a result,” she noted.
“Some of the links to adult usage are predictable, such as depression, tobacco use, and cannabis use in early adolescence,” said Dr. Boulter. “Surprising was the lack of correlation between anxiety, early alcohol use, child mistreatment, and sociodemographic factors with future opioid use,” she said.
The take-home message for clinicians is to screen children and adolescents for factors leading to opioid usage in young adults “with preventive strategies including avoidance of pain medication prescriptions and early referral and treatment for depression and use of cannabis and tobacco products using tools like SBIRT (Screening, Brief Intervention, and Referral to Treatment),” Dr. Boulter emphasized.
As for additional research, “It would be interesting to study e-cigarette usage and see if the correlation with future opioid usage is similar to older tobacco products,” she said. “Also helpful would be to delve deeper into connections between medical or dental diagnoses when opioids were first prescribed and later usage of those products,” Dr. Boulter noted.
The study was supported in part by the by the National Institute of Mental Health and the National Institute on Drug Abuse. The researchers had no financial conflicts to disclose. Dr. Boulter had no disclosures but serves on the Pediatric News Editorial Advisory Board.
Depression and tobacco use in childhood significantly increased the risk for opioid use in young adults, according to data from a prospective study of approximately 1,000 individuals.
Previous research, including the annual Monitoring the Future study, documents opioid use among adolescents in the United States, but childhood risk factors for opioid use in young adults have not been well studied, wrote Lilly Shanahan, PhD, of the University of Zürich, and colleagues.
In a prospective cohort study published in JAMA Pediatrics, the researchers identified 1,252 non-Hispanic White and American Indian opioid-naive individuals aged 9-16 years in rural North Carolina. They interviewed participants and parents up to 7 times between January 1993 and December 2000, and interviewed participants only at ages 19, 21, 25, and 30 years between January 1999 and December 2015.
Overall, 24.2% of study participants had used a nonheroin opioid by age 30 years, and both chronic depression and dysthymia were significantly associated with this use (odds ratios 5.43 and 7.13, respectively).
In addition, 155 participants (8.8%) reported weekly use of a nonheroin opioid, and 95 (6.6%) reported weekly heroin use by age 30 years. Chronic depression and dysthymia also were strongly associated with weekly nonheroin opioid use (OR 8.89 and 11.51, respectively).
In a multivariate analysis, depression, tobacco use, and cannabis use at ages 9-16 years were strongly associated with overall opioid use at ages 19-30 years.
“One possible reason childhood chronic depression increases the risk of later opioid use is self-medication, including the use of psychoactive substances, to alleviate depression,” the researchers noted. In addition, the mood-altering properties of opioids may increase their appeal to depressed youth as a way to relieve impaired reward system function, they said.
Potential mechanisms for the association between early tobacco use and later opioid use include the alterations to neurodevelopment caused by nicotine exposure in adolescence, as well as increased risk for depression, reduced pain thresholds, and use of nicotine as a gateway to harder drugs, the researchers added.
Several childhood risk factors were not associated with young adult opioid use in multivariate analysis in this study, including alcohol use, sociodemographic status, maltreatment, family dysfunction, and anxiety, the researchers wrote. “Previous studies typically measured these risk factors retrospectively or in late adolescence and young adulthood, and most did not consider depressive disorders, which may mediate associations between select childhood risk factors and later opioid use,” they said.
The study findings were limited by several factors, including the inability to distinguish between medical and nonmedical opioid use, the incomplete list of available opioids, and the exclusion of Black participants because of low sample size, the researchers noted. However, the results were strengthened by the longitudinal, community-representative design and the inclusion of up to 11 assessments of opioid use, they said.
“Our findings suggest strong opportunities for early prevention and intervention, including in primary care settings,” using known evidence-based strategies, they concluded.
More screening is needed
“Children in the United States are at high risk of serious adult health issues as a result of childhood factors such as ACEs (adverse childhood experiences),” said Suzanne C. Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H. “This study looks prospectively at other factors in childhood over a long period of time leading to opioid usage, with its serious risks and health consequences including overdose death,” she said. “It is unclear what the effects of COVID-19 will be on the population of children growing up now and how opioid usage might change as a result,” she noted.
“Some of the links to adult usage are predictable, such as depression, tobacco use, and cannabis use in early adolescence,” said Dr. Boulter. “Surprising was the lack of correlation between anxiety, early alcohol use, child mistreatment, and sociodemographic factors with future opioid use,” she said.
The take-home message for clinicians is to screen children and adolescents for factors leading to opioid usage in young adults “with preventive strategies including avoidance of pain medication prescriptions and early referral and treatment for depression and use of cannabis and tobacco products using tools like SBIRT (Screening, Brief Intervention, and Referral to Treatment),” Dr. Boulter emphasized.
As for additional research, “It would be interesting to study e-cigarette usage and see if the correlation with future opioid usage is similar to older tobacco products,” she said. “Also helpful would be to delve deeper into connections between medical or dental diagnoses when opioids were first prescribed and later usage of those products,” Dr. Boulter noted.
The study was supported in part by the by the National Institute of Mental Health and the National Institute on Drug Abuse. The researchers had no financial conflicts to disclose. Dr. Boulter had no disclosures but serves on the Pediatric News Editorial Advisory Board.
FROM JAMA PEDIATRICS
Endocrine Society calls for action to reduce insulin costs
The Endocrine Society has issued a new position statement calling on all stakeholders, including clinicians, to play a role in reducing the cost of insulin for patients with diabetes in the United States.
“Addressing Insulin Access and Affordability: An Endocrine Society Position Statement,” was published online Jan. 12 in the Journal of Clinical Endocrinology and Metabolism.
“The society believes all stakeholders across the supply chain have a role to play in addressing the high price of insulin,” said the 11 authors, who are all members of the society’s advocacy and public outreach core committee.
This is the first such statement from a major professional organization in 2021, which is the 100th anniversary of the discovery of insulin.
And the call for action was issued just a week prior to the inauguration of incoming U.S. President Joe Biden, who has pledged to “build on the Affordable Care Act by giving Americans more choice, reducing health care costs, and making our health care system less complex to navigate.”
The cost of insulin has nearly tripled in the past 15 years in the United States, and a lack of transparency in the drug supply chain has made it challenging to identify and address the causes of soaring costs.
The high cost of insulin has made access particularly difficult for people with diabetes with a low income, who have high-deductible health plans, are Medicare beneficiaries using Part B to cover insulin delivered via pump, or are in the Medicare Part D “donut hole,” as well as young adults once they reach their 26th birthday and can no longer be covered under their parents’ insurance.
“Inventors Frederick Banting and Charles Best sold the insulin patent for a mere $1 in the 1920s because they wanted their discovery to save lives and for insulin to be affordable and accessible to everyone who needed it,” said Endocrine Society President-elect Carol Wysham, MD, of the Rockwood/MultiCare Health Systems, Spokane, Wash.
“People with diabetes without full insurance are often paying increasing out-of-pocket costs for insulin resulting in many rationing their medication or skipping lifesaving doses altogether,” she said.
The society’s statement called for allowing government negotiation of drug prices and greater transparency across the supply chain to elucidate the reasons for rising insulin costs.
For physicians in particular, they advised training in use of lower-cost human NPH and regular insulin for appropriate patients with type 2 diabetes, and considering patients’ individual financial and coverage status when prescribing insulin.
Pharmacists are advised to learn about and share information with patients about lower-cost options offered by manufacturers.
Other policy recommendations for relevant stakeholders include:
- Limit future insulin list price increases to the rate of inflation.
- Limit out-of-pocket costs without increasing premiums or deductibles by limiting cost sharing to copays of no more than $35, providing first-dollar coverage, or capping costs at no more than $100 per month.
- Eliminate rebates or pass savings from rebates along to consumers without increasing premiums or deductibles.
- Expedite approval of insulin biosimilars to create market competition.
- Include real-time benefit information in electronic medical records.
- Develop a payment model for Medicare Part B beneficiaries, as well as Part D, to lower out-of-pocket copays.
For manufacturers, the society also recommended improving patient assistance programs to be less restrictive and more accountable. And employers, they said, should limit copays without increasing premiums or deductibles, and seek plan options that benefit people with diabetes and provide education about these options during open enrollment.
Of the 11 writing panel members, 4 have pharmaceutical industry disclosures.
A version of this article first appeared on Medscape.com.
The Endocrine Society has issued a new position statement calling on all stakeholders, including clinicians, to play a role in reducing the cost of insulin for patients with diabetes in the United States.
“Addressing Insulin Access and Affordability: An Endocrine Society Position Statement,” was published online Jan. 12 in the Journal of Clinical Endocrinology and Metabolism.
“The society believes all stakeholders across the supply chain have a role to play in addressing the high price of insulin,” said the 11 authors, who are all members of the society’s advocacy and public outreach core committee.
This is the first such statement from a major professional organization in 2021, which is the 100th anniversary of the discovery of insulin.
And the call for action was issued just a week prior to the inauguration of incoming U.S. President Joe Biden, who has pledged to “build on the Affordable Care Act by giving Americans more choice, reducing health care costs, and making our health care system less complex to navigate.”
The cost of insulin has nearly tripled in the past 15 years in the United States, and a lack of transparency in the drug supply chain has made it challenging to identify and address the causes of soaring costs.
The high cost of insulin has made access particularly difficult for people with diabetes with a low income, who have high-deductible health plans, are Medicare beneficiaries using Part B to cover insulin delivered via pump, or are in the Medicare Part D “donut hole,” as well as young adults once they reach their 26th birthday and can no longer be covered under their parents’ insurance.
“Inventors Frederick Banting and Charles Best sold the insulin patent for a mere $1 in the 1920s because they wanted their discovery to save lives and for insulin to be affordable and accessible to everyone who needed it,” said Endocrine Society President-elect Carol Wysham, MD, of the Rockwood/MultiCare Health Systems, Spokane, Wash.
“People with diabetes without full insurance are often paying increasing out-of-pocket costs for insulin resulting in many rationing their medication or skipping lifesaving doses altogether,” she said.
The society’s statement called for allowing government negotiation of drug prices and greater transparency across the supply chain to elucidate the reasons for rising insulin costs.
For physicians in particular, they advised training in use of lower-cost human NPH and regular insulin for appropriate patients with type 2 diabetes, and considering patients’ individual financial and coverage status when prescribing insulin.
Pharmacists are advised to learn about and share information with patients about lower-cost options offered by manufacturers.
Other policy recommendations for relevant stakeholders include:
- Limit future insulin list price increases to the rate of inflation.
- Limit out-of-pocket costs without increasing premiums or deductibles by limiting cost sharing to copays of no more than $35, providing first-dollar coverage, or capping costs at no more than $100 per month.
- Eliminate rebates or pass savings from rebates along to consumers without increasing premiums or deductibles.
- Expedite approval of insulin biosimilars to create market competition.
- Include real-time benefit information in electronic medical records.
- Develop a payment model for Medicare Part B beneficiaries, as well as Part D, to lower out-of-pocket copays.
For manufacturers, the society also recommended improving patient assistance programs to be less restrictive and more accountable. And employers, they said, should limit copays without increasing premiums or deductibles, and seek plan options that benefit people with diabetes and provide education about these options during open enrollment.
Of the 11 writing panel members, 4 have pharmaceutical industry disclosures.
A version of this article first appeared on Medscape.com.
The Endocrine Society has issued a new position statement calling on all stakeholders, including clinicians, to play a role in reducing the cost of insulin for patients with diabetes in the United States.
“Addressing Insulin Access and Affordability: An Endocrine Society Position Statement,” was published online Jan. 12 in the Journal of Clinical Endocrinology and Metabolism.
“The society believes all stakeholders across the supply chain have a role to play in addressing the high price of insulin,” said the 11 authors, who are all members of the society’s advocacy and public outreach core committee.
This is the first such statement from a major professional organization in 2021, which is the 100th anniversary of the discovery of insulin.
And the call for action was issued just a week prior to the inauguration of incoming U.S. President Joe Biden, who has pledged to “build on the Affordable Care Act by giving Americans more choice, reducing health care costs, and making our health care system less complex to navigate.”
The cost of insulin has nearly tripled in the past 15 years in the United States, and a lack of transparency in the drug supply chain has made it challenging to identify and address the causes of soaring costs.
The high cost of insulin has made access particularly difficult for people with diabetes with a low income, who have high-deductible health plans, are Medicare beneficiaries using Part B to cover insulin delivered via pump, or are in the Medicare Part D “donut hole,” as well as young adults once they reach their 26th birthday and can no longer be covered under their parents’ insurance.
“Inventors Frederick Banting and Charles Best sold the insulin patent for a mere $1 in the 1920s because they wanted their discovery to save lives and for insulin to be affordable and accessible to everyone who needed it,” said Endocrine Society President-elect Carol Wysham, MD, of the Rockwood/MultiCare Health Systems, Spokane, Wash.
“People with diabetes without full insurance are often paying increasing out-of-pocket costs for insulin resulting in many rationing their medication or skipping lifesaving doses altogether,” she said.
The society’s statement called for allowing government negotiation of drug prices and greater transparency across the supply chain to elucidate the reasons for rising insulin costs.
For physicians in particular, they advised training in use of lower-cost human NPH and regular insulin for appropriate patients with type 2 diabetes, and considering patients’ individual financial and coverage status when prescribing insulin.
Pharmacists are advised to learn about and share information with patients about lower-cost options offered by manufacturers.
Other policy recommendations for relevant stakeholders include:
- Limit future insulin list price increases to the rate of inflation.
- Limit out-of-pocket costs without increasing premiums or deductibles by limiting cost sharing to copays of no more than $35, providing first-dollar coverage, or capping costs at no more than $100 per month.
- Eliminate rebates or pass savings from rebates along to consumers without increasing premiums or deductibles.
- Expedite approval of insulin biosimilars to create market competition.
- Include real-time benefit information in electronic medical records.
- Develop a payment model for Medicare Part B beneficiaries, as well as Part D, to lower out-of-pocket copays.
For manufacturers, the society also recommended improving patient assistance programs to be less restrictive and more accountable. And employers, they said, should limit copays without increasing premiums or deductibles, and seek plan options that benefit people with diabetes and provide education about these options during open enrollment.
Of the 11 writing panel members, 4 have pharmaceutical industry disclosures.
A version of this article first appeared on Medscape.com.
Averting COVID hospitalizations with monoclonal antibodies
The United States has allocated more than 641,000 monoclonal antibody treatments for outpatients to ease pressure on strained hospitals, but officials from Operation Warp Speed report that more than half of that reserve sits unused as clinicians grapple with best practices.
There are space and personnel limitations in hospitals right now, Janet Woodcock, MD, therapeutics lead on Operation Warp Speed, acknowledges in an interview with this news organization. “Special areas and procedures must be set up.” And the operation is in the process of broadening availability beyond hospitals, she points out.
But for frontline clinicians, questions about treatment efficacy and the logistics of administering intravenous drugs to infectious outpatients loom large.
More than 50 monoclonal antibody products that target SARS-CoV-2 are now in development. The U.S. Food and Drug Administration has already issued Emergency Use Authorization (EUA) for two such drugs on the basis of phase 2 trial data – bamlanivimab, made by Eli Lilly, and a cocktail of casirivimab plus imdevimab, made by Regeneron – and another two-antibody cocktail from AstraZeneca, AZD7442, has started phase 3 clinical trials. The Regeneron combination was used to treat President Donald Trump when he contracted COVID-19 in October.
Monoclonal antibody drugs are based on the natural antibodies that the body uses to fight infections. They work by binding to a specific target and then blocking its action or flagging it for destruction by other parts of the immune system. Both bamlanivimab and the casirivimab plus imdevimab combination target the spike protein of the virus and stop it from attaching to and entering human cells.
Targeting the spike protein out of the hospital
The antibody drugs covered by EUAs do not cure COVID-19, but they have been shown to reduce hospitalizations and visits to the emergency department for patients at high risk for disease progression. They are approved to treat patients older than 12 years with mild to moderate COVID-19 who are at high risk of progressing to severe disease or hospitalization. They are not authorized for use in patients who have been hospitalized or who are on ventilators. The hope is that antibody drugs will reduce the number of severe cases of COVID-19 and ease pressure on overstretched hospitals.
Most COVID-19 patients are outpatients, so we need something to keep them from getting worse.
This is important because it targets the greatest need in COVID-19 therapeutics, says Rajesh Gandhi, MD, an infectious disease physician at Harvard Medical School in Boston, who is a member of two panels evaluating COVID-19 treatments: one for the Infectious Disease Society of America and the other for the National Institutes of Health. “Up to now, most of the focus has been on hospitalized patients,” he says, but “most COVID-19 patients are outpatients, so we need something to keep them from getting worse.”
Both panels have said that, despite the EUAs, more evidence is needed to be sure of the efficacy of the drugs and to determine which patients will benefit the most from them.
These aren’t the mature data from drug development that guideline groups are accustomed to working with, Dr. Woodcock points out. “But this is an emergency and the data taken as a whole are pretty convincing,” she says. “As I look at the totality of the evidence, monoclonal antibodies will have a big effect in keeping people out of the hospital and helping them recover faster.”
High-risk patients are eligible for treatment, especially those older than 65 years and those with comorbidities who are younger. Access to the drugs is increasing for clinicians who are able to infuse safely or work with a site that will.
In the Boston area, several hospitals, including Massachusetts General where Dr. Gandhi works, have set up infusion centers where newly diagnosed patients can get the antibody treatment if their doctor thinks it will benefit them. And Coram, a provider of at-home infusion therapy owned by the CVS pharmacy chain, is running a pilot program offering the Eli Lilly drug to people in seven cities – including Boston, Chicago, Los Angeles, and Tampa – and their surrounding communities with a physician referral.
Getting that referral could be tricky, however, for patients without a primary care physician or for those whose doctor isn’t already connected to one of the institutions providing the infusions. The hospitals are sending out communications on how patients and physicians can get the therapy, but Dr. Gandhi says that making information about access available should be a priority. The window for the effective treatment is small – the drugs appear to work best before patients begin to make their own antibodies, says Dr. Gandhi – so it’s vital that doctors act quickly if they have a patient who is eligible.
And rolling out the new therapies to patients around the world will be a major logistical undertaking.
The first hurdle will be making enough of them to go around. Case numbers are skyrocketing around the globe, and producing the drugs is a complex time- and labor-intensive process that requires specialized facilities. Antibodies are produced by cell lines in bioreactors, so a plant that churns out generic aspirin tablets can’t simply be converted into an antibody factory.
“These types of drugs are manufactured in a sterile injectables plant, which is different from a plant where oral solids are made,” says Kim Crabtree, senior director of pharma portfolio management for Henry Schein Medical, a medical supplies distributor. “Those are not as plentiful as a standard pill factory.”
The doses required are also relatively high – 1.2 g of each antibody in Regeneron’s cocktail – which will further strain production capacity. Leah Lipsich, PhD, vice president of strategic program direction at Regeneron, says the company is prepared for high demand and has been able to respond, thanks to its rapid development and manufacturing technology, known as VelociSuite, which allows it to rapidly scale-up from discovery to productions in weeks instead of months.
“We knew supply would be a huge problem for COVID-19, but because we had such confidence in our technology, we went immediately from research-scale to our largest-scale manufacturing,” she says. “We’ve been manufacturing our cocktail for months now.”
The company has also partnered with Roche, the biggest manufacturer and vendor of monoclonal antibodies in the world, to manufacture and supply the drugs. Once full manufacturing capacity is reached in 2021, the companies expect to produce at least 2 million doses a year.
Then there is the issue of getting the drugs from the factories to the places they will be used.
Antibodies are temperature sensitive and need to be refrigerated during transport and storage, so a cold-chain-compliant supply chain is required. Fortunately, they can be kept at standard refrigerator temperatures, ranging from 2° C to 8° C, rather than the ultra-low temperatures required by some COVID-19 vaccines.
Two million doses a year
Medical logistics companies have a lot of experience dealing with products like these and are well prepared to handle the new antibody drugs. “There are quite a few products like these on the market, and the supply chain is used to shipping them,” Ms. Crabtree says.
They will be shipped to distribution centers in refrigerated trucks, repacked into smaller lots that can sustain the correct temperature for 24 hours, and then sent to their final destination, often in something as simple as a Styrofoam cooler filled with dry ice.
The expected rise in demand shouldn’t be too much of an issue for distributors either, says Ms. Crabtree; they have built systems that can deal with short-term surges in volume. The annual flu vaccine, for example, involves shipping a lot of product in a very short time, usually from August to November. “The distribution system is used to seasonal variations and peaks in demand,” she says.
The next question is how the treatments will be administered. Although most patients who will receive monoclonal antibodies will be ambulatory and not hospitalized, the administration requires intravenous infusion. Hospitals, of course, have a lot of experience with intravenous drugs, but typically give them only to inpatients. Most other monoclonal antibody drugs – such as those for cancer and autoimmune disorders – are given in specialized suites in doctor’s offices or in stand-alone infusion clinics.
That means that the places best suited to treat COVID-19 patients with antibodies are those that regularly deal with people who are immunocompromised, and such patients should not be interacting with people who have an infectious disease. “How do we protect the staff and other patients?” Dr. Gandhi asks.
Protecting staff and other patients
This is not an insurmountable obstacle, he points out, but it is one that requires careful thought and planning to accommodate COVID-19 patients without unduly disrupting life-saving treatments for other patients. It might involve, for example, treating COVID-19 patients in sequestered parts of the clinic or at different times of day, with even greater attention paid to cleaning, he explains. “We now have many months of experience with infection control, so we know how to do this; it’s just a question of logistics.”
But even once all the details around manufacturing, transporting, and administering the drugs are sorted out, there is still the issue of how they will be distributed fairly and equitably.
Despite multiple companies working to produce an array of different antibody drugs, demand is still expected to exceed supply for many months. “With more than 200,000 new cases a day in the United States, there won’t be enough antibodies to treat all of the high-risk patients,” says Dr. Gandhi. “Most of us are worried that demand will far outstrip supply. People are talking about lotteries to determine who gets them.”
The Department of Health and Human Services will continue to distribute the drugs to states on the basis of their COVID-19 burdens, and the states will then decide how much to provide to each health care facility.
Although the HHS goal is to ensure that the drugs reach as many patients as possible, no matter where they live and regardless of their income, there are still concerns that larger facilities serving more affluent areas will end up being favored, if only because they are the ones best equipped to deal with the drugs right now.
“We are all aware that this has affected certain communities more, so we need to make sure that the drugs are used equitably and made available to the communities that were hardest hit,” says Dr. Gandhi. The ability to monitor drug distribution should be built into the rollout, so that institutions and governments will have some sense of whether they are being doled out evenly, he adds.
Equity in distribution will be an issue for the rest of the world as well. Currently, 80% of monoclonal antibodies are sold in Canada, Europe, and the United States; few, if any, are available in low- and middle-income countries. The treatments are expensive: the cost of producing one g of marketed monoclonal antibodies is between $95 and $200, which does not include the cost of R&D, packaging, shipping, or administration. The median price for antibody treatment not related to COVID-19 runs from $15,000 to $200,000 per year in the United States.
Regeneron’s Dr. Lipsich says that the company has not yet set a price for its antibody cocktail. The government paid $450 million for its 300,000 doses, but that price includes the costs of research, manufacturing, and distribution, so is not a useful indicator of the eventual per-dose price. “We’re not in a position to talk about how it will be priced yet, but we will do our best to make it affordable and accessible to all,” she says.
There are some projects underway to ensure that the drugs are made available in poorer countries. In April, the COVID-19 Therapeutics Accelerator – an initiative launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard to speed-up the response to the global pandemic – reserved manufacturing capacity with Fujifilm Diosynth Biotechnologies in Denmark for future monoclonal antibody therapies that will supply low- and middle-income countries. In October, the initiative announced that Eli Lilly would use that reserved capacity to produce its antibody drug starting in April 2021.
In the meantime, Lilly will make some of its product manufactured in other facilities available to lower-income countries. To help keep costs down, the company’s collaborators have agreed to waive their royalties on antibodies distributed in low- and middle-income countries.
“Everyone is looking carefully at how the drugs are distributed to ensure all will get access,” said Dr. Lipsich.
A version of this article first appeared on Medscape.com.
The United States has allocated more than 641,000 monoclonal antibody treatments for outpatients to ease pressure on strained hospitals, but officials from Operation Warp Speed report that more than half of that reserve sits unused as clinicians grapple with best practices.
There are space and personnel limitations in hospitals right now, Janet Woodcock, MD, therapeutics lead on Operation Warp Speed, acknowledges in an interview with this news organization. “Special areas and procedures must be set up.” And the operation is in the process of broadening availability beyond hospitals, she points out.
But for frontline clinicians, questions about treatment efficacy and the logistics of administering intravenous drugs to infectious outpatients loom large.
More than 50 monoclonal antibody products that target SARS-CoV-2 are now in development. The U.S. Food and Drug Administration has already issued Emergency Use Authorization (EUA) for two such drugs on the basis of phase 2 trial data – bamlanivimab, made by Eli Lilly, and a cocktail of casirivimab plus imdevimab, made by Regeneron – and another two-antibody cocktail from AstraZeneca, AZD7442, has started phase 3 clinical trials. The Regeneron combination was used to treat President Donald Trump when he contracted COVID-19 in October.
Monoclonal antibody drugs are based on the natural antibodies that the body uses to fight infections. They work by binding to a specific target and then blocking its action or flagging it for destruction by other parts of the immune system. Both bamlanivimab and the casirivimab plus imdevimab combination target the spike protein of the virus and stop it from attaching to and entering human cells.
Targeting the spike protein out of the hospital
The antibody drugs covered by EUAs do not cure COVID-19, but they have been shown to reduce hospitalizations and visits to the emergency department for patients at high risk for disease progression. They are approved to treat patients older than 12 years with mild to moderate COVID-19 who are at high risk of progressing to severe disease or hospitalization. They are not authorized for use in patients who have been hospitalized or who are on ventilators. The hope is that antibody drugs will reduce the number of severe cases of COVID-19 and ease pressure on overstretched hospitals.
Most COVID-19 patients are outpatients, so we need something to keep them from getting worse.
This is important because it targets the greatest need in COVID-19 therapeutics, says Rajesh Gandhi, MD, an infectious disease physician at Harvard Medical School in Boston, who is a member of two panels evaluating COVID-19 treatments: one for the Infectious Disease Society of America and the other for the National Institutes of Health. “Up to now, most of the focus has been on hospitalized patients,” he says, but “most COVID-19 patients are outpatients, so we need something to keep them from getting worse.”
Both panels have said that, despite the EUAs, more evidence is needed to be sure of the efficacy of the drugs and to determine which patients will benefit the most from them.
These aren’t the mature data from drug development that guideline groups are accustomed to working with, Dr. Woodcock points out. “But this is an emergency and the data taken as a whole are pretty convincing,” she says. “As I look at the totality of the evidence, monoclonal antibodies will have a big effect in keeping people out of the hospital and helping them recover faster.”
High-risk patients are eligible for treatment, especially those older than 65 years and those with comorbidities who are younger. Access to the drugs is increasing for clinicians who are able to infuse safely or work with a site that will.
In the Boston area, several hospitals, including Massachusetts General where Dr. Gandhi works, have set up infusion centers where newly diagnosed patients can get the antibody treatment if their doctor thinks it will benefit them. And Coram, a provider of at-home infusion therapy owned by the CVS pharmacy chain, is running a pilot program offering the Eli Lilly drug to people in seven cities – including Boston, Chicago, Los Angeles, and Tampa – and their surrounding communities with a physician referral.
Getting that referral could be tricky, however, for patients without a primary care physician or for those whose doctor isn’t already connected to one of the institutions providing the infusions. The hospitals are sending out communications on how patients and physicians can get the therapy, but Dr. Gandhi says that making information about access available should be a priority. The window for the effective treatment is small – the drugs appear to work best before patients begin to make their own antibodies, says Dr. Gandhi – so it’s vital that doctors act quickly if they have a patient who is eligible.
And rolling out the new therapies to patients around the world will be a major logistical undertaking.
The first hurdle will be making enough of them to go around. Case numbers are skyrocketing around the globe, and producing the drugs is a complex time- and labor-intensive process that requires specialized facilities. Antibodies are produced by cell lines in bioreactors, so a plant that churns out generic aspirin tablets can’t simply be converted into an antibody factory.
“These types of drugs are manufactured in a sterile injectables plant, which is different from a plant where oral solids are made,” says Kim Crabtree, senior director of pharma portfolio management for Henry Schein Medical, a medical supplies distributor. “Those are not as plentiful as a standard pill factory.”
The doses required are also relatively high – 1.2 g of each antibody in Regeneron’s cocktail – which will further strain production capacity. Leah Lipsich, PhD, vice president of strategic program direction at Regeneron, says the company is prepared for high demand and has been able to respond, thanks to its rapid development and manufacturing technology, known as VelociSuite, which allows it to rapidly scale-up from discovery to productions in weeks instead of months.
“We knew supply would be a huge problem for COVID-19, but because we had such confidence in our technology, we went immediately from research-scale to our largest-scale manufacturing,” she says. “We’ve been manufacturing our cocktail for months now.”
The company has also partnered with Roche, the biggest manufacturer and vendor of monoclonal antibodies in the world, to manufacture and supply the drugs. Once full manufacturing capacity is reached in 2021, the companies expect to produce at least 2 million doses a year.
Then there is the issue of getting the drugs from the factories to the places they will be used.
Antibodies are temperature sensitive and need to be refrigerated during transport and storage, so a cold-chain-compliant supply chain is required. Fortunately, they can be kept at standard refrigerator temperatures, ranging from 2° C to 8° C, rather than the ultra-low temperatures required by some COVID-19 vaccines.
Two million doses a year
Medical logistics companies have a lot of experience dealing with products like these and are well prepared to handle the new antibody drugs. “There are quite a few products like these on the market, and the supply chain is used to shipping them,” Ms. Crabtree says.
They will be shipped to distribution centers in refrigerated trucks, repacked into smaller lots that can sustain the correct temperature for 24 hours, and then sent to their final destination, often in something as simple as a Styrofoam cooler filled with dry ice.
The expected rise in demand shouldn’t be too much of an issue for distributors either, says Ms. Crabtree; they have built systems that can deal with short-term surges in volume. The annual flu vaccine, for example, involves shipping a lot of product in a very short time, usually from August to November. “The distribution system is used to seasonal variations and peaks in demand,” she says.
The next question is how the treatments will be administered. Although most patients who will receive monoclonal antibodies will be ambulatory and not hospitalized, the administration requires intravenous infusion. Hospitals, of course, have a lot of experience with intravenous drugs, but typically give them only to inpatients. Most other monoclonal antibody drugs – such as those for cancer and autoimmune disorders – are given in specialized suites in doctor’s offices or in stand-alone infusion clinics.
That means that the places best suited to treat COVID-19 patients with antibodies are those that regularly deal with people who are immunocompromised, and such patients should not be interacting with people who have an infectious disease. “How do we protect the staff and other patients?” Dr. Gandhi asks.
Protecting staff and other patients
This is not an insurmountable obstacle, he points out, but it is one that requires careful thought and planning to accommodate COVID-19 patients without unduly disrupting life-saving treatments for other patients. It might involve, for example, treating COVID-19 patients in sequestered parts of the clinic or at different times of day, with even greater attention paid to cleaning, he explains. “We now have many months of experience with infection control, so we know how to do this; it’s just a question of logistics.”
But even once all the details around manufacturing, transporting, and administering the drugs are sorted out, there is still the issue of how they will be distributed fairly and equitably.
Despite multiple companies working to produce an array of different antibody drugs, demand is still expected to exceed supply for many months. “With more than 200,000 new cases a day in the United States, there won’t be enough antibodies to treat all of the high-risk patients,” says Dr. Gandhi. “Most of us are worried that demand will far outstrip supply. People are talking about lotteries to determine who gets them.”
The Department of Health and Human Services will continue to distribute the drugs to states on the basis of their COVID-19 burdens, and the states will then decide how much to provide to each health care facility.
Although the HHS goal is to ensure that the drugs reach as many patients as possible, no matter where they live and regardless of their income, there are still concerns that larger facilities serving more affluent areas will end up being favored, if only because they are the ones best equipped to deal with the drugs right now.
“We are all aware that this has affected certain communities more, so we need to make sure that the drugs are used equitably and made available to the communities that were hardest hit,” says Dr. Gandhi. The ability to monitor drug distribution should be built into the rollout, so that institutions and governments will have some sense of whether they are being doled out evenly, he adds.
Equity in distribution will be an issue for the rest of the world as well. Currently, 80% of monoclonal antibodies are sold in Canada, Europe, and the United States; few, if any, are available in low- and middle-income countries. The treatments are expensive: the cost of producing one g of marketed monoclonal antibodies is between $95 and $200, which does not include the cost of R&D, packaging, shipping, or administration. The median price for antibody treatment not related to COVID-19 runs from $15,000 to $200,000 per year in the United States.
Regeneron’s Dr. Lipsich says that the company has not yet set a price for its antibody cocktail. The government paid $450 million for its 300,000 doses, but that price includes the costs of research, manufacturing, and distribution, so is not a useful indicator of the eventual per-dose price. “We’re not in a position to talk about how it will be priced yet, but we will do our best to make it affordable and accessible to all,” she says.
There are some projects underway to ensure that the drugs are made available in poorer countries. In April, the COVID-19 Therapeutics Accelerator – an initiative launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard to speed-up the response to the global pandemic – reserved manufacturing capacity with Fujifilm Diosynth Biotechnologies in Denmark for future monoclonal antibody therapies that will supply low- and middle-income countries. In October, the initiative announced that Eli Lilly would use that reserved capacity to produce its antibody drug starting in April 2021.
In the meantime, Lilly will make some of its product manufactured in other facilities available to lower-income countries. To help keep costs down, the company’s collaborators have agreed to waive their royalties on antibodies distributed in low- and middle-income countries.
“Everyone is looking carefully at how the drugs are distributed to ensure all will get access,” said Dr. Lipsich.
A version of this article first appeared on Medscape.com.
The United States has allocated more than 641,000 monoclonal antibody treatments for outpatients to ease pressure on strained hospitals, but officials from Operation Warp Speed report that more than half of that reserve sits unused as clinicians grapple with best practices.
There are space and personnel limitations in hospitals right now, Janet Woodcock, MD, therapeutics lead on Operation Warp Speed, acknowledges in an interview with this news organization. “Special areas and procedures must be set up.” And the operation is in the process of broadening availability beyond hospitals, she points out.
But for frontline clinicians, questions about treatment efficacy and the logistics of administering intravenous drugs to infectious outpatients loom large.
More than 50 monoclonal antibody products that target SARS-CoV-2 are now in development. The U.S. Food and Drug Administration has already issued Emergency Use Authorization (EUA) for two such drugs on the basis of phase 2 trial data – bamlanivimab, made by Eli Lilly, and a cocktail of casirivimab plus imdevimab, made by Regeneron – and another two-antibody cocktail from AstraZeneca, AZD7442, has started phase 3 clinical trials. The Regeneron combination was used to treat President Donald Trump when he contracted COVID-19 in October.
Monoclonal antibody drugs are based on the natural antibodies that the body uses to fight infections. They work by binding to a specific target and then blocking its action or flagging it for destruction by other parts of the immune system. Both bamlanivimab and the casirivimab plus imdevimab combination target the spike protein of the virus and stop it from attaching to and entering human cells.
Targeting the spike protein out of the hospital
The antibody drugs covered by EUAs do not cure COVID-19, but they have been shown to reduce hospitalizations and visits to the emergency department for patients at high risk for disease progression. They are approved to treat patients older than 12 years with mild to moderate COVID-19 who are at high risk of progressing to severe disease or hospitalization. They are not authorized for use in patients who have been hospitalized or who are on ventilators. The hope is that antibody drugs will reduce the number of severe cases of COVID-19 and ease pressure on overstretched hospitals.
Most COVID-19 patients are outpatients, so we need something to keep them from getting worse.
This is important because it targets the greatest need in COVID-19 therapeutics, says Rajesh Gandhi, MD, an infectious disease physician at Harvard Medical School in Boston, who is a member of two panels evaluating COVID-19 treatments: one for the Infectious Disease Society of America and the other for the National Institutes of Health. “Up to now, most of the focus has been on hospitalized patients,” he says, but “most COVID-19 patients are outpatients, so we need something to keep them from getting worse.”
Both panels have said that, despite the EUAs, more evidence is needed to be sure of the efficacy of the drugs and to determine which patients will benefit the most from them.
These aren’t the mature data from drug development that guideline groups are accustomed to working with, Dr. Woodcock points out. “But this is an emergency and the data taken as a whole are pretty convincing,” she says. “As I look at the totality of the evidence, monoclonal antibodies will have a big effect in keeping people out of the hospital and helping them recover faster.”
High-risk patients are eligible for treatment, especially those older than 65 years and those with comorbidities who are younger. Access to the drugs is increasing for clinicians who are able to infuse safely or work with a site that will.
In the Boston area, several hospitals, including Massachusetts General where Dr. Gandhi works, have set up infusion centers where newly diagnosed patients can get the antibody treatment if their doctor thinks it will benefit them. And Coram, a provider of at-home infusion therapy owned by the CVS pharmacy chain, is running a pilot program offering the Eli Lilly drug to people in seven cities – including Boston, Chicago, Los Angeles, and Tampa – and their surrounding communities with a physician referral.
Getting that referral could be tricky, however, for patients without a primary care physician or for those whose doctor isn’t already connected to one of the institutions providing the infusions. The hospitals are sending out communications on how patients and physicians can get the therapy, but Dr. Gandhi says that making information about access available should be a priority. The window for the effective treatment is small – the drugs appear to work best before patients begin to make their own antibodies, says Dr. Gandhi – so it’s vital that doctors act quickly if they have a patient who is eligible.
And rolling out the new therapies to patients around the world will be a major logistical undertaking.
The first hurdle will be making enough of them to go around. Case numbers are skyrocketing around the globe, and producing the drugs is a complex time- and labor-intensive process that requires specialized facilities. Antibodies are produced by cell lines in bioreactors, so a plant that churns out generic aspirin tablets can’t simply be converted into an antibody factory.
“These types of drugs are manufactured in a sterile injectables plant, which is different from a plant where oral solids are made,” says Kim Crabtree, senior director of pharma portfolio management for Henry Schein Medical, a medical supplies distributor. “Those are not as plentiful as a standard pill factory.”
The doses required are also relatively high – 1.2 g of each antibody in Regeneron’s cocktail – which will further strain production capacity. Leah Lipsich, PhD, vice president of strategic program direction at Regeneron, says the company is prepared for high demand and has been able to respond, thanks to its rapid development and manufacturing technology, known as VelociSuite, which allows it to rapidly scale-up from discovery to productions in weeks instead of months.
“We knew supply would be a huge problem for COVID-19, but because we had such confidence in our technology, we went immediately from research-scale to our largest-scale manufacturing,” she says. “We’ve been manufacturing our cocktail for months now.”
The company has also partnered with Roche, the biggest manufacturer and vendor of monoclonal antibodies in the world, to manufacture and supply the drugs. Once full manufacturing capacity is reached in 2021, the companies expect to produce at least 2 million doses a year.
Then there is the issue of getting the drugs from the factories to the places they will be used.
Antibodies are temperature sensitive and need to be refrigerated during transport and storage, so a cold-chain-compliant supply chain is required. Fortunately, they can be kept at standard refrigerator temperatures, ranging from 2° C to 8° C, rather than the ultra-low temperatures required by some COVID-19 vaccines.
Two million doses a year
Medical logistics companies have a lot of experience dealing with products like these and are well prepared to handle the new antibody drugs. “There are quite a few products like these on the market, and the supply chain is used to shipping them,” Ms. Crabtree says.
They will be shipped to distribution centers in refrigerated trucks, repacked into smaller lots that can sustain the correct temperature for 24 hours, and then sent to their final destination, often in something as simple as a Styrofoam cooler filled with dry ice.
The expected rise in demand shouldn’t be too much of an issue for distributors either, says Ms. Crabtree; they have built systems that can deal with short-term surges in volume. The annual flu vaccine, for example, involves shipping a lot of product in a very short time, usually from August to November. “The distribution system is used to seasonal variations and peaks in demand,” she says.
The next question is how the treatments will be administered. Although most patients who will receive monoclonal antibodies will be ambulatory and not hospitalized, the administration requires intravenous infusion. Hospitals, of course, have a lot of experience with intravenous drugs, but typically give them only to inpatients. Most other monoclonal antibody drugs – such as those for cancer and autoimmune disorders – are given in specialized suites in doctor’s offices or in stand-alone infusion clinics.
That means that the places best suited to treat COVID-19 patients with antibodies are those that regularly deal with people who are immunocompromised, and such patients should not be interacting with people who have an infectious disease. “How do we protect the staff and other patients?” Dr. Gandhi asks.
Protecting staff and other patients
This is not an insurmountable obstacle, he points out, but it is one that requires careful thought and planning to accommodate COVID-19 patients without unduly disrupting life-saving treatments for other patients. It might involve, for example, treating COVID-19 patients in sequestered parts of the clinic or at different times of day, with even greater attention paid to cleaning, he explains. “We now have many months of experience with infection control, so we know how to do this; it’s just a question of logistics.”
But even once all the details around manufacturing, transporting, and administering the drugs are sorted out, there is still the issue of how they will be distributed fairly and equitably.
Despite multiple companies working to produce an array of different antibody drugs, demand is still expected to exceed supply for many months. “With more than 200,000 new cases a day in the United States, there won’t be enough antibodies to treat all of the high-risk patients,” says Dr. Gandhi. “Most of us are worried that demand will far outstrip supply. People are talking about lotteries to determine who gets them.”
The Department of Health and Human Services will continue to distribute the drugs to states on the basis of their COVID-19 burdens, and the states will then decide how much to provide to each health care facility.
Although the HHS goal is to ensure that the drugs reach as many patients as possible, no matter where they live and regardless of their income, there are still concerns that larger facilities serving more affluent areas will end up being favored, if only because they are the ones best equipped to deal with the drugs right now.
“We are all aware that this has affected certain communities more, so we need to make sure that the drugs are used equitably and made available to the communities that were hardest hit,” says Dr. Gandhi. The ability to monitor drug distribution should be built into the rollout, so that institutions and governments will have some sense of whether they are being doled out evenly, he adds.
Equity in distribution will be an issue for the rest of the world as well. Currently, 80% of monoclonal antibodies are sold in Canada, Europe, and the United States; few, if any, are available in low- and middle-income countries. The treatments are expensive: the cost of producing one g of marketed monoclonal antibodies is between $95 and $200, which does not include the cost of R&D, packaging, shipping, or administration. The median price for antibody treatment not related to COVID-19 runs from $15,000 to $200,000 per year in the United States.
Regeneron’s Dr. Lipsich says that the company has not yet set a price for its antibody cocktail. The government paid $450 million for its 300,000 doses, but that price includes the costs of research, manufacturing, and distribution, so is not a useful indicator of the eventual per-dose price. “We’re not in a position to talk about how it will be priced yet, but we will do our best to make it affordable and accessible to all,” she says.
There are some projects underway to ensure that the drugs are made available in poorer countries. In April, the COVID-19 Therapeutics Accelerator – an initiative launched by the Bill & Melinda Gates Foundation, Wellcome, and Mastercard to speed-up the response to the global pandemic – reserved manufacturing capacity with Fujifilm Diosynth Biotechnologies in Denmark for future monoclonal antibody therapies that will supply low- and middle-income countries. In October, the initiative announced that Eli Lilly would use that reserved capacity to produce its antibody drug starting in April 2021.
In the meantime, Lilly will make some of its product manufactured in other facilities available to lower-income countries. To help keep costs down, the company’s collaborators have agreed to waive their royalties on antibodies distributed in low- and middle-income countries.
“Everyone is looking carefully at how the drugs are distributed to ensure all will get access,” said Dr. Lipsich.
A version of this article first appeared on Medscape.com.
In COVID-19 patients, risk of bleeding rivals risk of thromboembolism
There is no question that COVID-19 infection increases the risks of serious thromboembolic events, including pulmonary embolism (PE), but it also increases the risk of bleeding, complicating the benefit-to-risk calculations for anticoagulation, according to a review of data at the virtual Going Back to the Heart of Cardiology meeting.
“Bleeding is a significant cause of morbidity in patients with COVID-19, and this is an important concept to appreciate,” reported Rachel P. Rosovsky, MD, director of thrombosis research, Massachusetts General Hospital, Boston.
At least five guidelines, including those issued by the American College of Cardiology, International Society on Thrombosis and Haemostasis (ISTH), and the American College of Chest Physicians, have recently addressed anticoagulation in patients infected with COVID-19, but there are “substantive differences” between them, according to Dr. Rosovsky. The reason is that they are essentially no high quality trials to guide practice. Rather, the recommendations are based primarily on retrospective studies and expert opinion.
The single most common theme from the guidelines is that anticoagulation must be individualized to balance patient-specific risks of venous thromboembolism (VTE) and bleeding, said Dr. Rosovsky, whose group published a recent comparison of these guidelines (Flaczyk A et al. Crit Care 2020;24:559).
Although there is general consensus that all hospitalized patients with COVID-19 should receive anticoagulation unless there are contraindications, there are differences in the recommended intensity of the anticoagulation for different risk groups and there is even less is less consensus on the need to anticoagulate outpatients or patients after discharge, according to Dr. Rosovsky
In her own center, the standard is a prophylactic dose of low molecular weight heparin (LMWH) in an algorithm that calls for dose adjustments for some groups such as those with renal impairment or obesity. Alternative forms of anticoagulation are recommended for patients with a history of thrombocytopenia or are at high risk for hemorrhage. Full dose LMWH is recommended in patients already on an oral anticoagulant at time of hospitalization.
“The biggest question right now is when to consider increasing from a prophylactic dose to intermediate or full dose anticoagulation in high risk patients, especially those in the ICU patients,” Dr. Rosovsky said.
Current practices are diverse, according to a recently published survey led by Dr. Rosovsky (Rosovsky RP et al. Res Pract Thromb Haemost. 2020;4:969-83). According to the survey, which had responses from more than 500 physicians in 41 countries, 30% of centers escalate from a prophylactic dose of anticoagulation to an intermediate dose when patients move to the ICU. Although not all answered this question, 25% reported that they do not escalate at ICU transfer. For 15% of respondents, dose escalation is being offered to patients with a D-dimer exceeding six-times the upper limit of normal.
These practices have developed in the absence of prospective clinical trials, which are urgently needed, according to Dr. Rosovsky. The reason that trials specific to COVID-19 are particularly important is that this infection also engenders a high risk of major bleeding.
For example, in a multicenter retrospective study of 400 hospital-admitted COVID-19 patients the rates of major bleeding was 4.8% or exactly the same as the rate of radiographically confirmed VTE. At 7.6%, the rates of VTE and major bleeding were also exactly the same for ICU patients (Al-Samkari H et al. Blood 2020;136:489-500).
“An elevated D-dimer was a marker for both VTE and major bleeding,” reported Dr. Rosovsky, who was the senior author of this study. On the basis of odds ratio (OR), the risk of VTE was increased more than six-fold (OR, 6.79) and the risk of major bleeding by more than three-fold (OR, 3.56) when the D-dimer exceeded 2,500 ng/mL.
The risk of VTE from COVID-19 infection is well documented. For example, autopsy studies have shown widespread thrombosis, including PE, in patients who have died from COVID-19 infection, according to Dr. Rosovsky.
There is also evidence of benefit from anticoagulation. In an retrospective study from China undertaken early in the pandemic, there was no overall mortality benefit at 28 days among those who did receive LMWH when compared to those who did not, but there was a 20% absolute mortality benefit (52.4% vs. 32.8%; P = .017) in those with a D-dimer six-fold ULN (Tang N et al. J Thromb Haemost 2020;18:1094-9).
These types of data support the use of anticoagulation to manage VTE risk in at least some patients, but the reported rates of VTE across institutions and across inpatient and outpatient settings have varied “dramatically,” according to Dr. Rosovsky. The balance of VTE and major bleeding is delicate. In one retrospective study, the mortality advantage for therapeutic versus prophylactic dose of LMWH did not reach statistical significance, but the rate of major bleeding was nearly doubled (3.0% vs. 1.7%) (Nadkarni GN et al J Am Coll Cardiol 2020;76:1815-26).
Because of the many variables that might affect risk of VTE and risk of major bleeding in any individual patient, the benefit-to-risk calculation of anticoagulation is “complex,” according to Dr. Rosovsky. It is for this reason she urged clinicians to consider entering patients into clinical trials designed to generate evidence-based answers.
There is large and growing body of retrospective data that have helped characterize the risk of VTE and bleeding in patients with COVID-19, but “there is no substitute for a well-controlled clinical trial,” agreed Robert A. Harrington, MD, chairman of the department of medicine, Stanford (Calif.) University.
He and the comoderator of the session in which these data were presented agreed that anticoagulation must be administered within a narrow therapeutic window that will be best defined through controlled trial designs.
“There is a significant risk of doing harm,” said Fatima Rodriguez, MD, assistant professor of cardiology at Stanford University. She seconded the critical role of trial participation when possible and the need for clinical trials to better guide treatment decisions.
The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
There is no question that COVID-19 infection increases the risks of serious thromboembolic events, including pulmonary embolism (PE), but it also increases the risk of bleeding, complicating the benefit-to-risk calculations for anticoagulation, according to a review of data at the virtual Going Back to the Heart of Cardiology meeting.
“Bleeding is a significant cause of morbidity in patients with COVID-19, and this is an important concept to appreciate,” reported Rachel P. Rosovsky, MD, director of thrombosis research, Massachusetts General Hospital, Boston.
At least five guidelines, including those issued by the American College of Cardiology, International Society on Thrombosis and Haemostasis (ISTH), and the American College of Chest Physicians, have recently addressed anticoagulation in patients infected with COVID-19, but there are “substantive differences” between them, according to Dr. Rosovsky. The reason is that they are essentially no high quality trials to guide practice. Rather, the recommendations are based primarily on retrospective studies and expert opinion.
The single most common theme from the guidelines is that anticoagulation must be individualized to balance patient-specific risks of venous thromboembolism (VTE) and bleeding, said Dr. Rosovsky, whose group published a recent comparison of these guidelines (Flaczyk A et al. Crit Care 2020;24:559).
Although there is general consensus that all hospitalized patients with COVID-19 should receive anticoagulation unless there are contraindications, there are differences in the recommended intensity of the anticoagulation for different risk groups and there is even less is less consensus on the need to anticoagulate outpatients or patients after discharge, according to Dr. Rosovsky
In her own center, the standard is a prophylactic dose of low molecular weight heparin (LMWH) in an algorithm that calls for dose adjustments for some groups such as those with renal impairment or obesity. Alternative forms of anticoagulation are recommended for patients with a history of thrombocytopenia or are at high risk for hemorrhage. Full dose LMWH is recommended in patients already on an oral anticoagulant at time of hospitalization.
“The biggest question right now is when to consider increasing from a prophylactic dose to intermediate or full dose anticoagulation in high risk patients, especially those in the ICU patients,” Dr. Rosovsky said.
Current practices are diverse, according to a recently published survey led by Dr. Rosovsky (Rosovsky RP et al. Res Pract Thromb Haemost. 2020;4:969-83). According to the survey, which had responses from more than 500 physicians in 41 countries, 30% of centers escalate from a prophylactic dose of anticoagulation to an intermediate dose when patients move to the ICU. Although not all answered this question, 25% reported that they do not escalate at ICU transfer. For 15% of respondents, dose escalation is being offered to patients with a D-dimer exceeding six-times the upper limit of normal.
These practices have developed in the absence of prospective clinical trials, which are urgently needed, according to Dr. Rosovsky. The reason that trials specific to COVID-19 are particularly important is that this infection also engenders a high risk of major bleeding.
For example, in a multicenter retrospective study of 400 hospital-admitted COVID-19 patients the rates of major bleeding was 4.8% or exactly the same as the rate of radiographically confirmed VTE. At 7.6%, the rates of VTE and major bleeding were also exactly the same for ICU patients (Al-Samkari H et al. Blood 2020;136:489-500).
“An elevated D-dimer was a marker for both VTE and major bleeding,” reported Dr. Rosovsky, who was the senior author of this study. On the basis of odds ratio (OR), the risk of VTE was increased more than six-fold (OR, 6.79) and the risk of major bleeding by more than three-fold (OR, 3.56) when the D-dimer exceeded 2,500 ng/mL.
The risk of VTE from COVID-19 infection is well documented. For example, autopsy studies have shown widespread thrombosis, including PE, in patients who have died from COVID-19 infection, according to Dr. Rosovsky.
There is also evidence of benefit from anticoagulation. In an retrospective study from China undertaken early in the pandemic, there was no overall mortality benefit at 28 days among those who did receive LMWH when compared to those who did not, but there was a 20% absolute mortality benefit (52.4% vs. 32.8%; P = .017) in those with a D-dimer six-fold ULN (Tang N et al. J Thromb Haemost 2020;18:1094-9).
These types of data support the use of anticoagulation to manage VTE risk in at least some patients, but the reported rates of VTE across institutions and across inpatient and outpatient settings have varied “dramatically,” according to Dr. Rosovsky. The balance of VTE and major bleeding is delicate. In one retrospective study, the mortality advantage for therapeutic versus prophylactic dose of LMWH did not reach statistical significance, but the rate of major bleeding was nearly doubled (3.0% vs. 1.7%) (Nadkarni GN et al J Am Coll Cardiol 2020;76:1815-26).
Because of the many variables that might affect risk of VTE and risk of major bleeding in any individual patient, the benefit-to-risk calculation of anticoagulation is “complex,” according to Dr. Rosovsky. It is for this reason she urged clinicians to consider entering patients into clinical trials designed to generate evidence-based answers.
There is large and growing body of retrospective data that have helped characterize the risk of VTE and bleeding in patients with COVID-19, but “there is no substitute for a well-controlled clinical trial,” agreed Robert A. Harrington, MD, chairman of the department of medicine, Stanford (Calif.) University.
He and the comoderator of the session in which these data were presented agreed that anticoagulation must be administered within a narrow therapeutic window that will be best defined through controlled trial designs.
“There is a significant risk of doing harm,” said Fatima Rodriguez, MD, assistant professor of cardiology at Stanford University. She seconded the critical role of trial participation when possible and the need for clinical trials to better guide treatment decisions.
The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
There is no question that COVID-19 infection increases the risks of serious thromboembolic events, including pulmonary embolism (PE), but it also increases the risk of bleeding, complicating the benefit-to-risk calculations for anticoagulation, according to a review of data at the virtual Going Back to the Heart of Cardiology meeting.
“Bleeding is a significant cause of morbidity in patients with COVID-19, and this is an important concept to appreciate,” reported Rachel P. Rosovsky, MD, director of thrombosis research, Massachusetts General Hospital, Boston.
At least five guidelines, including those issued by the American College of Cardiology, International Society on Thrombosis and Haemostasis (ISTH), and the American College of Chest Physicians, have recently addressed anticoagulation in patients infected with COVID-19, but there are “substantive differences” between them, according to Dr. Rosovsky. The reason is that they are essentially no high quality trials to guide practice. Rather, the recommendations are based primarily on retrospective studies and expert opinion.
The single most common theme from the guidelines is that anticoagulation must be individualized to balance patient-specific risks of venous thromboembolism (VTE) and bleeding, said Dr. Rosovsky, whose group published a recent comparison of these guidelines (Flaczyk A et al. Crit Care 2020;24:559).
Although there is general consensus that all hospitalized patients with COVID-19 should receive anticoagulation unless there are contraindications, there are differences in the recommended intensity of the anticoagulation for different risk groups and there is even less is less consensus on the need to anticoagulate outpatients or patients after discharge, according to Dr. Rosovsky
In her own center, the standard is a prophylactic dose of low molecular weight heparin (LMWH) in an algorithm that calls for dose adjustments for some groups such as those with renal impairment or obesity. Alternative forms of anticoagulation are recommended for patients with a history of thrombocytopenia or are at high risk for hemorrhage. Full dose LMWH is recommended in patients already on an oral anticoagulant at time of hospitalization.
“The biggest question right now is when to consider increasing from a prophylactic dose to intermediate or full dose anticoagulation in high risk patients, especially those in the ICU patients,” Dr. Rosovsky said.
Current practices are diverse, according to a recently published survey led by Dr. Rosovsky (Rosovsky RP et al. Res Pract Thromb Haemost. 2020;4:969-83). According to the survey, which had responses from more than 500 physicians in 41 countries, 30% of centers escalate from a prophylactic dose of anticoagulation to an intermediate dose when patients move to the ICU. Although not all answered this question, 25% reported that they do not escalate at ICU transfer. For 15% of respondents, dose escalation is being offered to patients with a D-dimer exceeding six-times the upper limit of normal.
These practices have developed in the absence of prospective clinical trials, which are urgently needed, according to Dr. Rosovsky. The reason that trials specific to COVID-19 are particularly important is that this infection also engenders a high risk of major bleeding.
For example, in a multicenter retrospective study of 400 hospital-admitted COVID-19 patients the rates of major bleeding was 4.8% or exactly the same as the rate of radiographically confirmed VTE. At 7.6%, the rates of VTE and major bleeding were also exactly the same for ICU patients (Al-Samkari H et al. Blood 2020;136:489-500).
“An elevated D-dimer was a marker for both VTE and major bleeding,” reported Dr. Rosovsky, who was the senior author of this study. On the basis of odds ratio (OR), the risk of VTE was increased more than six-fold (OR, 6.79) and the risk of major bleeding by more than three-fold (OR, 3.56) when the D-dimer exceeded 2,500 ng/mL.
The risk of VTE from COVID-19 infection is well documented. For example, autopsy studies have shown widespread thrombosis, including PE, in patients who have died from COVID-19 infection, according to Dr. Rosovsky.
There is also evidence of benefit from anticoagulation. In an retrospective study from China undertaken early in the pandemic, there was no overall mortality benefit at 28 days among those who did receive LMWH when compared to those who did not, but there was a 20% absolute mortality benefit (52.4% vs. 32.8%; P = .017) in those with a D-dimer six-fold ULN (Tang N et al. J Thromb Haemost 2020;18:1094-9).
These types of data support the use of anticoagulation to manage VTE risk in at least some patients, but the reported rates of VTE across institutions and across inpatient and outpatient settings have varied “dramatically,” according to Dr. Rosovsky. The balance of VTE and major bleeding is delicate. In one retrospective study, the mortality advantage for therapeutic versus prophylactic dose of LMWH did not reach statistical significance, but the rate of major bleeding was nearly doubled (3.0% vs. 1.7%) (Nadkarni GN et al J Am Coll Cardiol 2020;76:1815-26).
Because of the many variables that might affect risk of VTE and risk of major bleeding in any individual patient, the benefit-to-risk calculation of anticoagulation is “complex,” according to Dr. Rosovsky. It is for this reason she urged clinicians to consider entering patients into clinical trials designed to generate evidence-based answers.
There is large and growing body of retrospective data that have helped characterize the risk of VTE and bleeding in patients with COVID-19, but “there is no substitute for a well-controlled clinical trial,” agreed Robert A. Harrington, MD, chairman of the department of medicine, Stanford (Calif.) University.
He and the comoderator of the session in which these data were presented agreed that anticoagulation must be administered within a narrow therapeutic window that will be best defined through controlled trial designs.
“There is a significant risk of doing harm,” said Fatima Rodriguez, MD, assistant professor of cardiology at Stanford University. She seconded the critical role of trial participation when possible and the need for clinical trials to better guide treatment decisions.
The meeting was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM THE GOING BACK TO THE HEART OF CARDIOLOGY MEETING
Bedside EEG test aids prognosis in patients with brain injury
results of a new study suggest. The study showed that the use of a paradigm that measures the strength of responses to speech improved the accuracy of prognosis for these patients, compared with prognoses made solely on the basis of standard clinical characteristics.
“What we found is really compelling evidence” of the usefulness of the test, lead study author Rodika Sokoliuk, PhD, a postdoctoral researcher at the Center for Human Brain Health, University of Birmingham (England), said in an interview.
The passive measure of comprehension, which doesn’t require any other response from the patient, can reduce uncertainty at a critical phase of decision-making in the ICU, said Dr. Sokoliuk.
The study was published online Dec. 23, 2020, in Annals of Neurology.
Useful information at a time of ‘considerable prognostic uncertainty’
Accurate, early prognostication is vital for efficient stratification of patients after a TBI, the authors wrote. This can often be achieved from patient behavior and CT at admission, but some patients continue to fail to obey commands after washout of sedation.
These patients pose a significant challenge for neurologic prognostication, they noted. In these cases, clinicians and families must decide whether to “wait and see” or consider treatment withdrawal.
The authors noted that a lack of command following early in the postsedation period is associated with poor outcome, including vegetative state/unresponsive wakefulness syndrome (VS/UWS). This, they said, represents a “window of opportunity” for cessation of life-sustaining therapy at a time of considerable prognostic uncertainty.
Recent research shows that a significant proportion of unresponsive patients retain a level of cognition, and even consciousness, that isn’t evident from their external behavior – the so-called cognitive-motor dissociation.
The new study included 28 adult patients who had experienced a TBI and were admitted to the ICU of the Queen Elizabeth Hospital in Birmingham, England. The patients had a Glasgow Coma Scale motor score less than 6 (i.e., they were incapable of obeying commands). They had been sedation free for 2-7 days.
For the paradigm, researchers constructed 288 English words using the male voice of the Apple synthesizer. The words required the same amount of time to be generated (320 ms) and were monosyllabic, so the rhythms of the sounds were the same.
The words were presented in a specific order: an adjective, then a noun, then a verb, then a noun. Two words – for example, an adjective and noun – “would build a meaningful phrase,” and four words would build a sentence, said Dr. Sokoliuk.
The researchers built 72 of these four-word sentences. A trial comprised 12 of these sentences, resulting in a total of 864 four-word sentences.
Dr. Sokoliuk likened the paradigm to a rap song with a specific beat that is continually repeated. “Basically, we play 12 of these four-word sentences in a row, without any gaps,” she said.
Each sentence was played to patients, in random order, a minimum of eight and a maximum of nine times per patient throughout the experiment. The patients’ brain activity was recorded on EEG.
Dr. Sokoliuk noted that brain activity in healthy people synchronizes only with the rhythm of phrases and sentences when listeners consciously comprehend the speech. The researchers assessed the level of comprehension in the unresponsive patients by measuring the strength of this synchronicity or brain pattern.
After exclusions, 17 patients were available for outcome assessment 3 months post EEG, and 16 patients were available 6 months post EEG.
The analysis showed that outcome significantly correlated with the strength of patients’ acute cortical tracking of phrases and sentences (r > 0.6; P < .007), quantified by intertrial phase coherence.
Linear regressions revealed that the strength of this comprehension response (beta, 0.603; P = .006) significantly improved the accuracy of prognoses relative to clinical characteristics alone, such as the Glasgow Coma Scale or CT grade.
Previous studies showed that, if there is no understanding of the language used or if the subject is asleep, the brain doesn’t have the “signature” of tracking phrases and sentences, so it doesn’t have the synchronicity or the pattern of individuals with normal cognition, said Dr. Sokoliuk.
“You need a certain level of consciousness, and you need to understand the language, so your brain can actually track sentences or phrases,” she said.
Dr. Sokoliuk explained that the paradigm shows that patients are understanding the sentences and are not just hearing them.
“It’s not showing us that they only hear it, because there are no obvious gaps between the sentences; if there were gaps between sentences, it would probably only show that they hear it. It could be both, that they hear and understand it, but we wouldn’t know.”
A receiver operating characteristics analysis indicated 100% sensitivity and 80% specificity for a distinction between bad outcome (death, VS/UWS) and good outcome at 6 months.
“We could actually define a threshold of the tracking,” said Dr. Sokoliuk. “Patients who had phrases and sentences tracking below this threshold had worse outcome than those whose tracking value was above this threshold.”
The study illustrates that some posttraumatic patients who remain in an unresponsive state despite being sedation free may nevertheless comprehend speech.
The EEG paradigm approach, the authors said, may significantly reduce prognostic uncertainty in a critical phase of medical decision-making. It could also help clinicians make more appropriate decisions about whether or not to continue life-sustaining therapy and ensure more appropriate distribution of limited rehabilitation resources to patients most likely to benefit.
Dr. Sokoliuk stressed that the paradigm could be used at the bedside soon after a brain injury. “The critical thing is, we can actually use it during the acute phase, which is very important for clinical decisions about life-sustaining methods, therapy, and long-term care.”
A prognostic tool
The simple approach promises to be more accessible than fMRI, said Dr. Sokoliuk. “Putting an unresponsive coma patient in a scanner is very difficult and also much more expensive,” she said.
The next step, said Dr. Sokoliuk, is to repeat the study with a larger sample. “The number in the current study was quite small, and we can’t say if the sensitivity of the paradigm is strong enough to use it as a standard prognostic tool.”
To use it in clinical setting, “we really have to have robust measures,” she added.
She aims to conduct a collaborative study involving several institutions and more patients.
The research team plans to eventually build “an open-access toolbox” that would include the auditory streams to be played during EEG recordings and a program to analyze the data, said Dr. Sokoliuk. “Then, in the end, you would get a threshold or a value of tracking for phrases and sentences, and this could then classify a patient to be in a good-outcome or in bad-outcome group.”
She stressed this is a prognostic tool, not a diagnostic tool, and it should not be used in isolation. “It’s important to know that no clinician should only use this paradigm to prognosticate a patient; our paradigm should be part of a bigger battery of tests.”
But it could go a long way toward helping families as well as physicians. “If they know that the patient would be better in 3 months’ time, it’s easier for them to decide what should come next,” she said.
And it’s heartening to know that when families talk to their unresponsive loved one, the patient understands them, she added.
Promising basic research
Commenting on the study in an interview, Christine Blume, PhD, of the Center for Chronobiology, University of Basel (Switzerland), whose research interests include cognitive processing of patients with disorders of consciousness, described it as “very elegant and appealing” and the paradigm it used as “really promising.”
“However, we do, of course, not yet know about the prognostic value on a single-subject level, as the authors performed only group analyses,” said Dr. Blume. “This will require more extensive and perhaps even multicenter studies.”
It would also require developing a “solution” that “allows clinicians with limited time resources and perhaps lacking expert knowledge on the paradigm and the necessary analyses to apply the paradigm at bedside,” said Dr. Blume.
She agreed that a passive paradigm that helps determine whether a patient consciously understands speech, without the need for further processing, “has the potential to really improve the diagnostic process and uncover covert consciousness.”
One should bear in mind, though, that the paradigm “makes one essential assumption: that patients can understand speech,” said Dr. Blume. “For example, an aphasic patient might not understand but still be conscious.”
In this context, she added, “it’s essential to note that while the presence of a response suggests consciousness, the absence of a response does not suggest the absence of consciousness.”
Dr. Blume cautioned that the approach used in the study “is still at the stage of basic research.” Although the paradigm is promising, “I do not think it is ‘around the corner,’ ” she said.
The study was funded by the Medical Research Council. It was further supported by the National Institute for Health Research Surgical Reconstruction and Microbiology Research Center. Dr. Sokoliuk and Dr. Blume have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
results of a new study suggest. The study showed that the use of a paradigm that measures the strength of responses to speech improved the accuracy of prognosis for these patients, compared with prognoses made solely on the basis of standard clinical characteristics.
“What we found is really compelling evidence” of the usefulness of the test, lead study author Rodika Sokoliuk, PhD, a postdoctoral researcher at the Center for Human Brain Health, University of Birmingham (England), said in an interview.
The passive measure of comprehension, which doesn’t require any other response from the patient, can reduce uncertainty at a critical phase of decision-making in the ICU, said Dr. Sokoliuk.
The study was published online Dec. 23, 2020, in Annals of Neurology.
Useful information at a time of ‘considerable prognostic uncertainty’
Accurate, early prognostication is vital for efficient stratification of patients after a TBI, the authors wrote. This can often be achieved from patient behavior and CT at admission, but some patients continue to fail to obey commands after washout of sedation.
These patients pose a significant challenge for neurologic prognostication, they noted. In these cases, clinicians and families must decide whether to “wait and see” or consider treatment withdrawal.
The authors noted that a lack of command following early in the postsedation period is associated with poor outcome, including vegetative state/unresponsive wakefulness syndrome (VS/UWS). This, they said, represents a “window of opportunity” for cessation of life-sustaining therapy at a time of considerable prognostic uncertainty.
Recent research shows that a significant proportion of unresponsive patients retain a level of cognition, and even consciousness, that isn’t evident from their external behavior – the so-called cognitive-motor dissociation.
The new study included 28 adult patients who had experienced a TBI and were admitted to the ICU of the Queen Elizabeth Hospital in Birmingham, England. The patients had a Glasgow Coma Scale motor score less than 6 (i.e., they were incapable of obeying commands). They had been sedation free for 2-7 days.
For the paradigm, researchers constructed 288 English words using the male voice of the Apple synthesizer. The words required the same amount of time to be generated (320 ms) and were monosyllabic, so the rhythms of the sounds were the same.
The words were presented in a specific order: an adjective, then a noun, then a verb, then a noun. Two words – for example, an adjective and noun – “would build a meaningful phrase,” and four words would build a sentence, said Dr. Sokoliuk.
The researchers built 72 of these four-word sentences. A trial comprised 12 of these sentences, resulting in a total of 864 four-word sentences.
Dr. Sokoliuk likened the paradigm to a rap song with a specific beat that is continually repeated. “Basically, we play 12 of these four-word sentences in a row, without any gaps,” she said.
Each sentence was played to patients, in random order, a minimum of eight and a maximum of nine times per patient throughout the experiment. The patients’ brain activity was recorded on EEG.
Dr. Sokoliuk noted that brain activity in healthy people synchronizes only with the rhythm of phrases and sentences when listeners consciously comprehend the speech. The researchers assessed the level of comprehension in the unresponsive patients by measuring the strength of this synchronicity or brain pattern.
After exclusions, 17 patients were available for outcome assessment 3 months post EEG, and 16 patients were available 6 months post EEG.
The analysis showed that outcome significantly correlated with the strength of patients’ acute cortical tracking of phrases and sentences (r > 0.6; P < .007), quantified by intertrial phase coherence.
Linear regressions revealed that the strength of this comprehension response (beta, 0.603; P = .006) significantly improved the accuracy of prognoses relative to clinical characteristics alone, such as the Glasgow Coma Scale or CT grade.
Previous studies showed that, if there is no understanding of the language used or if the subject is asleep, the brain doesn’t have the “signature” of tracking phrases and sentences, so it doesn’t have the synchronicity or the pattern of individuals with normal cognition, said Dr. Sokoliuk.
“You need a certain level of consciousness, and you need to understand the language, so your brain can actually track sentences or phrases,” she said.
Dr. Sokoliuk explained that the paradigm shows that patients are understanding the sentences and are not just hearing them.
“It’s not showing us that they only hear it, because there are no obvious gaps between the sentences; if there were gaps between sentences, it would probably only show that they hear it. It could be both, that they hear and understand it, but we wouldn’t know.”
A receiver operating characteristics analysis indicated 100% sensitivity and 80% specificity for a distinction between bad outcome (death, VS/UWS) and good outcome at 6 months.
“We could actually define a threshold of the tracking,” said Dr. Sokoliuk. “Patients who had phrases and sentences tracking below this threshold had worse outcome than those whose tracking value was above this threshold.”
The study illustrates that some posttraumatic patients who remain in an unresponsive state despite being sedation free may nevertheless comprehend speech.
The EEG paradigm approach, the authors said, may significantly reduce prognostic uncertainty in a critical phase of medical decision-making. It could also help clinicians make more appropriate decisions about whether or not to continue life-sustaining therapy and ensure more appropriate distribution of limited rehabilitation resources to patients most likely to benefit.
Dr. Sokoliuk stressed that the paradigm could be used at the bedside soon after a brain injury. “The critical thing is, we can actually use it during the acute phase, which is very important for clinical decisions about life-sustaining methods, therapy, and long-term care.”
A prognostic tool
The simple approach promises to be more accessible than fMRI, said Dr. Sokoliuk. “Putting an unresponsive coma patient in a scanner is very difficult and also much more expensive,” she said.
The next step, said Dr. Sokoliuk, is to repeat the study with a larger sample. “The number in the current study was quite small, and we can’t say if the sensitivity of the paradigm is strong enough to use it as a standard prognostic tool.”
To use it in clinical setting, “we really have to have robust measures,” she added.
She aims to conduct a collaborative study involving several institutions and more patients.
The research team plans to eventually build “an open-access toolbox” that would include the auditory streams to be played during EEG recordings and a program to analyze the data, said Dr. Sokoliuk. “Then, in the end, you would get a threshold or a value of tracking for phrases and sentences, and this could then classify a patient to be in a good-outcome or in bad-outcome group.”
She stressed this is a prognostic tool, not a diagnostic tool, and it should not be used in isolation. “It’s important to know that no clinician should only use this paradigm to prognosticate a patient; our paradigm should be part of a bigger battery of tests.”
But it could go a long way toward helping families as well as physicians. “If they know that the patient would be better in 3 months’ time, it’s easier for them to decide what should come next,” she said.
And it’s heartening to know that when families talk to their unresponsive loved one, the patient understands them, she added.
Promising basic research
Commenting on the study in an interview, Christine Blume, PhD, of the Center for Chronobiology, University of Basel (Switzerland), whose research interests include cognitive processing of patients with disorders of consciousness, described it as “very elegant and appealing” and the paradigm it used as “really promising.”
“However, we do, of course, not yet know about the prognostic value on a single-subject level, as the authors performed only group analyses,” said Dr. Blume. “This will require more extensive and perhaps even multicenter studies.”
It would also require developing a “solution” that “allows clinicians with limited time resources and perhaps lacking expert knowledge on the paradigm and the necessary analyses to apply the paradigm at bedside,” said Dr. Blume.
She agreed that a passive paradigm that helps determine whether a patient consciously understands speech, without the need for further processing, “has the potential to really improve the diagnostic process and uncover covert consciousness.”
One should bear in mind, though, that the paradigm “makes one essential assumption: that patients can understand speech,” said Dr. Blume. “For example, an aphasic patient might not understand but still be conscious.”
In this context, she added, “it’s essential to note that while the presence of a response suggests consciousness, the absence of a response does not suggest the absence of consciousness.”
Dr. Blume cautioned that the approach used in the study “is still at the stage of basic research.” Although the paradigm is promising, “I do not think it is ‘around the corner,’ ” she said.
The study was funded by the Medical Research Council. It was further supported by the National Institute for Health Research Surgical Reconstruction and Microbiology Research Center. Dr. Sokoliuk and Dr. Blume have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
results of a new study suggest. The study showed that the use of a paradigm that measures the strength of responses to speech improved the accuracy of prognosis for these patients, compared with prognoses made solely on the basis of standard clinical characteristics.
“What we found is really compelling evidence” of the usefulness of the test, lead study author Rodika Sokoliuk, PhD, a postdoctoral researcher at the Center for Human Brain Health, University of Birmingham (England), said in an interview.
The passive measure of comprehension, which doesn’t require any other response from the patient, can reduce uncertainty at a critical phase of decision-making in the ICU, said Dr. Sokoliuk.
The study was published online Dec. 23, 2020, in Annals of Neurology.
Useful information at a time of ‘considerable prognostic uncertainty’
Accurate, early prognostication is vital for efficient stratification of patients after a TBI, the authors wrote. This can often be achieved from patient behavior and CT at admission, but some patients continue to fail to obey commands after washout of sedation.
These patients pose a significant challenge for neurologic prognostication, they noted. In these cases, clinicians and families must decide whether to “wait and see” or consider treatment withdrawal.
The authors noted that a lack of command following early in the postsedation period is associated with poor outcome, including vegetative state/unresponsive wakefulness syndrome (VS/UWS). This, they said, represents a “window of opportunity” for cessation of life-sustaining therapy at a time of considerable prognostic uncertainty.
Recent research shows that a significant proportion of unresponsive patients retain a level of cognition, and even consciousness, that isn’t evident from their external behavior – the so-called cognitive-motor dissociation.
The new study included 28 adult patients who had experienced a TBI and were admitted to the ICU of the Queen Elizabeth Hospital in Birmingham, England. The patients had a Glasgow Coma Scale motor score less than 6 (i.e., they were incapable of obeying commands). They had been sedation free for 2-7 days.
For the paradigm, researchers constructed 288 English words using the male voice of the Apple synthesizer. The words required the same amount of time to be generated (320 ms) and were monosyllabic, so the rhythms of the sounds were the same.
The words were presented in a specific order: an adjective, then a noun, then a verb, then a noun. Two words – for example, an adjective and noun – “would build a meaningful phrase,” and four words would build a sentence, said Dr. Sokoliuk.
The researchers built 72 of these four-word sentences. A trial comprised 12 of these sentences, resulting in a total of 864 four-word sentences.
Dr. Sokoliuk likened the paradigm to a rap song with a specific beat that is continually repeated. “Basically, we play 12 of these four-word sentences in a row, without any gaps,” she said.
Each sentence was played to patients, in random order, a minimum of eight and a maximum of nine times per patient throughout the experiment. The patients’ brain activity was recorded on EEG.
Dr. Sokoliuk noted that brain activity in healthy people synchronizes only with the rhythm of phrases and sentences when listeners consciously comprehend the speech. The researchers assessed the level of comprehension in the unresponsive patients by measuring the strength of this synchronicity or brain pattern.
After exclusions, 17 patients were available for outcome assessment 3 months post EEG, and 16 patients were available 6 months post EEG.
The analysis showed that outcome significantly correlated with the strength of patients’ acute cortical tracking of phrases and sentences (r > 0.6; P < .007), quantified by intertrial phase coherence.
Linear regressions revealed that the strength of this comprehension response (beta, 0.603; P = .006) significantly improved the accuracy of prognoses relative to clinical characteristics alone, such as the Glasgow Coma Scale or CT grade.
Previous studies showed that, if there is no understanding of the language used or if the subject is asleep, the brain doesn’t have the “signature” of tracking phrases and sentences, so it doesn’t have the synchronicity or the pattern of individuals with normal cognition, said Dr. Sokoliuk.
“You need a certain level of consciousness, and you need to understand the language, so your brain can actually track sentences or phrases,” she said.
Dr. Sokoliuk explained that the paradigm shows that patients are understanding the sentences and are not just hearing them.
“It’s not showing us that they only hear it, because there are no obvious gaps between the sentences; if there were gaps between sentences, it would probably only show that they hear it. It could be both, that they hear and understand it, but we wouldn’t know.”
A receiver operating characteristics analysis indicated 100% sensitivity and 80% specificity for a distinction between bad outcome (death, VS/UWS) and good outcome at 6 months.
“We could actually define a threshold of the tracking,” said Dr. Sokoliuk. “Patients who had phrases and sentences tracking below this threshold had worse outcome than those whose tracking value was above this threshold.”
The study illustrates that some posttraumatic patients who remain in an unresponsive state despite being sedation free may nevertheless comprehend speech.
The EEG paradigm approach, the authors said, may significantly reduce prognostic uncertainty in a critical phase of medical decision-making. It could also help clinicians make more appropriate decisions about whether or not to continue life-sustaining therapy and ensure more appropriate distribution of limited rehabilitation resources to patients most likely to benefit.
Dr. Sokoliuk stressed that the paradigm could be used at the bedside soon after a brain injury. “The critical thing is, we can actually use it during the acute phase, which is very important for clinical decisions about life-sustaining methods, therapy, and long-term care.”
A prognostic tool
The simple approach promises to be more accessible than fMRI, said Dr. Sokoliuk. “Putting an unresponsive coma patient in a scanner is very difficult and also much more expensive,” she said.
The next step, said Dr. Sokoliuk, is to repeat the study with a larger sample. “The number in the current study was quite small, and we can’t say if the sensitivity of the paradigm is strong enough to use it as a standard prognostic tool.”
To use it in clinical setting, “we really have to have robust measures,” she added.
She aims to conduct a collaborative study involving several institutions and more patients.
The research team plans to eventually build “an open-access toolbox” that would include the auditory streams to be played during EEG recordings and a program to analyze the data, said Dr. Sokoliuk. “Then, in the end, you would get a threshold or a value of tracking for phrases and sentences, and this could then classify a patient to be in a good-outcome or in bad-outcome group.”
She stressed this is a prognostic tool, not a diagnostic tool, and it should not be used in isolation. “It’s important to know that no clinician should only use this paradigm to prognosticate a patient; our paradigm should be part of a bigger battery of tests.”
But it could go a long way toward helping families as well as physicians. “If they know that the patient would be better in 3 months’ time, it’s easier for them to decide what should come next,” she said.
And it’s heartening to know that when families talk to their unresponsive loved one, the patient understands them, she added.
Promising basic research
Commenting on the study in an interview, Christine Blume, PhD, of the Center for Chronobiology, University of Basel (Switzerland), whose research interests include cognitive processing of patients with disorders of consciousness, described it as “very elegant and appealing” and the paradigm it used as “really promising.”
“However, we do, of course, not yet know about the prognostic value on a single-subject level, as the authors performed only group analyses,” said Dr. Blume. “This will require more extensive and perhaps even multicenter studies.”
It would also require developing a “solution” that “allows clinicians with limited time resources and perhaps lacking expert knowledge on the paradigm and the necessary analyses to apply the paradigm at bedside,” said Dr. Blume.
She agreed that a passive paradigm that helps determine whether a patient consciously understands speech, without the need for further processing, “has the potential to really improve the diagnostic process and uncover covert consciousness.”
One should bear in mind, though, that the paradigm “makes one essential assumption: that patients can understand speech,” said Dr. Blume. “For example, an aphasic patient might not understand but still be conscious.”
In this context, she added, “it’s essential to note that while the presence of a response suggests consciousness, the absence of a response does not suggest the absence of consciousness.”
Dr. Blume cautioned that the approach used in the study “is still at the stage of basic research.” Although the paradigm is promising, “I do not think it is ‘around the corner,’ ” she said.
The study was funded by the Medical Research Council. It was further supported by the National Institute for Health Research Surgical Reconstruction and Microbiology Research Center. Dr. Sokoliuk and Dr. Blume have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ANNALS OF NEUROLOGY
Cloth masks provide inferior protection vs. medical masks, suggests evidence review
according to an evidence review published Jan. 11 in Annals of Family Medicine.
Nevertheless, cloth masks may provide some degree of protection, filtration studies indicate. If clinicians use cloth masks, they should take into account the fit, material, and number of layers, the review authors wrote.
And if cloth masks are used as a last resort, such as during shortages of personal protective equipment (PPE), additional measures may help, such as pairing cloth masks with plastic face shields.
“We recommend frequent cloth mask changes to reduce the risk of moisture retention and washing according to hospital laundry standards to decrease the risk of ineffective cleaning,” review author Ariel Kiyomi Daoud, a researcher at the University of Colorado at Denver, Aurora, and colleagues wrote.
The investigators identified and analyzed nine studies related to cloth masks’ ability to prevent respiratory viral infections among health care clinicians. The studies generally were not specific to SARS-CoV-2. They focused on four nonrandomized trials, three laboratory efficacy studies, one single-case experiment, and one randomized controlled trial.
Filtration and fit
“Seven publications addressed the filtration efficacy of commercial cloth masks or materials used to create homemade masks ... in a laboratory setting,” the researchers wrote. These studies found that cloth materials prevent some level of penetration, but generally have “lesser filtration efficiency and greater variability than medical masks” do.
One study found that the materials with the greatest filtration efficacy – vacuum bags and tea towels – had low airflow, which limits their use.
Two studies found that additional layers may increase the viral filtration efficacy of cloth masks.
Several studies that assessed mask fit and airflow found that cloth masks “have worse fit and a greater level of particle leakage, compared to medical masks,” the authors reported. Most studies did not examine cloth masks’ ability to protect wearers from respiratory droplets or contact, which the World Health Organization consider the primary means of SARS-CoV-2 spread, with aerosols playing a smaller role. “Thus, we must interpret these results with caution in the context of COVID-19,” the authors wrote. “For a primary care clinician without access to medical masks, our qualitative synthesis of the literature suggests that it is better to wear a cloth mask than no mask,” as long as other protective measures are considered along with cloth mask use.
Generally consistent guidance
Agencies and researchers have shared similar recommendations about the use of cloth masks in health care settings.
“Health care workers are at the frontline and they need to be protected,” said Abrar Ahmad Chughtai, MBBS, MPH, PhD, an epidemiologist at University of New South Wales, Sydney, in an interview. “Many studies show that respirators are more effective, compared to medical masks, and medical masks are more effective, compared to cloth masks. So ideally, all frontline health care workers should use respirators. If respirators are not available, then medical masks should be used. Cloth masks are not as effective as medical masks and ideally should not be used in health care settings.”
Dr. Chughtai has written about cloth masks for protection against SARS-CoV-2 and was an investigator for a 2015 randomized trial that compared medical masks and cloth masks in health care workers.
In that trial, which was considered in the review, greater rates of influenza-like illness occurred in the cloth mask arm, compared with the medical mask arm.
“Studies show that three or more layers of cloth may reduce the spread of droplets and aerosols from the wearers,” Dr. Chughtai said. “So, cloth masks may be used in community settings to prevent spread of infections from the sick, particularly asymptomatic, people.”
In addition, cloth masks “may be used by health care workers as a last resort, if no other option is available,” he said. In that case, they should have at least three layers, fit to the face, and be washed regularly.
Not considered PPE
According to routine infection prevention and control recommendations for health care personnel from the Centers for Disease Control and Prevention, face masks – often referred to as surgical masks or procedure masks – should be worn by workers “at all times while they are in the healthcare facility, including in break rooms or other spaces where they might encounter coworkers.”
Unlike cloth masks, face masks offer “protection for the wearer against exposure to splashes and sprays of infectious material from others,” as well as source control, the agency says. Health care personnel “should remove their respirator or face mask, perform hand hygiene, and put on their cloth mask when leaving the facility at the end of their shift,” according to the CDC.
“Cloth masks are NOT PPE and should not be worn for the care of patients with suspected or confirmed COVID-19 or other situations where use of a respirator or face mask is recommended,” the agency notes.
When respirators or face masks are unavailable, health care personnel “might use cloth masks as a last resort for care of patients with suspected or confirmed diagnosis for which face mask or respirator use is normally recommended,” according to CDC guidance.
In that scenario, cloth masks “should ideally be used in combination with a face shield that covers the entire front (that extends to the chin or below) and sides of the face,” the CDC says.
Limited data for comparisons
A Dec. 29, 2020, update in Annals of Internal Medicine about masks for prevention of respiratory virus infections highlighted two recent studies in the United States that reported on mask use in health care settings. A study of more than 16,000 health care workers and first responders found that those who used an N95 or surgical mask all of the time were less likely to have SARS-CoV-2 antibodies, compared with workers who did not wear masks all the time. The adjusted odds ratio with consistent N95 use was 0.83, and the aOR with consistent surgical mask use was 0.86.
In the second study, which included more than 20,000 asymptomatic health care workers, risk for infection was reduced with any mask use versus no mask use (OR, 0.58). An N95 mask was associated with decreased risk versus a surgical mask (OR, 0.76). The studies had methodological limitations, however, and “evidence for various comparisons about mask use in health care settings and risk for SARS-CoV-2 remains insufficient,” the authors of the update wrote.
The Annals of Family Medicine review authors had no relevant disclosures. Dr. Chughtai has tested filtration of 3M masks and worked with CleanSpace Technology to research fit testing of respirators, and the 2015 randomized trial was funded by an Australian Research Council Linkage Grant with 3M as a partner on the grant. The Dec. 29, 2020, update was of a review that originally was supported by grants from the Agency for Healthcare Research Quality.
SOURCE: Daoud AK et al. Ann Fam Med. 2020 Jan 11. doi: 10.1370/afm.2640.
according to an evidence review published Jan. 11 in Annals of Family Medicine.
Nevertheless, cloth masks may provide some degree of protection, filtration studies indicate. If clinicians use cloth masks, they should take into account the fit, material, and number of layers, the review authors wrote.
And if cloth masks are used as a last resort, such as during shortages of personal protective equipment (PPE), additional measures may help, such as pairing cloth masks with plastic face shields.
“We recommend frequent cloth mask changes to reduce the risk of moisture retention and washing according to hospital laundry standards to decrease the risk of ineffective cleaning,” review author Ariel Kiyomi Daoud, a researcher at the University of Colorado at Denver, Aurora, and colleagues wrote.
The investigators identified and analyzed nine studies related to cloth masks’ ability to prevent respiratory viral infections among health care clinicians. The studies generally were not specific to SARS-CoV-2. They focused on four nonrandomized trials, three laboratory efficacy studies, one single-case experiment, and one randomized controlled trial.
Filtration and fit
“Seven publications addressed the filtration efficacy of commercial cloth masks or materials used to create homemade masks ... in a laboratory setting,” the researchers wrote. These studies found that cloth materials prevent some level of penetration, but generally have “lesser filtration efficiency and greater variability than medical masks” do.
One study found that the materials with the greatest filtration efficacy – vacuum bags and tea towels – had low airflow, which limits their use.
Two studies found that additional layers may increase the viral filtration efficacy of cloth masks.
Several studies that assessed mask fit and airflow found that cloth masks “have worse fit and a greater level of particle leakage, compared to medical masks,” the authors reported. Most studies did not examine cloth masks’ ability to protect wearers from respiratory droplets or contact, which the World Health Organization consider the primary means of SARS-CoV-2 spread, with aerosols playing a smaller role. “Thus, we must interpret these results with caution in the context of COVID-19,” the authors wrote. “For a primary care clinician without access to medical masks, our qualitative synthesis of the literature suggests that it is better to wear a cloth mask than no mask,” as long as other protective measures are considered along with cloth mask use.
Generally consistent guidance
Agencies and researchers have shared similar recommendations about the use of cloth masks in health care settings.
“Health care workers are at the frontline and they need to be protected,” said Abrar Ahmad Chughtai, MBBS, MPH, PhD, an epidemiologist at University of New South Wales, Sydney, in an interview. “Many studies show that respirators are more effective, compared to medical masks, and medical masks are more effective, compared to cloth masks. So ideally, all frontline health care workers should use respirators. If respirators are not available, then medical masks should be used. Cloth masks are not as effective as medical masks and ideally should not be used in health care settings.”
Dr. Chughtai has written about cloth masks for protection against SARS-CoV-2 and was an investigator for a 2015 randomized trial that compared medical masks and cloth masks in health care workers.
In that trial, which was considered in the review, greater rates of influenza-like illness occurred in the cloth mask arm, compared with the medical mask arm.
“Studies show that three or more layers of cloth may reduce the spread of droplets and aerosols from the wearers,” Dr. Chughtai said. “So, cloth masks may be used in community settings to prevent spread of infections from the sick, particularly asymptomatic, people.”
In addition, cloth masks “may be used by health care workers as a last resort, if no other option is available,” he said. In that case, they should have at least three layers, fit to the face, and be washed regularly.
Not considered PPE
According to routine infection prevention and control recommendations for health care personnel from the Centers for Disease Control and Prevention, face masks – often referred to as surgical masks or procedure masks – should be worn by workers “at all times while they are in the healthcare facility, including in break rooms or other spaces where they might encounter coworkers.”
Unlike cloth masks, face masks offer “protection for the wearer against exposure to splashes and sprays of infectious material from others,” as well as source control, the agency says. Health care personnel “should remove their respirator or face mask, perform hand hygiene, and put on their cloth mask when leaving the facility at the end of their shift,” according to the CDC.
“Cloth masks are NOT PPE and should not be worn for the care of patients with suspected or confirmed COVID-19 or other situations where use of a respirator or face mask is recommended,” the agency notes.
When respirators or face masks are unavailable, health care personnel “might use cloth masks as a last resort for care of patients with suspected or confirmed diagnosis for which face mask or respirator use is normally recommended,” according to CDC guidance.
In that scenario, cloth masks “should ideally be used in combination with a face shield that covers the entire front (that extends to the chin or below) and sides of the face,” the CDC says.
Limited data for comparisons
A Dec. 29, 2020, update in Annals of Internal Medicine about masks for prevention of respiratory virus infections highlighted two recent studies in the United States that reported on mask use in health care settings. A study of more than 16,000 health care workers and first responders found that those who used an N95 or surgical mask all of the time were less likely to have SARS-CoV-2 antibodies, compared with workers who did not wear masks all the time. The adjusted odds ratio with consistent N95 use was 0.83, and the aOR with consistent surgical mask use was 0.86.
In the second study, which included more than 20,000 asymptomatic health care workers, risk for infection was reduced with any mask use versus no mask use (OR, 0.58). An N95 mask was associated with decreased risk versus a surgical mask (OR, 0.76). The studies had methodological limitations, however, and “evidence for various comparisons about mask use in health care settings and risk for SARS-CoV-2 remains insufficient,” the authors of the update wrote.
The Annals of Family Medicine review authors had no relevant disclosures. Dr. Chughtai has tested filtration of 3M masks and worked with CleanSpace Technology to research fit testing of respirators, and the 2015 randomized trial was funded by an Australian Research Council Linkage Grant with 3M as a partner on the grant. The Dec. 29, 2020, update was of a review that originally was supported by grants from the Agency for Healthcare Research Quality.
SOURCE: Daoud AK et al. Ann Fam Med. 2020 Jan 11. doi: 10.1370/afm.2640.
according to an evidence review published Jan. 11 in Annals of Family Medicine.
Nevertheless, cloth masks may provide some degree of protection, filtration studies indicate. If clinicians use cloth masks, they should take into account the fit, material, and number of layers, the review authors wrote.
And if cloth masks are used as a last resort, such as during shortages of personal protective equipment (PPE), additional measures may help, such as pairing cloth masks with plastic face shields.
“We recommend frequent cloth mask changes to reduce the risk of moisture retention and washing according to hospital laundry standards to decrease the risk of ineffective cleaning,” review author Ariel Kiyomi Daoud, a researcher at the University of Colorado at Denver, Aurora, and colleagues wrote.
The investigators identified and analyzed nine studies related to cloth masks’ ability to prevent respiratory viral infections among health care clinicians. The studies generally were not specific to SARS-CoV-2. They focused on four nonrandomized trials, three laboratory efficacy studies, one single-case experiment, and one randomized controlled trial.
Filtration and fit
“Seven publications addressed the filtration efficacy of commercial cloth masks or materials used to create homemade masks ... in a laboratory setting,” the researchers wrote. These studies found that cloth materials prevent some level of penetration, but generally have “lesser filtration efficiency and greater variability than medical masks” do.
One study found that the materials with the greatest filtration efficacy – vacuum bags and tea towels – had low airflow, which limits their use.
Two studies found that additional layers may increase the viral filtration efficacy of cloth masks.
Several studies that assessed mask fit and airflow found that cloth masks “have worse fit and a greater level of particle leakage, compared to medical masks,” the authors reported. Most studies did not examine cloth masks’ ability to protect wearers from respiratory droplets or contact, which the World Health Organization consider the primary means of SARS-CoV-2 spread, with aerosols playing a smaller role. “Thus, we must interpret these results with caution in the context of COVID-19,” the authors wrote. “For a primary care clinician without access to medical masks, our qualitative synthesis of the literature suggests that it is better to wear a cloth mask than no mask,” as long as other protective measures are considered along with cloth mask use.
Generally consistent guidance
Agencies and researchers have shared similar recommendations about the use of cloth masks in health care settings.
“Health care workers are at the frontline and they need to be protected,” said Abrar Ahmad Chughtai, MBBS, MPH, PhD, an epidemiologist at University of New South Wales, Sydney, in an interview. “Many studies show that respirators are more effective, compared to medical masks, and medical masks are more effective, compared to cloth masks. So ideally, all frontline health care workers should use respirators. If respirators are not available, then medical masks should be used. Cloth masks are not as effective as medical masks and ideally should not be used in health care settings.”
Dr. Chughtai has written about cloth masks for protection against SARS-CoV-2 and was an investigator for a 2015 randomized trial that compared medical masks and cloth masks in health care workers.
In that trial, which was considered in the review, greater rates of influenza-like illness occurred in the cloth mask arm, compared with the medical mask arm.
“Studies show that three or more layers of cloth may reduce the spread of droplets and aerosols from the wearers,” Dr. Chughtai said. “So, cloth masks may be used in community settings to prevent spread of infections from the sick, particularly asymptomatic, people.”
In addition, cloth masks “may be used by health care workers as a last resort, if no other option is available,” he said. In that case, they should have at least three layers, fit to the face, and be washed regularly.
Not considered PPE
According to routine infection prevention and control recommendations for health care personnel from the Centers for Disease Control and Prevention, face masks – often referred to as surgical masks or procedure masks – should be worn by workers “at all times while they are in the healthcare facility, including in break rooms or other spaces where they might encounter coworkers.”
Unlike cloth masks, face masks offer “protection for the wearer against exposure to splashes and sprays of infectious material from others,” as well as source control, the agency says. Health care personnel “should remove their respirator or face mask, perform hand hygiene, and put on their cloth mask when leaving the facility at the end of their shift,” according to the CDC.
“Cloth masks are NOT PPE and should not be worn for the care of patients with suspected or confirmed COVID-19 or other situations where use of a respirator or face mask is recommended,” the agency notes.
When respirators or face masks are unavailable, health care personnel “might use cloth masks as a last resort for care of patients with suspected or confirmed diagnosis for which face mask or respirator use is normally recommended,” according to CDC guidance.
In that scenario, cloth masks “should ideally be used in combination with a face shield that covers the entire front (that extends to the chin or below) and sides of the face,” the CDC says.
Limited data for comparisons
A Dec. 29, 2020, update in Annals of Internal Medicine about masks for prevention of respiratory virus infections highlighted two recent studies in the United States that reported on mask use in health care settings. A study of more than 16,000 health care workers and first responders found that those who used an N95 or surgical mask all of the time were less likely to have SARS-CoV-2 antibodies, compared with workers who did not wear masks all the time. The adjusted odds ratio with consistent N95 use was 0.83, and the aOR with consistent surgical mask use was 0.86.
In the second study, which included more than 20,000 asymptomatic health care workers, risk for infection was reduced with any mask use versus no mask use (OR, 0.58). An N95 mask was associated with decreased risk versus a surgical mask (OR, 0.76). The studies had methodological limitations, however, and “evidence for various comparisons about mask use in health care settings and risk for SARS-CoV-2 remains insufficient,” the authors of the update wrote.
The Annals of Family Medicine review authors had no relevant disclosures. Dr. Chughtai has tested filtration of 3M masks and worked with CleanSpace Technology to research fit testing of respirators, and the 2015 randomized trial was funded by an Australian Research Council Linkage Grant with 3M as a partner on the grant. The Dec. 29, 2020, update was of a review that originally was supported by grants from the Agency for Healthcare Research Quality.
SOURCE: Daoud AK et al. Ann Fam Med. 2020 Jan 11. doi: 10.1370/afm.2640.
FROM ANNALS OF FAMILY MEDICINE
Feds authorize $3 billion to boost vaccine rollout
The CDC will send $3 billion to the states to boost a lagging national COVID-19 vaccination program.
The Department of Health and Human Services announced the new funding as only 30% of the more than 22 million doses of vaccine distributed in the U.S. has been injected into Americans’ arms.
Along with the $3 billion, HHS said another $19 billion is headed to states and jurisdictions to boost COVID-19 testing programs. The amount each state will receive will be determined by population.
The news comes days after President-elect Joe Biden said he planned to release all available doses of vaccine after he takes office on Jan. 20. The Trump administration has been holding back millions of doses to ensure supply of vaccine to provide the necessary second dose for those who received the first shot.
“This funding is another timely investment that will strengthen our nation’s efforts to stop the COVID-19 pandemic in America,” CDC Director Robert Redfield, MD, said in a statement. “Particularly now, it is crucial that states and communities have the resources they need to conduct testing, and to distribute and administer safe, high-quality COVID-19 vaccines safely and equitably.”
Federal officials and public health experts, however, expressed concerns this weekend about Biden’s plan.
Outgoing Trump administration officials and others said they worry that doing so will leave providers without enough second doses for people getting the two-shot vaccines.
If Biden releases all available doses and the vaccine-making process has an issue, they said, that could pose a supply risk.
“We have product that is going through QC right now – quality control – for sterility, identity check that we have tens and tens of millions of product. We always will. But batches fail. Sterility fails ... and then you don’t have a product for that second dose,” Alex Azar, secretary of health and human services, told the American Hospital Association on Jan. 8, according to CNN.
“And frankly, talking about that or encouraging that can really undermine a critical public health need, which is that people come back for their second vaccine,” he said.
One of the main roadblocks in the vaccine rollout has been administering the doses that have already been distributed. The U.S. has shipped 22.1 million doses, and 6.6 million first shots have been given, according to the latest CDC data updated Jan. 8. Mr. Azar and other federal health officials have encouraged states to use their current supply and expand vaccine access to more priority groups.
“We would be delighted to learn that jurisdictions have actually administered many more doses than they are presently reporting,” a spokesman for the U.S. Department of Health and Human Services told CNN. “We are encouraging jurisdictions to expand their priority groups as needed to ensure no vaccine is sitting on the shelf after having been delivered to the jurisdiction-directed locations.”
Releasing more vaccines for first doses could create ethical concerns as well, since people getting vaccines expect to get a second dose in the proper amount of time, according to The Week. Biden’s transition team said on Jan. 8 that he won’t delay the second dose but, instead, plans to ramp up production to stay on track.
To do this well, the federal government should create a coordinated vaccine strategy that sets expectations for an around-the-clock operation and help state and local vaccination programs meet their goals, Leana Wen, MD, a professor at George Washington University, wrote in an editorial for The Washington Post.
“The Biden team’s urgency around vaccinations is commendable,” she added in a Twitter post on Jan. 11. “I’d like to see a guarantee that every 1st dose given will be followed with a timely 2nd dose. Otherwise, there are ethical concerns that could add to vaccine hesitancy.”
Biden has pledged that 100 million doses will be administered in his first 100 days in office. He has grown frustrated as concerns grow that his administration could fall short of the promise, according to Politico. His coronavirus response team has noted several challenges, including what they say is a lack of long-term planning by the Trump administration and an initial refusal to share key information.
“We’re uncovering new information each day, and we’re unearthing – of course – more work to be done,” Vivek Murthy, MD, Biden’s nominee for surgeon general, told Politico.
The team has uncovered staffing shortages, technology problems, and issues with health care insurance coverage. The incoming Biden team has developed several initiatives, such as mobile vaccination units and new federal sites to give shots. It could take weeks to get the vaccine rollout on track, the news outlet reported.
“Will this be challenging? Absolutely,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and Biden’s incoming chief medical adviser on the coronavirus, told Politico. “This is an unprecedented effort to vaccinate the entire country over a period of time that’s fighting against people dying at record numbers. To say it’s not a challenge would be unrealistic. Do I think it can be done? Yes.”
A version of this article first appeared on WebMD.com.
The CDC will send $3 billion to the states to boost a lagging national COVID-19 vaccination program.
The Department of Health and Human Services announced the new funding as only 30% of the more than 22 million doses of vaccine distributed in the U.S. has been injected into Americans’ arms.
Along with the $3 billion, HHS said another $19 billion is headed to states and jurisdictions to boost COVID-19 testing programs. The amount each state will receive will be determined by population.
The news comes days after President-elect Joe Biden said he planned to release all available doses of vaccine after he takes office on Jan. 20. The Trump administration has been holding back millions of doses to ensure supply of vaccine to provide the necessary second dose for those who received the first shot.
“This funding is another timely investment that will strengthen our nation’s efforts to stop the COVID-19 pandemic in America,” CDC Director Robert Redfield, MD, said in a statement. “Particularly now, it is crucial that states and communities have the resources they need to conduct testing, and to distribute and administer safe, high-quality COVID-19 vaccines safely and equitably.”
Federal officials and public health experts, however, expressed concerns this weekend about Biden’s plan.
Outgoing Trump administration officials and others said they worry that doing so will leave providers without enough second doses for people getting the two-shot vaccines.
If Biden releases all available doses and the vaccine-making process has an issue, they said, that could pose a supply risk.
“We have product that is going through QC right now – quality control – for sterility, identity check that we have tens and tens of millions of product. We always will. But batches fail. Sterility fails ... and then you don’t have a product for that second dose,” Alex Azar, secretary of health and human services, told the American Hospital Association on Jan. 8, according to CNN.
“And frankly, talking about that or encouraging that can really undermine a critical public health need, which is that people come back for their second vaccine,” he said.
One of the main roadblocks in the vaccine rollout has been administering the doses that have already been distributed. The U.S. has shipped 22.1 million doses, and 6.6 million first shots have been given, according to the latest CDC data updated Jan. 8. Mr. Azar and other federal health officials have encouraged states to use their current supply and expand vaccine access to more priority groups.
“We would be delighted to learn that jurisdictions have actually administered many more doses than they are presently reporting,” a spokesman for the U.S. Department of Health and Human Services told CNN. “We are encouraging jurisdictions to expand their priority groups as needed to ensure no vaccine is sitting on the shelf after having been delivered to the jurisdiction-directed locations.”
Releasing more vaccines for first doses could create ethical concerns as well, since people getting vaccines expect to get a second dose in the proper amount of time, according to The Week. Biden’s transition team said on Jan. 8 that he won’t delay the second dose but, instead, plans to ramp up production to stay on track.
To do this well, the federal government should create a coordinated vaccine strategy that sets expectations for an around-the-clock operation and help state and local vaccination programs meet their goals, Leana Wen, MD, a professor at George Washington University, wrote in an editorial for The Washington Post.
“The Biden team’s urgency around vaccinations is commendable,” she added in a Twitter post on Jan. 11. “I’d like to see a guarantee that every 1st dose given will be followed with a timely 2nd dose. Otherwise, there are ethical concerns that could add to vaccine hesitancy.”
Biden has pledged that 100 million doses will be administered in his first 100 days in office. He has grown frustrated as concerns grow that his administration could fall short of the promise, according to Politico. His coronavirus response team has noted several challenges, including what they say is a lack of long-term planning by the Trump administration and an initial refusal to share key information.
“We’re uncovering new information each day, and we’re unearthing – of course – more work to be done,” Vivek Murthy, MD, Biden’s nominee for surgeon general, told Politico.
The team has uncovered staffing shortages, technology problems, and issues with health care insurance coverage. The incoming Biden team has developed several initiatives, such as mobile vaccination units and new federal sites to give shots. It could take weeks to get the vaccine rollout on track, the news outlet reported.
“Will this be challenging? Absolutely,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and Biden’s incoming chief medical adviser on the coronavirus, told Politico. “This is an unprecedented effort to vaccinate the entire country over a period of time that’s fighting against people dying at record numbers. To say it’s not a challenge would be unrealistic. Do I think it can be done? Yes.”
A version of this article first appeared on WebMD.com.
The CDC will send $3 billion to the states to boost a lagging national COVID-19 vaccination program.
The Department of Health and Human Services announced the new funding as only 30% of the more than 22 million doses of vaccine distributed in the U.S. has been injected into Americans’ arms.
Along with the $3 billion, HHS said another $19 billion is headed to states and jurisdictions to boost COVID-19 testing programs. The amount each state will receive will be determined by population.
The news comes days after President-elect Joe Biden said he planned to release all available doses of vaccine after he takes office on Jan. 20. The Trump administration has been holding back millions of doses to ensure supply of vaccine to provide the necessary second dose for those who received the first shot.
“This funding is another timely investment that will strengthen our nation’s efforts to stop the COVID-19 pandemic in America,” CDC Director Robert Redfield, MD, said in a statement. “Particularly now, it is crucial that states and communities have the resources they need to conduct testing, and to distribute and administer safe, high-quality COVID-19 vaccines safely and equitably.”
Federal officials and public health experts, however, expressed concerns this weekend about Biden’s plan.
Outgoing Trump administration officials and others said they worry that doing so will leave providers without enough second doses for people getting the two-shot vaccines.
If Biden releases all available doses and the vaccine-making process has an issue, they said, that could pose a supply risk.
“We have product that is going through QC right now – quality control – for sterility, identity check that we have tens and tens of millions of product. We always will. But batches fail. Sterility fails ... and then you don’t have a product for that second dose,” Alex Azar, secretary of health and human services, told the American Hospital Association on Jan. 8, according to CNN.
“And frankly, talking about that or encouraging that can really undermine a critical public health need, which is that people come back for their second vaccine,” he said.
One of the main roadblocks in the vaccine rollout has been administering the doses that have already been distributed. The U.S. has shipped 22.1 million doses, and 6.6 million first shots have been given, according to the latest CDC data updated Jan. 8. Mr. Azar and other federal health officials have encouraged states to use their current supply and expand vaccine access to more priority groups.
“We would be delighted to learn that jurisdictions have actually administered many more doses than they are presently reporting,” a spokesman for the U.S. Department of Health and Human Services told CNN. “We are encouraging jurisdictions to expand their priority groups as needed to ensure no vaccine is sitting on the shelf after having been delivered to the jurisdiction-directed locations.”
Releasing more vaccines for first doses could create ethical concerns as well, since people getting vaccines expect to get a second dose in the proper amount of time, according to The Week. Biden’s transition team said on Jan. 8 that he won’t delay the second dose but, instead, plans to ramp up production to stay on track.
To do this well, the federal government should create a coordinated vaccine strategy that sets expectations for an around-the-clock operation and help state and local vaccination programs meet their goals, Leana Wen, MD, a professor at George Washington University, wrote in an editorial for The Washington Post.
“The Biden team’s urgency around vaccinations is commendable,” she added in a Twitter post on Jan. 11. “I’d like to see a guarantee that every 1st dose given will be followed with a timely 2nd dose. Otherwise, there are ethical concerns that could add to vaccine hesitancy.”
Biden has pledged that 100 million doses will be administered in his first 100 days in office. He has grown frustrated as concerns grow that his administration could fall short of the promise, according to Politico. His coronavirus response team has noted several challenges, including what they say is a lack of long-term planning by the Trump administration and an initial refusal to share key information.
“We’re uncovering new information each day, and we’re unearthing – of course – more work to be done,” Vivek Murthy, MD, Biden’s nominee for surgeon general, told Politico.
The team has uncovered staffing shortages, technology problems, and issues with health care insurance coverage. The incoming Biden team has developed several initiatives, such as mobile vaccination units and new federal sites to give shots. It could take weeks to get the vaccine rollout on track, the news outlet reported.
“Will this be challenging? Absolutely,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases and Biden’s incoming chief medical adviser on the coronavirus, told Politico. “This is an unprecedented effort to vaccinate the entire country over a period of time that’s fighting against people dying at record numbers. To say it’s not a challenge would be unrealistic. Do I think it can be done? Yes.”
A version of this article first appeared on WebMD.com.
Study reveals how aspirin may inhibit colorectal cancer
Aspirin “rescued” a cystic intestinal phenotype driven by the Wnt pathway, reduced stem cell expression and function, and increased the expression of Dickkopf (DKK)–1, a Wnt antagonist that is frequently lost as colorectal cancer (CRC) progresses, according to recent study findings.
“Dysregulated Wnt signaling, [which is] primarily driven by adenomatous polyposis coli (APC) gene mutations, is fundamental to cancer initiation in both sporadic CRC and familial adenomatous polyposis (FAP). ... Our observations reveal a novel mechanism of aspirin-mediated Wnt inhibition through DKK-1 increase and potential ‘pheno-markers’ for chemoprevention and adjuvant aspirin human trials,” wrote Karen Dunbar, PhD, and her associates in Cellular and Molecular Gastroenterology and Hepatology.
Aspirin shows benefits in sporadic and familial adenoma, significantly reduces CRC incidence, and may delay disease progression while improving survival. “Understanding the biology responsible for this protective effect is key to developing biomarker-led approaches for rational clinical use,” wrote Dr. Dunbar, now with the University of Dundee (Scotland) and colleagues.
She and her coinvestigators found that aspirin promoted the wild-type (budding, noncystic) phenotype in intestinal organoids derived from APC-deficient mice and humans with FAP. They saw the same effect in live APC-deficient mice. With the help of an RNAscope, they confirmed that aspirin significantly reduced RNA transcripts for Lgr5 and TROY, which are stem cell markers in CRC. Aspirin also reduced Lgr5 expression in APC-deficient mice and in human organoids derived from normal colonic mucosa, sporadic colorectal tumors, and colorectal tumors from patients with FAP.
In wound-closure models, aspirin inhibited Wnt and epithelial-mesenchymal transition (EMT) while decreasing migration and invasion by colorectal cancer cells. Aspirin accomplished this by increasing the phosphorylation of GSK-3beta and beta-catenin. Notably, aspirin increased the production of E-cadherin, which buffers excess beta-catenin and thereby limits overactivated Wnt to promote an epithelial, rather than mesenchymal, phenotype. “The novel observation that the aspirin-mediated E-cadherin increase is paralleled by greater E-cadherin–beta-catenin binding further supports the hypothesis that aspirin promotes an epithelial phenotype through Wnt inhibition,” the researchers wrote.
In colorectal cells and FAP organoids, aspirin also increased the expression of the Wnt antagonist DKK-1, which in turn correlated with lower stem cell function. “In humans, high serum DKK-1 correlates with increasing colorectal cancer stage, whereas tissue DKK-1 expression is lost with cancer progression,” the researchers explained. “Here, we demonstrate that aspirin robustly increases DKK-1 expression in CRC models, which contributes to EMT and [cancer stem cell] inhibition observed with aspirin.”
Taken together, the findings “highlight two novel phenotypic indicators of aspirin response, the cystic-phenotype rescue and reduced stem cell marker expression, which may serve as enhanced biomarkers, compared with individual Wnt components,” they concluded. “Through targeting Wnt signaling at multiple levels, aspirin enhances commitment to differentiation, and hence, phenotypic markers of Wnt inhibition represent better targets [for] therapeutic exploitation.”
Dr. Dunbar and her associates reported having no relevant conflicts of interest. The work was supported by Cancer Research UK and the Chief Scientist Office of Scotland, the MRC Centre, and the CRUK.
SOURCE: Dunbar K et al. Cell Mol Gastroenterol Hepatol. 2020 Sep 21. doi: 10.1016/j.jcmgh.2020.09.010.
It is well known that aspirin protects against colorectal polyps and cancers, but the molecular mechanisms by which aspirin confers this protection remain obscure. By developing new models and identifying the molecular targets of aspirin, therapies may be developed that prevent colorectal polyps and cancers but avoid the negative effects of aspirin. Most colorectal cancers (CRC), both spontaneous and familiar, arise from abnormal activation of an important molecular pathway known as the Wnt signaling pathway. Specific mutations in a key member of this pathway, the tumor suppressor APC, are an early event in spontaneous cancers and are the cause of a condition known as familial adenomatous polyposis (FAP). Wnt signaling also drives CRC by regulating cancer stem cells and a process known as epithelial-mesenchymal transition (EMT).
With use of established CRC cell lines, mouse models of FAP, and organoids – three-dimensional models of colonic epithelium – from mice and from human FAP patients, Dunbar and colleagues performed a comprehensive study to define the mechanisms by which aspirin acts to prevent the development and progression of CRC. Here, Dunbar and colleagues found that aspirin limits cancer stem cell populations and the development of EMT, which together are important for tumor cell propagation, invasion, and dissemination. Importantly, they also showed that aspirin increases the expression of a natural Wnt pathway antagonist known as DKK-1, providing a mechanism by which aspirin inhibits Wnt signaling in the context of CRC. Future studies can build on this work by exploring these findings to develop targeted approaches to Wnt inhibition and to prevent colorectal polyps and cancers.
Jonathan P. Katz, MD, is an associate professor of medicine in the division of gastroenterology, department of medicine at the University of Pennsylvania, Philadelphia. He has no conflicts of interest.
It is well known that aspirin protects against colorectal polyps and cancers, but the molecular mechanisms by which aspirin confers this protection remain obscure. By developing new models and identifying the molecular targets of aspirin, therapies may be developed that prevent colorectal polyps and cancers but avoid the negative effects of aspirin. Most colorectal cancers (CRC), both spontaneous and familiar, arise from abnormal activation of an important molecular pathway known as the Wnt signaling pathway. Specific mutations in a key member of this pathway, the tumor suppressor APC, are an early event in spontaneous cancers and are the cause of a condition known as familial adenomatous polyposis (FAP). Wnt signaling also drives CRC by regulating cancer stem cells and a process known as epithelial-mesenchymal transition (EMT).
With use of established CRC cell lines, mouse models of FAP, and organoids – three-dimensional models of colonic epithelium – from mice and from human FAP patients, Dunbar and colleagues performed a comprehensive study to define the mechanisms by which aspirin acts to prevent the development and progression of CRC. Here, Dunbar and colleagues found that aspirin limits cancer stem cell populations and the development of EMT, which together are important for tumor cell propagation, invasion, and dissemination. Importantly, they also showed that aspirin increases the expression of a natural Wnt pathway antagonist known as DKK-1, providing a mechanism by which aspirin inhibits Wnt signaling in the context of CRC. Future studies can build on this work by exploring these findings to develop targeted approaches to Wnt inhibition and to prevent colorectal polyps and cancers.
Jonathan P. Katz, MD, is an associate professor of medicine in the division of gastroenterology, department of medicine at the University of Pennsylvania, Philadelphia. He has no conflicts of interest.
It is well known that aspirin protects against colorectal polyps and cancers, but the molecular mechanisms by which aspirin confers this protection remain obscure. By developing new models and identifying the molecular targets of aspirin, therapies may be developed that prevent colorectal polyps and cancers but avoid the negative effects of aspirin. Most colorectal cancers (CRC), both spontaneous and familiar, arise from abnormal activation of an important molecular pathway known as the Wnt signaling pathway. Specific mutations in a key member of this pathway, the tumor suppressor APC, are an early event in spontaneous cancers and are the cause of a condition known as familial adenomatous polyposis (FAP). Wnt signaling also drives CRC by regulating cancer stem cells and a process known as epithelial-mesenchymal transition (EMT).
With use of established CRC cell lines, mouse models of FAP, and organoids – three-dimensional models of colonic epithelium – from mice and from human FAP patients, Dunbar and colleagues performed a comprehensive study to define the mechanisms by which aspirin acts to prevent the development and progression of CRC. Here, Dunbar and colleagues found that aspirin limits cancer stem cell populations and the development of EMT, which together are important for tumor cell propagation, invasion, and dissemination. Importantly, they also showed that aspirin increases the expression of a natural Wnt pathway antagonist known as DKK-1, providing a mechanism by which aspirin inhibits Wnt signaling in the context of CRC. Future studies can build on this work by exploring these findings to develop targeted approaches to Wnt inhibition and to prevent colorectal polyps and cancers.
Jonathan P. Katz, MD, is an associate professor of medicine in the division of gastroenterology, department of medicine at the University of Pennsylvania, Philadelphia. He has no conflicts of interest.
Aspirin “rescued” a cystic intestinal phenotype driven by the Wnt pathway, reduced stem cell expression and function, and increased the expression of Dickkopf (DKK)–1, a Wnt antagonist that is frequently lost as colorectal cancer (CRC) progresses, according to recent study findings.
“Dysregulated Wnt signaling, [which is] primarily driven by adenomatous polyposis coli (APC) gene mutations, is fundamental to cancer initiation in both sporadic CRC and familial adenomatous polyposis (FAP). ... Our observations reveal a novel mechanism of aspirin-mediated Wnt inhibition through DKK-1 increase and potential ‘pheno-markers’ for chemoprevention and adjuvant aspirin human trials,” wrote Karen Dunbar, PhD, and her associates in Cellular and Molecular Gastroenterology and Hepatology.
Aspirin shows benefits in sporadic and familial adenoma, significantly reduces CRC incidence, and may delay disease progression while improving survival. “Understanding the biology responsible for this protective effect is key to developing biomarker-led approaches for rational clinical use,” wrote Dr. Dunbar, now with the University of Dundee (Scotland) and colleagues.
She and her coinvestigators found that aspirin promoted the wild-type (budding, noncystic) phenotype in intestinal organoids derived from APC-deficient mice and humans with FAP. They saw the same effect in live APC-deficient mice. With the help of an RNAscope, they confirmed that aspirin significantly reduced RNA transcripts for Lgr5 and TROY, which are stem cell markers in CRC. Aspirin also reduced Lgr5 expression in APC-deficient mice and in human organoids derived from normal colonic mucosa, sporadic colorectal tumors, and colorectal tumors from patients with FAP.
In wound-closure models, aspirin inhibited Wnt and epithelial-mesenchymal transition (EMT) while decreasing migration and invasion by colorectal cancer cells. Aspirin accomplished this by increasing the phosphorylation of GSK-3beta and beta-catenin. Notably, aspirin increased the production of E-cadherin, which buffers excess beta-catenin and thereby limits overactivated Wnt to promote an epithelial, rather than mesenchymal, phenotype. “The novel observation that the aspirin-mediated E-cadherin increase is paralleled by greater E-cadherin–beta-catenin binding further supports the hypothesis that aspirin promotes an epithelial phenotype through Wnt inhibition,” the researchers wrote.
In colorectal cells and FAP organoids, aspirin also increased the expression of the Wnt antagonist DKK-1, which in turn correlated with lower stem cell function. “In humans, high serum DKK-1 correlates with increasing colorectal cancer stage, whereas tissue DKK-1 expression is lost with cancer progression,” the researchers explained. “Here, we demonstrate that aspirin robustly increases DKK-1 expression in CRC models, which contributes to EMT and [cancer stem cell] inhibition observed with aspirin.”
Taken together, the findings “highlight two novel phenotypic indicators of aspirin response, the cystic-phenotype rescue and reduced stem cell marker expression, which may serve as enhanced biomarkers, compared with individual Wnt components,” they concluded. “Through targeting Wnt signaling at multiple levels, aspirin enhances commitment to differentiation, and hence, phenotypic markers of Wnt inhibition represent better targets [for] therapeutic exploitation.”
Dr. Dunbar and her associates reported having no relevant conflicts of interest. The work was supported by Cancer Research UK and the Chief Scientist Office of Scotland, the MRC Centre, and the CRUK.
SOURCE: Dunbar K et al. Cell Mol Gastroenterol Hepatol. 2020 Sep 21. doi: 10.1016/j.jcmgh.2020.09.010.
Aspirin “rescued” a cystic intestinal phenotype driven by the Wnt pathway, reduced stem cell expression and function, and increased the expression of Dickkopf (DKK)–1, a Wnt antagonist that is frequently lost as colorectal cancer (CRC) progresses, according to recent study findings.
“Dysregulated Wnt signaling, [which is] primarily driven by adenomatous polyposis coli (APC) gene mutations, is fundamental to cancer initiation in both sporadic CRC and familial adenomatous polyposis (FAP). ... Our observations reveal a novel mechanism of aspirin-mediated Wnt inhibition through DKK-1 increase and potential ‘pheno-markers’ for chemoprevention and adjuvant aspirin human trials,” wrote Karen Dunbar, PhD, and her associates in Cellular and Molecular Gastroenterology and Hepatology.
Aspirin shows benefits in sporadic and familial adenoma, significantly reduces CRC incidence, and may delay disease progression while improving survival. “Understanding the biology responsible for this protective effect is key to developing biomarker-led approaches for rational clinical use,” wrote Dr. Dunbar, now with the University of Dundee (Scotland) and colleagues.
She and her coinvestigators found that aspirin promoted the wild-type (budding, noncystic) phenotype in intestinal organoids derived from APC-deficient mice and humans with FAP. They saw the same effect in live APC-deficient mice. With the help of an RNAscope, they confirmed that aspirin significantly reduced RNA transcripts for Lgr5 and TROY, which are stem cell markers in CRC. Aspirin also reduced Lgr5 expression in APC-deficient mice and in human organoids derived from normal colonic mucosa, sporadic colorectal tumors, and colorectal tumors from patients with FAP.
In wound-closure models, aspirin inhibited Wnt and epithelial-mesenchymal transition (EMT) while decreasing migration and invasion by colorectal cancer cells. Aspirin accomplished this by increasing the phosphorylation of GSK-3beta and beta-catenin. Notably, aspirin increased the production of E-cadherin, which buffers excess beta-catenin and thereby limits overactivated Wnt to promote an epithelial, rather than mesenchymal, phenotype. “The novel observation that the aspirin-mediated E-cadherin increase is paralleled by greater E-cadherin–beta-catenin binding further supports the hypothesis that aspirin promotes an epithelial phenotype through Wnt inhibition,” the researchers wrote.
In colorectal cells and FAP organoids, aspirin also increased the expression of the Wnt antagonist DKK-1, which in turn correlated with lower stem cell function. “In humans, high serum DKK-1 correlates with increasing colorectal cancer stage, whereas tissue DKK-1 expression is lost with cancer progression,” the researchers explained. “Here, we demonstrate that aspirin robustly increases DKK-1 expression in CRC models, which contributes to EMT and [cancer stem cell] inhibition observed with aspirin.”
Taken together, the findings “highlight two novel phenotypic indicators of aspirin response, the cystic-phenotype rescue and reduced stem cell marker expression, which may serve as enhanced biomarkers, compared with individual Wnt components,” they concluded. “Through targeting Wnt signaling at multiple levels, aspirin enhances commitment to differentiation, and hence, phenotypic markers of Wnt inhibition represent better targets [for] therapeutic exploitation.”
Dr. Dunbar and her associates reported having no relevant conflicts of interest. The work was supported by Cancer Research UK and the Chief Scientist Office of Scotland, the MRC Centre, and the CRUK.
SOURCE: Dunbar K et al. Cell Mol Gastroenterol Hepatol. 2020 Sep 21. doi: 10.1016/j.jcmgh.2020.09.010.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Updated ACC decision pathway embraces new heart failure treatment strategies
A newly updated expert consensus from the American College of Cardiology for management of heart failure with reduced ejection fraction includes several new guideline-directed medical therapies among other substantial changes relative to its 2017 predecessor.
The advances in treatment of heart failure with reduced ejection fraction (HFrEF) have resulted in a substantial increase in complexity in reaching treatment goals, according to the authors of the new guidance. Structured similarly to the 2017 ACC Expert Consensus Decision Pathway, the update accommodates a series of practical tips to bring all patients on board with the newer as well as the established therapies with lifesaving potential.
The potential return from implementing these recommendations is not trivial. Relative to an ACE inhibitor and a beta-blocker alone, optimal implementation of the current guideline-directed medical therapies (GDMT) “can extend medical survival by more than 6 years,” according to Gregg C. Fonarow, MD, chief of cardiology at the University of California, Los Angeles.
A member of the writing committee for the 2021 update, Dr. Fonarow explained that the consensus pathway is more than a list of therapies and recommended doses. The detailed advice on how to overcome the barriers to GDMT is meant to close the substantial gap between current practice and unmet opportunities for inhibiting HFrEF progression.
“Optimal GDMT among HFrEF patients is distressingly low, due in part to the number and complexity of medications that now constitute GDMT,” said the chair of the writing committee, Thomas M. Maddox, MD, executive director, Healthcare Innovation Lab, BJC HealthCare/Washington University, St. Louis. Like Dr. Fonarow, Dr. Maddox emphasized that the importance of the update for the practical strategies it offers to place patients on optimal care.
In the 2017 guidance, 10 pivotal issues were tackled, ranging from advice of how to put HFrEF patients on the multiple drugs that now constitute optimal therapy to when to transition patients to hospice care. The 2021 update covers the same ground but incorporates new information that has changed the definition of optimal care.
Perhaps most importantly, sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNi), and SGLT2 inhibitors represent major new additions in HFrEF GDMT. Dr. Maddox called the practical information about how these should be incorporated into HFrEF management represents one of the “major highlights” of the update.
Two algorithms outline the expert consensus recommendations of the order and the dose of the multiple drugs that now constitute the current GDMT. With the goal of explaining exactly how to place patients on all the HFrEF therapies associated with improved outcome, “I think these figures can really help us in guiding our patients to optimal medication regimens and dosages,” Dr. Maddox said. If successful, clinicians “can make a significant difference in these patients’ length and quality of life.”
Most cardiologists and others who treat HFrEF are likely aware of the major improvements in outcome documented in large trials when an ARNi and a SGLT2 inhibitor were added to previously established GDMT, but the update like the 2017 document is focused on the practical strategies of implementation, according to Larry A. Allen, MD, medical director of advanced heart failure at the University of Colorado at Denver, Aurora.
“The 2017 Expert Consensus Decision Pathway got a lot of attention because it takes a very practical approach to questions that clinicians and their patients have to tackle everyday but for which there was not always clean answers from the data,” said Dr. Allen, a member of the writing committee for both the 2017 expert consensus and the 2021 update. He noted that the earlier document was one of the most downloaded articles from the ACC’s journal in the year it appeared.
“There is excellent data on the benefits of beta-blockers, ARNi, mineralocorticoid antagonists, and SGLT2 inhibitors, but how does one decide what order to use them in?” Dr. Allen asked in outlining goals of the expert consensus.
While the new update “focuses on the newer drug classes, particularly SGLT2 inhibitors,” it traces care from first-line therapies to end-of-life management, according to Dr. Allen. This includes information on when to consider advanced therapies, such as left ventricular assist devices or transplant in order to get patients to these treatments before the opportunity for benefit is missed.
Both the 2017 version and the update offer a table to summarize triggers for referral. The complexity of individualizing care in a group of patients likely to have variable manifestations of disease and multiple comorbidities was a theme of the 2017 document that has been reprised in the 2021 update,
“Good communication and team-based care” is one of common management gaps that the update addresses, Dr. Allen said. He indicated that the checklists and algorithms in the update would help with complex decision-making and encourage the multidisciplinary care that ensures optimal management.
SOURCE: Maddox TM et al. J Am Coll Cardiol. 2021 Jan 11. doi: 10.1016/j.jacc.2020.11.022.
A newly updated expert consensus from the American College of Cardiology for management of heart failure with reduced ejection fraction includes several new guideline-directed medical therapies among other substantial changes relative to its 2017 predecessor.
The advances in treatment of heart failure with reduced ejection fraction (HFrEF) have resulted in a substantial increase in complexity in reaching treatment goals, according to the authors of the new guidance. Structured similarly to the 2017 ACC Expert Consensus Decision Pathway, the update accommodates a series of practical tips to bring all patients on board with the newer as well as the established therapies with lifesaving potential.
The potential return from implementing these recommendations is not trivial. Relative to an ACE inhibitor and a beta-blocker alone, optimal implementation of the current guideline-directed medical therapies (GDMT) “can extend medical survival by more than 6 years,” according to Gregg C. Fonarow, MD, chief of cardiology at the University of California, Los Angeles.
A member of the writing committee for the 2021 update, Dr. Fonarow explained that the consensus pathway is more than a list of therapies and recommended doses. The detailed advice on how to overcome the barriers to GDMT is meant to close the substantial gap between current practice and unmet opportunities for inhibiting HFrEF progression.
“Optimal GDMT among HFrEF patients is distressingly low, due in part to the number and complexity of medications that now constitute GDMT,” said the chair of the writing committee, Thomas M. Maddox, MD, executive director, Healthcare Innovation Lab, BJC HealthCare/Washington University, St. Louis. Like Dr. Fonarow, Dr. Maddox emphasized that the importance of the update for the practical strategies it offers to place patients on optimal care.
In the 2017 guidance, 10 pivotal issues were tackled, ranging from advice of how to put HFrEF patients on the multiple drugs that now constitute optimal therapy to when to transition patients to hospice care. The 2021 update covers the same ground but incorporates new information that has changed the definition of optimal care.
Perhaps most importantly, sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNi), and SGLT2 inhibitors represent major new additions in HFrEF GDMT. Dr. Maddox called the practical information about how these should be incorporated into HFrEF management represents one of the “major highlights” of the update.
Two algorithms outline the expert consensus recommendations of the order and the dose of the multiple drugs that now constitute the current GDMT. With the goal of explaining exactly how to place patients on all the HFrEF therapies associated with improved outcome, “I think these figures can really help us in guiding our patients to optimal medication regimens and dosages,” Dr. Maddox said. If successful, clinicians “can make a significant difference in these patients’ length and quality of life.”
Most cardiologists and others who treat HFrEF are likely aware of the major improvements in outcome documented in large trials when an ARNi and a SGLT2 inhibitor were added to previously established GDMT, but the update like the 2017 document is focused on the practical strategies of implementation, according to Larry A. Allen, MD, medical director of advanced heart failure at the University of Colorado at Denver, Aurora.
“The 2017 Expert Consensus Decision Pathway got a lot of attention because it takes a very practical approach to questions that clinicians and their patients have to tackle everyday but for which there was not always clean answers from the data,” said Dr. Allen, a member of the writing committee for both the 2017 expert consensus and the 2021 update. He noted that the earlier document was one of the most downloaded articles from the ACC’s journal in the year it appeared.
“There is excellent data on the benefits of beta-blockers, ARNi, mineralocorticoid antagonists, and SGLT2 inhibitors, but how does one decide what order to use them in?” Dr. Allen asked in outlining goals of the expert consensus.
While the new update “focuses on the newer drug classes, particularly SGLT2 inhibitors,” it traces care from first-line therapies to end-of-life management, according to Dr. Allen. This includes information on when to consider advanced therapies, such as left ventricular assist devices or transplant in order to get patients to these treatments before the opportunity for benefit is missed.
Both the 2017 version and the update offer a table to summarize triggers for referral. The complexity of individualizing care in a group of patients likely to have variable manifestations of disease and multiple comorbidities was a theme of the 2017 document that has been reprised in the 2021 update,
“Good communication and team-based care” is one of common management gaps that the update addresses, Dr. Allen said. He indicated that the checklists and algorithms in the update would help with complex decision-making and encourage the multidisciplinary care that ensures optimal management.
SOURCE: Maddox TM et al. J Am Coll Cardiol. 2021 Jan 11. doi: 10.1016/j.jacc.2020.11.022.
A newly updated expert consensus from the American College of Cardiology for management of heart failure with reduced ejection fraction includes several new guideline-directed medical therapies among other substantial changes relative to its 2017 predecessor.
The advances in treatment of heart failure with reduced ejection fraction (HFrEF) have resulted in a substantial increase in complexity in reaching treatment goals, according to the authors of the new guidance. Structured similarly to the 2017 ACC Expert Consensus Decision Pathway, the update accommodates a series of practical tips to bring all patients on board with the newer as well as the established therapies with lifesaving potential.
The potential return from implementing these recommendations is not trivial. Relative to an ACE inhibitor and a beta-blocker alone, optimal implementation of the current guideline-directed medical therapies (GDMT) “can extend medical survival by more than 6 years,” according to Gregg C. Fonarow, MD, chief of cardiology at the University of California, Los Angeles.
A member of the writing committee for the 2021 update, Dr. Fonarow explained that the consensus pathway is more than a list of therapies and recommended doses. The detailed advice on how to overcome the barriers to GDMT is meant to close the substantial gap between current practice and unmet opportunities for inhibiting HFrEF progression.
“Optimal GDMT among HFrEF patients is distressingly low, due in part to the number and complexity of medications that now constitute GDMT,” said the chair of the writing committee, Thomas M. Maddox, MD, executive director, Healthcare Innovation Lab, BJC HealthCare/Washington University, St. Louis. Like Dr. Fonarow, Dr. Maddox emphasized that the importance of the update for the practical strategies it offers to place patients on optimal care.
In the 2017 guidance, 10 pivotal issues were tackled, ranging from advice of how to put HFrEF patients on the multiple drugs that now constitute optimal therapy to when to transition patients to hospice care. The 2021 update covers the same ground but incorporates new information that has changed the definition of optimal care.
Perhaps most importantly, sacubitril/valsartan, an angiotensin receptor neprilysin inhibitor (ARNi), and SGLT2 inhibitors represent major new additions in HFrEF GDMT. Dr. Maddox called the practical information about how these should be incorporated into HFrEF management represents one of the “major highlights” of the update.
Two algorithms outline the expert consensus recommendations of the order and the dose of the multiple drugs that now constitute the current GDMT. With the goal of explaining exactly how to place patients on all the HFrEF therapies associated with improved outcome, “I think these figures can really help us in guiding our patients to optimal medication regimens and dosages,” Dr. Maddox said. If successful, clinicians “can make a significant difference in these patients’ length and quality of life.”
Most cardiologists and others who treat HFrEF are likely aware of the major improvements in outcome documented in large trials when an ARNi and a SGLT2 inhibitor were added to previously established GDMT, but the update like the 2017 document is focused on the practical strategies of implementation, according to Larry A. Allen, MD, medical director of advanced heart failure at the University of Colorado at Denver, Aurora.
“The 2017 Expert Consensus Decision Pathway got a lot of attention because it takes a very practical approach to questions that clinicians and their patients have to tackle everyday but for which there was not always clean answers from the data,” said Dr. Allen, a member of the writing committee for both the 2017 expert consensus and the 2021 update. He noted that the earlier document was one of the most downloaded articles from the ACC’s journal in the year it appeared.
“There is excellent data on the benefits of beta-blockers, ARNi, mineralocorticoid antagonists, and SGLT2 inhibitors, but how does one decide what order to use them in?” Dr. Allen asked in outlining goals of the expert consensus.
While the new update “focuses on the newer drug classes, particularly SGLT2 inhibitors,” it traces care from first-line therapies to end-of-life management, according to Dr. Allen. This includes information on when to consider advanced therapies, such as left ventricular assist devices or transplant in order to get patients to these treatments before the opportunity for benefit is missed.
Both the 2017 version and the update offer a table to summarize triggers for referral. The complexity of individualizing care in a group of patients likely to have variable manifestations of disease and multiple comorbidities was a theme of the 2017 document that has been reprised in the 2021 update,
“Good communication and team-based care” is one of common management gaps that the update addresses, Dr. Allen said. He indicated that the checklists and algorithms in the update would help with complex decision-making and encourage the multidisciplinary care that ensures optimal management.
SOURCE: Maddox TM et al. J Am Coll Cardiol. 2021 Jan 11. doi: 10.1016/j.jacc.2020.11.022.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY