“We must accept finite disappointment, but never lose infinite hope,” Martin Luther King, Jr.

This holiday season will be like no other. We will remember it for the rest of our lives, and we will look back to see how we faced the holidays during a pandemic.

DjelicS/Getty Images

Like the rest of 2020, the holidays will need to be reimagined. Years and even decades of tradition will be broken as we place health above merriment.

Here are a few tips to help all of us and our patients make the most of this holiday season.

• Reprioritize: This holiday season will be about depth not breadth, quality not quantity, and less not more. Trips are canceled and gatherings have shrunk. We are not running from store to store or party to party. Instead, you will find yourself surrounded by fewer friends and family. Some will be alone to optimally protect their health and the health of others. Do your best to focus on the half-full portion.
• Embrace change: Don’t compare or try to make this year like previous years. Be creative and try to find ways to make a new format fun. Meeting during the day and limiting alcohol intake can assist in making sure everyone stays safe. It has been interesting to see how many of my patients have decreased their alcohol use during quarantine. I hope this pattern will continue over the next weeks and months.
• Practice self-care: As health care professionals, we must remember the old adage “physician, heal thyself.” This year has been so difficult for almost all of us. It was filled with unprecedented levels of personal and professional stress. Holidays are often about what we can do for others, but this year we may need to place self-care first. Do what brings you happiness.

With lines between home and work even more eroded as we practice telemedicine, it is important to take time off. Even though you aren’t traveling, you can still disconnect from work. Set up a schedule and stick to it making sure you take plenty of time to rest and enjoy. Many of us have been working extremely long hours and a break is so needed. Take it if you possibly can. Detox from your screen! Limit the news. Creativity and productivity will be enhanced in 2021 if we can come in recharged.

For those remaining on the front lines, be patient; the end is nearing. Take care of yourself when you are not working. We are all so grateful to those in our field who have sacrificed so much to care for others. Eat, drink, and rest well to keep your immune system strong.

• Acknowledge your negative emotions: As we all know, if you try to deny negative emotions, they continue to pop up. If we give them time and space to be felt, we will find they diminish in intensity. Long work hours may have prevented us from feeling our emotions, so don’t be surprised if they surface when we take a break.

Let yourself feel the sadness for what you have experienced this year. Be open about missing those who can’t be with you because of travel or other restrictions. Let yourself feel the disappointment about your holiday travel plans that you can’t embark upon.

You may elect to share these emotions with someone close to you or with a professional. To paraphrase Carl Jung, “what we resist, persists,” so don’t try to hide from your negative emotions. Most of us had lots of them in 2020, so don’t be shy about admitting it.

• Focus on growth: What have we learned from 2020 and how can we be better equipped in 2021 and beyond?

Trauma can bring growth not just disorder. This year has returned well-deserved prestige to our fields. We are being lauded as heroes as we have scarified our health and the health of our loved ones to serve others. Can we choose to celebrate our accomplishments?

We have become more resilient and learned to continue on in the face of great hardship. Many of us have gained confidence as we confronted this historic challenge. As we have been reminded of death daily, we learn to appreciate life more fully and not take any day for granted.

I am proud to be a physician during this pandemic, and I hope you are, too!

• Find joy: Often times, we find real happiness in smaller moments and experiences. For many, this time of year is filled with so much stress that it can be hard to carve out moments of joy. As we may be less busy socially this holiday season, might we find even more joy?

Joy can only be experienced in the present moment. Tap into all your senses. Eat slowly making sure to smell and taste every bite. Cherish those who can still gather at your table. If you find yourself alone, embrace that experience. Safety must continue to come first, and we can’t let down our guard now.

• Reflect: New Year’s Eve is always a time for reflection and hope for the future. Most of us will be glad to see 2020 in the rearview mirror. With multiple and very promising vaccines on the horizon, we can anticipate a brighter future. We must continue to work hard; remain patient; and be creative, resilient, and optimistic. Let’s try to fill our days with hope and purpose and work together to achieve a brighter future for all.
•  

“Learn from yesterday, live for today, hope for tomorrow,” Albert Einstein


Wishing you health and happiness in this holiday season and beyond.

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018). She also is founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world.

“We must accept finite disappointment, but never lose infinite hope,” Martin Luther King, Jr.

This holiday season will be like no other. We will remember it for the rest of our lives, and we will look back to see how we faced the holidays during a pandemic.

DjelicS/Getty Images

Like the rest of 2020, the holidays will need to be reimagined. Years and even decades of tradition will be broken as we place health above merriment.

Here are a few tips to help all of us and our patients make the most of this holiday season.

• Reprioritize: This holiday season will be about depth not breadth, quality not quantity, and less not more. Trips are canceled and gatherings have shrunk. We are not running from store to store or party to party. Instead, you will find yourself surrounded by fewer friends and family. Some will be alone to optimally protect their health and the health of others. Do your best to focus on the half-full portion.
• Embrace change: Don’t compare or try to make this year like previous years. Be creative and try to find ways to make a new format fun. Meeting during the day and limiting alcohol intake can assist in making sure everyone stays safe. It has been interesting to see how many of my patients have decreased their alcohol use during quarantine. I hope this pattern will continue over the next weeks and months.
• Practice self-care: As health care professionals, we must remember the old adage “physician, heal thyself.” This year has been so difficult for almost all of us. It was filled with unprecedented levels of personal and professional stress. Holidays are often about what we can do for others, but this year we may need to place self-care first. Do what brings you happiness.

With lines between home and work even more eroded as we practice telemedicine, it is important to take time off. Even though you aren’t traveling, you can still disconnect from work. Set up a schedule and stick to it making sure you take plenty of time to rest and enjoy. Many of us have been working extremely long hours and a break is so needed. Take it if you possibly can. Detox from your screen! Limit the news. Creativity and productivity will be enhanced in 2021 if we can come in recharged.

For those remaining on the front lines, be patient; the end is nearing. Take care of yourself when you are not working. We are all so grateful to those in our field who have sacrificed so much to care for others. Eat, drink, and rest well to keep your immune system strong.

• Acknowledge your negative emotions: As we all know, if you try to deny negative emotions, they continue to pop up. If we give them time and space to be felt, we will find they diminish in intensity. Long work hours may have prevented us from feeling our emotions, so don’t be surprised if they surface when we take a break.

Let yourself feel the sadness for what you have experienced this year. Be open about missing those who can’t be with you because of travel or other restrictions. Let yourself feel the disappointment about your holiday travel plans that you can’t embark upon.

You may elect to share these emotions with someone close to you or with a professional. To paraphrase Carl Jung, “what we resist, persists,” so don’t try to hide from your negative emotions. Most of us had lots of them in 2020, so don’t be shy about admitting it.

• Focus on growth: What have we learned from 2020 and how can we be better equipped in 2021 and beyond?

Trauma can bring growth not just disorder. This year has returned well-deserved prestige to our fields. We are being lauded as heroes as we have scarified our health and the health of our loved ones to serve others. Can we choose to celebrate our accomplishments?

We have become more resilient and learned to continue on in the face of great hardship. Many of us have gained confidence as we confronted this historic challenge. As we have been reminded of death daily, we learn to appreciate life more fully and not take any day for granted.

I am proud to be a physician during this pandemic, and I hope you are, too!

• Find joy: Often times, we find real happiness in smaller moments and experiences. For many, this time of year is filled with so much stress that it can be hard to carve out moments of joy. As we may be less busy socially this holiday season, might we find even more joy?

Joy can only be experienced in the present moment. Tap into all your senses. Eat slowly making sure to smell and taste every bite. Cherish those who can still gather at your table. If you find yourself alone, embrace that experience. Safety must continue to come first, and we can’t let down our guard now.

• Reflect: New Year’s Eve is always a time for reflection and hope for the future. Most of us will be glad to see 2020 in the rearview mirror. With multiple and very promising vaccines on the horizon, we can anticipate a brighter future. We must continue to work hard; remain patient; and be creative, resilient, and optimistic. Let’s try to fill our days with hope and purpose and work together to achieve a brighter future for all.
•  

“Learn from yesterday, live for today, hope for tomorrow,” Albert Einstein


Wishing you health and happiness in this holiday season and beyond.

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018). She also is founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world.

“We must accept finite disappointment, but never lose infinite hope,” Martin Luther King, Jr.

This holiday season will be like no other. We will remember it for the rest of our lives, and we will look back to see how we faced the holidays during a pandemic.

DjelicS/Getty Images

Like the rest of 2020, the holidays will need to be reimagined. Years and even decades of tradition will be broken as we place health above merriment.

Here are a few tips to help all of us and our patients make the most of this holiday season.

• Reprioritize: This holiday season will be about depth not breadth, quality not quantity, and less not more. Trips are canceled and gatherings have shrunk. We are not running from store to store or party to party. Instead, you will find yourself surrounded by fewer friends and family. Some will be alone to optimally protect their health and the health of others. Do your best to focus on the half-full portion.
• Embrace change: Don’t compare or try to make this year like previous years. Be creative and try to find ways to make a new format fun. Meeting during the day and limiting alcohol intake can assist in making sure everyone stays safe. It has been interesting to see how many of my patients have decreased their alcohol use during quarantine. I hope this pattern will continue over the next weeks and months.
• Practice self-care: As health care professionals, we must remember the old adage “physician, heal thyself.” This year has been so difficult for almost all of us. It was filled with unprecedented levels of personal and professional stress. Holidays are often about what we can do for others, but this year we may need to place self-care first. Do what brings you happiness.

With lines between home and work even more eroded as we practice telemedicine, it is important to take time off. Even though you aren’t traveling, you can still disconnect from work. Set up a schedule and stick to it making sure you take plenty of time to rest and enjoy. Many of us have been working extremely long hours and a break is so needed. Take it if you possibly can. Detox from your screen! Limit the news. Creativity and productivity will be enhanced in 2021 if we can come in recharged.

For those remaining on the front lines, be patient; the end is nearing. Take care of yourself when you are not working. We are all so grateful to those in our field who have sacrificed so much to care for others. Eat, drink, and rest well to keep your immune system strong.

• Acknowledge your negative emotions: As we all know, if you try to deny negative emotions, they continue to pop up. If we give them time and space to be felt, we will find they diminish in intensity. Long work hours may have prevented us from feeling our emotions, so don’t be surprised if they surface when we take a break.

Let yourself feel the sadness for what you have experienced this year. Be open about missing those who can’t be with you because of travel or other restrictions. Let yourself feel the disappointment about your holiday travel plans that you can’t embark upon.

You may elect to share these emotions with someone close to you or with a professional. To paraphrase Carl Jung, “what we resist, persists,” so don’t try to hide from your negative emotions. Most of us had lots of them in 2020, so don’t be shy about admitting it.

• Focus on growth: What have we learned from 2020 and how can we be better equipped in 2021 and beyond?

Trauma can bring growth not just disorder. This year has returned well-deserved prestige to our fields. We are being lauded as heroes as we have scarified our health and the health of our loved ones to serve others. Can we choose to celebrate our accomplishments?

We have become more resilient and learned to continue on in the face of great hardship. Many of us have gained confidence as we confronted this historic challenge. As we have been reminded of death daily, we learn to appreciate life more fully and not take any day for granted.

I am proud to be a physician during this pandemic, and I hope you are, too!

• Find joy: Often times, we find real happiness in smaller moments and experiences. For many, this time of year is filled with so much stress that it can be hard to carve out moments of joy. As we may be less busy socially this holiday season, might we find even more joy?

Joy can only be experienced in the present moment. Tap into all your senses. Eat slowly making sure to smell and taste every bite. Cherish those who can still gather at your table. If you find yourself alone, embrace that experience. Safety must continue to come first, and we can’t let down our guard now.

• Reflect: New Year’s Eve is always a time for reflection and hope for the future. Most of us will be glad to see 2020 in the rearview mirror. With multiple and very promising vaccines on the horizon, we can anticipate a brighter future. We must continue to work hard; remain patient; and be creative, resilient, and optimistic. Let’s try to fill our days with hope and purpose and work together to achieve a brighter future for all.
•  

“Learn from yesterday, live for today, hope for tomorrow,” Albert Einstein


Wishing you health and happiness in this holiday season and beyond.

Dr. Ritvo, a psychiatrist with more than 25 years’ experience, practices in Miami Beach. She is the author of “Bekindr – The Transformative Power of Kindness” (Hellertown, Pa.: Momosa Publishing, 2018). She also is founder of the Bekindr Global Initiative, a movement aimed at cultivating kindness in the world.

One-third of COVID-19 exposures among health care providers (HCPs) in Minnesota are caused by family or community exposure, not patient care, according to a study conducted by the Minnesota Department of Health and published online Oct. 30 in Morbidity and Mortality Weekly Report. And nonwork exposures were more likely to lead to COVID-19 infections.

Between March 6 and July 11, 2020, researchers with the Minnesota Department of Health evaluated 21,406 incidences of HCP exposure to confirmed COVID-19 cases. Of those, 5,374 (25%) were classified as higher-risk exposures, meaning the provider had close contact for 15 minutes or more, or during an aerosol-generating procedure.

Two-thirds (66%) of the higher-risk exposures occurred during direct patient care and 34% were related to nonpatient care interactions (e.g., coworkers and social and household contacts). Overall, 6.9% (373) of the HCPs with a higher-risk exposure received a positive SARS-CoV-2 test result within 14 days of the exposure. Notably, HCPs with household or social exposure had the highest positivity rate across all exposure types at 13%.

“Since the time period covered in this report, we’ve seen a significant increase in the proportion of HCPs who have had higher-risk exposures outside of work due to household or social contacts,” said lead author Ashley Fell, MPH, from the Minnesota Department of Health.

“HCPs with household or social exposures are also more likely to test positive than HCPs with higher risk exposures within the healthcare setting, which is an important message for both HCPs and the community at large that more COVID-19 spreading in our communities poses a greater risk to our HCPs and health care system,” Ms. Fell said in an interview.

When evaluating personal protective equipment use among exposed HCPs, researchers found that 90% of providers in acute or ambulatory care were wearing a respirator or medical-grade face mask at time of exposure, compared with just 68% of HCPs working in congregate living or long-term care facilities.

Further, investigators found that an HCP with a positive SARS-CoV-2 test working in a congregate living or long-term care facility resulted in exposure of a median of three additional HCPs (interquartile range, 1-6), compared with a median of one additional HCP exposure in acute or ambulatory care (IQR, 1-3).

The researchers also found that, compared with HCPs in acute or ambulatory settings, HCPs working in long-term care or congregate living settings were more likely to return to work following a high-risk exposure (57% vs. 37%) and work while symptomatic (4.8% vs. 1.3%).

When asked whether these findings apply to HCPs in other states, Andrew T. Chan, MD, from Massachusetts General Hospital, Boston, noted: “These data are not surprising and confirm what many of us have been seeing in our own areas.

“Clearly, the risk of contracting COVID-19 is particularly high for frontline health care workers in long-term care facilities and nursing homes,” Dr. Chan said.

“Furthermore, the infection control practices in these care settings are often not as rigorous, and together these factors are probably contributing to higher risks of infection,” he said.

The authors acknowledged potential study limitations including misclassification of HCP risk for exposure or misclassification of community exposure as workplace exposure.

“We also recognize that HCPs, like the rest of the community, are experiencing COVID fatigue and that facilities have to constantly be innovative and vigilant to help HCPs maintain rigorous safety precautions with their patients and around their colleagues,” Ms. Fell concluded.

The authors and Dr. Chan disclosed no relevant financial relationships.

For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.

This article first appeared on Medscape.com.

One-third of COVID-19 exposures among health care providers (HCPs) in Minnesota are caused by family or community exposure, not patient care, according to a study conducted by the Minnesota Department of Health and published online Oct. 30 in Morbidity and Mortality Weekly Report. And nonwork exposures were more likely to lead to COVID-19 infections.

Between March 6 and July 11, 2020, researchers with the Minnesota Department of Health evaluated 21,406 incidences of HCP exposure to confirmed COVID-19 cases. Of those, 5,374 (25%) were classified as higher-risk exposures, meaning the provider had close contact for 15 minutes or more, or during an aerosol-generating procedure.

Two-thirds (66%) of the higher-risk exposures occurred during direct patient care and 34% were related to nonpatient care interactions (e.g., coworkers and social and household contacts). Overall, 6.9% (373) of the HCPs with a higher-risk exposure received a positive SARS-CoV-2 test result within 14 days of the exposure. Notably, HCPs with household or social exposure had the highest positivity rate across all exposure types at 13%.

“Since the time period covered in this report, we’ve seen a significant increase in the proportion of HCPs who have had higher-risk exposures outside of work due to household or social contacts,” said lead author Ashley Fell, MPH, from the Minnesota Department of Health.

“HCPs with household or social exposures are also more likely to test positive than HCPs with higher risk exposures within the healthcare setting, which is an important message for both HCPs and the community at large that more COVID-19 spreading in our communities poses a greater risk to our HCPs and health care system,” Ms. Fell said in an interview.

When evaluating personal protective equipment use among exposed HCPs, researchers found that 90% of providers in acute or ambulatory care were wearing a respirator or medical-grade face mask at time of exposure, compared with just 68% of HCPs working in congregate living or long-term care facilities.

Further, investigators found that an HCP with a positive SARS-CoV-2 test working in a congregate living or long-term care facility resulted in exposure of a median of three additional HCPs (interquartile range, 1-6), compared with a median of one additional HCP exposure in acute or ambulatory care (IQR, 1-3).

The researchers also found that, compared with HCPs in acute or ambulatory settings, HCPs working in long-term care or congregate living settings were more likely to return to work following a high-risk exposure (57% vs. 37%) and work while symptomatic (4.8% vs. 1.3%).

When asked whether these findings apply to HCPs in other states, Andrew T. Chan, MD, from Massachusetts General Hospital, Boston, noted: “These data are not surprising and confirm what many of us have been seeing in our own areas.

“Clearly, the risk of contracting COVID-19 is particularly high for frontline health care workers in long-term care facilities and nursing homes,” Dr. Chan said.

“Furthermore, the infection control practices in these care settings are often not as rigorous, and together these factors are probably contributing to higher risks of infection,” he said.

The authors acknowledged potential study limitations including misclassification of HCP risk for exposure or misclassification of community exposure as workplace exposure.

“We also recognize that HCPs, like the rest of the community, are experiencing COVID fatigue and that facilities have to constantly be innovative and vigilant to help HCPs maintain rigorous safety precautions with their patients and around their colleagues,” Ms. Fell concluded.

The authors and Dr. Chan disclosed no relevant financial relationships.

For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.

This article first appeared on Medscape.com.

One-third of COVID-19 exposures among health care providers (HCPs) in Minnesota are caused by family or community exposure, not patient care, according to a study conducted by the Minnesota Department of Health and published online Oct. 30 in Morbidity and Mortality Weekly Report. And nonwork exposures were more likely to lead to COVID-19 infections.

Between March 6 and July 11, 2020, researchers with the Minnesota Department of Health evaluated 21,406 incidences of HCP exposure to confirmed COVID-19 cases. Of those, 5,374 (25%) were classified as higher-risk exposures, meaning the provider had close contact for 15 minutes or more, or during an aerosol-generating procedure.

Two-thirds (66%) of the higher-risk exposures occurred during direct patient care and 34% were related to nonpatient care interactions (e.g., coworkers and social and household contacts). Overall, 6.9% (373) of the HCPs with a higher-risk exposure received a positive SARS-CoV-2 test result within 14 days of the exposure. Notably, HCPs with household or social exposure had the highest positivity rate across all exposure types at 13%.

“Since the time period covered in this report, we’ve seen a significant increase in the proportion of HCPs who have had higher-risk exposures outside of work due to household or social contacts,” said lead author Ashley Fell, MPH, from the Minnesota Department of Health.

“HCPs with household or social exposures are also more likely to test positive than HCPs with higher risk exposures within the healthcare setting, which is an important message for both HCPs and the community at large that more COVID-19 spreading in our communities poses a greater risk to our HCPs and health care system,” Ms. Fell said in an interview.

When evaluating personal protective equipment use among exposed HCPs, researchers found that 90% of providers in acute or ambulatory care were wearing a respirator or medical-grade face mask at time of exposure, compared with just 68% of HCPs working in congregate living or long-term care facilities.

Further, investigators found that an HCP with a positive SARS-CoV-2 test working in a congregate living or long-term care facility resulted in exposure of a median of three additional HCPs (interquartile range, 1-6), compared with a median of one additional HCP exposure in acute or ambulatory care (IQR, 1-3).

The researchers also found that, compared with HCPs in acute or ambulatory settings, HCPs working in long-term care or congregate living settings were more likely to return to work following a high-risk exposure (57% vs. 37%) and work while symptomatic (4.8% vs. 1.3%).

When asked whether these findings apply to HCPs in other states, Andrew T. Chan, MD, from Massachusetts General Hospital, Boston, noted: “These data are not surprising and confirm what many of us have been seeing in our own areas.

“Clearly, the risk of contracting COVID-19 is particularly high for frontline health care workers in long-term care facilities and nursing homes,” Dr. Chan said.

“Furthermore, the infection control practices in these care settings are often not as rigorous, and together these factors are probably contributing to higher risks of infection,” he said.

The authors acknowledged potential study limitations including misclassification of HCP risk for exposure or misclassification of community exposure as workplace exposure.

“We also recognize that HCPs, like the rest of the community, are experiencing COVID fatigue and that facilities have to constantly be innovative and vigilant to help HCPs maintain rigorous safety precautions with their patients and around their colleagues,” Ms. Fell concluded.

The authors and Dr. Chan disclosed no relevant financial relationships.

For the latest clinical guidance, education, research and physician resources about coronavirus, visit the AGA COVID-19 Resource Center at www.gastro.org/COVID.

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.

The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.

The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.

The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.

The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.

“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.

“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.

As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.

The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).

The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.

The FDA emphasizes that an EUA is not a full FDA approval.

In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.

“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.

The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.

The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.

The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.

The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.

“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.

“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.

As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.

The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).

The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.

The FDA emphasizes that an EUA is not a full FDA approval.

In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.

“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
 

This article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) Nov. 19 issued an emergency use authorization (EUA) for the Janus kinase inhibitor baricitinib (Olumiant, Eli Lilly) in combination with remdesivir (Veklury, Gilead) for treating hospitalized adults and children at least 2 years old with suspected or confirmed COVID-19.

The combination treatment is meant for patients who need supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).

Baricitinib/remdesivir was shown in a clinical trial to reduce time to recovery within 29 days of starting the treatment compared with a control group who received placebo/remdesivir, according to the FDA press release.

The median time to recovery from COVID-19 was 7 days for the combination group vs. 8 days for those in the placebo/remdesivir group. Recovery was defined as either discharge from the hospital or “being hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care,” the agency explained in the press release.

The odds of a patient dying or being ventilated at day 29 was lower in the combination group compared with those taking placebo/remdesivir, the press release said without providing specific data. “For all of these endpoints, the effects were statistically significant,” the agency stated.

The safety and efficacy continues to be evaluated. Baricitinib alone is not approved as a treatment for COVID-19.

“The FDA’s emergency authorization of this combination therapy represents an incremental step forward in the treatment of COVID-19 in hospitalized patients, and FDA’s first authorization of a drug that acts on the inflammation pathway,” said Patrizia Cavazzoni, MD, acting director of the FDA’s Center for Drug Evaluation and Research.

“Despite advances in the management of COVID-19 infection since the onset of the pandemic, we need more therapies to accelerate recovery and additional clinical research will be essential to identifying therapies that slow disease progression and lower mortality in the sicker patients,” she said.

As a JAK inhibitor, baricitinib interferes with a pathway that leads to inflammation. Baricitinib is already prescribed as an oral medication and is FDA-approved for treating moderate to severe rheumatoid arthritis.

The data supporting the EUA for the combination treatment are based on a randomized, double-blind, placebo-controlled clinical trial (ACTT-2), conducted by the National Institute of Allergy and Infectious Diseases (NIAID).

The trial followed patients for 29 days and included 1,033 patients with moderate to severe COVID-19; 515 patients received baricitinib/remdesivir, and 518 patients received placebo/remdesivir.

The FDA emphasizes that an EUA is not a full FDA approval.

In reviewing the combination, the FDA “determined that it is reasonable to believe that baricitinib, in combination with remdesivir, may be effective in treating COVID-19 for the authorized population” and the known benefits outweigh the known and potential risks. Additionally, there are no adequate, approved, and available alternatives for the treatment population.

“Today’s action demonstrates the FDA’s steadfast efforts to make potential COVID-19 treatments available in a timely manner, where appropriate, while continuing to support research to further evaluate whether they are safe and effective,” said FDA Commissioner Stephen M. Hahn, MD. “As part of our Coronavirus Treatment Acceleration Program, the FDA continues to use every possible avenue to facilitate new treatments for patients as quickly as possible to combat COVID-19.”
 

This article first appeared on Medscape.com.

Combining the recombinant Flt3 ligand CDX-301 with the dendritic cell–targeted vaccine CDX-1401 enhanced vaccine-induced immune responses in patients with high-risk melanoma, according to results from a phase 2 trial.

“[This] study supports the potential of combining [the] CDX-1401 vaccine and CDX-301 with checkpoint inhibitors, which are standard-of-care therapy,” study author Nina Bhardwaj, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.

The team described their study in Nature Cancer.

The multicenter, open-label, randomized study included 60 patients with resected stage IIb-IV melanoma, all of whom had not received any prior treatment, including radiotherapy, biologics, and chemotherapy.

Patients randomized to the combination arm (cohort 1; n = 30) received the anti–DEC-205-NY-ESO-1 vaccine CDX-1401 and were pretreated with CDX-301, while those in the comparator arm (cohort 2; n = 30) received CDX-1401 alone.

Serial blood samples were collected to evaluate response to the vaccine antigen (NY-ESO-1) before each cycle, as well as 4 weeks and 12 weeks after the last vaccination. The primary endpoint was immune response prior to the third vaccination.

T-cell responses were detected in 76% of patients who received CDX-301 and 33% of patients who did not (P < .0011). In addition, the magnitude of response was significantly higher with the combination than with CDX-1401 alone (mean of 41 and 17 corrected spots per well, respectively; P = .032).

“All 30 (100%) cohort 1 participants had NY-ESO-1–specific T-cell responses for at least one time point, whereas 8 (27%) cohort 2 participants had no responses at any time point,” the researchers wrote.

Responses were maintained up to 12 weeks after the final vaccination, but there was no statistically significant difference between cohorts 1 and 2 at 12 weeks (54% and 38%, respectively; P = .2).

The researchers acknowledged that a key limitation of this trial was that it was not sized to evaluate relapse or overall survival.

“Given that ipilimumab, pembrolizumab, and nivolumab are approved as adjuvant therapy for high-risk stage III melanoma, vaccines incorporating CDX-301 and suitable antigen-containing platforms merit clinical investigation in the adjuvant setting in combination with immune checkpoint blockade,” the authors wrote.

“I am hopeful that highly immunogenic cancer vaccines can be added to currently approved immunotherapies, thus boosting an individual’s anticancer immune response even further,” Dr. Bhardwaj said in an interview.

This study was supported by grant funding from the National Cancer Institute. Some authors reported financial affiliations with Celldex Therapeutics, NanoString Technologies, and Oncovir. Dr. Bhardwaj disclosed relationships with Celldex and Oncovir.

SOURCE: Bhardwaj N et al. Nat Cancer. 2020 Nov 16. doi: 10.1038/s43018-020-00143-y.

Combining the recombinant Flt3 ligand CDX-301 with the dendritic cell–targeted vaccine CDX-1401 enhanced vaccine-induced immune responses in patients with high-risk melanoma, according to results from a phase 2 trial.

“[This] study supports the potential of combining [the] CDX-1401 vaccine and CDX-301 with checkpoint inhibitors, which are standard-of-care therapy,” study author Nina Bhardwaj, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.

The team described their study in Nature Cancer.

The multicenter, open-label, randomized study included 60 patients with resected stage IIb-IV melanoma, all of whom had not received any prior treatment, including radiotherapy, biologics, and chemotherapy.

Patients randomized to the combination arm (cohort 1; n = 30) received the anti–DEC-205-NY-ESO-1 vaccine CDX-1401 and were pretreated with CDX-301, while those in the comparator arm (cohort 2; n = 30) received CDX-1401 alone.

Serial blood samples were collected to evaluate response to the vaccine antigen (NY-ESO-1) before each cycle, as well as 4 weeks and 12 weeks after the last vaccination. The primary endpoint was immune response prior to the third vaccination.

T-cell responses were detected in 76% of patients who received CDX-301 and 33% of patients who did not (P < .0011). In addition, the magnitude of response was significantly higher with the combination than with CDX-1401 alone (mean of 41 and 17 corrected spots per well, respectively; P = .032).

“All 30 (100%) cohort 1 participants had NY-ESO-1–specific T-cell responses for at least one time point, whereas 8 (27%) cohort 2 participants had no responses at any time point,” the researchers wrote.

Responses were maintained up to 12 weeks after the final vaccination, but there was no statistically significant difference between cohorts 1 and 2 at 12 weeks (54% and 38%, respectively; P = .2).

The researchers acknowledged that a key limitation of this trial was that it was not sized to evaluate relapse or overall survival.

“Given that ipilimumab, pembrolizumab, and nivolumab are approved as adjuvant therapy for high-risk stage III melanoma, vaccines incorporating CDX-301 and suitable antigen-containing platforms merit clinical investigation in the adjuvant setting in combination with immune checkpoint blockade,” the authors wrote.

“I am hopeful that highly immunogenic cancer vaccines can be added to currently approved immunotherapies, thus boosting an individual’s anticancer immune response even further,” Dr. Bhardwaj said in an interview.

This study was supported by grant funding from the National Cancer Institute. Some authors reported financial affiliations with Celldex Therapeutics, NanoString Technologies, and Oncovir. Dr. Bhardwaj disclosed relationships with Celldex and Oncovir.

SOURCE: Bhardwaj N et al. Nat Cancer. 2020 Nov 16. doi: 10.1038/s43018-020-00143-y.

Combining the recombinant Flt3 ligand CDX-301 with the dendritic cell–targeted vaccine CDX-1401 enhanced vaccine-induced immune responses in patients with high-risk melanoma, according to results from a phase 2 trial.

“[This] study supports the potential of combining [the] CDX-1401 vaccine and CDX-301 with checkpoint inhibitors, which are standard-of-care therapy,” study author Nina Bhardwaj, MD, PhD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues wrote.

The team described their study in Nature Cancer.

The multicenter, open-label, randomized study included 60 patients with resected stage IIb-IV melanoma, all of whom had not received any prior treatment, including radiotherapy, biologics, and chemotherapy.

Patients randomized to the combination arm (cohort 1; n = 30) received the anti–DEC-205-NY-ESO-1 vaccine CDX-1401 and were pretreated with CDX-301, while those in the comparator arm (cohort 2; n = 30) received CDX-1401 alone.

Serial blood samples were collected to evaluate response to the vaccine antigen (NY-ESO-1) before each cycle, as well as 4 weeks and 12 weeks after the last vaccination. The primary endpoint was immune response prior to the third vaccination.

T-cell responses were detected in 76% of patients who received CDX-301 and 33% of patients who did not (P < .0011). In addition, the magnitude of response was significantly higher with the combination than with CDX-1401 alone (mean of 41 and 17 corrected spots per well, respectively; P = .032).

“All 30 (100%) cohort 1 participants had NY-ESO-1–specific T-cell responses for at least one time point, whereas 8 (27%) cohort 2 participants had no responses at any time point,” the researchers wrote.

Responses were maintained up to 12 weeks after the final vaccination, but there was no statistically significant difference between cohorts 1 and 2 at 12 weeks (54% and 38%, respectively; P = .2).

The researchers acknowledged that a key limitation of this trial was that it was not sized to evaluate relapse or overall survival.

“Given that ipilimumab, pembrolizumab, and nivolumab are approved as adjuvant therapy for high-risk stage III melanoma, vaccines incorporating CDX-301 and suitable antigen-containing platforms merit clinical investigation in the adjuvant setting in combination with immune checkpoint blockade,” the authors wrote.

“I am hopeful that highly immunogenic cancer vaccines can be added to currently approved immunotherapies, thus boosting an individual’s anticancer immune response even further,” Dr. Bhardwaj said in an interview.

This study was supported by grant funding from the National Cancer Institute. Some authors reported financial affiliations with Celldex Therapeutics, NanoString Technologies, and Oncovir. Dr. Bhardwaj disclosed relationships with Celldex and Oncovir.

SOURCE: Bhardwaj N et al. Nat Cancer. 2020 Nov 16. doi: 10.1038/s43018-020-00143-y.

Greater involvement of the patient and family in decision-making, clarity on the role of genetic testing and parameters for team-oriented care, and use of high-volume specialty centers are cornerstones of the first update in almost a decade of the American Heart Association/American College of Cardiology guideline for patients with hypertrophic cardiomyopathy (HCM).

The update lists 133 recommendations for HCM care in six categories: shared decision-making; role of high-volume HCM centers; diagnosis, initial evaluation, and follow-up; risk assessment and prevention of sudden cardiac death (SCD); management of HCM; and lifestyle considerations for patients.

“The guideline puts the patient front and center in the shared decision-making process and emphasizes the importance of incorporating patient’s lifestyle choices and preferences when making complex, life-altering decisions,” writing committee vice chair Seema Mital, MD, of the University of Toronto and the Hospital for Sick Children, also in Toronto, said in an interview.

The fully updated guideline, authored by a joint committee of the AHA and ACC with input from other specialty societies, has been published online in the Journal of the American College of Cardiology. It replaces the 2011 guideline.

Another key component of the update is the strong recommendation to utilize multidisciplinary care, said Matthew W. Martinez, MD, a writing committee member and sports cardiologists at Morristown (N.J.) Medical Center. “This is not only as a part of shared decision-making, but really in care for the patients,” he said, “that there’s a level of expertise that is provided by centers of excellence who handle HCM, and we did lay out some recommendations with regards to surgery, imaging, interventionists, and management with electrophysiology, and the care of athletes with potential for HCM and pregnant women.”

The update ranks recommendations by class of recommendation (COR), ranging from strong benefit much greater than risk to harm with risk exceeding benefit, and level of evidence (LOE). The recommendation for shared decision making, for example, carries at COR of 1, the highest rating, and a mid-level LOE of B-NR, meaning from nonrandomized studies. Patients who need septal reduction therapy (SRT) should be referred to a comprehensive or primary HCM center – a recommendation with a COR of 1 but an LOE of C-LD, meaning there are limited data.
 

From diagnosis to follow-up

The most extensive list of recommendations falls under the category covering diagnosis, initial evaluation and follow-up. They include a three-generation family history as part of the initial diagnostic assessment (COR, 1; LOE, B-NR), high-level recommendations for use of transthoracic echocardiogram in the initial work-up, every 1 or 2 years or when the patient’s status changes in confirmed cases, as well as parameters for using other imaging and diagnostic tests. Cardiovascular MRI, for example, is indicated when echocardiography is inconclusive (COR, 1; LOE, B-NR) and in other scenarios. When echocardiography is inconclusive but cardiac MRI isn’t available, cardiac CT is an option, albeit at a lower level of evidence (COR, 2b; LOE, C-LD).

Heart rhythm assessment has a high level of recommendation in multiple scenarios, even in first-degree relatives of HCM patients. Invasive hemodynamic assessment is in order for candidates of SRT whose left ventricular (LV) outflow tract obstruction status is unknown. This category also sets parameters for angiography, and exercise stress testing.

The most extensive recommendations for diagnosis and follow-up cover genetic testing; it consists of nine high-level recommendations.

“The guideline highlights not only the importance of genetic testing of an affected patient and genetic screening of family members, but also emphasizes ongoing reassessment of variant classification as this may evolve with time and change how we recommend ongoing family screening,” Dr. Mital noted.

“The guideline proposes initiating screening of family members at the earliest regardless of age given HCM can manifest at any age in affected families,” she added.

The guideline notes that the usefulness of genetic testing to evaluate the risk of sudden cardiac death (SCD) is uncertain. There’s even guidance for implementing those test results. Further testing is recommended for patients who are genotype positive and phenotype negative for HCM (COR, 1; LOE, B-NR). Those same patients may participate in competitive sports (COR, 2a; LOE, C-LD), but a pacemaker isn’t recommended as a primary prevention (COR, 3 [no benefit]; LOE, B-NR).
 

Risk evaluation and prevention

For SCD risk evaluation and prevention, the guideline spells out five components for the initial and follow-up evaluations (COR, 1; LOE, B-NR). That includes maximal LV wall thickness, ejection fraction, and LV apical aneurysm. The section include multiple recommendations for patient selection for placement of an implantable cardioverter-defibrillator (ICD). For example, it’s recommended for patient’s who’ve had a heart attack or sustained ventricular tachycardia (COR, 1; LOE, B-NR), but not so much for patients without risk factors or for participating in sports (COR, 3 [harm]; LOE, B-NR). The guideline even provides recommendations for selecting an ICD.

Management recommendations address when medical therapy is indicated, including which therapies are indicated for specific scenarios, as well as higher level interventions such as SRT for severely symptomatic patients with obstructive HCM (COR, 2b; LOE, C-LD) and surgical myectomy with ablation in patients with HCM and atrial fibrillation (COR, 2a; LOE, B-NR). This section also provides recommendations for managing patients with HCM and ventricular arrhythmias or advanced heart failure.

The guideline also includes a host of lifestyle considerations. Mild to moderate exercise is beneficial (COR, 1; LOE, B-NR), but athletes with HCM should consult with an “expert provider” (COR, 1; LOE, C, meaning based on expert opinion). Truck drivers, pilots and people who do strenuous physical labor with HCM should meet specific standards.

These recommendations again emphasize the role of shared decision-making, said Dr. Martinez. “It’s not a cookie-cutter discussion. It is taking all of the information, incorporating what the patient’s needs are, and then making sure you appropriately tell them what are the risks of exercising and not exercising. I have as many discussions through the day about what the risks of exercise are as I do the risks of not exercising.”
 

Refining nomenclature, pathophysiology

The writing committee addressed the nomenclature for HCM. The use of HCM to describe increased LV wall thickness linked to systemic diseases or secondary to LV hypertrophy “can lead to confusion,” the committee stated, so other cardiac or systemic causes of LV hypertrophy shouldn’t be labeled HCM. Other etiologies can cause secondary LV hypertrophy that can overlap with HCM; clinical markers and testing can help differentiate these mimickers from HCM. When echocardiography is inconclusive, cardiovascular MRI is indicated (COR, 1; LOE, B-NR).

The guideline update also provides clarity on the pathophysiology of HCM: It consists of dynamic LV outflow tract obstruction, mitral regurgitation, diastolic dysfunction, myocardial ischemia, arrhythmias, or autonomic dysfunction. “For a given patient with HCM, the clinical outcome may be dominated by one of these components or may be the result of a complex interplay,” the guideline states. The clinical evaluation should consider all these conditions.

This update also provides “clear separation” between care of HCM with and without obstruction, Dr. Martinez said. “The role of advanced therapies and referrals with advanced treatment options such as heart transplantation or CRT therapy in this group is different than before, recognizing that people with obstruction have symptoms that may be similar to those without obstruction, and the individual should be [thoroughly] investigated to make sure that you can discern between those two groups to make appropriate recommendations.”

The guideline was developed in collaboration with and endorsed by the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society for Cardiovascular Magnetic Resonance. It’s also been endorsed by the Pediatric & Congenital Electrophysiology Society.

Dr. Mital and Dr. Martinez have no relevant financial relationships to disclose.

SOURCE: Mital S et al. J Am Coll Cardiol. 2020 Nov 20. doi: 10.1016/j.jacc.2020.08.044.

Greater involvement of the patient and family in decision-making, clarity on the role of genetic testing and parameters for team-oriented care, and use of high-volume specialty centers are cornerstones of the first update in almost a decade of the American Heart Association/American College of Cardiology guideline for patients with hypertrophic cardiomyopathy (HCM).

The update lists 133 recommendations for HCM care in six categories: shared decision-making; role of high-volume HCM centers; diagnosis, initial evaluation, and follow-up; risk assessment and prevention of sudden cardiac death (SCD); management of HCM; and lifestyle considerations for patients.

“The guideline puts the patient front and center in the shared decision-making process and emphasizes the importance of incorporating patient’s lifestyle choices and preferences when making complex, life-altering decisions,” writing committee vice chair Seema Mital, MD, of the University of Toronto and the Hospital for Sick Children, also in Toronto, said in an interview.

The fully updated guideline, authored by a joint committee of the AHA and ACC with input from other specialty societies, has been published online in the Journal of the American College of Cardiology. It replaces the 2011 guideline.

Another key component of the update is the strong recommendation to utilize multidisciplinary care, said Matthew W. Martinez, MD, a writing committee member and sports cardiologists at Morristown (N.J.) Medical Center. “This is not only as a part of shared decision-making, but really in care for the patients,” he said, “that there’s a level of expertise that is provided by centers of excellence who handle HCM, and we did lay out some recommendations with regards to surgery, imaging, interventionists, and management with electrophysiology, and the care of athletes with potential for HCM and pregnant women.”

The update ranks recommendations by class of recommendation (COR), ranging from strong benefit much greater than risk to harm with risk exceeding benefit, and level of evidence (LOE). The recommendation for shared decision making, for example, carries at COR of 1, the highest rating, and a mid-level LOE of B-NR, meaning from nonrandomized studies. Patients who need septal reduction therapy (SRT) should be referred to a comprehensive or primary HCM center – a recommendation with a COR of 1 but an LOE of C-LD, meaning there are limited data.
 

From diagnosis to follow-up

The most extensive list of recommendations falls under the category covering diagnosis, initial evaluation and follow-up. They include a three-generation family history as part of the initial diagnostic assessment (COR, 1; LOE, B-NR), high-level recommendations for use of transthoracic echocardiogram in the initial work-up, every 1 or 2 years or when the patient’s status changes in confirmed cases, as well as parameters for using other imaging and diagnostic tests. Cardiovascular MRI, for example, is indicated when echocardiography is inconclusive (COR, 1; LOE, B-NR) and in other scenarios. When echocardiography is inconclusive but cardiac MRI isn’t available, cardiac CT is an option, albeit at a lower level of evidence (COR, 2b; LOE, C-LD).

Heart rhythm assessment has a high level of recommendation in multiple scenarios, even in first-degree relatives of HCM patients. Invasive hemodynamic assessment is in order for candidates of SRT whose left ventricular (LV) outflow tract obstruction status is unknown. This category also sets parameters for angiography, and exercise stress testing.

The most extensive recommendations for diagnosis and follow-up cover genetic testing; it consists of nine high-level recommendations.

“The guideline highlights not only the importance of genetic testing of an affected patient and genetic screening of family members, but also emphasizes ongoing reassessment of variant classification as this may evolve with time and change how we recommend ongoing family screening,” Dr. Mital noted.

“The guideline proposes initiating screening of family members at the earliest regardless of age given HCM can manifest at any age in affected families,” she added.

The guideline notes that the usefulness of genetic testing to evaluate the risk of sudden cardiac death (SCD) is uncertain. There’s even guidance for implementing those test results. Further testing is recommended for patients who are genotype positive and phenotype negative for HCM (COR, 1; LOE, B-NR). Those same patients may participate in competitive sports (COR, 2a; LOE, C-LD), but a pacemaker isn’t recommended as a primary prevention (COR, 3 [no benefit]; LOE, B-NR).
 

Risk evaluation and prevention

For SCD risk evaluation and prevention, the guideline spells out five components for the initial and follow-up evaluations (COR, 1; LOE, B-NR). That includes maximal LV wall thickness, ejection fraction, and LV apical aneurysm. The section include multiple recommendations for patient selection for placement of an implantable cardioverter-defibrillator (ICD). For example, it’s recommended for patient’s who’ve had a heart attack or sustained ventricular tachycardia (COR, 1; LOE, B-NR), but not so much for patients without risk factors or for participating in sports (COR, 3 [harm]; LOE, B-NR). The guideline even provides recommendations for selecting an ICD.

Management recommendations address when medical therapy is indicated, including which therapies are indicated for specific scenarios, as well as higher level interventions such as SRT for severely symptomatic patients with obstructive HCM (COR, 2b; LOE, C-LD) and surgical myectomy with ablation in patients with HCM and atrial fibrillation (COR, 2a; LOE, B-NR). This section also provides recommendations for managing patients with HCM and ventricular arrhythmias or advanced heart failure.

The guideline also includes a host of lifestyle considerations. Mild to moderate exercise is beneficial (COR, 1; LOE, B-NR), but athletes with HCM should consult with an “expert provider” (COR, 1; LOE, C, meaning based on expert opinion). Truck drivers, pilots and people who do strenuous physical labor with HCM should meet specific standards.

These recommendations again emphasize the role of shared decision-making, said Dr. Martinez. “It’s not a cookie-cutter discussion. It is taking all of the information, incorporating what the patient’s needs are, and then making sure you appropriately tell them what are the risks of exercising and not exercising. I have as many discussions through the day about what the risks of exercise are as I do the risks of not exercising.”
 

Refining nomenclature, pathophysiology

The writing committee addressed the nomenclature for HCM. The use of HCM to describe increased LV wall thickness linked to systemic diseases or secondary to LV hypertrophy “can lead to confusion,” the committee stated, so other cardiac or systemic causes of LV hypertrophy shouldn’t be labeled HCM. Other etiologies can cause secondary LV hypertrophy that can overlap with HCM; clinical markers and testing can help differentiate these mimickers from HCM. When echocardiography is inconclusive, cardiovascular MRI is indicated (COR, 1; LOE, B-NR).

The guideline update also provides clarity on the pathophysiology of HCM: It consists of dynamic LV outflow tract obstruction, mitral regurgitation, diastolic dysfunction, myocardial ischemia, arrhythmias, or autonomic dysfunction. “For a given patient with HCM, the clinical outcome may be dominated by one of these components or may be the result of a complex interplay,” the guideline states. The clinical evaluation should consider all these conditions.

This update also provides “clear separation” between care of HCM with and without obstruction, Dr. Martinez said. “The role of advanced therapies and referrals with advanced treatment options such as heart transplantation or CRT therapy in this group is different than before, recognizing that people with obstruction have symptoms that may be similar to those without obstruction, and the individual should be [thoroughly] investigated to make sure that you can discern between those two groups to make appropriate recommendations.”

The guideline was developed in collaboration with and endorsed by the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society for Cardiovascular Magnetic Resonance. It’s also been endorsed by the Pediatric & Congenital Electrophysiology Society.

Dr. Mital and Dr. Martinez have no relevant financial relationships to disclose.

SOURCE: Mital S et al. J Am Coll Cardiol. 2020 Nov 20. doi: 10.1016/j.jacc.2020.08.044.

Greater involvement of the patient and family in decision-making, clarity on the role of genetic testing and parameters for team-oriented care, and use of high-volume specialty centers are cornerstones of the first update in almost a decade of the American Heart Association/American College of Cardiology guideline for patients with hypertrophic cardiomyopathy (HCM).

The update lists 133 recommendations for HCM care in six categories: shared decision-making; role of high-volume HCM centers; diagnosis, initial evaluation, and follow-up; risk assessment and prevention of sudden cardiac death (SCD); management of HCM; and lifestyle considerations for patients.

“The guideline puts the patient front and center in the shared decision-making process and emphasizes the importance of incorporating patient’s lifestyle choices and preferences when making complex, life-altering decisions,” writing committee vice chair Seema Mital, MD, of the University of Toronto and the Hospital for Sick Children, also in Toronto, said in an interview.

The fully updated guideline, authored by a joint committee of the AHA and ACC with input from other specialty societies, has been published online in the Journal of the American College of Cardiology. It replaces the 2011 guideline.

Another key component of the update is the strong recommendation to utilize multidisciplinary care, said Matthew W. Martinez, MD, a writing committee member and sports cardiologists at Morristown (N.J.) Medical Center. “This is not only as a part of shared decision-making, but really in care for the patients,” he said, “that there’s a level of expertise that is provided by centers of excellence who handle HCM, and we did lay out some recommendations with regards to surgery, imaging, interventionists, and management with electrophysiology, and the care of athletes with potential for HCM and pregnant women.”

The update ranks recommendations by class of recommendation (COR), ranging from strong benefit much greater than risk to harm with risk exceeding benefit, and level of evidence (LOE). The recommendation for shared decision making, for example, carries at COR of 1, the highest rating, and a mid-level LOE of B-NR, meaning from nonrandomized studies. Patients who need septal reduction therapy (SRT) should be referred to a comprehensive or primary HCM center – a recommendation with a COR of 1 but an LOE of C-LD, meaning there are limited data.
 

From diagnosis to follow-up

The most extensive list of recommendations falls under the category covering diagnosis, initial evaluation and follow-up. They include a three-generation family history as part of the initial diagnostic assessment (COR, 1; LOE, B-NR), high-level recommendations for use of transthoracic echocardiogram in the initial work-up, every 1 or 2 years or when the patient’s status changes in confirmed cases, as well as parameters for using other imaging and diagnostic tests. Cardiovascular MRI, for example, is indicated when echocardiography is inconclusive (COR, 1; LOE, B-NR) and in other scenarios. When echocardiography is inconclusive but cardiac MRI isn’t available, cardiac CT is an option, albeit at a lower level of evidence (COR, 2b; LOE, C-LD).

Heart rhythm assessment has a high level of recommendation in multiple scenarios, even in first-degree relatives of HCM patients. Invasive hemodynamic assessment is in order for candidates of SRT whose left ventricular (LV) outflow tract obstruction status is unknown. This category also sets parameters for angiography, and exercise stress testing.

The most extensive recommendations for diagnosis and follow-up cover genetic testing; it consists of nine high-level recommendations.

“The guideline highlights not only the importance of genetic testing of an affected patient and genetic screening of family members, but also emphasizes ongoing reassessment of variant classification as this may evolve with time and change how we recommend ongoing family screening,” Dr. Mital noted.

“The guideline proposes initiating screening of family members at the earliest regardless of age given HCM can manifest at any age in affected families,” she added.

The guideline notes that the usefulness of genetic testing to evaluate the risk of sudden cardiac death (SCD) is uncertain. There’s even guidance for implementing those test results. Further testing is recommended for patients who are genotype positive and phenotype negative for HCM (COR, 1; LOE, B-NR). Those same patients may participate in competitive sports (COR, 2a; LOE, C-LD), but a pacemaker isn’t recommended as a primary prevention (COR, 3 [no benefit]; LOE, B-NR).
 

Risk evaluation and prevention

For SCD risk evaluation and prevention, the guideline spells out five components for the initial and follow-up evaluations (COR, 1; LOE, B-NR). That includes maximal LV wall thickness, ejection fraction, and LV apical aneurysm. The section include multiple recommendations for patient selection for placement of an implantable cardioverter-defibrillator (ICD). For example, it’s recommended for patient’s who’ve had a heart attack or sustained ventricular tachycardia (COR, 1; LOE, B-NR), but not so much for patients without risk factors or for participating in sports (COR, 3 [harm]; LOE, B-NR). The guideline even provides recommendations for selecting an ICD.

Management recommendations address when medical therapy is indicated, including which therapies are indicated for specific scenarios, as well as higher level interventions such as SRT for severely symptomatic patients with obstructive HCM (COR, 2b; LOE, C-LD) and surgical myectomy with ablation in patients with HCM and atrial fibrillation (COR, 2a; LOE, B-NR). This section also provides recommendations for managing patients with HCM and ventricular arrhythmias or advanced heart failure.

The guideline also includes a host of lifestyle considerations. Mild to moderate exercise is beneficial (COR, 1; LOE, B-NR), but athletes with HCM should consult with an “expert provider” (COR, 1; LOE, C, meaning based on expert opinion). Truck drivers, pilots and people who do strenuous physical labor with HCM should meet specific standards.

These recommendations again emphasize the role of shared decision-making, said Dr. Martinez. “It’s not a cookie-cutter discussion. It is taking all of the information, incorporating what the patient’s needs are, and then making sure you appropriately tell them what are the risks of exercising and not exercising. I have as many discussions through the day about what the risks of exercise are as I do the risks of not exercising.”
 

Refining nomenclature, pathophysiology

The writing committee addressed the nomenclature for HCM. The use of HCM to describe increased LV wall thickness linked to systemic diseases or secondary to LV hypertrophy “can lead to confusion,” the committee stated, so other cardiac or systemic causes of LV hypertrophy shouldn’t be labeled HCM. Other etiologies can cause secondary LV hypertrophy that can overlap with HCM; clinical markers and testing can help differentiate these mimickers from HCM. When echocardiography is inconclusive, cardiovascular MRI is indicated (COR, 1; LOE, B-NR).

The guideline update also provides clarity on the pathophysiology of HCM: It consists of dynamic LV outflow tract obstruction, mitral regurgitation, diastolic dysfunction, myocardial ischemia, arrhythmias, or autonomic dysfunction. “For a given patient with HCM, the clinical outcome may be dominated by one of these components or may be the result of a complex interplay,” the guideline states. The clinical evaluation should consider all these conditions.

This update also provides “clear separation” between care of HCM with and without obstruction, Dr. Martinez said. “The role of advanced therapies and referrals with advanced treatment options such as heart transplantation or CRT therapy in this group is different than before, recognizing that people with obstruction have symptoms that may be similar to those without obstruction, and the individual should be [thoroughly] investigated to make sure that you can discern between those two groups to make appropriate recommendations.”

The guideline was developed in collaboration with and endorsed by the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society for Cardiovascular Magnetic Resonance. It’s also been endorsed by the Pediatric & Congenital Electrophysiology Society.

Dr. Mital and Dr. Martinez have no relevant financial relationships to disclose.

SOURCE: Mital S et al. J Am Coll Cardiol. 2020 Nov 20. doi: 10.1016/j.jacc.2020.08.044.

Loss of the hepatitis B surface antigen (HBsAg), a marker for functional cure of hepatitis B infection, is nearly six times more common among White patients than Asian patients following cessation of therapy with a nucleotide or nucleoside analogue, investigators in the RETRACT-B study group report.

Among 1,541 patients in a global retrospective cohort, the cumulative rate of HBsAg loss 4 years after cessation of therapy with entecavir (ETV), tenofovir disoproxil fumarate (TDF), or other nucleoside/nucleotide analogue (“nuc” or NA) was 11% in Asian patients, compared with 41% in Whites, which translated in multivariate analysis into a hazard ratio (HR) of 5.8 (P < .001), said Grishma Hirode, a clinical research associate and PhD candidate at the Toronto Centre for Liver Disease.

“On univariate Cox regression, the rate of S [antigen] loss was significantly higher among older patients, among [Whites], and among tenofovir-treated patients prior to stopping,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

Although NAs are effective at suppressing hepatitis B viral activity, functional cure as indicated by HBsAg loss is uncommon, Ms. Hirode noted.

“Finite use of antiviral therapy has been proposed as an alternative to long-term therapy, and the rationale for stopping nuc therapy is to induce a durable virologic remission in the form of an inactive carrier state, and ideally a functional cure,” she said.

The RETRACT-B (Response after End of Treatment with Antivirals in Chronic Hepatitis B) study group, comprising liver treatment centers in Canada, Europe, Hong Kong, and Taiwan, studies outcomes following cessation of nucleos(t)ide analogue therapy.

The investigators looked at data on 1,541 patients, including those with both hepatitis B e-antigen (HBeAg) positive and HBeAg-negative disease at the start of therapy, all of whom were HBeAg negative at the time of antiviral cessation and had undetectable serum HBV DNA. Patients with hepatitis C, hepatitis D and/or HIV co-infection were excluded, as were patients who had received interferon treatment less than 12 months before stopping.

The mean age at baseline was 53 years. Men comprised 73% of the sample. In all, 88% of patients were Asian, 10% White, and 2% other.

In patients for whom genotype data was known, 0.5% had type A, 43% type B, 11% type C, and 2% type D.

Nearly two-thirds of patients (60%) were on ETV at the time of drug cessation, 29% were on TDF, and 11% were on other agents.

In all, 5% of patients had cirrhosis at the time of nucleos(t)ide cessation, the mean HBsAg was 2.6 log₁₀ IU/mL, and the mean alanine aminotransferase (ALT) level was 0.6 times the upper limit of normal.

The median duration of NA therapy was 3 years.

The cumulative rates of HBsAg loss over time among all patients was 3% at 1 year, 8% at 2 years. 12% at 3 years, and 14% at 4 years. Cumulative rates of antigen loss at year 4 were significantly greater for patients 50 and older vs. those younger than 50 (18% vs. 9%, respectively, P = .01), Whites vs. Asians (41% vs. 11%, P < .001), and in those who had been on TDF vs. ETV (17% vs. 12%, P = .001). There was no significant difference in cumulative HBsAg loss between patients who were HBeAg positive or negative at the start of NA therapy.

Cumulative rates of retreatment were 30% at 1 year, 43% at 2 years, 50% at 3 years, and 56% at 4 years. The only significant predictor for retreatment was age, with patients 50 and older being significantly more likely to be retreated by year 4 (63% vs. 45%, respectively, P < .001).

In a univariate model for HBsAg loss, the HR for age 50 and older was 1.7 (P = .01), the HR for White vs. Asian patients was 5.5 (P < .001), and the HR for TDF vs. ETV was 2.0 (P = .001).

A univariate model for retreatment showed an HR of 1.6 for patients 50 and older; all other parameters (sex, race, NA type, and HBeAg status at start of therapy) were not significantly different.

In multivariate models, only race/ethnicity remained significant as a predictor for HBsAg loss, with a HR of 5.8 for Whites vs. Asians (P < .001), and only age 50 and older remained significant as a predictor for retreatment, with a HR of 1.6 (P < .001).

The 4-year cumulative rate of virologic relapse, defined as an HBV DNA of 2000 IU/mL or higher) was 74%, the rate of combined DNA plus ALT relapse (ALT 2 or more times the upper limit of normal) was 56%, and the rate of ALT flares (5 or more times the upper limit of normal) was 33%.

In all, 15 patients (1%) experienced hepatic decompensation, and 12 (0.96%) died, with 9 of the deaths reported as liver-related.
 

Race/ethnicity differences previously seen

Liver specialist Anna Suk-Fong Lok, MD, professor of medicine at the University of Michigan in Ann Arbor, who was not involved in the study, said that the findings are not especially surprising.

“When the studies came out from Asian countries showing that patients who were taken off treatment had a higher rate of S antigen loss than patients who stayed on treatment, the rate of S antigen loss was not all that impressive, but when you look at the European studies the rate of S antigen loss was very high,” she said in an interview.

“The question of course is ‘Why?’ I don’t think we understand completely why. We can speculate, but none of these type studies give us a definitive answer,” she said.

Possible reasons for the racial differences in HBsAg loss include differences in hepatitis B genotype, she said.

“Another possibility is that Asian patients may have been infected either at the time of birth or as a young kid, so they may have been infected for a much longer period of time than [Whites], who usually acquire infections as adults,” Dr. Lok said.

There may also be differences between patient populations in immune responses following cessation of antiviral therapy, she added.

The study was supported by the RETRACT-B group. Ms. Hirode and Dr. Lok reported no relevant disclosures.

SOURCE: Hirode G et al. AASLD 2020. Abstract 23.

Loss of the hepatitis B surface antigen (HBsAg), a marker for functional cure of hepatitis B infection, is nearly six times more common among White patients than Asian patients following cessation of therapy with a nucleotide or nucleoside analogue, investigators in the RETRACT-B study group report.

Among 1,541 patients in a global retrospective cohort, the cumulative rate of HBsAg loss 4 years after cessation of therapy with entecavir (ETV), tenofovir disoproxil fumarate (TDF), or other nucleoside/nucleotide analogue (“nuc” or NA) was 11% in Asian patients, compared with 41% in Whites, which translated in multivariate analysis into a hazard ratio (HR) of 5.8 (P < .001), said Grishma Hirode, a clinical research associate and PhD candidate at the Toronto Centre for Liver Disease.

“On univariate Cox regression, the rate of S [antigen] loss was significantly higher among older patients, among [Whites], and among tenofovir-treated patients prior to stopping,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

Although NAs are effective at suppressing hepatitis B viral activity, functional cure as indicated by HBsAg loss is uncommon, Ms. Hirode noted.

“Finite use of antiviral therapy has been proposed as an alternative to long-term therapy, and the rationale for stopping nuc therapy is to induce a durable virologic remission in the form of an inactive carrier state, and ideally a functional cure,” she said.

The RETRACT-B (Response after End of Treatment with Antivirals in Chronic Hepatitis B) study group, comprising liver treatment centers in Canada, Europe, Hong Kong, and Taiwan, studies outcomes following cessation of nucleos(t)ide analogue therapy.

The investigators looked at data on 1,541 patients, including those with both hepatitis B e-antigen (HBeAg) positive and HBeAg-negative disease at the start of therapy, all of whom were HBeAg negative at the time of antiviral cessation and had undetectable serum HBV DNA. Patients with hepatitis C, hepatitis D and/or HIV co-infection were excluded, as were patients who had received interferon treatment less than 12 months before stopping.

The mean age at baseline was 53 years. Men comprised 73% of the sample. In all, 88% of patients were Asian, 10% White, and 2% other.

In patients for whom genotype data was known, 0.5% had type A, 43% type B, 11% type C, and 2% type D.

Nearly two-thirds of patients (60%) were on ETV at the time of drug cessation, 29% were on TDF, and 11% were on other agents.

In all, 5% of patients had cirrhosis at the time of nucleos(t)ide cessation, the mean HBsAg was 2.6 log₁₀ IU/mL, and the mean alanine aminotransferase (ALT) level was 0.6 times the upper limit of normal.

The median duration of NA therapy was 3 years.

The cumulative rates of HBsAg loss over time among all patients was 3% at 1 year, 8% at 2 years. 12% at 3 years, and 14% at 4 years. Cumulative rates of antigen loss at year 4 were significantly greater for patients 50 and older vs. those younger than 50 (18% vs. 9%, respectively, P = .01), Whites vs. Asians (41% vs. 11%, P < .001), and in those who had been on TDF vs. ETV (17% vs. 12%, P = .001). There was no significant difference in cumulative HBsAg loss between patients who were HBeAg positive or negative at the start of NA therapy.

Cumulative rates of retreatment were 30% at 1 year, 43% at 2 years, 50% at 3 years, and 56% at 4 years. The only significant predictor for retreatment was age, with patients 50 and older being significantly more likely to be retreated by year 4 (63% vs. 45%, respectively, P < .001).

In a univariate model for HBsAg loss, the HR for age 50 and older was 1.7 (P = .01), the HR for White vs. Asian patients was 5.5 (P < .001), and the HR for TDF vs. ETV was 2.0 (P = .001).

A univariate model for retreatment showed an HR of 1.6 for patients 50 and older; all other parameters (sex, race, NA type, and HBeAg status at start of therapy) were not significantly different.

In multivariate models, only race/ethnicity remained significant as a predictor for HBsAg loss, with a HR of 5.8 for Whites vs. Asians (P < .001), and only age 50 and older remained significant as a predictor for retreatment, with a HR of 1.6 (P < .001).

The 4-year cumulative rate of virologic relapse, defined as an HBV DNA of 2000 IU/mL or higher) was 74%, the rate of combined DNA plus ALT relapse (ALT 2 or more times the upper limit of normal) was 56%, and the rate of ALT flares (5 or more times the upper limit of normal) was 33%.

In all, 15 patients (1%) experienced hepatic decompensation, and 12 (0.96%) died, with 9 of the deaths reported as liver-related.
 

Race/ethnicity differences previously seen

Liver specialist Anna Suk-Fong Lok, MD, professor of medicine at the University of Michigan in Ann Arbor, who was not involved in the study, said that the findings are not especially surprising.

“When the studies came out from Asian countries showing that patients who were taken off treatment had a higher rate of S antigen loss than patients who stayed on treatment, the rate of S antigen loss was not all that impressive, but when you look at the European studies the rate of S antigen loss was very high,” she said in an interview.

“The question of course is ‘Why?’ I don’t think we understand completely why. We can speculate, but none of these type studies give us a definitive answer,” she said.

Possible reasons for the racial differences in HBsAg loss include differences in hepatitis B genotype, she said.

“Another possibility is that Asian patients may have been infected either at the time of birth or as a young kid, so they may have been infected for a much longer period of time than [Whites], who usually acquire infections as adults,” Dr. Lok said.

There may also be differences between patient populations in immune responses following cessation of antiviral therapy, she added.

The study was supported by the RETRACT-B group. Ms. Hirode and Dr. Lok reported no relevant disclosures.

SOURCE: Hirode G et al. AASLD 2020. Abstract 23.

Loss of the hepatitis B surface antigen (HBsAg), a marker for functional cure of hepatitis B infection, is nearly six times more common among White patients than Asian patients following cessation of therapy with a nucleotide or nucleoside analogue, investigators in the RETRACT-B study group report.

Among 1,541 patients in a global retrospective cohort, the cumulative rate of HBsAg loss 4 years after cessation of therapy with entecavir (ETV), tenofovir disoproxil fumarate (TDF), or other nucleoside/nucleotide analogue (“nuc” or NA) was 11% in Asian patients, compared with 41% in Whites, which translated in multivariate analysis into a hazard ratio (HR) of 5.8 (P < .001), said Grishma Hirode, a clinical research associate and PhD candidate at the Toronto Centre for Liver Disease.

“On univariate Cox regression, the rate of S [antigen] loss was significantly higher among older patients, among [Whites], and among tenofovir-treated patients prior to stopping,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

Although NAs are effective at suppressing hepatitis B viral activity, functional cure as indicated by HBsAg loss is uncommon, Ms. Hirode noted.

“Finite use of antiviral therapy has been proposed as an alternative to long-term therapy, and the rationale for stopping nuc therapy is to induce a durable virologic remission in the form of an inactive carrier state, and ideally a functional cure,” she said.

The RETRACT-B (Response after End of Treatment with Antivirals in Chronic Hepatitis B) study group, comprising liver treatment centers in Canada, Europe, Hong Kong, and Taiwan, studies outcomes following cessation of nucleos(t)ide analogue therapy.

The investigators looked at data on 1,541 patients, including those with both hepatitis B e-antigen (HBeAg) positive and HBeAg-negative disease at the start of therapy, all of whom were HBeAg negative at the time of antiviral cessation and had undetectable serum HBV DNA. Patients with hepatitis C, hepatitis D and/or HIV co-infection were excluded, as were patients who had received interferon treatment less than 12 months before stopping.

The mean age at baseline was 53 years. Men comprised 73% of the sample. In all, 88% of patients were Asian, 10% White, and 2% other.

In patients for whom genotype data was known, 0.5% had type A, 43% type B, 11% type C, and 2% type D.

Nearly two-thirds of patients (60%) were on ETV at the time of drug cessation, 29% were on TDF, and 11% were on other agents.

In all, 5% of patients had cirrhosis at the time of nucleos(t)ide cessation, the mean HBsAg was 2.6 log₁₀ IU/mL, and the mean alanine aminotransferase (ALT) level was 0.6 times the upper limit of normal.

The median duration of NA therapy was 3 years.

The cumulative rates of HBsAg loss over time among all patients was 3% at 1 year, 8% at 2 years. 12% at 3 years, and 14% at 4 years. Cumulative rates of antigen loss at year 4 were significantly greater for patients 50 and older vs. those younger than 50 (18% vs. 9%, respectively, P = .01), Whites vs. Asians (41% vs. 11%, P < .001), and in those who had been on TDF vs. ETV (17% vs. 12%, P = .001). There was no significant difference in cumulative HBsAg loss between patients who were HBeAg positive or negative at the start of NA therapy.

Cumulative rates of retreatment were 30% at 1 year, 43% at 2 years, 50% at 3 years, and 56% at 4 years. The only significant predictor for retreatment was age, with patients 50 and older being significantly more likely to be retreated by year 4 (63% vs. 45%, respectively, P < .001).

In a univariate model for HBsAg loss, the HR for age 50 and older was 1.7 (P = .01), the HR for White vs. Asian patients was 5.5 (P < .001), and the HR for TDF vs. ETV was 2.0 (P = .001).

A univariate model for retreatment showed an HR of 1.6 for patients 50 and older; all other parameters (sex, race, NA type, and HBeAg status at start of therapy) were not significantly different.

In multivariate models, only race/ethnicity remained significant as a predictor for HBsAg loss, with a HR of 5.8 for Whites vs. Asians (P < .001), and only age 50 and older remained significant as a predictor for retreatment, with a HR of 1.6 (P < .001).

The 4-year cumulative rate of virologic relapse, defined as an HBV DNA of 2000 IU/mL or higher) was 74%, the rate of combined DNA plus ALT relapse (ALT 2 or more times the upper limit of normal) was 56%, and the rate of ALT flares (5 or more times the upper limit of normal) was 33%.

In all, 15 patients (1%) experienced hepatic decompensation, and 12 (0.96%) died, with 9 of the deaths reported as liver-related.
 

Race/ethnicity differences previously seen

Liver specialist Anna Suk-Fong Lok, MD, professor of medicine at the University of Michigan in Ann Arbor, who was not involved in the study, said that the findings are not especially surprising.

“When the studies came out from Asian countries showing that patients who were taken off treatment had a higher rate of S antigen loss than patients who stayed on treatment, the rate of S antigen loss was not all that impressive, but when you look at the European studies the rate of S antigen loss was very high,” she said in an interview.

“The question of course is ‘Why?’ I don’t think we understand completely why. We can speculate, but none of these type studies give us a definitive answer,” she said.

Possible reasons for the racial differences in HBsAg loss include differences in hepatitis B genotype, she said.

“Another possibility is that Asian patients may have been infected either at the time of birth or as a young kid, so they may have been infected for a much longer period of time than [Whites], who usually acquire infections as adults,” Dr. Lok said.

There may also be differences between patient populations in immune responses following cessation of antiviral therapy, she added.

The study was supported by the RETRACT-B group. Ms. Hirode and Dr. Lok reported no relevant disclosures.

SOURCE: Hirode G et al. AASLD 2020. Abstract 23.

One of the most remarkable stories in medicine must be the relatively brief 25 years between the discovery of the hepatitis C virus (HCV) in 1989 to its eventual cure in 2014.

HCV afflicted over 5 million Americans and was the cause of death in approximately 10,000 patients annually, the leading indication for liver transplantation, and the leading risk factor for hepatocellular carcinoma, clearly signaling it as one of the era’s major public health villains. Within that span of time, it is the work beginning in the mid-1990s until today that perhaps best defines the race for the HCV “cure.”

In the early to mid-1990s, polymerase chain reaction techniques were just becoming commonplace for HCV diagnosis, whereas HCV genotypes were emerging as major factors determining response to interferon therapy. The sustained viral response (SVR) rates were mired at around 6%-12% for a 24- to 48-week course of three-times-weekly injection therapy. Severe side effects were common and there was a relatively high relapse rate, even in patients who responded to treatment.

By 1996, the addition of ribavirin to the interferon treatment was associated with a modest but significant improvement in SVR rates to above 20%. And by 2000, the use of pegylated interferon – allowing once-weekly injection therapy – along with ribavirin, improved SVR rates to above 50% for the first time. The therapy was still poorly tolerated but was associated with better compliance.

The real breakthrough in therapy came in the early 2000s with the discovery and availability of HCV protease inhibitors: telaprevir and boceprevir. These agents could induce a more rapid decline in viral replication than interferon but could not be administered alone owing to the rapid emergence of resistant HCV variants. Therefore, these agents were administered with interferon and ribavirin as a three-drug cocktail to take advantage of interferon to prevent emergence of resistant variants. Although SVR rates improved substantially to around 75%, adverse events also increased and limited its usefulness in patients with more advanced liver disease, precisely those who were most in need of better therapies.

Nonetheless, the incredible advances in understanding the replication machinery of HCV that led to the discovery of the protease inhibitors in turn led to further elucidation and unlocking of three additional classes of HCV protein targets and inhibitors: NS5A complex inhibitors (e.g., ledipasvir), the NS5B nonnucleoside inhibitors (e.g., dasabuvir), and NS5B nucleoside inhibitors (e.g., sofosbuvir). It quickly became apparent that the use of combinations of these direct-acting antivirals (DAAs) could limit emergence of resistant variants while also providing rapid and profound viral suppression. Because HCV required viral replication to persist in the hepatocyte, it became possible to induce HCV eradication, and thus cure, with combinations of DAAs.

In addition, investigators soon learned that the duration of therapy no longer needed to be the generally accepted 24-48 weeks for SVR, but instead could be reduced eventually to 8-12 weeks. This shortened treatment duration allowed for more rapid testing of new agents and combinations, and the field took a rapid step forward between 2011 and 2017. HCV cure rates rose to 90%-95%.

The competition for Food and Drug Administration approval of new agents among several pharmaceutical companies also meant that the time-honored process of issuing treatment guidelines every 3-5 years by societies would not be adequate. Therefore, in 2013, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America joined forces to establish more nimble and responsive online HCV guidance. This important resource debuted in January 2014 just as the FDA approved the first DAA therapies.

The high cost initially associated with many of these new therapies (up to $1,000 per pill) significantly limited uptake owing to insurance and health plan cost factors. Early on, the cost was also analyzed by price per cure, seemingly to justify the high cost by the high cure rate. However, advocacy and negotiations ultimately led to marked reductions in the cost of a course of therapy (with some therapies at $225 per pill), thus making these treatments now widely available.

By 2020, the HCV field has shifted from therapeutic development to improving the care cascade by enhanced identification and testing of unsuspected but HCV infected individuals. This is our current challenge.
 

Moving toward noninvasive tests

While curative therapy has revolutionized HCV management, innovation in diagnostics eliminated a significant barrier in access to therapy: the liver biopsy.

Staging, or accurately identifying advanced fibrosis in persons infected with HCV, is essential for long-term follow-up. The presence of advanced disease affects drug choices, especially before the approval of all-oral therapy. Historically, a liver biopsy was obligatory before treatment. Invasive with a significant risk for complications, this requirement effectively prevented treatment in those who were unwilling to undergo the procedure and deterred those at risk from even being tested.

Over the past 25 years, numerous methods to noninvasively assess for liver fibrosis have been used. Serum biomarkers can be either indirect (based on routine tests) or direct (reflecting components of the extracellular matrix). Although highly available, they are only moderately useful for identifying advanced fibrosis and thus cannot replace liver biopsy in the care cascade. The technique of elastography dates back to the 1980s, though the role of vibration-controlled transient liver elastography in the assessment of hepatic fibrosis in patients with HCV was not recognized until around 2005 and it was not commonly used for nearly another decade.

Yet, a paradigm shift in the care cascade occurred with the release of the AASLD/IDSA guidance document in 2014. For the first time in the United States, noninvasive tests were recommended as first-line testing for the assessment of advanced fibrosis. Prior guidelines specifically stated that although noninvasive tests might be useful, they “should not replace the liver biopsy in routine clinical practice.” Current guidelines recommend combining elastography with serum biomarkers and considering biopsy only in patients with discordant results if the biopsy would affect clinical decision-making.
 

The last frontier

Curative therapy has also allowed the unthinkable: willingly exposing patients to the virus through donor-positive/recipient-negative solid organ transplant. Traditionally, an HCV-infected donor would be considered only for an HCV-positive recipient; however, with effective DAA therapy, the number of HCV actively infected patients in need of transplant has dwindled.

Unfortunately as a consequence of the opioid epidemic, the HCV-exposed donor population has blossomed. Given that HCV therapy is near universally curative, using organs from HCV-viremic donors can greatly expand the organ transplantation pool. Small studies[1-5] have demonstrated the safety and efficacy of this approach, both in HCV-positive liver donors as well as in other solid organs.
 

A disease pegged for elimination

In the past 25 years, HCV has evolved from non-A, non-B hepatitis into a disease pegged for elimination. This is a direct reflection of improved therapeutics with highly effective DAAs. Yet, without improved diagnostics, we would be unable to navigate patients through the clinical care cascade. These incredible strides in diagnostics and therapeutics allow us to push the cutting edge through iatrogenic infection of organ recipients, while recognizing that the largest hurdle to elimination remains in finding those who are chronically infected. Ultimately, the crux of elimination remains unchanged over the past 25 years and resides in screening and diagnosis with effective linkage to care.

Donald M. Jensen, MD, is a professor of medicine at Rush University Medical Center, Chicago. He was previously the director of the Center for Liver Disease at the University of Chicago until 2015. His research interest has been in newer HCV therapies. He recently received the Distinguished Service Award from the AASLD for his many contributions to the field.

Nancy S. Reau, MD, is chief of the hepatology section at Rush University Medical Center and a regular contributor to Medscape. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the AASLD and the IDSA, as well as educational chair for the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels.
 

References

Woolley AE et al. Heart and lung transplants from HCV-infected donors to uninfected recipients. N Engl J Med. 2019;380:1606-17.

Franco A et al. Renal transplantation from seropositive hepatitis C virus donors to seronegative recipients in Spain: A prospective study. Transpl Int. 2019;32:710-6.

Goldberg DS et al. Transplanting HCV-infected kidneys into uninfected recipients. N Engl J Med. 2017;377:1105.

Kwong AJ et al. Liver transplantation for hepatitis C virus (HCV) nonviremic recipients with HCV viremic donors. Am J Transplant. 2019;19:1380-7.

Bethea E et al. Immediate administration of antiviral therapy after transplantation of hepatitis C–infected livers into uninfected recipients: Implications for therapeutic planning. Am J Transplant. 2020;20:1619-28.

This article first appeared on Medscape.com.

One of the most remarkable stories in medicine must be the relatively brief 25 years between the discovery of the hepatitis C virus (HCV) in 1989 to its eventual cure in 2014.

HCV afflicted over 5 million Americans and was the cause of death in approximately 10,000 patients annually, the leading indication for liver transplantation, and the leading risk factor for hepatocellular carcinoma, clearly signaling it as one of the era’s major public health villains. Within that span of time, it is the work beginning in the mid-1990s until today that perhaps best defines the race for the HCV “cure.”

In the early to mid-1990s, polymerase chain reaction techniques were just becoming commonplace for HCV diagnosis, whereas HCV genotypes were emerging as major factors determining response to interferon therapy. The sustained viral response (SVR) rates were mired at around 6%-12% for a 24- to 48-week course of three-times-weekly injection therapy. Severe side effects were common and there was a relatively high relapse rate, even in patients who responded to treatment.

By 1996, the addition of ribavirin to the interferon treatment was associated with a modest but significant improvement in SVR rates to above 20%. And by 2000, the use of pegylated interferon – allowing once-weekly injection therapy – along with ribavirin, improved SVR rates to above 50% for the first time. The therapy was still poorly tolerated but was associated with better compliance.

The real breakthrough in therapy came in the early 2000s with the discovery and availability of HCV protease inhibitors: telaprevir and boceprevir. These agents could induce a more rapid decline in viral replication than interferon but could not be administered alone owing to the rapid emergence of resistant HCV variants. Therefore, these agents were administered with interferon and ribavirin as a three-drug cocktail to take advantage of interferon to prevent emergence of resistant variants. Although SVR rates improved substantially to around 75%, adverse events also increased and limited its usefulness in patients with more advanced liver disease, precisely those who were most in need of better therapies.

Nonetheless, the incredible advances in understanding the replication machinery of HCV that led to the discovery of the protease inhibitors in turn led to further elucidation and unlocking of three additional classes of HCV protein targets and inhibitors: NS5A complex inhibitors (e.g., ledipasvir), the NS5B nonnucleoside inhibitors (e.g., dasabuvir), and NS5B nucleoside inhibitors (e.g., sofosbuvir). It quickly became apparent that the use of combinations of these direct-acting antivirals (DAAs) could limit emergence of resistant variants while also providing rapid and profound viral suppression. Because HCV required viral replication to persist in the hepatocyte, it became possible to induce HCV eradication, and thus cure, with combinations of DAAs.

In addition, investigators soon learned that the duration of therapy no longer needed to be the generally accepted 24-48 weeks for SVR, but instead could be reduced eventually to 8-12 weeks. This shortened treatment duration allowed for more rapid testing of new agents and combinations, and the field took a rapid step forward between 2011 and 2017. HCV cure rates rose to 90%-95%.

The competition for Food and Drug Administration approval of new agents among several pharmaceutical companies also meant that the time-honored process of issuing treatment guidelines every 3-5 years by societies would not be adequate. Therefore, in 2013, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America joined forces to establish more nimble and responsive online HCV guidance. This important resource debuted in January 2014 just as the FDA approved the first DAA therapies.

The high cost initially associated with many of these new therapies (up to $1,000 per pill) significantly limited uptake owing to insurance and health plan cost factors. Early on, the cost was also analyzed by price per cure, seemingly to justify the high cost by the high cure rate. However, advocacy and negotiations ultimately led to marked reductions in the cost of a course of therapy (with some therapies at $225 per pill), thus making these treatments now widely available.

By 2020, the HCV field has shifted from therapeutic development to improving the care cascade by enhanced identification and testing of unsuspected but HCV infected individuals. This is our current challenge.
 

Moving toward noninvasive tests

While curative therapy has revolutionized HCV management, innovation in diagnostics eliminated a significant barrier in access to therapy: the liver biopsy.

Staging, or accurately identifying advanced fibrosis in persons infected with HCV, is essential for long-term follow-up. The presence of advanced disease affects drug choices, especially before the approval of all-oral therapy. Historically, a liver biopsy was obligatory before treatment. Invasive with a significant risk for complications, this requirement effectively prevented treatment in those who were unwilling to undergo the procedure and deterred those at risk from even being tested.

Over the past 25 years, numerous methods to noninvasively assess for liver fibrosis have been used. Serum biomarkers can be either indirect (based on routine tests) or direct (reflecting components of the extracellular matrix). Although highly available, they are only moderately useful for identifying advanced fibrosis and thus cannot replace liver biopsy in the care cascade. The technique of elastography dates back to the 1980s, though the role of vibration-controlled transient liver elastography in the assessment of hepatic fibrosis in patients with HCV was not recognized until around 2005 and it was not commonly used for nearly another decade.

Yet, a paradigm shift in the care cascade occurred with the release of the AASLD/IDSA guidance document in 2014. For the first time in the United States, noninvasive tests were recommended as first-line testing for the assessment of advanced fibrosis. Prior guidelines specifically stated that although noninvasive tests might be useful, they “should not replace the liver biopsy in routine clinical practice.” Current guidelines recommend combining elastography with serum biomarkers and considering biopsy only in patients with discordant results if the biopsy would affect clinical decision-making.
 

The last frontier

Curative therapy has also allowed the unthinkable: willingly exposing patients to the virus through donor-positive/recipient-negative solid organ transplant. Traditionally, an HCV-infected donor would be considered only for an HCV-positive recipient; however, with effective DAA therapy, the number of HCV actively infected patients in need of transplant has dwindled.

Unfortunately as a consequence of the opioid epidemic, the HCV-exposed donor population has blossomed. Given that HCV therapy is near universally curative, using organs from HCV-viremic donors can greatly expand the organ transplantation pool. Small studies[1-5] have demonstrated the safety and efficacy of this approach, both in HCV-positive liver donors as well as in other solid organs.
 

A disease pegged for elimination

In the past 25 years, HCV has evolved from non-A, non-B hepatitis into a disease pegged for elimination. This is a direct reflection of improved therapeutics with highly effective DAAs. Yet, without improved diagnostics, we would be unable to navigate patients through the clinical care cascade. These incredible strides in diagnostics and therapeutics allow us to push the cutting edge through iatrogenic infection of organ recipients, while recognizing that the largest hurdle to elimination remains in finding those who are chronically infected. Ultimately, the crux of elimination remains unchanged over the past 25 years and resides in screening and diagnosis with effective linkage to care.

Donald M. Jensen, MD, is a professor of medicine at Rush University Medical Center, Chicago. He was previously the director of the Center for Liver Disease at the University of Chicago until 2015. His research interest has been in newer HCV therapies. He recently received the Distinguished Service Award from the AASLD for his many contributions to the field.

Nancy S. Reau, MD, is chief of the hepatology section at Rush University Medical Center and a regular contributor to Medscape. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the AASLD and the IDSA, as well as educational chair for the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels.
 

References

Woolley AE et al. Heart and lung transplants from HCV-infected donors to uninfected recipients. N Engl J Med. 2019;380:1606-17.

Franco A et al. Renal transplantation from seropositive hepatitis C virus donors to seronegative recipients in Spain: A prospective study. Transpl Int. 2019;32:710-6.

Goldberg DS et al. Transplanting HCV-infected kidneys into uninfected recipients. N Engl J Med. 2017;377:1105.

Kwong AJ et al. Liver transplantation for hepatitis C virus (HCV) nonviremic recipients with HCV viremic donors. Am J Transplant. 2019;19:1380-7.

Bethea E et al. Immediate administration of antiviral therapy after transplantation of hepatitis C–infected livers into uninfected recipients: Implications for therapeutic planning. Am J Transplant. 2020;20:1619-28.

This article first appeared on Medscape.com.

One of the most remarkable stories in medicine must be the relatively brief 25 years between the discovery of the hepatitis C virus (HCV) in 1989 to its eventual cure in 2014.

HCV afflicted over 5 million Americans and was the cause of death in approximately 10,000 patients annually, the leading indication for liver transplantation, and the leading risk factor for hepatocellular carcinoma, clearly signaling it as one of the era’s major public health villains. Within that span of time, it is the work beginning in the mid-1990s until today that perhaps best defines the race for the HCV “cure.”

In the early to mid-1990s, polymerase chain reaction techniques were just becoming commonplace for HCV diagnosis, whereas HCV genotypes were emerging as major factors determining response to interferon therapy. The sustained viral response (SVR) rates were mired at around 6%-12% for a 24- to 48-week course of three-times-weekly injection therapy. Severe side effects were common and there was a relatively high relapse rate, even in patients who responded to treatment.

By 1996, the addition of ribavirin to the interferon treatment was associated with a modest but significant improvement in SVR rates to above 20%. And by 2000, the use of pegylated interferon – allowing once-weekly injection therapy – along with ribavirin, improved SVR rates to above 50% for the first time. The therapy was still poorly tolerated but was associated with better compliance.

The real breakthrough in therapy came in the early 2000s with the discovery and availability of HCV protease inhibitors: telaprevir and boceprevir. These agents could induce a more rapid decline in viral replication than interferon but could not be administered alone owing to the rapid emergence of resistant HCV variants. Therefore, these agents were administered with interferon and ribavirin as a three-drug cocktail to take advantage of interferon to prevent emergence of resistant variants. Although SVR rates improved substantially to around 75%, adverse events also increased and limited its usefulness in patients with more advanced liver disease, precisely those who were most in need of better therapies.

Nonetheless, the incredible advances in understanding the replication machinery of HCV that led to the discovery of the protease inhibitors in turn led to further elucidation and unlocking of three additional classes of HCV protein targets and inhibitors: NS5A complex inhibitors (e.g., ledipasvir), the NS5B nonnucleoside inhibitors (e.g., dasabuvir), and NS5B nucleoside inhibitors (e.g., sofosbuvir). It quickly became apparent that the use of combinations of these direct-acting antivirals (DAAs) could limit emergence of resistant variants while also providing rapid and profound viral suppression. Because HCV required viral replication to persist in the hepatocyte, it became possible to induce HCV eradication, and thus cure, with combinations of DAAs.

In addition, investigators soon learned that the duration of therapy no longer needed to be the generally accepted 24-48 weeks for SVR, but instead could be reduced eventually to 8-12 weeks. This shortened treatment duration allowed for more rapid testing of new agents and combinations, and the field took a rapid step forward between 2011 and 2017. HCV cure rates rose to 90%-95%.

The competition for Food and Drug Administration approval of new agents among several pharmaceutical companies also meant that the time-honored process of issuing treatment guidelines every 3-5 years by societies would not be adequate. Therefore, in 2013, the American Association for the Study of Liver Diseases and the Infectious Diseases Society of America joined forces to establish more nimble and responsive online HCV guidance. This important resource debuted in January 2014 just as the FDA approved the first DAA therapies.

The high cost initially associated with many of these new therapies (up to $1,000 per pill) significantly limited uptake owing to insurance and health plan cost factors. Early on, the cost was also analyzed by price per cure, seemingly to justify the high cost by the high cure rate. However, advocacy and negotiations ultimately led to marked reductions in the cost of a course of therapy (with some therapies at $225 per pill), thus making these treatments now widely available.

By 2020, the HCV field has shifted from therapeutic development to improving the care cascade by enhanced identification and testing of unsuspected but HCV infected individuals. This is our current challenge.
 

Moving toward noninvasive tests

While curative therapy has revolutionized HCV management, innovation in diagnostics eliminated a significant barrier in access to therapy: the liver biopsy.

Staging, or accurately identifying advanced fibrosis in persons infected with HCV, is essential for long-term follow-up. The presence of advanced disease affects drug choices, especially before the approval of all-oral therapy. Historically, a liver biopsy was obligatory before treatment. Invasive with a significant risk for complications, this requirement effectively prevented treatment in those who were unwilling to undergo the procedure and deterred those at risk from even being tested.

Over the past 25 years, numerous methods to noninvasively assess for liver fibrosis have been used. Serum biomarkers can be either indirect (based on routine tests) or direct (reflecting components of the extracellular matrix). Although highly available, they are only moderately useful for identifying advanced fibrosis and thus cannot replace liver biopsy in the care cascade. The technique of elastography dates back to the 1980s, though the role of vibration-controlled transient liver elastography in the assessment of hepatic fibrosis in patients with HCV was not recognized until around 2005 and it was not commonly used for nearly another decade.

Yet, a paradigm shift in the care cascade occurred with the release of the AASLD/IDSA guidance document in 2014. For the first time in the United States, noninvasive tests were recommended as first-line testing for the assessment of advanced fibrosis. Prior guidelines specifically stated that although noninvasive tests might be useful, they “should not replace the liver biopsy in routine clinical practice.” Current guidelines recommend combining elastography with serum biomarkers and considering biopsy only in patients with discordant results if the biopsy would affect clinical decision-making.
 

The last frontier

Curative therapy has also allowed the unthinkable: willingly exposing patients to the virus through donor-positive/recipient-negative solid organ transplant. Traditionally, an HCV-infected donor would be considered only for an HCV-positive recipient; however, with effective DAA therapy, the number of HCV actively infected patients in need of transplant has dwindled.

Unfortunately as a consequence of the opioid epidemic, the HCV-exposed donor population has blossomed. Given that HCV therapy is near universally curative, using organs from HCV-viremic donors can greatly expand the organ transplantation pool. Small studies[1-5] have demonstrated the safety and efficacy of this approach, both in HCV-positive liver donors as well as in other solid organs.
 

A disease pegged for elimination

In the past 25 years, HCV has evolved from non-A, non-B hepatitis into a disease pegged for elimination. This is a direct reflection of improved therapeutics with highly effective DAAs. Yet, without improved diagnostics, we would be unable to navigate patients through the clinical care cascade. These incredible strides in diagnostics and therapeutics allow us to push the cutting edge through iatrogenic infection of organ recipients, while recognizing that the largest hurdle to elimination remains in finding those who are chronically infected. Ultimately, the crux of elimination remains unchanged over the past 25 years and resides in screening and diagnosis with effective linkage to care.

Donald M. Jensen, MD, is a professor of medicine at Rush University Medical Center, Chicago. He was previously the director of the Center for Liver Disease at the University of Chicago until 2015. His research interest has been in newer HCV therapies. He recently received the Distinguished Service Award from the AASLD for his many contributions to the field.

Nancy S. Reau, MD, is chief of the hepatology section at Rush University Medical Center and a regular contributor to Medscape. She serves as editor of Clinical Liver Disease, a multimedia review journal, and recently as a member of HCVGuidelines.org, a web-based resource from the AASLD and the IDSA, as well as educational chair for the AASLD hepatitis C special interest group. She continues to have an active role in the hepatology interest group of the World Gastroenterology Organisation and the American Liver Foundation at the regional and national levels.
 

References

Woolley AE et al. Heart and lung transplants from HCV-infected donors to uninfected recipients. N Engl J Med. 2019;380:1606-17.

Franco A et al. Renal transplantation from seropositive hepatitis C virus donors to seronegative recipients in Spain: A prospective study. Transpl Int. 2019;32:710-6.

Goldberg DS et al. Transplanting HCV-infected kidneys into uninfected recipients. N Engl J Med. 2017;377:1105.

Kwong AJ et al. Liver transplantation for hepatitis C virus (HCV) nonviremic recipients with HCV viremic donors. Am J Transplant. 2019;19:1380-7.

Bethea E et al. Immediate administration of antiviral therapy after transplantation of hepatitis C–infected livers into uninfected recipients: Implications for therapeutic planning. Am J Transplant. 2020;20:1619-28.

This article first appeared on Medscape.com.

Throughout the chaos of the COVID-19 pandemic, advanced practice providers (APPs) – physician assistants (PAs) and nurse practitioners (NPs) – have become an integral component of the hospitalist response. As many physicians began shifting into telemedicine and away from direct patient care, APPs have been eagerly jumping in to fill the gaps. Their work has been changing almost as dramatically and quickly as the pandemic itself, bringing with it expected challenges but bestowing hugely satisfying, often unanticipated, rewards.

APPs on the rise

As the coronavirus pandemic evolves, the role of APPs is evolving right alongside it. With the current relaxation of hospital bylaw restrictions on APPs, their utilization has increased, said Tracy Cardin, ACNP-BC, SFHM, a nurse practitioner and vice president of advanced practice providers at Sound Physicians. “We have not really furloughed any advanced practice providers,” Ms. Cardin said. “In fact, I consider them to be, within hospital medicine, a key lever to finding more cost-effective care delivery models.”

Ms. Cardin said APPs have been working more independently since COVID-19 started, seeing patients on their own and using physician consultation and backup via telemedicine or telephone as needed. With the reduction in elective surgeries and patient volumes at many hospitals, APP-led care also saves money. Because one of the biggest costs is labor, Ms. Cardin said, offering this high-quality care delivery model using APPs in collaboration with physician providers helps defray some of that cost. “We’re hoping that advanced practice providers are really a solution to some of these financial pressures in a lot of different ways,” she said.

“COVID … forced us to expedite conversations about how to maximize caseloads using APPs,” said Alicia Sheffer, AGAC-AGPC NP, a nurse practitioner and Great Lakes regional director of advanced practice providers at Sound Physicians in Cincinnati. Some of those staffing model changes have included using APPs while transitioning ICUs and med-surg units to COVID cohort units, APP-led COVID cohorts, and APP-led ICUs.

“At first the hospital system had ideas about bringing in telemedicine as an alternative to seeing patients, rather than just putting APPs on the front lines and having them go in and see patients,” said Jessica Drane, APRN, PhD, DNP FNP-C, a nurse practitioner and regional director of advanced practice provider services and hospital medicine at Sound Physicians in San Antonio. In Texas at the beginning of the pandemic, hospital numbers were so low that Dr. Drane did not work at all in April. “We were all afraid we were going to lose our jobs,” she said. Then the state got slammed and APPs have been desperately needed.

Ilaria Gadalla, DMSc, PA-C, a PA at Treasure Coast Hospitalists in Port St. Lucie, Fla., and the PA program director at South University, West Palm Beach, Fla., noted that many of her APP colleagues have pivoted fluidly from other specialties to the hospitalist realm as the need for frontline workers has increased. “Hospitalists have shined through this and their value has been recognized even more than previously as a result of COVID-19,” Dr. Gadalla said.

“I don’t think it’s any surprise that hospitalists became a pillar of the COVID pandemic,” said Bridget McGrath, PA-C, a physician assistant and director of the NP/PAs service line for the section of hospital medicine at the University of Chicago. “There are just some innate traits that hospitalists have, such as the ability to be flexible, to problem solve, and to be the solution to the problem.”
 

Building team camaraderie

Ms. Cardin says that the need for APPs has led to an evolving integration between physicians and APPs. The growing teamwork and bonding between colleagues have been some of the most rewarding aspects of the pandemic for Dr. Gadalla. “We rely even more on each other and there isn’t really a line of, ‘I’m a physician versus an NP or PA or nurse.’ We’re all working together with the same goal,” she said.

Ms. McGrath said she has been learning what it means to lead a team during a challenging time. It has been gratifying for her to watch mentors get down to the bare bones of patient care and see everyone unify, putting aside roles and titles and coming together to care for their patients in innovative ways.

“This pandemic has really opened up a lot of doors for us because up until now, we were used almost like scribes for physicians,” Dr. Drane said. She has seen even the most resistant hospital systems beginning to rely on APPs as the pandemic has progressed. “They have become pleasantly surprised at what an APP can do.”
 

Work challenges

Obviously, challenges abound. Dr. Gadalla listed hers as visiting restrictions that invariably lead to slower patient visits thanks to obligatory phone calls, constantly fluctuating patient censuses, sporadic elective surgeries, watching colleagues become furloughed, and trying to balance external perceptions with what’s actually happening in the hospital.

Overall, though, “There have been a lot more rewards than barriers,” added Dr. Drane.

One of the biggest obstacles for health care workers navigating a pandemic is balancing work and home life, not to mention having time to unwind while working long hours. “Finding time for my family has been very limited. My kids feel really neglected,” said Dr. Gadalla. Some days, she gets up extra early to exercise to help clear her head, but other times she’s just too exhausted to even move.

Dr. Drane agreed that the work can get overwhelming. “We’re changing the way we practice almost every week, which can make you doubt yourself as an educator, as a practitioner. You constantly feel like you’re not sure what you’re doing, and people trust you to heal them,” she said. “Today is my first day off in 24 days. I only got it off because I said I needed a moment.”

Ms. Sheffer’s crazy days were at the beginning of the pandemic when she had to self-quarantine from her family and was working nonstop. “I would come home and sleep and work and wake up in the middle of the night and double check and triple check and go back to sleep and work, and that consumed me for several months,” she said.

The biggest challenge for Ms. Sheffer has been coping with public fear. “No matter how logical our medical approach has been, I think the constant feeling of the public threat of COVID has had this insidious effect on how patients approach their health,” she said. “We’re spending a lot more time shaping our approach to best address their fears first and not to politicize COVID so we can actually deal with the health issue at hand.”
 

Complications of COVID

With all the restrictions, caring for patients these days has meant learning to interact with them in different ways that aren’t as personal, Ms. McGrath said. It has been difficult to lose “that humanity of medicine, the usual ways that you interact with your patients that are going through a vulnerable time,” she noted.

Additionally, students in the medical field are being held back from graduation because they cannot participate in direct patient care. This is particularly problematic for PAs and medical students who must touch patients to graduate, Dr. Gadalla said. “All of this is slowing down future providers. We’re going to have trouble catching up. Who’s going to relieve us? That’s a huge problem and no one is finding solutions for that yet,” she said.

At the University of Chicago, Ms. McGrath explained, they created virtual rotations so that PA students could continue to do them at the university. Not only has the experience reminded Ms. McGrath how much she loves being a medical educator and fighting for the education of PA students, but she was surprised to find that her patients came to appreciate the time they spent with her students on the virtual platform as well.

“It’s isolating for patients to be in the hospital in a vulnerable state and with no support system,” she said. “I think being a part of [the PA students’] education gave some meaning to their hospitalization and highlighted that collaboration and connection is a human need.”

Despite everything, there’s a noticeable emphasis on the flowering buds of hope, unity, compassion, and pride that have been quietly blooming from the daily hardships. As Ms. Cardin puts it, “It’s so cliché to say that there’s a crisis. The other word is ‘opportunity,’ and it’s true, there are opportunities here.”
 

Taking care of each other

Creating resources for providers has been a priority at the University of Chicago, according to Ms. McGrath. “As hospitalists, we’re used to taking care of a variety of patients, but our section leadership and providers on the front lines quickly realized that COVID patients are more akin to trauma patients with their quick changes in health, as well as their isolation, fear, and unexpected deterioration,” she said. Her facility has implemented wellness initiatives to help prevent burnout and mental health problems in COVID providers so they can continue to give the best care to their patients.

Both Ms. Sheffer and Dr. Drane say that they have a peer network of APPs at Sound Physicians to call on for questions and support. And it’s encouraging to know you’re not alone and to keep tabs on how colleagues in other states are doing, Ms. Sheffer noted.

“The peer support system has been helpful,” Dr. Drane said. “This job, right now, takes pieces of you every day. Sometimes it’s so emotional that you can’t put it into words. You just have to cry and get it out so that you can go be with your family.”
 

Getting back to basics

The changes in patient care have turned into something Ms. McGrath said she appreciates. “This pandemic has really stripped away the extra fluff of medicine and brought us back to the reason why many of us have gotten into the field, because it became about the patients again,” she says. “You quickly learn your strengths and weaknesses as a provider and as a leader, and that flows into the decisions you’re making for your team and for your patients.”

Ms. Sheffer acknowledged that it is difficult to deal with patients’ family members who don’t understand that they can’t visit their sick relatives, but she said the flip side is that frontline workers become surrogate family members, an outcome she considers to be an honor.

“You step into the emotion with the family or with the patient because you’re all they have. That is a beautiful, honorable role, but it’s also tremendously emotional and sometimes devastating,” she said. “But to me, it’s one of the most beautiful things I’ve been able to offer in a time where we don’t even know what to do with COVID.”

Limited resources mixed with a healthy dose of fear can stifle creativity, Dr. Drane said. Right away, she noticed that despite the abundance of incentive spirometers at her hospital, they were not being utilized. She came in 2 hours early for 3 days to pass one out to every patient under investigation or COVID-positive patient and enlisted the help of her chief nursing officer, CEO, and regional medical director to get everyone on board.

Dr. Drane’s out-of-the-box thinking has enabled people to go home without oxygen 2 days earlier and cut the hospital’s length of stay by 5%. “It’s something so small, but it has such a great end reward,” she said. “I’m proud of this project because it didn’t take money; it was getting creative with what we already have.”
 

Renewed pride and passion

Dr. Drane is intensely proud of being an NP and working on the front lines. She sees that the pandemic has encouraged her and other APPs to expand their horizons.

“For me, it’s made me work to get dual certified,” she said. “APPs can be all-inclusive. I feel like I’m doing what I was meant to do and it’s not just a job anymore.”

Ms. McGrath is even more passionate about being a hospitalist now, as she has realized how valuable their unique skill sets are. “I think other people have also been able to realize that our ability to see the patient as a whole has allowed us to take care of this pandemic, because this disease impacts all organ systems and has a trickle-down effect that we as hospitalists are well versed to manage,” she said.

Ms. Cardin’s work involves communicating with APPs all around the country. Recently she had a phone exchange with an APP who needed to vent.

“She was weeping, and I thought she was going to say, ‘I can’t do this anymore, I need to go home,’ ” said Ms. Cardin. “Instead, she said, ‘I just want to make a difference in one of these people’s lives.’ And that is who the advanced practice providers are. They’re willing to go into those COVID units. They’re willing to be in the front lines. They are dedicated. They’re just intensely inspirational to me.”

Throughout the chaos of the COVID-19 pandemic, advanced practice providers (APPs) – physician assistants (PAs) and nurse practitioners (NPs) – have become an integral component of the hospitalist response. As many physicians began shifting into telemedicine and away from direct patient care, APPs have been eagerly jumping in to fill the gaps. Their work has been changing almost as dramatically and quickly as the pandemic itself, bringing with it expected challenges but bestowing hugely satisfying, often unanticipated, rewards.

APPs on the rise

As the coronavirus pandemic evolves, the role of APPs is evolving right alongside it. With the current relaxation of hospital bylaw restrictions on APPs, their utilization has increased, said Tracy Cardin, ACNP-BC, SFHM, a nurse practitioner and vice president of advanced practice providers at Sound Physicians. “We have not really furloughed any advanced practice providers,” Ms. Cardin said. “In fact, I consider them to be, within hospital medicine, a key lever to finding more cost-effective care delivery models.”

Ms. Cardin said APPs have been working more independently since COVID-19 started, seeing patients on their own and using physician consultation and backup via telemedicine or telephone as needed. With the reduction in elective surgeries and patient volumes at many hospitals, APP-led care also saves money. Because one of the biggest costs is labor, Ms. Cardin said, offering this high-quality care delivery model using APPs in collaboration with physician providers helps defray some of that cost. “We’re hoping that advanced practice providers are really a solution to some of these financial pressures in a lot of different ways,” she said.

“COVID … forced us to expedite conversations about how to maximize caseloads using APPs,” said Alicia Sheffer, AGAC-AGPC NP, a nurse practitioner and Great Lakes regional director of advanced practice providers at Sound Physicians in Cincinnati. Some of those staffing model changes have included using APPs while transitioning ICUs and med-surg units to COVID cohort units, APP-led COVID cohorts, and APP-led ICUs.

“At first the hospital system had ideas about bringing in telemedicine as an alternative to seeing patients, rather than just putting APPs on the front lines and having them go in and see patients,” said Jessica Drane, APRN, PhD, DNP FNP-C, a nurse practitioner and regional director of advanced practice provider services and hospital medicine at Sound Physicians in San Antonio. In Texas at the beginning of the pandemic, hospital numbers were so low that Dr. Drane did not work at all in April. “We were all afraid we were going to lose our jobs,” she said. Then the state got slammed and APPs have been desperately needed.

Ilaria Gadalla, DMSc, PA-C, a PA at Treasure Coast Hospitalists in Port St. Lucie, Fla., and the PA program director at South University, West Palm Beach, Fla., noted that many of her APP colleagues have pivoted fluidly from other specialties to the hospitalist realm as the need for frontline workers has increased. “Hospitalists have shined through this and their value has been recognized even more than previously as a result of COVID-19,” Dr. Gadalla said.

“I don’t think it’s any surprise that hospitalists became a pillar of the COVID pandemic,” said Bridget McGrath, PA-C, a physician assistant and director of the NP/PAs service line for the section of hospital medicine at the University of Chicago. “There are just some innate traits that hospitalists have, such as the ability to be flexible, to problem solve, and to be the solution to the problem.”
 

Building team camaraderie

Ms. Cardin says that the need for APPs has led to an evolving integration between physicians and APPs. The growing teamwork and bonding between colleagues have been some of the most rewarding aspects of the pandemic for Dr. Gadalla. “We rely even more on each other and there isn’t really a line of, ‘I’m a physician versus an NP or PA or nurse.’ We’re all working together with the same goal,” she said.

Ms. McGrath said she has been learning what it means to lead a team during a challenging time. It has been gratifying for her to watch mentors get down to the bare bones of patient care and see everyone unify, putting aside roles and titles and coming together to care for their patients in innovative ways.

“This pandemic has really opened up a lot of doors for us because up until now, we were used almost like scribes for physicians,” Dr. Drane said. She has seen even the most resistant hospital systems beginning to rely on APPs as the pandemic has progressed. “They have become pleasantly surprised at what an APP can do.”
 

Work challenges

Obviously, challenges abound. Dr. Gadalla listed hers as visiting restrictions that invariably lead to slower patient visits thanks to obligatory phone calls, constantly fluctuating patient censuses, sporadic elective surgeries, watching colleagues become furloughed, and trying to balance external perceptions with what’s actually happening in the hospital.

Overall, though, “There have been a lot more rewards than barriers,” added Dr. Drane.

One of the biggest obstacles for health care workers navigating a pandemic is balancing work and home life, not to mention having time to unwind while working long hours. “Finding time for my family has been very limited. My kids feel really neglected,” said Dr. Gadalla. Some days, she gets up extra early to exercise to help clear her head, but other times she’s just too exhausted to even move.

Dr. Drane agreed that the work can get overwhelming. “We’re changing the way we practice almost every week, which can make you doubt yourself as an educator, as a practitioner. You constantly feel like you’re not sure what you’re doing, and people trust you to heal them,” she said. “Today is my first day off in 24 days. I only got it off because I said I needed a moment.”

Ms. Sheffer’s crazy days were at the beginning of the pandemic when she had to self-quarantine from her family and was working nonstop. “I would come home and sleep and work and wake up in the middle of the night and double check and triple check and go back to sleep and work, and that consumed me for several months,” she said.

The biggest challenge for Ms. Sheffer has been coping with public fear. “No matter how logical our medical approach has been, I think the constant feeling of the public threat of COVID has had this insidious effect on how patients approach their health,” she said. “We’re spending a lot more time shaping our approach to best address their fears first and not to politicize COVID so we can actually deal with the health issue at hand.”
 

Complications of COVID

With all the restrictions, caring for patients these days has meant learning to interact with them in different ways that aren’t as personal, Ms. McGrath said. It has been difficult to lose “that humanity of medicine, the usual ways that you interact with your patients that are going through a vulnerable time,” she noted.

Additionally, students in the medical field are being held back from graduation because they cannot participate in direct patient care. This is particularly problematic for PAs and medical students who must touch patients to graduate, Dr. Gadalla said. “All of this is slowing down future providers. We’re going to have trouble catching up. Who’s going to relieve us? That’s a huge problem and no one is finding solutions for that yet,” she said.

At the University of Chicago, Ms. McGrath explained, they created virtual rotations so that PA students could continue to do them at the university. Not only has the experience reminded Ms. McGrath how much she loves being a medical educator and fighting for the education of PA students, but she was surprised to find that her patients came to appreciate the time they spent with her students on the virtual platform as well.

“It’s isolating for patients to be in the hospital in a vulnerable state and with no support system,” she said. “I think being a part of [the PA students’] education gave some meaning to their hospitalization and highlighted that collaboration and connection is a human need.”

Despite everything, there’s a noticeable emphasis on the flowering buds of hope, unity, compassion, and pride that have been quietly blooming from the daily hardships. As Ms. Cardin puts it, “It’s so cliché to say that there’s a crisis. The other word is ‘opportunity,’ and it’s true, there are opportunities here.”
 

Taking care of each other

Creating resources for providers has been a priority at the University of Chicago, according to Ms. McGrath. “As hospitalists, we’re used to taking care of a variety of patients, but our section leadership and providers on the front lines quickly realized that COVID patients are more akin to trauma patients with their quick changes in health, as well as their isolation, fear, and unexpected deterioration,” she said. Her facility has implemented wellness initiatives to help prevent burnout and mental health problems in COVID providers so they can continue to give the best care to their patients.

Both Ms. Sheffer and Dr. Drane say that they have a peer network of APPs at Sound Physicians to call on for questions and support. And it’s encouraging to know you’re not alone and to keep tabs on how colleagues in other states are doing, Ms. Sheffer noted.

“The peer support system has been helpful,” Dr. Drane said. “This job, right now, takes pieces of you every day. Sometimes it’s so emotional that you can’t put it into words. You just have to cry and get it out so that you can go be with your family.”
 

Getting back to basics

The changes in patient care have turned into something Ms. McGrath said she appreciates. “This pandemic has really stripped away the extra fluff of medicine and brought us back to the reason why many of us have gotten into the field, because it became about the patients again,” she says. “You quickly learn your strengths and weaknesses as a provider and as a leader, and that flows into the decisions you’re making for your team and for your patients.”

Ms. Sheffer acknowledged that it is difficult to deal with patients’ family members who don’t understand that they can’t visit their sick relatives, but she said the flip side is that frontline workers become surrogate family members, an outcome she considers to be an honor.

“You step into the emotion with the family or with the patient because you’re all they have. That is a beautiful, honorable role, but it’s also tremendously emotional and sometimes devastating,” she said. “But to me, it’s one of the most beautiful things I’ve been able to offer in a time where we don’t even know what to do with COVID.”

Limited resources mixed with a healthy dose of fear can stifle creativity, Dr. Drane said. Right away, she noticed that despite the abundance of incentive spirometers at her hospital, they were not being utilized. She came in 2 hours early for 3 days to pass one out to every patient under investigation or COVID-positive patient and enlisted the help of her chief nursing officer, CEO, and regional medical director to get everyone on board.

Dr. Drane’s out-of-the-box thinking has enabled people to go home without oxygen 2 days earlier and cut the hospital’s length of stay by 5%. “It’s something so small, but it has such a great end reward,” she said. “I’m proud of this project because it didn’t take money; it was getting creative with what we already have.”
 

Renewed pride and passion

Dr. Drane is intensely proud of being an NP and working on the front lines. She sees that the pandemic has encouraged her and other APPs to expand their horizons.

“For me, it’s made me work to get dual certified,” she said. “APPs can be all-inclusive. I feel like I’m doing what I was meant to do and it’s not just a job anymore.”

Ms. McGrath is even more passionate about being a hospitalist now, as she has realized how valuable their unique skill sets are. “I think other people have also been able to realize that our ability to see the patient as a whole has allowed us to take care of this pandemic, because this disease impacts all organ systems and has a trickle-down effect that we as hospitalists are well versed to manage,” she said.

Ms. Cardin’s work involves communicating with APPs all around the country. Recently she had a phone exchange with an APP who needed to vent.

“She was weeping, and I thought she was going to say, ‘I can’t do this anymore, I need to go home,’ ” said Ms. Cardin. “Instead, she said, ‘I just want to make a difference in one of these people’s lives.’ And that is who the advanced practice providers are. They’re willing to go into those COVID units. They’re willing to be in the front lines. They are dedicated. They’re just intensely inspirational to me.”

Throughout the chaos of the COVID-19 pandemic, advanced practice providers (APPs) – physician assistants (PAs) and nurse practitioners (NPs) – have become an integral component of the hospitalist response. As many physicians began shifting into telemedicine and away from direct patient care, APPs have been eagerly jumping in to fill the gaps. Their work has been changing almost as dramatically and quickly as the pandemic itself, bringing with it expected challenges but bestowing hugely satisfying, often unanticipated, rewards.

APPs on the rise

As the coronavirus pandemic evolves, the role of APPs is evolving right alongside it. With the current relaxation of hospital bylaw restrictions on APPs, their utilization has increased, said Tracy Cardin, ACNP-BC, SFHM, a nurse practitioner and vice president of advanced practice providers at Sound Physicians. “We have not really furloughed any advanced practice providers,” Ms. Cardin said. “In fact, I consider them to be, within hospital medicine, a key lever to finding more cost-effective care delivery models.”

Ms. Cardin said APPs have been working more independently since COVID-19 started, seeing patients on their own and using physician consultation and backup via telemedicine or telephone as needed. With the reduction in elective surgeries and patient volumes at many hospitals, APP-led care also saves money. Because one of the biggest costs is labor, Ms. Cardin said, offering this high-quality care delivery model using APPs in collaboration with physician providers helps defray some of that cost. “We’re hoping that advanced practice providers are really a solution to some of these financial pressures in a lot of different ways,” she said.

“COVID … forced us to expedite conversations about how to maximize caseloads using APPs,” said Alicia Sheffer, AGAC-AGPC NP, a nurse practitioner and Great Lakes regional director of advanced practice providers at Sound Physicians in Cincinnati. Some of those staffing model changes have included using APPs while transitioning ICUs and med-surg units to COVID cohort units, APP-led COVID cohorts, and APP-led ICUs.

“At first the hospital system had ideas about bringing in telemedicine as an alternative to seeing patients, rather than just putting APPs on the front lines and having them go in and see patients,” said Jessica Drane, APRN, PhD, DNP FNP-C, a nurse practitioner and regional director of advanced practice provider services and hospital medicine at Sound Physicians in San Antonio. In Texas at the beginning of the pandemic, hospital numbers were so low that Dr. Drane did not work at all in April. “We were all afraid we were going to lose our jobs,” she said. Then the state got slammed and APPs have been desperately needed.

Ilaria Gadalla, DMSc, PA-C, a PA at Treasure Coast Hospitalists in Port St. Lucie, Fla., and the PA program director at South University, West Palm Beach, Fla., noted that many of her APP colleagues have pivoted fluidly from other specialties to the hospitalist realm as the need for frontline workers has increased. “Hospitalists have shined through this and their value has been recognized even more than previously as a result of COVID-19,” Dr. Gadalla said.

“I don’t think it’s any surprise that hospitalists became a pillar of the COVID pandemic,” said Bridget McGrath, PA-C, a physician assistant and director of the NP/PAs service line for the section of hospital medicine at the University of Chicago. “There are just some innate traits that hospitalists have, such as the ability to be flexible, to problem solve, and to be the solution to the problem.”
 

Building team camaraderie

Ms. Cardin says that the need for APPs has led to an evolving integration between physicians and APPs. The growing teamwork and bonding between colleagues have been some of the most rewarding aspects of the pandemic for Dr. Gadalla. “We rely even more on each other and there isn’t really a line of, ‘I’m a physician versus an NP or PA or nurse.’ We’re all working together with the same goal,” she said.

Ms. McGrath said she has been learning what it means to lead a team during a challenging time. It has been gratifying for her to watch mentors get down to the bare bones of patient care and see everyone unify, putting aside roles and titles and coming together to care for their patients in innovative ways.

“This pandemic has really opened up a lot of doors for us because up until now, we were used almost like scribes for physicians,” Dr. Drane said. She has seen even the most resistant hospital systems beginning to rely on APPs as the pandemic has progressed. “They have become pleasantly surprised at what an APP can do.”
 

Work challenges

Obviously, challenges abound. Dr. Gadalla listed hers as visiting restrictions that invariably lead to slower patient visits thanks to obligatory phone calls, constantly fluctuating patient censuses, sporadic elective surgeries, watching colleagues become furloughed, and trying to balance external perceptions with what’s actually happening in the hospital.

Overall, though, “There have been a lot more rewards than barriers,” added Dr. Drane.

One of the biggest obstacles for health care workers navigating a pandemic is balancing work and home life, not to mention having time to unwind while working long hours. “Finding time for my family has been very limited. My kids feel really neglected,” said Dr. Gadalla. Some days, she gets up extra early to exercise to help clear her head, but other times she’s just too exhausted to even move.

Dr. Drane agreed that the work can get overwhelming. “We’re changing the way we practice almost every week, which can make you doubt yourself as an educator, as a practitioner. You constantly feel like you’re not sure what you’re doing, and people trust you to heal them,” she said. “Today is my first day off in 24 days. I only got it off because I said I needed a moment.”

Ms. Sheffer’s crazy days were at the beginning of the pandemic when she had to self-quarantine from her family and was working nonstop. “I would come home and sleep and work and wake up in the middle of the night and double check and triple check and go back to sleep and work, and that consumed me for several months,” she said.

The biggest challenge for Ms. Sheffer has been coping with public fear. “No matter how logical our medical approach has been, I think the constant feeling of the public threat of COVID has had this insidious effect on how patients approach their health,” she said. “We’re spending a lot more time shaping our approach to best address their fears first and not to politicize COVID so we can actually deal with the health issue at hand.”
 

Complications of COVID

With all the restrictions, caring for patients these days has meant learning to interact with them in different ways that aren’t as personal, Ms. McGrath said. It has been difficult to lose “that humanity of medicine, the usual ways that you interact with your patients that are going through a vulnerable time,” she noted.

Additionally, students in the medical field are being held back from graduation because they cannot participate in direct patient care. This is particularly problematic for PAs and medical students who must touch patients to graduate, Dr. Gadalla said. “All of this is slowing down future providers. We’re going to have trouble catching up. Who’s going to relieve us? That’s a huge problem and no one is finding solutions for that yet,” she said.

At the University of Chicago, Ms. McGrath explained, they created virtual rotations so that PA students could continue to do them at the university. Not only has the experience reminded Ms. McGrath how much she loves being a medical educator and fighting for the education of PA students, but she was surprised to find that her patients came to appreciate the time they spent with her students on the virtual platform as well.

“It’s isolating for patients to be in the hospital in a vulnerable state and with no support system,” she said. “I think being a part of [the PA students’] education gave some meaning to their hospitalization and highlighted that collaboration and connection is a human need.”

Despite everything, there’s a noticeable emphasis on the flowering buds of hope, unity, compassion, and pride that have been quietly blooming from the daily hardships. As Ms. Cardin puts it, “It’s so cliché to say that there’s a crisis. The other word is ‘opportunity,’ and it’s true, there are opportunities here.”
 

Taking care of each other

Creating resources for providers has been a priority at the University of Chicago, according to Ms. McGrath. “As hospitalists, we’re used to taking care of a variety of patients, but our section leadership and providers on the front lines quickly realized that COVID patients are more akin to trauma patients with their quick changes in health, as well as their isolation, fear, and unexpected deterioration,” she said. Her facility has implemented wellness initiatives to help prevent burnout and mental health problems in COVID providers so they can continue to give the best care to their patients.

Both Ms. Sheffer and Dr. Drane say that they have a peer network of APPs at Sound Physicians to call on for questions and support. And it’s encouraging to know you’re not alone and to keep tabs on how colleagues in other states are doing, Ms. Sheffer noted.

“The peer support system has been helpful,” Dr. Drane said. “This job, right now, takes pieces of you every day. Sometimes it’s so emotional that you can’t put it into words. You just have to cry and get it out so that you can go be with your family.”
 

Getting back to basics

The changes in patient care have turned into something Ms. McGrath said she appreciates. “This pandemic has really stripped away the extra fluff of medicine and brought us back to the reason why many of us have gotten into the field, because it became about the patients again,” she says. “You quickly learn your strengths and weaknesses as a provider and as a leader, and that flows into the decisions you’re making for your team and for your patients.”

Ms. Sheffer acknowledged that it is difficult to deal with patients’ family members who don’t understand that they can’t visit their sick relatives, but she said the flip side is that frontline workers become surrogate family members, an outcome she considers to be an honor.

“You step into the emotion with the family or with the patient because you’re all they have. That is a beautiful, honorable role, but it’s also tremendously emotional and sometimes devastating,” she said. “But to me, it’s one of the most beautiful things I’ve been able to offer in a time where we don’t even know what to do with COVID.”

Limited resources mixed with a healthy dose of fear can stifle creativity, Dr. Drane said. Right away, she noticed that despite the abundance of incentive spirometers at her hospital, they were not being utilized. She came in 2 hours early for 3 days to pass one out to every patient under investigation or COVID-positive patient and enlisted the help of her chief nursing officer, CEO, and regional medical director to get everyone on board.

Dr. Drane’s out-of-the-box thinking has enabled people to go home without oxygen 2 days earlier and cut the hospital’s length of stay by 5%. “It’s something so small, but it has such a great end reward,” she said. “I’m proud of this project because it didn’t take money; it was getting creative with what we already have.”
 

Renewed pride and passion

Dr. Drane is intensely proud of being an NP and working on the front lines. She sees that the pandemic has encouraged her and other APPs to expand their horizons.

“For me, it’s made me work to get dual certified,” she said. “APPs can be all-inclusive. I feel like I’m doing what I was meant to do and it’s not just a job anymore.”

Ms. McGrath is even more passionate about being a hospitalist now, as she has realized how valuable their unique skill sets are. “I think other people have also been able to realize that our ability to see the patient as a whole has allowed us to take care of this pandemic, because this disease impacts all organ systems and has a trickle-down effect that we as hospitalists are well versed to manage,” she said.

Ms. Cardin’s work involves communicating with APPs all around the country. Recently she had a phone exchange with an APP who needed to vent.

“She was weeping, and I thought she was going to say, ‘I can’t do this anymore, I need to go home,’ ” said Ms. Cardin. “Instead, she said, ‘I just want to make a difference in one of these people’s lives.’ And that is who the advanced practice providers are. They’re willing to go into those COVID units. They’re willing to be in the front lines. They are dedicated. They’re just intensely inspirational to me.”

The incidence rate of hepatocellular carcinoma in urban areas of the United States began to slow in 2009, but the rate in rural areas of the nation continued to rise at a steady pace, especially among non-Hispanic Whites and Blacks, investigators have found.

Although overall hepatocellular carcinoma (HCC) incidence rates were consistently lower among people living in nonmetro (rural) versus metro (urban) areas, the average annual percentage change in urban areas began to slow from 5.3% for the period of 1995 through 2009 to 2.7% thereafter. In contrast, the average annual percentage change in rural areas remained steady at 5.7%, a disparity that remained even after adjusting for differences among subgroups, reported Christina Gainey, MD, a third-year resident in internal medicine at the University of Southern California Medical Center, Los Angeles.

“We found that there are striking urban-rural disparities in HCC incidence trends that vary by race and ethnicity, and these disparities are growing over time,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

“Our study really highlights a critical public health issue that’s disproportionately affecting rural Americans. They already face considerable health inequities when it comes to access to care, health outcomes, and public health infrastructure and resources, and as of now we still don’t know why cases of HCC continue to rise in these areas,” she said.

Dr. Gainey noted that HCC is the fastest-growing cancer in the United States, according to the 2020 Annual Report to the Nation on the Status of Cancer, issued jointly by the Centers for Disease Control and Prevention, the North American Association of Central Cancer Registries, the American Cancer Society, and the National Cancer Institute.

Previous studies have identified disparities between urban and rural regions in care of patients with cervical cancer, colorectal cancer, and other malignancies, but there are very few data on urban-rural differences in HCC incidence, she said.
 

Incidence trends

To better understand whether such differences exists, the investigators compared trends in age-adjusted incidence rates of HCC in both rural and urban areas of the United States from 1995 to 2016, with stratification of trends by race/ethnicity and other demographic factors.

They drew from the NAACR database, which captures 93% of the U.S. population, in contrast to the CDC’s Surveillance, Epidemiology, and End Results (SEER) database which samples just 18% of the population.

Patients with HCC were defined by diagnostic codes, with diagnoses of intrahepatic bile duct cancers excluded.

They used 2013 U.S. Department of Agriculture Rural-Urban Continuum Codes to identify rural areas (regions of open countryside with town populations fewer than 2,500 people) and urban areas (populations ranging from 2,500 to 49,999, but not part of a larger labor market area).

The investigators identified a total of 310,635 HCC cases, 85% in urban areas and 15% in rural areas. Three-fourths of the patients (77%) were male. The median age ranged from 55-59 years.

There were notable demographic differences between the regions with non-Hispanic Whites comprising only 57% of the urban sample, but 82% of the rural sample. The urban sample included 16% non-Hispanic Blacks, 10% Asian/Pacific Islanders, and 17% Hispanics. The respective proportions in the rural areas were 8%, 2%, and 8%.

As noted before, age-adjusted incidence rates (adjusted to the year 2000 U.S. population) were lower in rural areas, at 4.9 per 100,000 population, compared with 6.9/100,000 in urban areas.

But when they looked at the average annual percentage changes using jointpoint regression, they saw that beginning in 2009 the AAPC in urban areas began to slow, from 5.3% for the period prior to 2009 to 2.7% thereafter, while the average annual percentage change in urban areas remained steady at 5.7%.

The largest increase in incidence over the course of the study was among rural non-Hispanic Whites, with an AAPC of 5.7%. Among urban non-Hispanic Blacks, the AAPC rose by 6.6% from 1995 to 2009, but slowed thereafter.

In contrast, among rural non-Hispanic Blacks the AAPC remained steady, at 5.4%.

The only group to see a decline in incidence was urban Asians/Pacific Islanders, who had an overall decline of 1%.

Among all groups, rural Hispanics had the highest age-adjusted incidence rates, at 14.9 per 100,000 in 2016.
 

Awareness gap?

 Lewis R. Roberts, MB, ChB, PhD, a hepatobiliary cancer researcher at the Mayo Clinic in Rochester, Minn., who was not involved in the study, said in an interview that the difference in incidence rates between cities and the country may be attributable to a number of factors, including the opioid crisis, which can lead to an increase in injectable drug use or sexual behaviors resulting in increases in chronic hepatitis C infections and cirrhosis, known risk factors for HCC, as well as a lack of awareness of infections as a risk factor.

“In order for people to find these diseases, they have to be looking, and many of these are hidden diseases in our community,” he said. “What the study made me wonder was whether it just happens to be that they are in some ways more hidden in a rural community than they are in an urban community.”

He noted that clinicians in urban communities are more accustomed to treating more diverse populations who may have higher susceptibility to viral hepatitis, for example, and that screening and treatment for hepatitis C may be more common in urban areas than rural areas, he said.

No funding source for the study was reported. Dr. Gainey and Dr. Roberts reported having no conflicts of interest to disclose.

SOURCE: Gainey C et al. Liver Meeting 2020, Abstract 136.

The incidence rate of hepatocellular carcinoma in urban areas of the United States began to slow in 2009, but the rate in rural areas of the nation continued to rise at a steady pace, especially among non-Hispanic Whites and Blacks, investigators have found.

Although overall hepatocellular carcinoma (HCC) incidence rates were consistently lower among people living in nonmetro (rural) versus metro (urban) areas, the average annual percentage change in urban areas began to slow from 5.3% for the period of 1995 through 2009 to 2.7% thereafter. In contrast, the average annual percentage change in rural areas remained steady at 5.7%, a disparity that remained even after adjusting for differences among subgroups, reported Christina Gainey, MD, a third-year resident in internal medicine at the University of Southern California Medical Center, Los Angeles.

“We found that there are striking urban-rural disparities in HCC incidence trends that vary by race and ethnicity, and these disparities are growing over time,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

“Our study really highlights a critical public health issue that’s disproportionately affecting rural Americans. They already face considerable health inequities when it comes to access to care, health outcomes, and public health infrastructure and resources, and as of now we still don’t know why cases of HCC continue to rise in these areas,” she said.

Dr. Gainey noted that HCC is the fastest-growing cancer in the United States, according to the 2020 Annual Report to the Nation on the Status of Cancer, issued jointly by the Centers for Disease Control and Prevention, the North American Association of Central Cancer Registries, the American Cancer Society, and the National Cancer Institute.

Previous studies have identified disparities between urban and rural regions in care of patients with cervical cancer, colorectal cancer, and other malignancies, but there are very few data on urban-rural differences in HCC incidence, she said.
 

Incidence trends

To better understand whether such differences exists, the investigators compared trends in age-adjusted incidence rates of HCC in both rural and urban areas of the United States from 1995 to 2016, with stratification of trends by race/ethnicity and other demographic factors.

They drew from the NAACR database, which captures 93% of the U.S. population, in contrast to the CDC’s Surveillance, Epidemiology, and End Results (SEER) database which samples just 18% of the population.

Patients with HCC were defined by diagnostic codes, with diagnoses of intrahepatic bile duct cancers excluded.

They used 2013 U.S. Department of Agriculture Rural-Urban Continuum Codes to identify rural areas (regions of open countryside with town populations fewer than 2,500 people) and urban areas (populations ranging from 2,500 to 49,999, but not part of a larger labor market area).

The investigators identified a total of 310,635 HCC cases, 85% in urban areas and 15% in rural areas. Three-fourths of the patients (77%) were male. The median age ranged from 55-59 years.

There were notable demographic differences between the regions with non-Hispanic Whites comprising only 57% of the urban sample, but 82% of the rural sample. The urban sample included 16% non-Hispanic Blacks, 10% Asian/Pacific Islanders, and 17% Hispanics. The respective proportions in the rural areas were 8%, 2%, and 8%.

As noted before, age-adjusted incidence rates (adjusted to the year 2000 U.S. population) were lower in rural areas, at 4.9 per 100,000 population, compared with 6.9/100,000 in urban areas.

But when they looked at the average annual percentage changes using jointpoint regression, they saw that beginning in 2009 the AAPC in urban areas began to slow, from 5.3% for the period prior to 2009 to 2.7% thereafter, while the average annual percentage change in urban areas remained steady at 5.7%.

The largest increase in incidence over the course of the study was among rural non-Hispanic Whites, with an AAPC of 5.7%. Among urban non-Hispanic Blacks, the AAPC rose by 6.6% from 1995 to 2009, but slowed thereafter.

In contrast, among rural non-Hispanic Blacks the AAPC remained steady, at 5.4%.

The only group to see a decline in incidence was urban Asians/Pacific Islanders, who had an overall decline of 1%.

Among all groups, rural Hispanics had the highest age-adjusted incidence rates, at 14.9 per 100,000 in 2016.
 

Awareness gap?

 Lewis R. Roberts, MB, ChB, PhD, a hepatobiliary cancer researcher at the Mayo Clinic in Rochester, Minn., who was not involved in the study, said in an interview that the difference in incidence rates between cities and the country may be attributable to a number of factors, including the opioid crisis, which can lead to an increase in injectable drug use or sexual behaviors resulting in increases in chronic hepatitis C infections and cirrhosis, known risk factors for HCC, as well as a lack of awareness of infections as a risk factor.

“In order for people to find these diseases, they have to be looking, and many of these are hidden diseases in our community,” he said. “What the study made me wonder was whether it just happens to be that they are in some ways more hidden in a rural community than they are in an urban community.”

He noted that clinicians in urban communities are more accustomed to treating more diverse populations who may have higher susceptibility to viral hepatitis, for example, and that screening and treatment for hepatitis C may be more common in urban areas than rural areas, he said.

No funding source for the study was reported. Dr. Gainey and Dr. Roberts reported having no conflicts of interest to disclose.

SOURCE: Gainey C et al. Liver Meeting 2020, Abstract 136.

The incidence rate of hepatocellular carcinoma in urban areas of the United States began to slow in 2009, but the rate in rural areas of the nation continued to rise at a steady pace, especially among non-Hispanic Whites and Blacks, investigators have found.

Although overall hepatocellular carcinoma (HCC) incidence rates were consistently lower among people living in nonmetro (rural) versus metro (urban) areas, the average annual percentage change in urban areas began to slow from 5.3% for the period of 1995 through 2009 to 2.7% thereafter. In contrast, the average annual percentage change in rural areas remained steady at 5.7%, a disparity that remained even after adjusting for differences among subgroups, reported Christina Gainey, MD, a third-year resident in internal medicine at the University of Southern California Medical Center, Los Angeles.

“We found that there are striking urban-rural disparities in HCC incidence trends that vary by race and ethnicity, and these disparities are growing over time,” she said during the virtual annual meeting of the American Association for the Study of Liver Diseases.

“Our study really highlights a critical public health issue that’s disproportionately affecting rural Americans. They already face considerable health inequities when it comes to access to care, health outcomes, and public health infrastructure and resources, and as of now we still don’t know why cases of HCC continue to rise in these areas,” she said.

Dr. Gainey noted that HCC is the fastest-growing cancer in the United States, according to the 2020 Annual Report to the Nation on the Status of Cancer, issued jointly by the Centers for Disease Control and Prevention, the North American Association of Central Cancer Registries, the American Cancer Society, and the National Cancer Institute.

Previous studies have identified disparities between urban and rural regions in care of patients with cervical cancer, colorectal cancer, and other malignancies, but there are very few data on urban-rural differences in HCC incidence, she said.
 

Incidence trends

To better understand whether such differences exists, the investigators compared trends in age-adjusted incidence rates of HCC in both rural and urban areas of the United States from 1995 to 2016, with stratification of trends by race/ethnicity and other demographic factors.

They drew from the NAACR database, which captures 93% of the U.S. population, in contrast to the CDC’s Surveillance, Epidemiology, and End Results (SEER) database which samples just 18% of the population.

Patients with HCC were defined by diagnostic codes, with diagnoses of intrahepatic bile duct cancers excluded.

They used 2013 U.S. Department of Agriculture Rural-Urban Continuum Codes to identify rural areas (regions of open countryside with town populations fewer than 2,500 people) and urban areas (populations ranging from 2,500 to 49,999, but not part of a larger labor market area).

The investigators identified a total of 310,635 HCC cases, 85% in urban areas and 15% in rural areas. Three-fourths of the patients (77%) were male. The median age ranged from 55-59 years.

There were notable demographic differences between the regions with non-Hispanic Whites comprising only 57% of the urban sample, but 82% of the rural sample. The urban sample included 16% non-Hispanic Blacks, 10% Asian/Pacific Islanders, and 17% Hispanics. The respective proportions in the rural areas were 8%, 2%, and 8%.

As noted before, age-adjusted incidence rates (adjusted to the year 2000 U.S. population) were lower in rural areas, at 4.9 per 100,000 population, compared with 6.9/100,000 in urban areas.

But when they looked at the average annual percentage changes using jointpoint regression, they saw that beginning in 2009 the AAPC in urban areas began to slow, from 5.3% for the period prior to 2009 to 2.7% thereafter, while the average annual percentage change in urban areas remained steady at 5.7%.

The largest increase in incidence over the course of the study was among rural non-Hispanic Whites, with an AAPC of 5.7%. Among urban non-Hispanic Blacks, the AAPC rose by 6.6% from 1995 to 2009, but slowed thereafter.

In contrast, among rural non-Hispanic Blacks the AAPC remained steady, at 5.4%.

The only group to see a decline in incidence was urban Asians/Pacific Islanders, who had an overall decline of 1%.

Among all groups, rural Hispanics had the highest age-adjusted incidence rates, at 14.9 per 100,000 in 2016.
 

Awareness gap?

 Lewis R. Roberts, MB, ChB, PhD, a hepatobiliary cancer researcher at the Mayo Clinic in Rochester, Minn., who was not involved in the study, said in an interview that the difference in incidence rates between cities and the country may be attributable to a number of factors, including the opioid crisis, which can lead to an increase in injectable drug use or sexual behaviors resulting in increases in chronic hepatitis C infections and cirrhosis, known risk factors for HCC, as well as a lack of awareness of infections as a risk factor.

“In order for people to find these diseases, they have to be looking, and many of these are hidden diseases in our community,” he said. “What the study made me wonder was whether it just happens to be that they are in some ways more hidden in a rural community than they are in an urban community.”

He noted that clinicians in urban communities are more accustomed to treating more diverse populations who may have higher susceptibility to viral hepatitis, for example, and that screening and treatment for hepatitis C may be more common in urban areas than rural areas, he said.

No funding source for the study was reported. Dr. Gainey and Dr. Roberts reported having no conflicts of interest to disclose.

SOURCE: Gainey C et al. Liver Meeting 2020, Abstract 136.

Patients with hemophilia A or von Willebrand disease undergoing anterior cruciate ligament (ACL) reconstruction had rates of postoperative complications and ACL reinjuries that were not significantly different from those control patients. However, the cost of health care utilization was significantly greater for the hemophilia A and von Willebrand disease patients, according to a large retrospective database study published online in The Knee.

All patients who underwent an ACL reconstruction from 2010 to 2014 in a large commercial database were assessed. Patients with hemophilia A, hemophilia B, and von Willebrand disease were identified. Patient demographics, cost of surgery, blood product use, concomitant injuries, repeat ACL injury, complications, and various operative variables were collected.

A total of 33 patients with hemophilia A, 3 with hemophilia B patients, 63 with von Willebrand disease and 103,478 control patients who had ACL reconstruction were compared, according to Connor Zale, MD, and colleagues at Penn State Hershey (Pa.) Medical Center.
 

Similar outcomes, higher costs

Complications – including length of hospital stay, postoperative hemorrhage within 14 days after surgery, infection rates within 90 days of surgery, lysis of adhesions or manipulation under anesthesia within 90 days of surgery, concomitant injuries to the knee, additional ACL injury within 1 year of surgery, deep-vein thrombosis, and pulmonary embolism – were not statistically different between the hemophilia/von Willebrand cohorts and the control group, according to the researchers.

However, surgery and postoperative care were costlier in the hemophilia A and von Willebrand cohorts. Total health care utilization within 30 days of ACL reconstruction was significantly more expensive for patients with hemophilia A ($25,982) and those with von Willebrand disease ($16,445), compared with those among controls ($12,887). In addition, the total health care utilization costs within 90 days of ACL reconstruction were significantly higher for patients with hemophilia A ($30,310) and those with von Willebrand disease ($20,355), compared with those among controls ($14,564), with all P values less than .001.

None of the patients with hemophilia A or those with von Willebrand received blood products perioperatively, had a known major hemarthrosis, or were readmitted within 30 or 90 days, the authors noted, adding that this finding differs from previous studies. The authors speculated that, since no blood products were administered and there was no significant difference in postoperative hemorrhage, the patients with hemophilia A were preoperatively optimized for an acceptable prothrombin time and international normalized ratio and/or were more effectively managed postoperatively.

“Many surgeons may be fearful of performing an ACL reconstruction on those with hemophilia A, hemophilia B, and von Willebrand disease due to concerns over risk of a major hemarthrosis and other complications postoperatively. This study observed that hemophilia A and von Willebrand disease patients who underwent an ACL reconstruction had rates of postoperative complications that were not statistically different than those who underwent ACL reconstructions and did not have a known hypocoagulable condition,” the researchers concluded.

The authors reported that they had no potential conflicts of interest to disclose.

[email protected]

SOURCE: Zale C et al. Knee. 2020;27(6):1729-34.

Patients with hemophilia A or von Willebrand disease undergoing anterior cruciate ligament (ACL) reconstruction had rates of postoperative complications and ACL reinjuries that were not significantly different from those control patients. However, the cost of health care utilization was significantly greater for the hemophilia A and von Willebrand disease patients, according to a large retrospective database study published online in The Knee.

All patients who underwent an ACL reconstruction from 2010 to 2014 in a large commercial database were assessed. Patients with hemophilia A, hemophilia B, and von Willebrand disease were identified. Patient demographics, cost of surgery, blood product use, concomitant injuries, repeat ACL injury, complications, and various operative variables were collected.

A total of 33 patients with hemophilia A, 3 with hemophilia B patients, 63 with von Willebrand disease and 103,478 control patients who had ACL reconstruction were compared, according to Connor Zale, MD, and colleagues at Penn State Hershey (Pa.) Medical Center.
 

Similar outcomes, higher costs

Complications – including length of hospital stay, postoperative hemorrhage within 14 days after surgery, infection rates within 90 days of surgery, lysis of adhesions or manipulation under anesthesia within 90 days of surgery, concomitant injuries to the knee, additional ACL injury within 1 year of surgery, deep-vein thrombosis, and pulmonary embolism – were not statistically different between the hemophilia/von Willebrand cohorts and the control group, according to the researchers.

However, surgery and postoperative care were costlier in the hemophilia A and von Willebrand cohorts. Total health care utilization within 30 days of ACL reconstruction was significantly more expensive for patients with hemophilia A ($25,982) and those with von Willebrand disease ($16,445), compared with those among controls ($12,887). In addition, the total health care utilization costs within 90 days of ACL reconstruction were significantly higher for patients with hemophilia A ($30,310) and those with von Willebrand disease ($20,355), compared with those among controls ($14,564), with all P values less than .001.

None of the patients with hemophilia A or those with von Willebrand received blood products perioperatively, had a known major hemarthrosis, or were readmitted within 30 or 90 days, the authors noted, adding that this finding differs from previous studies. The authors speculated that, since no blood products were administered and there was no significant difference in postoperative hemorrhage, the patients with hemophilia A were preoperatively optimized for an acceptable prothrombin time and international normalized ratio and/or were more effectively managed postoperatively.

“Many surgeons may be fearful of performing an ACL reconstruction on those with hemophilia A, hemophilia B, and von Willebrand disease due to concerns over risk of a major hemarthrosis and other complications postoperatively. This study observed that hemophilia A and von Willebrand disease patients who underwent an ACL reconstruction had rates of postoperative complications that were not statistically different than those who underwent ACL reconstructions and did not have a known hypocoagulable condition,” the researchers concluded.

The authors reported that they had no potential conflicts of interest to disclose.

[email protected]

SOURCE: Zale C et al. Knee. 2020;27(6):1729-34.

Patients with hemophilia A or von Willebrand disease undergoing anterior cruciate ligament (ACL) reconstruction had rates of postoperative complications and ACL reinjuries that were not significantly different from those control patients. However, the cost of health care utilization was significantly greater for the hemophilia A and von Willebrand disease patients, according to a large retrospective database study published online in The Knee.

All patients who underwent an ACL reconstruction from 2010 to 2014 in a large commercial database were assessed. Patients with hemophilia A, hemophilia B, and von Willebrand disease were identified. Patient demographics, cost of surgery, blood product use, concomitant injuries, repeat ACL injury, complications, and various operative variables were collected.

A total of 33 patients with hemophilia A, 3 with hemophilia B patients, 63 with von Willebrand disease and 103,478 control patients who had ACL reconstruction were compared, according to Connor Zale, MD, and colleagues at Penn State Hershey (Pa.) Medical Center.
 

Similar outcomes, higher costs

Complications – including length of hospital stay, postoperative hemorrhage within 14 days after surgery, infection rates within 90 days of surgery, lysis of adhesions or manipulation under anesthesia within 90 days of surgery, concomitant injuries to the knee, additional ACL injury within 1 year of surgery, deep-vein thrombosis, and pulmonary embolism – were not statistically different between the hemophilia/von Willebrand cohorts and the control group, according to the researchers.

However, surgery and postoperative care were costlier in the hemophilia A and von Willebrand cohorts. Total health care utilization within 30 days of ACL reconstruction was significantly more expensive for patients with hemophilia A ($25,982) and those with von Willebrand disease ($16,445), compared with those among controls ($12,887). In addition, the total health care utilization costs within 90 days of ACL reconstruction were significantly higher for patients with hemophilia A ($30,310) and those with von Willebrand disease ($20,355), compared with those among controls ($14,564), with all P values less than .001.

None of the patients with hemophilia A or those with von Willebrand received blood products perioperatively, had a known major hemarthrosis, or were readmitted within 30 or 90 days, the authors noted, adding that this finding differs from previous studies. The authors speculated that, since no blood products were administered and there was no significant difference in postoperative hemorrhage, the patients with hemophilia A were preoperatively optimized for an acceptable prothrombin time and international normalized ratio and/or were more effectively managed postoperatively.

“Many surgeons may be fearful of performing an ACL reconstruction on those with hemophilia A, hemophilia B, and von Willebrand disease due to concerns over risk of a major hemarthrosis and other complications postoperatively. This study observed that hemophilia A and von Willebrand disease patients who underwent an ACL reconstruction had rates of postoperative complications that were not statistically different than those who underwent ACL reconstructions and did not have a known hypocoagulable condition,” the researchers concluded.

The authors reported that they had no potential conflicts of interest to disclose.

[email protected]

SOURCE: Zale C et al. Knee. 2020;27(6):1729-34.