CHEST Physician

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In this two-part supplement to CHEST Physician, Brett Bade, MD, (Yale School of Medicine) and Gerard A. Silvestri, MD, MS, FCCP (Medical University of South Carolina) discuss the role that pulmonologists play in lung cancer treatment as well as the clinical relevance of biomarkers.

The content in this supplement is based on proceedings from the Lung Cancer Summit hosted by the American College of Chest Physicians last July. The summit successfully fostered key relationships between clinicians, educators, scientists, advocacy groups, payers, and government entities. Attendees identified opportunities to align efforts toward moving forward a research agenda, supporting the faster-paced adoption of key innovations in care, and improving the accessibility of those innovations to all patient populations. These papers highlight the key clinical elements of the summit. Dr. Silvestri served as Chair of the Summit Steering Committee. 

The supplement includes:

Part 1: Biomarker Use for Pulmonologists: Pulmonary Nodule Management

• Factors that influence the evaluation and management of indeterminate solid nodules
• Summary of key guidelines
• Emergence of biomarkers in clinical trials
   

Part 2: Biomarker Use in Metastatic Non-Small Cell Lung Cancer: What the Pulmonologist Needs to Know

• Expansion of systemic lung cancer treatments in recent years
• Clinical trials demonstrating improved patient outcomes
• Biomarkers being used in targeted therapies

Click to Read

Click to Read

In this two-part supplement to CHEST Physician, Brett Bade, MD, (Yale School of Medicine) and Gerard A. Silvestri, MD, MS, FCCP (Medical University of South Carolina) discuss the role that pulmonologists play in lung cancer treatment as well as the clinical relevance of biomarkers.

The content in this supplement is based on proceedings from the Lung Cancer Summit hosted by the American College of Chest Physicians last July. The summit successfully fostered key relationships between clinicians, educators, scientists, advocacy groups, payers, and government entities. Attendees identified opportunities to align efforts toward moving forward a research agenda, supporting the faster-paced adoption of key innovations in care, and improving the accessibility of those innovations to all patient populations. These papers highlight the key clinical elements of the summit. Dr. Silvestri served as Chair of the Summit Steering Committee. 

The supplement includes:

Part 1: Biomarker Use for Pulmonologists: Pulmonary Nodule Management

• Factors that influence the evaluation and management of indeterminate solid nodules
• Summary of key guidelines
• Emergence of biomarkers in clinical trials
   

Part 2: Biomarker Use in Metastatic Non-Small Cell Lung Cancer: What the Pulmonologist Needs to Know

• Expansion of systemic lung cancer treatments in recent years
• Clinical trials demonstrating improved patient outcomes
• Biomarkers being used in targeted therapies

Click to Read

Click to Read

In this two-part supplement to CHEST Physician, Brett Bade, MD, (Yale School of Medicine) and Gerard A. Silvestri, MD, MS, FCCP (Medical University of South Carolina) discuss the role that pulmonologists play in lung cancer treatment as well as the clinical relevance of biomarkers.

The content in this supplement is based on proceedings from the Lung Cancer Summit hosted by the American College of Chest Physicians last July. The summit successfully fostered key relationships between clinicians, educators, scientists, advocacy groups, payers, and government entities. Attendees identified opportunities to align efforts toward moving forward a research agenda, supporting the faster-paced adoption of key innovations in care, and improving the accessibility of those innovations to all patient populations. These papers highlight the key clinical elements of the summit. Dr. Silvestri served as Chair of the Summit Steering Committee. 

The supplement includes:

Part 1: Biomarker Use for Pulmonologists: Pulmonary Nodule Management

• Factors that influence the evaluation and management of indeterminate solid nodules
• Summary of key guidelines
• Emergence of biomarkers in clinical trials
   

Part 2: Biomarker Use in Metastatic Non-Small Cell Lung Cancer: What the Pulmonologist Needs to Know

• Expansion of systemic lung cancer treatments in recent years
• Clinical trials demonstrating improved patient outcomes
• Biomarkers being used in targeted therapies

Click to Read

August was National Immunization Awareness Month. ... just in time to address the precipitous drop in immunization delivered during the early months of the pandemic.

FatCamera/Getty Images

In May, the Centers for Disease Control and Prevention reported substantial reductions in vaccine doses ordered through the Vaccines for Children program after the declaration of national emergency because of COVID-19 on March 13. Approximately 2.5 million fewer doses of routine, noninfluenza vaccines were administered between Jan. 6 and April 2020, compared with a similar period last year (MMWR Morb Mortal Wkly Rep. 2020 May 15;69[19]:591-3). Declines in immunization rates were echoed by states and municipalities across the United States. Last month, the health system in which I work reported 40,000 children behind on at least one vaccine.

We all know that, when immunization rates drop, outbreaks of vaccine-preventable diseases follow. In order to avert another public health crisis, we need action as well as awareness to catch up with childhood immunizations, and that is going to take more than a single month.
 

Identify patients who’ve missed vaccinations

Simply being open and ready to vaccinate is not enough. The Centers for Disease Control and Prevention urges providers to identify patients who have missed vaccines, and call them to schedule in-person visits. Proactively let parents know about strategies implemented in your office to ensure a safe environment.

Pediatricians are accustomed to an influx of patients in the summer, as parents make sure their children have all of the vaccines required for school attendance. As noted in a Washington Post article from Aug. 4, 2020, schools have traditionally served as a backstop for immunization rates. But as many school districts opt to take education online this fall, the implications for vaccine requirements are unclear. District of Columbia public schools continue to require immunization for virtual school attendance, but it is not clear how easily this can be enforced. To read about how other school districts have chosen to address – or not address – immunization requirements for school, visit the the Immunization Action Coalition’s Repository of Resources for Maintaining Immunization during the COVID-19 Pandemic. The repository links to international, national, and state-level policies and guidance and advocacy materials, including talking points, webinars, press releases, media articles from around the United States and social media posts, as well as telehealth resources.
 

Get some inspiration to talk about vaccination

Need a little inspiration for talking to parents about vaccines? Check out the CDC’s #HowIRecommend video series. These are short videos, most under a minute in length, that explain the importance of vaccination, how to effectively address questions from parents about vaccine safety, and how clinicians routinely recommend same day vaccination to their patients. These videos are part of the CDC’s National Immunization Awareness Month (NIAM) toolkit for communication with health care professionals. A companion toolkit for communicating with parents and patients contains sample social media messages with graphics, along with educational resources to share with parents.

The “Comprehensive Vaccine Education Program – From Training to Practice,” a free online program offered by the Pediatric Infectious Diseases Society, takes a deeper dive into strategies to combat vaccine misinformation and address vaccine hesitancy. Available modules cover vaccine fundamentals, vaccine safety, clinical manifestations of vaccine-preventable diseases, and communication skills that lead to more effective conversations with patients and parents. The curriculum also includes the newest edition of The Vaccine Handbook app, a comprehensive source of practical information for vaccine providers.
 

Educate young children about vaccines

Don’t leave young children out of the conversation. Vax-Force is a children’s book that explores how vaccination works inside the human body. Dr. Vaxson the pediatrician explains how trusted doctors and scientists made Vicky the Vaccine. Her mission is to tell Willy the White Blood Cell and his Antibuddies how to find and fight bad-guy germs like measles, tetanus, and polio. The book was written by Kelsey Rowe, MD, while she was a medical student at Saint Louis University School of Medicine. Dr. Rowe, now a pediatric resident, notes, “In a world where anti-vaccination rhetoric threatens the health of our global community, this book’s mission is to teach children and adults alike that getting vaccinations is a safe, effective, and even exciting thing to do.” The book is available for purchase at https://www.vax-force.com/, and a small part of every sale is donated to Unicef USA.
 

Consider vaccination advocacy in your communities

Vaccinate Your Family, a national, nonprofit organization dedicated to protecting people of all ages from vaccine-preventable diseases, suggests that health care providers need to take an active role in raising immunization rates, not just in their own practices, but in their communities. One way to do this is to submit an opinion piece or letter to the editor to a local newspaper describing why it’s important for parents to make sure their child’s immunizations are current. Those who have never written an opinion-editorial should look at the guidance developed by Voices for Vaccines.
 

How are we doing?

Early data suggest a rebound in immunization rates in May and June, but that is unlikely to close the gap created by disruptions in health care delivery earlier in the year. Collectively, we need to set ambitious goals. Are we just trying to reach prepandemic immunization levels? In Kentucky, where I practice, only 71% of kids aged 19-45 months had received all doses of seven routinely recommended vaccines (≥4 DTaP doses, ≥3 polio doses, ≥1 MMR dose, Hib full series, ≥3 HepB doses, ≥1 varicella dose, and ≥4 PCV doses) based on 2017 National Immunization Survey data. The Healthy People 2020 target goal is 80%. Only 55% of Kentucky girls aged 13-17 years received at least one dose of HPV vaccine, and rates in boys were even lower. Flu vaccine coverage in children 6 months to 17 years also was 55%. The status quo sets the bar too low. To see how your state is doing, check out the interactive map developed by the American Academy of Pediatrics.

Are we attempting to avoid disaster or can we seize the opportunity to protect more children than ever from vaccine-preventable diseases? The latter would really be something to celebrate.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].

August was National Immunization Awareness Month. ... just in time to address the precipitous drop in immunization delivered during the early months of the pandemic.

FatCamera/Getty Images

In May, the Centers for Disease Control and Prevention reported substantial reductions in vaccine doses ordered through the Vaccines for Children program after the declaration of national emergency because of COVID-19 on March 13. Approximately 2.5 million fewer doses of routine, noninfluenza vaccines were administered between Jan. 6 and April 2020, compared with a similar period last year (MMWR Morb Mortal Wkly Rep. 2020 May 15;69[19]:591-3). Declines in immunization rates were echoed by states and municipalities across the United States. Last month, the health system in which I work reported 40,000 children behind on at least one vaccine.

We all know that, when immunization rates drop, outbreaks of vaccine-preventable diseases follow. In order to avert another public health crisis, we need action as well as awareness to catch up with childhood immunizations, and that is going to take more than a single month.
 

Identify patients who’ve missed vaccinations

Simply being open and ready to vaccinate is not enough. The Centers for Disease Control and Prevention urges providers to identify patients who have missed vaccines, and call them to schedule in-person visits. Proactively let parents know about strategies implemented in your office to ensure a safe environment.

Pediatricians are accustomed to an influx of patients in the summer, as parents make sure their children have all of the vaccines required for school attendance. As noted in a Washington Post article from Aug. 4, 2020, schools have traditionally served as a backstop for immunization rates. But as many school districts opt to take education online this fall, the implications for vaccine requirements are unclear. District of Columbia public schools continue to require immunization for virtual school attendance, but it is not clear how easily this can be enforced. To read about how other school districts have chosen to address – or not address – immunization requirements for school, visit the the Immunization Action Coalition’s Repository of Resources for Maintaining Immunization during the COVID-19 Pandemic. The repository links to international, national, and state-level policies and guidance and advocacy materials, including talking points, webinars, press releases, media articles from around the United States and social media posts, as well as telehealth resources.
 

Get some inspiration to talk about vaccination

Need a little inspiration for talking to parents about vaccines? Check out the CDC’s #HowIRecommend video series. These are short videos, most under a minute in length, that explain the importance of vaccination, how to effectively address questions from parents about vaccine safety, and how clinicians routinely recommend same day vaccination to their patients. These videos are part of the CDC’s National Immunization Awareness Month (NIAM) toolkit for communication with health care professionals. A companion toolkit for communicating with parents and patients contains sample social media messages with graphics, along with educational resources to share with parents.

The “Comprehensive Vaccine Education Program – From Training to Practice,” a free online program offered by the Pediatric Infectious Diseases Society, takes a deeper dive into strategies to combat vaccine misinformation and address vaccine hesitancy. Available modules cover vaccine fundamentals, vaccine safety, clinical manifestations of vaccine-preventable diseases, and communication skills that lead to more effective conversations with patients and parents. The curriculum also includes the newest edition of The Vaccine Handbook app, a comprehensive source of practical information for vaccine providers.
 

Educate young children about vaccines

Don’t leave young children out of the conversation. Vax-Force is a children’s book that explores how vaccination works inside the human body. Dr. Vaxson the pediatrician explains how trusted doctors and scientists made Vicky the Vaccine. Her mission is to tell Willy the White Blood Cell and his Antibuddies how to find and fight bad-guy germs like measles, tetanus, and polio. The book was written by Kelsey Rowe, MD, while she was a medical student at Saint Louis University School of Medicine. Dr. Rowe, now a pediatric resident, notes, “In a world where anti-vaccination rhetoric threatens the health of our global community, this book’s mission is to teach children and adults alike that getting vaccinations is a safe, effective, and even exciting thing to do.” The book is available for purchase at https://www.vax-force.com/, and a small part of every sale is donated to Unicef USA.
 

Consider vaccination advocacy in your communities

Vaccinate Your Family, a national, nonprofit organization dedicated to protecting people of all ages from vaccine-preventable diseases, suggests that health care providers need to take an active role in raising immunization rates, not just in their own practices, but in their communities. One way to do this is to submit an opinion piece or letter to the editor to a local newspaper describing why it’s important for parents to make sure their child’s immunizations are current. Those who have never written an opinion-editorial should look at the guidance developed by Voices for Vaccines.
 

How are we doing?

Early data suggest a rebound in immunization rates in May and June, but that is unlikely to close the gap created by disruptions in health care delivery earlier in the year. Collectively, we need to set ambitious goals. Are we just trying to reach prepandemic immunization levels? In Kentucky, where I practice, only 71% of kids aged 19-45 months had received all doses of seven routinely recommended vaccines (≥4 DTaP doses, ≥3 polio doses, ≥1 MMR dose, Hib full series, ≥3 HepB doses, ≥1 varicella dose, and ≥4 PCV doses) based on 2017 National Immunization Survey data. The Healthy People 2020 target goal is 80%. Only 55% of Kentucky girls aged 13-17 years received at least one dose of HPV vaccine, and rates in boys were even lower. Flu vaccine coverage in children 6 months to 17 years also was 55%. The status quo sets the bar too low. To see how your state is doing, check out the interactive map developed by the American Academy of Pediatrics.

Are we attempting to avoid disaster or can we seize the opportunity to protect more children than ever from vaccine-preventable diseases? The latter would really be something to celebrate.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].

August was National Immunization Awareness Month. ... just in time to address the precipitous drop in immunization delivered during the early months of the pandemic.

FatCamera/Getty Images

In May, the Centers for Disease Control and Prevention reported substantial reductions in vaccine doses ordered through the Vaccines for Children program after the declaration of national emergency because of COVID-19 on March 13. Approximately 2.5 million fewer doses of routine, noninfluenza vaccines were administered between Jan. 6 and April 2020, compared with a similar period last year (MMWR Morb Mortal Wkly Rep. 2020 May 15;69[19]:591-3). Declines in immunization rates were echoed by states and municipalities across the United States. Last month, the health system in which I work reported 40,000 children behind on at least one vaccine.

We all know that, when immunization rates drop, outbreaks of vaccine-preventable diseases follow. In order to avert another public health crisis, we need action as well as awareness to catch up with childhood immunizations, and that is going to take more than a single month.
 

Identify patients who’ve missed vaccinations

Simply being open and ready to vaccinate is not enough. The Centers for Disease Control and Prevention urges providers to identify patients who have missed vaccines, and call them to schedule in-person visits. Proactively let parents know about strategies implemented in your office to ensure a safe environment.

Pediatricians are accustomed to an influx of patients in the summer, as parents make sure their children have all of the vaccines required for school attendance. As noted in a Washington Post article from Aug. 4, 2020, schools have traditionally served as a backstop for immunization rates. But as many school districts opt to take education online this fall, the implications for vaccine requirements are unclear. District of Columbia public schools continue to require immunization for virtual school attendance, but it is not clear how easily this can be enforced. To read about how other school districts have chosen to address – or not address – immunization requirements for school, visit the the Immunization Action Coalition’s Repository of Resources for Maintaining Immunization during the COVID-19 Pandemic. The repository links to international, national, and state-level policies and guidance and advocacy materials, including talking points, webinars, press releases, media articles from around the United States and social media posts, as well as telehealth resources.
 

Get some inspiration to talk about vaccination

Need a little inspiration for talking to parents about vaccines? Check out the CDC’s #HowIRecommend video series. These are short videos, most under a minute in length, that explain the importance of vaccination, how to effectively address questions from parents about vaccine safety, and how clinicians routinely recommend same day vaccination to their patients. These videos are part of the CDC’s National Immunization Awareness Month (NIAM) toolkit for communication with health care professionals. A companion toolkit for communicating with parents and patients contains sample social media messages with graphics, along with educational resources to share with parents.

The “Comprehensive Vaccine Education Program – From Training to Practice,” a free online program offered by the Pediatric Infectious Diseases Society, takes a deeper dive into strategies to combat vaccine misinformation and address vaccine hesitancy. Available modules cover vaccine fundamentals, vaccine safety, clinical manifestations of vaccine-preventable diseases, and communication skills that lead to more effective conversations with patients and parents. The curriculum also includes the newest edition of The Vaccine Handbook app, a comprehensive source of practical information for vaccine providers.
 

Educate young children about vaccines

Don’t leave young children out of the conversation. Vax-Force is a children’s book that explores how vaccination works inside the human body. Dr. Vaxson the pediatrician explains how trusted doctors and scientists made Vicky the Vaccine. Her mission is to tell Willy the White Blood Cell and his Antibuddies how to find and fight bad-guy germs like measles, tetanus, and polio. The book was written by Kelsey Rowe, MD, while she was a medical student at Saint Louis University School of Medicine. Dr. Rowe, now a pediatric resident, notes, “In a world where anti-vaccination rhetoric threatens the health of our global community, this book’s mission is to teach children and adults alike that getting vaccinations is a safe, effective, and even exciting thing to do.” The book is available for purchase at https://www.vax-force.com/, and a small part of every sale is donated to Unicef USA.
 

Consider vaccination advocacy in your communities

Vaccinate Your Family, a national, nonprofit organization dedicated to protecting people of all ages from vaccine-preventable diseases, suggests that health care providers need to take an active role in raising immunization rates, not just in their own practices, but in their communities. One way to do this is to submit an opinion piece or letter to the editor to a local newspaper describing why it’s important for parents to make sure their child’s immunizations are current. Those who have never written an opinion-editorial should look at the guidance developed by Voices for Vaccines.
 

How are we doing?

Early data suggest a rebound in immunization rates in May and June, but that is unlikely to close the gap created by disruptions in health care delivery earlier in the year. Collectively, we need to set ambitious goals. Are we just trying to reach prepandemic immunization levels? In Kentucky, where I practice, only 71% of kids aged 19-45 months had received all doses of seven routinely recommended vaccines (≥4 DTaP doses, ≥3 polio doses, ≥1 MMR dose, Hib full series, ≥3 HepB doses, ≥1 varicella dose, and ≥4 PCV doses) based on 2017 National Immunization Survey data. The Healthy People 2020 target goal is 80%. Only 55% of Kentucky girls aged 13-17 years received at least one dose of HPV vaccine, and rates in boys were even lower. Flu vaccine coverage in children 6 months to 17 years also was 55%. The status quo sets the bar too low. To see how your state is doing, check out the interactive map developed by the American Academy of Pediatrics.

Are we attempting to avoid disaster or can we seize the opportunity to protect more children than ever from vaccine-preventable diseases? The latter would really be something to celebrate.
 

Dr. Bryant is a pediatrician specializing in infectious diseases at the University of Louisville (Ky.) and Norton Children’s Hospital, also in Louisville. She said she had no relevant financial disclosures. Email her at [email protected].

Many COVID-19 treatments, in addition to the infection, may be associated with adverse skin reactions and should be considered in a differential diagnosis, according to a review published in the Journal of the American Academy of Dermatology.

SARS-CoV-2 infection has been associated with a range of skin conditions, wrote Antonio Martinez-Lopez, MD, of Virgen de las Nieves University Hospital, Granada, Spain, and colleagues, who provided an overview of the cutaneous side effects associated with drugs used to treat COVID-19 infection.

“Cutaneous manifestations have recently been described in patients with the new coronavirus infection, similar to cutaneous involvement occurring in common viral infections,” they said. Infected individuals have experienced maculopapular eruption, pseudo-chilblain lesions, urticaria, monomorphic disseminated vesicular lesions, acral vesicular-pustulous lesions, and livedo or necrosis, they noted.

Diagnosing skin manifestations in patients with COVID-19 remains a challenge, because it is unclear whether the skin lesions are related to the virus, the authors said. “Skin diseases not related to coronavirus, other seasonal viral infections, and drug reactions should be considered in the differential diagnosis, especially in those patients suffering from nonspecific manifestations such as urticaria or maculopapular eruptions,” they wrote.

However, “urticarial lesions and maculopapular eruptions in SARS-CoV-2 infections usually appear at the same time as the systemic symptoms, while drug adverse reactions are likely to arise hours to days after the start of the treatment,” they said.

The reviewers noted several cutaneous side effects associated with several of the often-prescribed drugs for COVID-19 infection. The antimalarials hydroxychloroquine and chloroquine had been authorized for COVID-19 treatment by the Food and Drug Administration, but this emergency authorization was rescinded in June. They noted that up to 11.5% of patients on these drugs may experience cutaneous adverse effects, including some that “can be mistaken for skin manifestations of SARS-CoV-2, especially those with maculopapular rash or exanthematous reactions.” Another side effect is exacerbation of psoriasis, which has been described in patients with COVID-19, the authors said.

The oral antiretroviral combination lopinavir/ritonavir, under investigation in clinical trials for COVID-19, has been associated with skin rashes in as many as 5% of adults in HIV studies. Usually appearing after treatment is started, the maculopapular pruritic rash is “usually well tolerated,” they said, although there have been reports of Stevens-Johnson syndrome. Alopecia areata is among the other side effects reported.

Remdesivir also has been authorized for emergency treatment of COVID-19, and the small amount of data available suggest that cutaneous manifestations may be infrequent, the reviewers said. In a recent study of 53 patients treated with remdesivir for 10 days, approximately 8% developed a rash, but the study did not include any information “about rash morphology, distribution, or timeline in relation to remdesivir that may help clinicians differentiate from cutaneous manifestations of COVID-19,” they said.

Other potential treatments for complications of COVID-19 include imatinib, tocilizumab, anakinra, immunoglobulins, corticosteroids, colchicine, and low molecular weight heparins; all have the potential for association with skin reactions, but data on skin manifestations associated with COVID-19 are limited, the authors wrote.

Notably, data on the use of systemic corticosteroids for COVID-19 patients are controversial, although preliminary data showed some reduced mortality in COVID-19 patients who were on respiratory support, they noted. “With regard to differential diagnosis of cutaneous manifestations of COVID-19, the vascular fragility associated with corticosteroid use, especially in elderly patients, may be similar to the thrombotic complications of COVID-19 infection.”

Knowledge about the virology of COVID-19 continues to evolve rapidly, and the number of drugs being studied as treatments continues to expand, the authors pointed out.

“By considering adverse drug reactions in the differential diagnosis, dermatologists can be useful in assisting in the care of these patients,” they wrote. Drugs, rather than the infection, may be the cause of skin reactions in some COVID-19 patients, and “management is often symptomatic, but it is sometimes necessary to modify or discontinue the treatment, and some conditions can even be life-threatening,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Martinez-Lopez A et al. J Am Acad Dermatol. 2020 doi: 10.1016/j.jaad.2020.08.006.

Many COVID-19 treatments, in addition to the infection, may be associated with adverse skin reactions and should be considered in a differential diagnosis, according to a review published in the Journal of the American Academy of Dermatology.

SARS-CoV-2 infection has been associated with a range of skin conditions, wrote Antonio Martinez-Lopez, MD, of Virgen de las Nieves University Hospital, Granada, Spain, and colleagues, who provided an overview of the cutaneous side effects associated with drugs used to treat COVID-19 infection.

“Cutaneous manifestations have recently been described in patients with the new coronavirus infection, similar to cutaneous involvement occurring in common viral infections,” they said. Infected individuals have experienced maculopapular eruption, pseudo-chilblain lesions, urticaria, monomorphic disseminated vesicular lesions, acral vesicular-pustulous lesions, and livedo or necrosis, they noted.

Diagnosing skin manifestations in patients with COVID-19 remains a challenge, because it is unclear whether the skin lesions are related to the virus, the authors said. “Skin diseases not related to coronavirus, other seasonal viral infections, and drug reactions should be considered in the differential diagnosis, especially in those patients suffering from nonspecific manifestations such as urticaria or maculopapular eruptions,” they wrote.

However, “urticarial lesions and maculopapular eruptions in SARS-CoV-2 infections usually appear at the same time as the systemic symptoms, while drug adverse reactions are likely to arise hours to days after the start of the treatment,” they said.

The reviewers noted several cutaneous side effects associated with several of the often-prescribed drugs for COVID-19 infection. The antimalarials hydroxychloroquine and chloroquine had been authorized for COVID-19 treatment by the Food and Drug Administration, but this emergency authorization was rescinded in June. They noted that up to 11.5% of patients on these drugs may experience cutaneous adverse effects, including some that “can be mistaken for skin manifestations of SARS-CoV-2, especially those with maculopapular rash or exanthematous reactions.” Another side effect is exacerbation of psoriasis, which has been described in patients with COVID-19, the authors said.

The oral antiretroviral combination lopinavir/ritonavir, under investigation in clinical trials for COVID-19, has been associated with skin rashes in as many as 5% of adults in HIV studies. Usually appearing after treatment is started, the maculopapular pruritic rash is “usually well tolerated,” they said, although there have been reports of Stevens-Johnson syndrome. Alopecia areata is among the other side effects reported.

Remdesivir also has been authorized for emergency treatment of COVID-19, and the small amount of data available suggest that cutaneous manifestations may be infrequent, the reviewers said. In a recent study of 53 patients treated with remdesivir for 10 days, approximately 8% developed a rash, but the study did not include any information “about rash morphology, distribution, or timeline in relation to remdesivir that may help clinicians differentiate from cutaneous manifestations of COVID-19,” they said.

Other potential treatments for complications of COVID-19 include imatinib, tocilizumab, anakinra, immunoglobulins, corticosteroids, colchicine, and low molecular weight heparins; all have the potential for association with skin reactions, but data on skin manifestations associated with COVID-19 are limited, the authors wrote.

Notably, data on the use of systemic corticosteroids for COVID-19 patients are controversial, although preliminary data showed some reduced mortality in COVID-19 patients who were on respiratory support, they noted. “With regard to differential diagnosis of cutaneous manifestations of COVID-19, the vascular fragility associated with corticosteroid use, especially in elderly patients, may be similar to the thrombotic complications of COVID-19 infection.”

Knowledge about the virology of COVID-19 continues to evolve rapidly, and the number of drugs being studied as treatments continues to expand, the authors pointed out.

“By considering adverse drug reactions in the differential diagnosis, dermatologists can be useful in assisting in the care of these patients,” they wrote. Drugs, rather than the infection, may be the cause of skin reactions in some COVID-19 patients, and “management is often symptomatic, but it is sometimes necessary to modify or discontinue the treatment, and some conditions can even be life-threatening,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Martinez-Lopez A et al. J Am Acad Dermatol. 2020 doi: 10.1016/j.jaad.2020.08.006.

Many COVID-19 treatments, in addition to the infection, may be associated with adverse skin reactions and should be considered in a differential diagnosis, according to a review published in the Journal of the American Academy of Dermatology.

SARS-CoV-2 infection has been associated with a range of skin conditions, wrote Antonio Martinez-Lopez, MD, of Virgen de las Nieves University Hospital, Granada, Spain, and colleagues, who provided an overview of the cutaneous side effects associated with drugs used to treat COVID-19 infection.

“Cutaneous manifestations have recently been described in patients with the new coronavirus infection, similar to cutaneous involvement occurring in common viral infections,” they said. Infected individuals have experienced maculopapular eruption, pseudo-chilblain lesions, urticaria, monomorphic disseminated vesicular lesions, acral vesicular-pustulous lesions, and livedo or necrosis, they noted.

Diagnosing skin manifestations in patients with COVID-19 remains a challenge, because it is unclear whether the skin lesions are related to the virus, the authors said. “Skin diseases not related to coronavirus, other seasonal viral infections, and drug reactions should be considered in the differential diagnosis, especially in those patients suffering from nonspecific manifestations such as urticaria or maculopapular eruptions,” they wrote.

However, “urticarial lesions and maculopapular eruptions in SARS-CoV-2 infections usually appear at the same time as the systemic symptoms, while drug adverse reactions are likely to arise hours to days after the start of the treatment,” they said.

The reviewers noted several cutaneous side effects associated with several of the often-prescribed drugs for COVID-19 infection. The antimalarials hydroxychloroquine and chloroquine had been authorized for COVID-19 treatment by the Food and Drug Administration, but this emergency authorization was rescinded in June. They noted that up to 11.5% of patients on these drugs may experience cutaneous adverse effects, including some that “can be mistaken for skin manifestations of SARS-CoV-2, especially those with maculopapular rash or exanthematous reactions.” Another side effect is exacerbation of psoriasis, which has been described in patients with COVID-19, the authors said.

The oral antiretroviral combination lopinavir/ritonavir, under investigation in clinical trials for COVID-19, has been associated with skin rashes in as many as 5% of adults in HIV studies. Usually appearing after treatment is started, the maculopapular pruritic rash is “usually well tolerated,” they said, although there have been reports of Stevens-Johnson syndrome. Alopecia areata is among the other side effects reported.

Remdesivir also has been authorized for emergency treatment of COVID-19, and the small amount of data available suggest that cutaneous manifestations may be infrequent, the reviewers said. In a recent study of 53 patients treated with remdesivir for 10 days, approximately 8% developed a rash, but the study did not include any information “about rash morphology, distribution, or timeline in relation to remdesivir that may help clinicians differentiate from cutaneous manifestations of COVID-19,” they said.

Other potential treatments for complications of COVID-19 include imatinib, tocilizumab, anakinra, immunoglobulins, corticosteroids, colchicine, and low molecular weight heparins; all have the potential for association with skin reactions, but data on skin manifestations associated with COVID-19 are limited, the authors wrote.

Notably, data on the use of systemic corticosteroids for COVID-19 patients are controversial, although preliminary data showed some reduced mortality in COVID-19 patients who were on respiratory support, they noted. “With regard to differential diagnosis of cutaneous manifestations of COVID-19, the vascular fragility associated with corticosteroid use, especially in elderly patients, may be similar to the thrombotic complications of COVID-19 infection.”

Knowledge about the virology of COVID-19 continues to evolve rapidly, and the number of drugs being studied as treatments continues to expand, the authors pointed out.

“By considering adverse drug reactions in the differential diagnosis, dermatologists can be useful in assisting in the care of these patients,” they wrote. Drugs, rather than the infection, may be the cause of skin reactions in some COVID-19 patients, and “management is often symptomatic, but it is sometimes necessary to modify or discontinue the treatment, and some conditions can even be life-threatening,” they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

SOURCE: Martinez-Lopez A et al. J Am Acad Dermatol. 2020 doi: 10.1016/j.jaad.2020.08.006.

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

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

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

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

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

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

Differences in mortality, patients, treatment

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

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

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

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

More than fear of COVID-19?

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

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

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

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

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

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

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

The investigators reported having no financial conflicts of interest.

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

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

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

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

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

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

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

Differences in mortality, patients, treatment

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

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

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

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

More than fear of COVID-19?

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

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

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

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

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

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

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

The investigators reported having no financial conflicts of interest.

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

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

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

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

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

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

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

Differences in mortality, patients, treatment

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

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

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

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

More than fear of COVID-19?

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

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

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

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

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

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

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

The investigators reported having no financial conflicts of interest.

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

Mortality from non–small cell lung cancer (NSCLC) has fallen sharply in the United States over the past few years, and survival following its diagnosis has dramatically improved, the first analysis of its kind indicates.

“This analysis shows for the first time that nationwide mortality rates for the most common category of lung cancer, NSCLC, are declining faster than its incidence, an advance that correlates with the [FDA] approval of several targeted therapies for this cancer in recent years,” coauthor Douglas Lowy, MD, deputy director, National Cancer Institute, Bethesda, Md., said in a statement.

“Major improvements have been made in NSCLC treatment with the advent of targeted therapies and immunotherapies,” lead author Nadia Howlander, PhD, National Cancer Institute, and colleagues observed.

“The survival benefit for patients with NSCLC treated with targeted therapy has been shown in clinical trials, but our study highlights their possible effect at the population level,” they added.

In contrast, mortality from SCLC has dropped only in tandem with a decline in the incidence of SCLC, and survival has remained largely unchanged, the same analysis showed.

NSCLC is by far the most common type of lung cancer, accounting for more than 75% of all lung cancer cases in the United States. SCLC accounts for about 13%.

The study was published online Aug. 12 in the New England Journal of Medicine.

“Although overall mortality from lung cancer has been declining in the United States, little is known about mortality trends according to cancer subtype at the population level because death certificates do not record subtype information,” the authors commented.

“To address this data limitation, the U.S. Surveillance, Epidemiology and End Results (SEER) program has linked mortality records to incidence cancer cases,” the authors explained. This allowed them to calculate incidence-based mortality among men and women in the United States.

The incidence-based mortality method that the researchers used was applied to the SEER data to describe population-level mortality trends in the United States that were attributable to each subtype of lung cancer as well as gender from 2001 to 2016.

Among men, the incidence of NSCLC decreased gradually by 1.9% a year from 2001 to 2008, then more dramatically by 3.1% a year from 2008 to 2016.

Corresponding incidence-based mortality rates among men dropped by 3.2% a year from 2006 to 2013, then again more dramatically by 6.3% a year from 2013 to 2016.

“The 2-year relative survival among patients with lung cancer improved substantially from 26% among men with NSCLC diagnosed in 2001 to 35% among those with NSCLC diagnosed in 2014,” the researchers added.

Among women, the incidence of NSCLC remained unchanged between 2001 and 2006, after which it began to drop by 1.5% a year from 2006 to 2016.

“In contrast, incidence-based mortality decreased slowly [among women] by 2.3% annually ... from 2006 through 2014 and then at a faster rate of 5.9% annually ... from 2014 through 2016,” the authors noted.

The 2-year relative survival rate for patients with NSCLC was higher among women than among men, improving from 35% in 2001 to 44% in 2014.

Improvements in survival were also observed for all races and ethnicities, despite concerns that new cancer treatments might increase treatment disparities between races, because they are all so expensive, the authors commented.

Mortality from SCLC declined by 4.3% a year among men, but that decline was entirely due to a similar decrease in the incidence of SCLC. Survival at 2 years for patients with this subtype of lung cancer remained largely unchanged over the same interval.

Genetic testing

The accelerating decline in NSCLC mortality starting in 2013 corresponds to the period in which clinicians began to routinely test for molecular alterations in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), the authors pointed out.

In 2012, the National Comprehensive Cancer Network recommended that all patients with nonsquamous NSCLC undergo genetic testing for EGFR mutations and ALK rearrangements.

At about the same time, the FDA approved a number of targeted therapies for tumors that are sensitive to targeted tyrosine kinase inhibition.

More recently, immunotherapies that act as programmed cell death inhibitors have substantially improved NSCLC outcomes, the authors noted.

The first of these was approved for NSCLC in 2015 (pembrolizumab). It was followed by a number of similar agents. It is unlikely that their approval contributed to the observed decline in NSCLC mortality, which started to accelerate in 2013 in the United States, the authors commented.

Nevertheless, the effect that the immune checkpoint inhibitors has had on the survival of patients with NSCLC can be expected to continue and to extend improvement in survival beyond the current study endpoint in 2016, they suggest.

Another contributing factor is the decline in smoking that has occurred in the United States since the 1960s. This has led to the decrease in the incidence of lung cancer. The faster decrease in the incidence of SCLC, compared with NSCLC can be explained by the higher relative risk of smoking with regard to SCLC compared to NSCLC, they commented.

Similarly, the faster decrease in lung cancer incidence in men compared to women can be explained by the relative difference in the prevalence of smoking between men and women, they added.

The authors disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Mortality from non–small cell lung cancer (NSCLC) has fallen sharply in the United States over the past few years, and survival following its diagnosis has dramatically improved, the first analysis of its kind indicates.

“This analysis shows for the first time that nationwide mortality rates for the most common category of lung cancer, NSCLC, are declining faster than its incidence, an advance that correlates with the [FDA] approval of several targeted therapies for this cancer in recent years,” coauthor Douglas Lowy, MD, deputy director, National Cancer Institute, Bethesda, Md., said in a statement.

“Major improvements have been made in NSCLC treatment with the advent of targeted therapies and immunotherapies,” lead author Nadia Howlander, PhD, National Cancer Institute, and colleagues observed.

“The survival benefit for patients with NSCLC treated with targeted therapy has been shown in clinical trials, but our study highlights their possible effect at the population level,” they added.

In contrast, mortality from SCLC has dropped only in tandem with a decline in the incidence of SCLC, and survival has remained largely unchanged, the same analysis showed.

NSCLC is by far the most common type of lung cancer, accounting for more than 75% of all lung cancer cases in the United States. SCLC accounts for about 13%.

The study was published online Aug. 12 in the New England Journal of Medicine.

“Although overall mortality from lung cancer has been declining in the United States, little is known about mortality trends according to cancer subtype at the population level because death certificates do not record subtype information,” the authors commented.

“To address this data limitation, the U.S. Surveillance, Epidemiology and End Results (SEER) program has linked mortality records to incidence cancer cases,” the authors explained. This allowed them to calculate incidence-based mortality among men and women in the United States.

The incidence-based mortality method that the researchers used was applied to the SEER data to describe population-level mortality trends in the United States that were attributable to each subtype of lung cancer as well as gender from 2001 to 2016.

Among men, the incidence of NSCLC decreased gradually by 1.9% a year from 2001 to 2008, then more dramatically by 3.1% a year from 2008 to 2016.

Corresponding incidence-based mortality rates among men dropped by 3.2% a year from 2006 to 2013, then again more dramatically by 6.3% a year from 2013 to 2016.

“The 2-year relative survival among patients with lung cancer improved substantially from 26% among men with NSCLC diagnosed in 2001 to 35% among those with NSCLC diagnosed in 2014,” the researchers added.

Among women, the incidence of NSCLC remained unchanged between 2001 and 2006, after which it began to drop by 1.5% a year from 2006 to 2016.

“In contrast, incidence-based mortality decreased slowly [among women] by 2.3% annually ... from 2006 through 2014 and then at a faster rate of 5.9% annually ... from 2014 through 2016,” the authors noted.

The 2-year relative survival rate for patients with NSCLC was higher among women than among men, improving from 35% in 2001 to 44% in 2014.

Improvements in survival were also observed for all races and ethnicities, despite concerns that new cancer treatments might increase treatment disparities between races, because they are all so expensive, the authors commented.

Mortality from SCLC declined by 4.3% a year among men, but that decline was entirely due to a similar decrease in the incidence of SCLC. Survival at 2 years for patients with this subtype of lung cancer remained largely unchanged over the same interval.

Genetic testing

The accelerating decline in NSCLC mortality starting in 2013 corresponds to the period in which clinicians began to routinely test for molecular alterations in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), the authors pointed out.

In 2012, the National Comprehensive Cancer Network recommended that all patients with nonsquamous NSCLC undergo genetic testing for EGFR mutations and ALK rearrangements.

At about the same time, the FDA approved a number of targeted therapies for tumors that are sensitive to targeted tyrosine kinase inhibition.

More recently, immunotherapies that act as programmed cell death inhibitors have substantially improved NSCLC outcomes, the authors noted.

The first of these was approved for NSCLC in 2015 (pembrolizumab). It was followed by a number of similar agents. It is unlikely that their approval contributed to the observed decline in NSCLC mortality, which started to accelerate in 2013 in the United States, the authors commented.

Nevertheless, the effect that the immune checkpoint inhibitors has had on the survival of patients with NSCLC can be expected to continue and to extend improvement in survival beyond the current study endpoint in 2016, they suggest.

Another contributing factor is the decline in smoking that has occurred in the United States since the 1960s. This has led to the decrease in the incidence of lung cancer. The faster decrease in the incidence of SCLC, compared with NSCLC can be explained by the higher relative risk of smoking with regard to SCLC compared to NSCLC, they commented.

Similarly, the faster decrease in lung cancer incidence in men compared to women can be explained by the relative difference in the prevalence of smoking between men and women, they added.

The authors disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Mortality from non–small cell lung cancer (NSCLC) has fallen sharply in the United States over the past few years, and survival following its diagnosis has dramatically improved, the first analysis of its kind indicates.

“This analysis shows for the first time that nationwide mortality rates for the most common category of lung cancer, NSCLC, are declining faster than its incidence, an advance that correlates with the [FDA] approval of several targeted therapies for this cancer in recent years,” coauthor Douglas Lowy, MD, deputy director, National Cancer Institute, Bethesda, Md., said in a statement.

“Major improvements have been made in NSCLC treatment with the advent of targeted therapies and immunotherapies,” lead author Nadia Howlander, PhD, National Cancer Institute, and colleagues observed.

“The survival benefit for patients with NSCLC treated with targeted therapy has been shown in clinical trials, but our study highlights their possible effect at the population level,” they added.

In contrast, mortality from SCLC has dropped only in tandem with a decline in the incidence of SCLC, and survival has remained largely unchanged, the same analysis showed.

NSCLC is by far the most common type of lung cancer, accounting for more than 75% of all lung cancer cases in the United States. SCLC accounts for about 13%.

The study was published online Aug. 12 in the New England Journal of Medicine.

“Although overall mortality from lung cancer has been declining in the United States, little is known about mortality trends according to cancer subtype at the population level because death certificates do not record subtype information,” the authors commented.

“To address this data limitation, the U.S. Surveillance, Epidemiology and End Results (SEER) program has linked mortality records to incidence cancer cases,” the authors explained. This allowed them to calculate incidence-based mortality among men and women in the United States.

The incidence-based mortality method that the researchers used was applied to the SEER data to describe population-level mortality trends in the United States that were attributable to each subtype of lung cancer as well as gender from 2001 to 2016.

Among men, the incidence of NSCLC decreased gradually by 1.9% a year from 2001 to 2008, then more dramatically by 3.1% a year from 2008 to 2016.

Corresponding incidence-based mortality rates among men dropped by 3.2% a year from 2006 to 2013, then again more dramatically by 6.3% a year from 2013 to 2016.

“The 2-year relative survival among patients with lung cancer improved substantially from 26% among men with NSCLC diagnosed in 2001 to 35% among those with NSCLC diagnosed in 2014,” the researchers added.

Among women, the incidence of NSCLC remained unchanged between 2001 and 2006, after which it began to drop by 1.5% a year from 2006 to 2016.

“In contrast, incidence-based mortality decreased slowly [among women] by 2.3% annually ... from 2006 through 2014 and then at a faster rate of 5.9% annually ... from 2014 through 2016,” the authors noted.

The 2-year relative survival rate for patients with NSCLC was higher among women than among men, improving from 35% in 2001 to 44% in 2014.

Improvements in survival were also observed for all races and ethnicities, despite concerns that new cancer treatments might increase treatment disparities between races, because they are all so expensive, the authors commented.

Mortality from SCLC declined by 4.3% a year among men, but that decline was entirely due to a similar decrease in the incidence of SCLC. Survival at 2 years for patients with this subtype of lung cancer remained largely unchanged over the same interval.

Genetic testing

The accelerating decline in NSCLC mortality starting in 2013 corresponds to the period in which clinicians began to routinely test for molecular alterations in epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), the authors pointed out.

In 2012, the National Comprehensive Cancer Network recommended that all patients with nonsquamous NSCLC undergo genetic testing for EGFR mutations and ALK rearrangements.

At about the same time, the FDA approved a number of targeted therapies for tumors that are sensitive to targeted tyrosine kinase inhibition.

More recently, immunotherapies that act as programmed cell death inhibitors have substantially improved NSCLC outcomes, the authors noted.

The first of these was approved for NSCLC in 2015 (pembrolizumab). It was followed by a number of similar agents. It is unlikely that their approval contributed to the observed decline in NSCLC mortality, which started to accelerate in 2013 in the United States, the authors commented.

Nevertheless, the effect that the immune checkpoint inhibitors has had on the survival of patients with NSCLC can be expected to continue and to extend improvement in survival beyond the current study endpoint in 2016, they suggest.

Another contributing factor is the decline in smoking that has occurred in the United States since the 1960s. This has led to the decrease in the incidence of lung cancer. The faster decrease in the incidence of SCLC, compared with NSCLC can be explained by the higher relative risk of smoking with regard to SCLC compared to NSCLC, they commented.

Similarly, the faster decrease in lung cancer incidence in men compared to women can be explained by the relative difference in the prevalence of smoking between men and women, they added.

The authors disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

If people try telemedicine, they’ll like telemedicine. And if they want to avoid a doctor’s office, as most people do these days, they’ll try telemedicine. That is the message coming from 1,000 people surveyed for DocASAP, a provider of online patient access and engagement systems.

Here are a couple of numbers: 92% of those who made a telemedicine visit said they were satisfied with the overall appointment experience, and 91% said that they are more likely to schedule a telemedicine visit instead of an in-person appointment. All of the survey respondents had visited a health care provider in the past year, and 40% already had made a telemedicine visit, DocASAP reported.

“Telehealth has quickly emerged as the preferred care setting during the pandemic and will drive patient behavior in the future,” Puneet Maheshwari, DocASAP cofounder and CEO, said in a statement. “As providers continue to adopt innovative technology to power a more seamless, end-to-end digital consumer experience, I expect telehealth to become fully integrated into overall care management.”

For now, though, COVID-19 is an overriding concern and health care facilities are suspect. When respondents were asked to identify the types of public facilities where they felt safe, hospitals were named by 32%, doctors’ offices by 26%, and ED/urgent care by just 12%, the DocASAP report said. Even public transportation got 13%.

The safest place to be, according to 42% of the respondents? The grocery store.

Of those surveyed, 43% “indicated they will not feel safe entering any health care setting until at least the fall,” the company said. An even higher share of patients, 68%, canceled or postponed an in-person appointment during the pandemic.

“No longer are remote health services viewed as ‘nice to have’ – they are now a must-have care delivery option,” DocASAP said in their report.

Safety concerns involving COVID-19, named by 47% of the sample, were the leading factor that would influence patients’ decision to schedule a telemedicine visit. Insurance coverage was next at 43%, followed by “ease of accessing quality care” at 40%, the report said.

Among those who had made a telemedicine visit, scheduling the appointment was the most satisfying aspect of the experience, according to 54% of respondents, with day-of-appointment wait time next at 38% and quality of the video/audio technology tied with preappointment communication at almost 33%, the survey data show.

Conversely, scheduling the appointment also was declared the most frustrating aspect of the telemedicine experience, although the total in that category was a much lower 29%.

“The pandemic has thrust profound change on every aspect of life, particularly health care. … Innovations – like digital and telehealth solutions – designed to meet patient needs will likely become embedded into the health care delivery system,” DocASAP said.

The survey was commissioned by DocASAP and conducted by marketing research company OnePoll on June 29-30, 2020.
 

[email protected]

If people try telemedicine, they’ll like telemedicine. And if they want to avoid a doctor’s office, as most people do these days, they’ll try telemedicine. That is the message coming from 1,000 people surveyed for DocASAP, a provider of online patient access and engagement systems.

Here are a couple of numbers: 92% of those who made a telemedicine visit said they were satisfied with the overall appointment experience, and 91% said that they are more likely to schedule a telemedicine visit instead of an in-person appointment. All of the survey respondents had visited a health care provider in the past year, and 40% already had made a telemedicine visit, DocASAP reported.

“Telehealth has quickly emerged as the preferred care setting during the pandemic and will drive patient behavior in the future,” Puneet Maheshwari, DocASAP cofounder and CEO, said in a statement. “As providers continue to adopt innovative technology to power a more seamless, end-to-end digital consumer experience, I expect telehealth to become fully integrated into overall care management.”

For now, though, COVID-19 is an overriding concern and health care facilities are suspect. When respondents were asked to identify the types of public facilities where they felt safe, hospitals were named by 32%, doctors’ offices by 26%, and ED/urgent care by just 12%, the DocASAP report said. Even public transportation got 13%.

The safest place to be, according to 42% of the respondents? The grocery store.

Of those surveyed, 43% “indicated they will not feel safe entering any health care setting until at least the fall,” the company said. An even higher share of patients, 68%, canceled or postponed an in-person appointment during the pandemic.

“No longer are remote health services viewed as ‘nice to have’ – they are now a must-have care delivery option,” DocASAP said in their report.

Safety concerns involving COVID-19, named by 47% of the sample, were the leading factor that would influence patients’ decision to schedule a telemedicine visit. Insurance coverage was next at 43%, followed by “ease of accessing quality care” at 40%, the report said.

Among those who had made a telemedicine visit, scheduling the appointment was the most satisfying aspect of the experience, according to 54% of respondents, with day-of-appointment wait time next at 38% and quality of the video/audio technology tied with preappointment communication at almost 33%, the survey data show.

Conversely, scheduling the appointment also was declared the most frustrating aspect of the telemedicine experience, although the total in that category was a much lower 29%.

“The pandemic has thrust profound change on every aspect of life, particularly health care. … Innovations – like digital and telehealth solutions – designed to meet patient needs will likely become embedded into the health care delivery system,” DocASAP said.

The survey was commissioned by DocASAP and conducted by marketing research company OnePoll on June 29-30, 2020.
 

[email protected]

If people try telemedicine, they’ll like telemedicine. And if they want to avoid a doctor’s office, as most people do these days, they’ll try telemedicine. That is the message coming from 1,000 people surveyed for DocASAP, a provider of online patient access and engagement systems.

Here are a couple of numbers: 92% of those who made a telemedicine visit said they were satisfied with the overall appointment experience, and 91% said that they are more likely to schedule a telemedicine visit instead of an in-person appointment. All of the survey respondents had visited a health care provider in the past year, and 40% already had made a telemedicine visit, DocASAP reported.

“Telehealth has quickly emerged as the preferred care setting during the pandemic and will drive patient behavior in the future,” Puneet Maheshwari, DocASAP cofounder and CEO, said in a statement. “As providers continue to adopt innovative technology to power a more seamless, end-to-end digital consumer experience, I expect telehealth to become fully integrated into overall care management.”

For now, though, COVID-19 is an overriding concern and health care facilities are suspect. When respondents were asked to identify the types of public facilities where they felt safe, hospitals were named by 32%, doctors’ offices by 26%, and ED/urgent care by just 12%, the DocASAP report said. Even public transportation got 13%.

The safest place to be, according to 42% of the respondents? The grocery store.

Of those surveyed, 43% “indicated they will not feel safe entering any health care setting until at least the fall,” the company said. An even higher share of patients, 68%, canceled or postponed an in-person appointment during the pandemic.

“No longer are remote health services viewed as ‘nice to have’ – they are now a must-have care delivery option,” DocASAP said in their report.

Safety concerns involving COVID-19, named by 47% of the sample, were the leading factor that would influence patients’ decision to schedule a telemedicine visit. Insurance coverage was next at 43%, followed by “ease of accessing quality care” at 40%, the report said.

Among those who had made a telemedicine visit, scheduling the appointment was the most satisfying aspect of the experience, according to 54% of respondents, with day-of-appointment wait time next at 38% and quality of the video/audio technology tied with preappointment communication at almost 33%, the survey data show.

Conversely, scheduling the appointment also was declared the most frustrating aspect of the telemedicine experience, although the total in that category was a much lower 29%.

“The pandemic has thrust profound change on every aspect of life, particularly health care. … Innovations – like digital and telehealth solutions – designed to meet patient needs will likely become embedded into the health care delivery system,” DocASAP said.

The survey was commissioned by DocASAP and conducted by marketing research company OnePoll on June 29-30, 2020.
 

[email protected]

As hospitalists and other physicians at the University of Texas at Austin considered how to treat COVID-19 patients in the early weeks of the pandemic, one question they had to consider was: What about convalescent plasma?

All they had to go on were small case series in Ebola, SARS, and MERS and a few small, nonrandomized COVID-19 studies showing a possible benefit and minimal risk, but the evidence was only “toward the middle or bottom” of the evidence pyramid, said Johanna Busch, MD, of the department of internal medicine at Dell Medical Center at the university.

The center’s COVID-19 committee asked a few of its members – infectious disease and internal medicine physicians – to analyze the literature and other factors. In the end, the committee – which meets regularly and also includes pulmonology–critical care experts, nursing experts, and others – recommended using convalescent plasma because of the evidence and the available supply. But in subsequent meetings, as the pandemic surged in the South and the supply dwindled, the committee changed its recommendation for convalescent plasma to more limited use, she said during the virtual annual meeting of the Society of Hospital Medicine.

Dell’s experience with the therapy is one example of how the center had to quickly develop protocols for managing a pandemic with essentially no solid evidence for treatment and a system that had never been challenged before to the same degree.

“It’s all about teamwork,” said W. Michael Brode, MD, of the department of internal medicine at Dell. “The interprofessional team members know their roles and have shared expectations because they have a common understanding of the protocol.” It’s okay to deviate from the protocol, he said, as long as the language exists to communicate these deviations.

“Maybe the approach is more important than the actual content,” he said.

What Dr. Brode and Dr. Busch described was in large part a fine-tuning of communication – being available to communicate in real time and being aware of when certain specialists should be contacted – for instance, to determine at what oxygenation level internal medicine staff should get in touch with the pulmonary–critical care team.

Dr. Brode said that the groundwork is laid for productive meetings, with agendas announced ahead of time and readings assigned and presenters ready with near-finished products at meeting time, “with a clear path for operationalizing it.”

“We don’t want people kind of riffing off the top of their heads,” he said.

Committee members are encouraged to be as specific as possible when giving input into COVID-19 care decisions, he said.

“We’re so used to dealing with uncertainty, but that doesn’t really help when we’re trying to make tough decisions,” Dr. Brode said. They might be asked, “What are you going to write in your consult note template?” or “It’s 1:00 a.m. and your intern’s panicked and calling you – what are you going to tell them to do over the phone?”

The recommendations have to go into writing and are incorporated into the electronic medical record, a process that required some workarounds, he said. He also noted that the committee learned early on that they should assume that no one reads the e-mails – especially after being off for a period of time – so they likely won’t digest updates on an email-by-email basis.

“We quickly learned,” Dr. Brode said, “that this information needs to live on a Web site or [be] linked to the most up-to-date version in a cloud-sharing platform.”

In a question-and-answer discussion, session viewers expressed enthusiasm for the presenters’ one-page summary of protocols – much more, they said, and it could feel overwhelming.

Dr. Busch and Dr. Brode were asked how standardized order sets for COVID patients could be justified without comparison to a control group that didn’t use the standard order set.

Dr. Busch responded that, while there was no controlled trial, the order sets they use have evolved based on experience.

“At the beginning, we were following every inflammatory marker known to mankind, and then we realized as we gained more experience with COVID and COVID patients that some of those markers were not really informing any of our clinical decisions,” she said. “Obviously, as literature comes out we may reevaluate what goes into that standard order set and how frequently we follow labs.”

Dr. Brode said the context – a pandemic – has to be considered.

“In an ideal world, we could show that the intervention is superior through a randomized fashion with a control group, but really our thought process behind it is just, what is the default?” he said. “I looked at the order sets [as] not that they’re going to be dictating care, but it’s really like the guardrails of what’s reasonable. And when you’re in the middle of a surge, what is usually reasonable and easiest is what is going to be done.”

Dr. Busch and Dr. Brode reported no relevant financial relationships.

As hospitalists and other physicians at the University of Texas at Austin considered how to treat COVID-19 patients in the early weeks of the pandemic, one question they had to consider was: What about convalescent plasma?

All they had to go on were small case series in Ebola, SARS, and MERS and a few small, nonrandomized COVID-19 studies showing a possible benefit and minimal risk, but the evidence was only “toward the middle or bottom” of the evidence pyramid, said Johanna Busch, MD, of the department of internal medicine at Dell Medical Center at the university.

The center’s COVID-19 committee asked a few of its members – infectious disease and internal medicine physicians – to analyze the literature and other factors. In the end, the committee – which meets regularly and also includes pulmonology–critical care experts, nursing experts, and others – recommended using convalescent plasma because of the evidence and the available supply. But in subsequent meetings, as the pandemic surged in the South and the supply dwindled, the committee changed its recommendation for convalescent plasma to more limited use, she said during the virtual annual meeting of the Society of Hospital Medicine.

Dell’s experience with the therapy is one example of how the center had to quickly develop protocols for managing a pandemic with essentially no solid evidence for treatment and a system that had never been challenged before to the same degree.

“It’s all about teamwork,” said W. Michael Brode, MD, of the department of internal medicine at Dell. “The interprofessional team members know their roles and have shared expectations because they have a common understanding of the protocol.” It’s okay to deviate from the protocol, he said, as long as the language exists to communicate these deviations.

“Maybe the approach is more important than the actual content,” he said.

What Dr. Brode and Dr. Busch described was in large part a fine-tuning of communication – being available to communicate in real time and being aware of when certain specialists should be contacted – for instance, to determine at what oxygenation level internal medicine staff should get in touch with the pulmonary–critical care team.

Dr. Brode said that the groundwork is laid for productive meetings, with agendas announced ahead of time and readings assigned and presenters ready with near-finished products at meeting time, “with a clear path for operationalizing it.”

“We don’t want people kind of riffing off the top of their heads,” he said.

Committee members are encouraged to be as specific as possible when giving input into COVID-19 care decisions, he said.

“We’re so used to dealing with uncertainty, but that doesn’t really help when we’re trying to make tough decisions,” Dr. Brode said. They might be asked, “What are you going to write in your consult note template?” or “It’s 1:00 a.m. and your intern’s panicked and calling you – what are you going to tell them to do over the phone?”

The recommendations have to go into writing and are incorporated into the electronic medical record, a process that required some workarounds, he said. He also noted that the committee learned early on that they should assume that no one reads the e-mails – especially after being off for a period of time – so they likely won’t digest updates on an email-by-email basis.

“We quickly learned,” Dr. Brode said, “that this information needs to live on a Web site or [be] linked to the most up-to-date version in a cloud-sharing platform.”

In a question-and-answer discussion, session viewers expressed enthusiasm for the presenters’ one-page summary of protocols – much more, they said, and it could feel overwhelming.

Dr. Busch and Dr. Brode were asked how standardized order sets for COVID patients could be justified without comparison to a control group that didn’t use the standard order set.

Dr. Busch responded that, while there was no controlled trial, the order sets they use have evolved based on experience.

“At the beginning, we were following every inflammatory marker known to mankind, and then we realized as we gained more experience with COVID and COVID patients that some of those markers were not really informing any of our clinical decisions,” she said. “Obviously, as literature comes out we may reevaluate what goes into that standard order set and how frequently we follow labs.”

Dr. Brode said the context – a pandemic – has to be considered.

“In an ideal world, we could show that the intervention is superior through a randomized fashion with a control group, but really our thought process behind it is just, what is the default?” he said. “I looked at the order sets [as] not that they’re going to be dictating care, but it’s really like the guardrails of what’s reasonable. And when you’re in the middle of a surge, what is usually reasonable and easiest is what is going to be done.”

Dr. Busch and Dr. Brode reported no relevant financial relationships.

As hospitalists and other physicians at the University of Texas at Austin considered how to treat COVID-19 patients in the early weeks of the pandemic, one question they had to consider was: What about convalescent plasma?

All they had to go on were small case series in Ebola, SARS, and MERS and a few small, nonrandomized COVID-19 studies showing a possible benefit and minimal risk, but the evidence was only “toward the middle or bottom” of the evidence pyramid, said Johanna Busch, MD, of the department of internal medicine at Dell Medical Center at the university.

The center’s COVID-19 committee asked a few of its members – infectious disease and internal medicine physicians – to analyze the literature and other factors. In the end, the committee – which meets regularly and also includes pulmonology–critical care experts, nursing experts, and others – recommended using convalescent plasma because of the evidence and the available supply. But in subsequent meetings, as the pandemic surged in the South and the supply dwindled, the committee changed its recommendation for convalescent plasma to more limited use, she said during the virtual annual meeting of the Society of Hospital Medicine.

Dell’s experience with the therapy is one example of how the center had to quickly develop protocols for managing a pandemic with essentially no solid evidence for treatment and a system that had never been challenged before to the same degree.

“It’s all about teamwork,” said W. Michael Brode, MD, of the department of internal medicine at Dell. “The interprofessional team members know their roles and have shared expectations because they have a common understanding of the protocol.” It’s okay to deviate from the protocol, he said, as long as the language exists to communicate these deviations.

“Maybe the approach is more important than the actual content,” he said.

What Dr. Brode and Dr. Busch described was in large part a fine-tuning of communication – being available to communicate in real time and being aware of when certain specialists should be contacted – for instance, to determine at what oxygenation level internal medicine staff should get in touch with the pulmonary–critical care team.

Dr. Brode said that the groundwork is laid for productive meetings, with agendas announced ahead of time and readings assigned and presenters ready with near-finished products at meeting time, “with a clear path for operationalizing it.”

“We don’t want people kind of riffing off the top of their heads,” he said.

Committee members are encouraged to be as specific as possible when giving input into COVID-19 care decisions, he said.

“We’re so used to dealing with uncertainty, but that doesn’t really help when we’re trying to make tough decisions,” Dr. Brode said. They might be asked, “What are you going to write in your consult note template?” or “It’s 1:00 a.m. and your intern’s panicked and calling you – what are you going to tell them to do over the phone?”

The recommendations have to go into writing and are incorporated into the electronic medical record, a process that required some workarounds, he said. He also noted that the committee learned early on that they should assume that no one reads the e-mails – especially after being off for a period of time – so they likely won’t digest updates on an email-by-email basis.

“We quickly learned,” Dr. Brode said, “that this information needs to live on a Web site or [be] linked to the most up-to-date version in a cloud-sharing platform.”

In a question-and-answer discussion, session viewers expressed enthusiasm for the presenters’ one-page summary of protocols – much more, they said, and it could feel overwhelming.

Dr. Busch and Dr. Brode were asked how standardized order sets for COVID patients could be justified without comparison to a control group that didn’t use the standard order set.

Dr. Busch responded that, while there was no controlled trial, the order sets they use have evolved based on experience.

“At the beginning, we were following every inflammatory marker known to mankind, and then we realized as we gained more experience with COVID and COVID patients that some of those markers were not really informing any of our clinical decisions,” she said. “Obviously, as literature comes out we may reevaluate what goes into that standard order set and how frequently we follow labs.”

Dr. Brode said the context – a pandemic – has to be considered.

“In an ideal world, we could show that the intervention is superior through a randomized fashion with a control group, but really our thought process behind it is just, what is the default?” he said. “I looked at the order sets [as] not that they’re going to be dictating care, but it’s really like the guardrails of what’s reasonable. And when you’re in the middle of a surge, what is usually reasonable and easiest is what is going to be done.”

Dr. Busch and Dr. Brode reported no relevant financial relationships.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Patients with sarcoidosis have an increased risk of heart failure and other adverse outcomes, including all-cause mortality, according to a decade-long nationwide study of Danish patients with the inflammatory disease.

“Although these findings are suggestive of the need for regular monitoring of cardiac manifestations in patients with sarcoidosis, it is important to emphasize that no causal relationships can be established from an observational study. Further studies are therefore needed to confirm our findings,” said first author Adelina Yafasova, MB, of Copenhagen University Hospital in Denmark, in an interview. The study was published in the Journal of the American College of Cardiology.

To determine the long-term risk of cardiac outcomes, and beyond – including incident heart failure; a composite of implantable cardioverter-defibrillator (ICD) implantation, ventricular arrhythmias or cardiac arrest; and all-cause mortality – Dr. Yafasova and her colleagues analyzed data from all Danish residents 18 years or older who were diagnosed with sarcoidosis from 1996 to 2016. Patients with any history of cardiac events were excluded. Of the 12,883 diagnosed patients, 11,834 were matched with subjects from a nationwide background population of more than 47,000 based on age, sex, and comorbidity. The median age of both populations was 42.8 (33.1-55.8) and 54.3% were men.

Median follow-up was 8.2 years for the sarcoidosis population and 8.4 years for the background population. The absolute 10-year risk of heart failure was 3.18% (95% confidence interval, 2.83%-3.57%) for sarcoidosis patients and 1.72% (95% CI, 1.58%-1.86%) for their matched controls. The 10-year risk for the composite of ICD implantation, ventricular arrhythmias and cardiac arrest was 0.96% (95% CI, 0.77%-1.18%) for sarcoidosis patients and 0.45% (95% CI, 0.38%-0.53%) for the background population.

For all-cause mortality, the 10-year risk was 10.88% (95% CI, 10.23%-11.55%) for sarcoidosis patients and 7.43% (95% CI, 7.15%-7.72%) for the background population. In a secondary analysis that compared all-cause mortality between the 364 sarcoidosis patients who developed heart failure and the 1,456 patients with heart failure without a history of sarcoidosis, the sarcoidosis group had a 35% higher rate than the nonsarcoidosis group (adjusted hazard ratio 1.35; 95% CI, 1.10-1.64).

“It’s not necessarily surprising that sarcoidosis patients would have a higher rate of heart failure,” said Melissa A. Lyle, MD, of the Mayo Clinic in Jacksonville, Fla., in an interview. “But the key takeaway is that sarcoidosis was associated with a higher rate of all-cause mortality compared to patients with heart failure and no sarcoidosis. That was more of a surprise.”

“There’s been some discrepancy in previous studies describing the cardiovascular outcomes in sarcoidosis,” Dr. Lyle added, “so I think this study provides excellent information while also highlighting the need for additional large-scale studies. We need to have further data on cardiovascular outcomes, which will allow us to refine the consensus statements and guidelines for management and the diagnosis of cardiac sarcoidosis.”

Dr. Lyle and Leslie T. Cooper Jr., MD, also of the Mayo Clinic, extrapolated on those thoughts in an editorial that accompanied the study. In it, the two authors praised the size and lengthy follow-up of the study, while noting its limitations. Specifically, they stressed that the study’s Danish population “may not be representative of other general populations” because of notable differences in ethnicity, age, and comorbidities.

That said, they reinforced that the study did feature “important takeaways” and that its findings emphasize the “need for monitoring for cardiac manifestations in patients with systemic sarcoidosis.”

In addition to the limitations noted in the editorial, the study’s authors acknowledged that the observational nature limited its “assessment of cause-effect relationships” and that the diagnosis codes for sarcoidosis had not been validated in the Danish National Patient Registry.

The authors of both the study and the editorial reported no conflicts of interest.

SOURCE: Yafasova A et al. J Am Coll Cardiol. 2020 Aug 10. doi: 10.1016/j.jacc.2020.06.038.

Patients with sarcoidosis have an increased risk of heart failure and other adverse outcomes, including all-cause mortality, according to a decade-long nationwide study of Danish patients with the inflammatory disease.

“Although these findings are suggestive of the need for regular monitoring of cardiac manifestations in patients with sarcoidosis, it is important to emphasize that no causal relationships can be established from an observational study. Further studies are therefore needed to confirm our findings,” said first author Adelina Yafasova, MB, of Copenhagen University Hospital in Denmark, in an interview. The study was published in the Journal of the American College of Cardiology.

To determine the long-term risk of cardiac outcomes, and beyond – including incident heart failure; a composite of implantable cardioverter-defibrillator (ICD) implantation, ventricular arrhythmias or cardiac arrest; and all-cause mortality – Dr. Yafasova and her colleagues analyzed data from all Danish residents 18 years or older who were diagnosed with sarcoidosis from 1996 to 2016. Patients with any history of cardiac events were excluded. Of the 12,883 diagnosed patients, 11,834 were matched with subjects from a nationwide background population of more than 47,000 based on age, sex, and comorbidity. The median age of both populations was 42.8 (33.1-55.8) and 54.3% were men.

Median follow-up was 8.2 years for the sarcoidosis population and 8.4 years for the background population. The absolute 10-year risk of heart failure was 3.18% (95% confidence interval, 2.83%-3.57%) for sarcoidosis patients and 1.72% (95% CI, 1.58%-1.86%) for their matched controls. The 10-year risk for the composite of ICD implantation, ventricular arrhythmias and cardiac arrest was 0.96% (95% CI, 0.77%-1.18%) for sarcoidosis patients and 0.45% (95% CI, 0.38%-0.53%) for the background population.

For all-cause mortality, the 10-year risk was 10.88% (95% CI, 10.23%-11.55%) for sarcoidosis patients and 7.43% (95% CI, 7.15%-7.72%) for the background population. In a secondary analysis that compared all-cause mortality between the 364 sarcoidosis patients who developed heart failure and the 1,456 patients with heart failure without a history of sarcoidosis, the sarcoidosis group had a 35% higher rate than the nonsarcoidosis group (adjusted hazard ratio 1.35; 95% CI, 1.10-1.64).

“It’s not necessarily surprising that sarcoidosis patients would have a higher rate of heart failure,” said Melissa A. Lyle, MD, of the Mayo Clinic in Jacksonville, Fla., in an interview. “But the key takeaway is that sarcoidosis was associated with a higher rate of all-cause mortality compared to patients with heart failure and no sarcoidosis. That was more of a surprise.”

“There’s been some discrepancy in previous studies describing the cardiovascular outcomes in sarcoidosis,” Dr. Lyle added, “so I think this study provides excellent information while also highlighting the need for additional large-scale studies. We need to have further data on cardiovascular outcomes, which will allow us to refine the consensus statements and guidelines for management and the diagnosis of cardiac sarcoidosis.”

Dr. Lyle and Leslie T. Cooper Jr., MD, also of the Mayo Clinic, extrapolated on those thoughts in an editorial that accompanied the study. In it, the two authors praised the size and lengthy follow-up of the study, while noting its limitations. Specifically, they stressed that the study’s Danish population “may not be representative of other general populations” because of notable differences in ethnicity, age, and comorbidities.

That said, they reinforced that the study did feature “important takeaways” and that its findings emphasize the “need for monitoring for cardiac manifestations in patients with systemic sarcoidosis.”

In addition to the limitations noted in the editorial, the study’s authors acknowledged that the observational nature limited its “assessment of cause-effect relationships” and that the diagnosis codes for sarcoidosis had not been validated in the Danish National Patient Registry.

The authors of both the study and the editorial reported no conflicts of interest.

SOURCE: Yafasova A et al. J Am Coll Cardiol. 2020 Aug 10. doi: 10.1016/j.jacc.2020.06.038.

Patients with sarcoidosis have an increased risk of heart failure and other adverse outcomes, including all-cause mortality, according to a decade-long nationwide study of Danish patients with the inflammatory disease.

“Although these findings are suggestive of the need for regular monitoring of cardiac manifestations in patients with sarcoidosis, it is important to emphasize that no causal relationships can be established from an observational study. Further studies are therefore needed to confirm our findings,” said first author Adelina Yafasova, MB, of Copenhagen University Hospital in Denmark, in an interview. The study was published in the Journal of the American College of Cardiology.

To determine the long-term risk of cardiac outcomes, and beyond – including incident heart failure; a composite of implantable cardioverter-defibrillator (ICD) implantation, ventricular arrhythmias or cardiac arrest; and all-cause mortality – Dr. Yafasova and her colleagues analyzed data from all Danish residents 18 years or older who were diagnosed with sarcoidosis from 1996 to 2016. Patients with any history of cardiac events were excluded. Of the 12,883 diagnosed patients, 11,834 were matched with subjects from a nationwide background population of more than 47,000 based on age, sex, and comorbidity. The median age of both populations was 42.8 (33.1-55.8) and 54.3% were men.

Median follow-up was 8.2 years for the sarcoidosis population and 8.4 years for the background population. The absolute 10-year risk of heart failure was 3.18% (95% confidence interval, 2.83%-3.57%) for sarcoidosis patients and 1.72% (95% CI, 1.58%-1.86%) for their matched controls. The 10-year risk for the composite of ICD implantation, ventricular arrhythmias and cardiac arrest was 0.96% (95% CI, 0.77%-1.18%) for sarcoidosis patients and 0.45% (95% CI, 0.38%-0.53%) for the background population.

For all-cause mortality, the 10-year risk was 10.88% (95% CI, 10.23%-11.55%) for sarcoidosis patients and 7.43% (95% CI, 7.15%-7.72%) for the background population. In a secondary analysis that compared all-cause mortality between the 364 sarcoidosis patients who developed heart failure and the 1,456 patients with heart failure without a history of sarcoidosis, the sarcoidosis group had a 35% higher rate than the nonsarcoidosis group (adjusted hazard ratio 1.35; 95% CI, 1.10-1.64).

“It’s not necessarily surprising that sarcoidosis patients would have a higher rate of heart failure,” said Melissa A. Lyle, MD, of the Mayo Clinic in Jacksonville, Fla., in an interview. “But the key takeaway is that sarcoidosis was associated with a higher rate of all-cause mortality compared to patients with heart failure and no sarcoidosis. That was more of a surprise.”

“There’s been some discrepancy in previous studies describing the cardiovascular outcomes in sarcoidosis,” Dr. Lyle added, “so I think this study provides excellent information while also highlighting the need for additional large-scale studies. We need to have further data on cardiovascular outcomes, which will allow us to refine the consensus statements and guidelines for management and the diagnosis of cardiac sarcoidosis.”

Dr. Lyle and Leslie T. Cooper Jr., MD, also of the Mayo Clinic, extrapolated on those thoughts in an editorial that accompanied the study. In it, the two authors praised the size and lengthy follow-up of the study, while noting its limitations. Specifically, they stressed that the study’s Danish population “may not be representative of other general populations” because of notable differences in ethnicity, age, and comorbidities.

That said, they reinforced that the study did feature “important takeaways” and that its findings emphasize the “need for monitoring for cardiac manifestations in patients with systemic sarcoidosis.”

In addition to the limitations noted in the editorial, the study’s authors acknowledged that the observational nature limited its “assessment of cause-effect relationships” and that the diagnosis codes for sarcoidosis had not been validated in the Danish National Patient Registry.

The authors of both the study and the editorial reported no conflicts of interest.

SOURCE: Yafasova A et al. J Am Coll Cardiol. 2020 Aug 10. doi: 10.1016/j.jacc.2020.06.038.

For some patients, a bout of COVID-19 may not be over after hospital discharge, acute symptoms subside, or a couple of tests for SARS-CoV-2 come back negative. Those who have reached these milestones of conquering the disease may find that their recovery journey has only begun. Debilitating symptoms such as fatigue, headache, and dyspnea may linger for weeks or longer. Patients with persistent symptoms, often referred to as “long haulers” in reference to the duration of their recovery, are looking for answers about their condition and when their COVID-19 illness will finally resolve.

Long-haul patients organize

What started as an accumulation of anecdotal evidence in social media, blogs, and the mainstream press about slow recovery and long-lasting symptoms of COVID-19 is now the focus of clinical trials in the population of recovering patients. Projects such as the COVID Symptom Study, initiated by the Massachusetts General Hospital, Boston; the Harvard School of Public Health, Boston; King’s College London; and Stanford (Calif.) University, are collecting data on symptoms from millions of patients and will eventually contribute to a better understanding of prolonged recovery.

Patients looking for answers have created groups on social media such as Facebook to exchange information about their experiences (e.g., Survivor Corps, COVID-19 Support Group, COVID-19 Recovered Survivors). Recovering patients have created patient-led research organizations (Body Politic COVID-19 Support Group) to explore persistent symptoms and begin to create data for research.
 

Some data on lingering symptoms

A small study of 143 previously hospitalized, recovering patients in Italy found that 87.4% of the cohort had at least one persistent symptom 2 months or longer after initial onset and at more than a month after discharge. In this sample, only 5% had been intubated. (JAMA 2020 Jul 9. doi: 10.1001/jama.2020.12603).

One study found that even patients who have had relatively mild symptoms and were not hospitalized can have persistent symptoms. The Centers for Disease Control and Prevention conducted a survey of adults who tested positive for the positive reverse transcription–polymerase chain reaction test for SARS-CoV-2 and found that, among the 292 respondents, 35% were still feeling the impact of the disease 2-3 weeks after testing. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms. The survey found that delayed recovery was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization (MMWR. 2020 Jul 24. doi: 10.15585/mmwr.mm6930e1).

Sachin Gupta, MD, FCCP, ATSF, a pulmonologist and member of the CHEST Physician editorial advisory board, has treated patients with COVID-19 and shared some of his thoughts on the problem of prolonged symptoms of COVID-19.
 

Q: Should clinicians expect to see COVID-19 patients who have symptoms persisting weeks after they are diagnosed?

Dr. Gupta: I think clinicians, especially in primary care, are already seeing many patients with lingering symptoms, both respiratory and nonrespiratory related, and debility. A few patients here in the San Francisco Bay Area that I have spoken with 4-6 weeks out from their acute illness have complained of persisting, though improving, fatigue and cough. Early studies are confirming this as a topical issue. There may be other long-lasting sequelae of COVID-19 beyond the common mild lingering symptoms. It will also be important to consider (and get more data on) to what degree asymptomatic patients develop some degree of mild inflammatory and subsequent fibrotic changes in organs like the lungs and heart

Q: How does the recovery phase of COVID-19 compare with recovery from severe influenza or ARDS?

Dr. Gupta: Most prior influenza and acute respiratory distress syndrome (ARDS) studies have provided initial follow-up at 3 months and beyond, so technically speaking, it is a little difficult to compare the symptomatology patterns in the JAMA study of 2 months on follow-up. Nevertheless, the key takeaway is that, even though few patients in the study had ARDS requiring intubation (severe disease), many patients with milder disease had significant lingering symptoms (55% with three or more symptoms) at 2 months.

This fits logically with the premise, which we have some limited data on with ARDS (N Engl J Med. 2003;348:683-93. doi: 10.1056/NEJMoa022450) and severe influenza infection survivors (Nature Sci Rep. 2017;7:17275. doi: 10.1038/s41598-017-17497-6) that varying degrees of the inflammation cascade triggered by certain viruses can lead to changes in important patient-reported outcomes, and objective measures such as pulmonary function over the long term.

Q: What can you do for patients with lingering symptoms of COVID-19 or what can you tell them about their symptoms?

Dr. Gupta: For many patients, there is fear, given the novel nature of the virus/pandemic, that their symptoms may persist long term. Acknowledgment of their symptoms is validating and important for us to recognize as we learn more about the virus. As we are finding, many patients are going online to find answers, after sometimes feeling rushed or dismissed initially in the clinical setting.

In my experience, the bar is fairly high for most patients to reach out to their physicians with complaints of lingering symptoms after acute infection. For the ones who do reach out, they tend to have either a greater constellation of symptoms or higher severity of one or two key symptoms. After assessing and, when appropriate, ruling out secondary infections or newly developed conditions, I shift toward symptom management. I encourage such patients to build up slowly. I suggest they work first on their activities of daily living (bathing, grooming), then their instrumental activities of daily living (cooking, cleaning, checking the mail), and then to engage, based on their tolerance of symptoms, to light purposeful exercise. There are many online resources for at-home exercise activities that I recommend to patients who are more debilitated; some larger centers are beginning to offer some forms of telepulmonary rehab.

Based on what we know about other causes of viral pneumonitis and ARDS, I ask such symptomatic patients to expect a slow, gradual, and in most cases a complete recovery, and depending on the individual case, I recommend pulmonary function tests and imaging that may be helpful to track that progress.

I remind myself, and patients, that our understanding may change as we learn more over time. Checking in at set intervals, even if not in person but through a phone call, can go a long way in a setting where we do not have a specific therapy, other than gradual exercise training, to help these patients recover faster. Reassurance and encouragement are vital for patients who are struggling with the lingering burden of disease and who may find it difficult to return to work or function as usual at home. The final point is to be mindful of our patient’s mental health and, where our reassurance is not enough, to consider appropriate mental health referrals.

Q: Can you handle this kind of problem with telemedicine or which patients with lingering symptoms need to come into the office – or failing that, the ED?

Dr. Gupta: Telemedicine in the outpatient setting provides a helpful tool to assess and manage patients, in my experience, with limited and straightforward complaints. Its scope is limited diagnostically (assessing symptoms and signs) as is its reach (ability to connect with elderly, disabled, or patients without/limited telemedicine access). In many instances, telemedicine limits our ability to connect with patients emotionally and build trust. Many patients who have gone through the acute illness that we see in pulmonary clinic on follow-up are older in age, and for many, video visits are not a practical solution. Telemedicine visits can sometimes present challenges for me as well in terms of thoroughly conveying lifestyle and symptom management strategies. Health literacy is typically easier to gauge and address in person.

For patients with any degree of enduring dyspnea, more so in the acute phase, I recommend home pulse oximetry for monitoring their oxygen saturation if it is financially and technically feasible for them to obtain one. Sending a patient to the ED is an option of last resort, but one that is necessary in some cases. I expect patients with lingering symptoms to tell me that symptoms may be persisting, hopefully gradually improving, and not getting worse. If post–COVID-19 symptoms such as fever, dyspnea, fatigue, or lightheadedness are new or worsening, particularly rapidly, the safest and best option I advise patients is to go to the ED for further assessment and testing. Postviral bacterial pneumonia is something we should consider, and there is some potential for aspergillosis as well.

Q: Do you have any concerns about patients with asthma, chronic obstructive pulmonary disease, or other pulmonary issues having lingering symptoms that may mask exacerbations or may cause exacerbation of their disease?

Dr. Gupta: So far, patients with chronic lung conditions do not appear to have not been disproportionately affected by the pandemic in terms of absolute numbers or percentage wise compared to the general public. I think that sheltering in place has been readily followed by many of these patients, and in addition, I assume better adherence to their maintenance therapies has likely helped. The very few cases of patients with underlying chronic obstructive pulmonary disease and interstitial lung disease that I have seen have fared very poorly when they were diagnosed with COVID-19 in the hospital. There are emerging data about short-term outcomes from severe COVID-19 infection in patients with interstitial lung disease in Europe (medRxiv. 2020 Jul 17. doi: 10.1101/2020.07.15.20152967), and from physicians treating pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (Ann Am Thorac Soc. 2020 Jul 29. doi: 10.1513/AnnalsATS.202005-521OC). But so far, little has been published on the outcomes of mild disease in these patients with chronic lung disease.

Q: It’s still early days to know the significance of lingering symptoms. But at what point do you begin to consider the possibility of some kind of relapse? And what is your next move if the symptoms get worse?

Dr. Gupta: COVID-19 recurrence, whether because of reinfection or relapse, is a potential concern but not one that is very commonly seen so far in my purview. Generally, symptoms of post–COVID-19 infection that are lingering trend toward getting better, even if slowly. If post–COVID-19 infection symptoms are progressing (particularly if rapidly), that would be a strong indication to evaluate that patient in the ED (less likely in clinic), reswab them for SARS-CoV-2, and obtain further testing such as blood work and imaging. A significant challenge from a research perspective will be determining if coinfection with another virus is playing a role as we move closer to the fall season.

[email protected]

For some patients, a bout of COVID-19 may not be over after hospital discharge, acute symptoms subside, or a couple of tests for SARS-CoV-2 come back negative. Those who have reached these milestones of conquering the disease may find that their recovery journey has only begun. Debilitating symptoms such as fatigue, headache, and dyspnea may linger for weeks or longer. Patients with persistent symptoms, often referred to as “long haulers” in reference to the duration of their recovery, are looking for answers about their condition and when their COVID-19 illness will finally resolve.

Long-haul patients organize

What started as an accumulation of anecdotal evidence in social media, blogs, and the mainstream press about slow recovery and long-lasting symptoms of COVID-19 is now the focus of clinical trials in the population of recovering patients. Projects such as the COVID Symptom Study, initiated by the Massachusetts General Hospital, Boston; the Harvard School of Public Health, Boston; King’s College London; and Stanford (Calif.) University, are collecting data on symptoms from millions of patients and will eventually contribute to a better understanding of prolonged recovery.

Patients looking for answers have created groups on social media such as Facebook to exchange information about their experiences (e.g., Survivor Corps, COVID-19 Support Group, COVID-19 Recovered Survivors). Recovering patients have created patient-led research organizations (Body Politic COVID-19 Support Group) to explore persistent symptoms and begin to create data for research.
 

Some data on lingering symptoms

A small study of 143 previously hospitalized, recovering patients in Italy found that 87.4% of the cohort had at least one persistent symptom 2 months or longer after initial onset and at more than a month after discharge. In this sample, only 5% had been intubated. (JAMA 2020 Jul 9. doi: 10.1001/jama.2020.12603).

One study found that even patients who have had relatively mild symptoms and were not hospitalized can have persistent symptoms. The Centers for Disease Control and Prevention conducted a survey of adults who tested positive for the positive reverse transcription–polymerase chain reaction test for SARS-CoV-2 and found that, among the 292 respondents, 35% were still feeling the impact of the disease 2-3 weeks after testing. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms. The survey found that delayed recovery was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization (MMWR. 2020 Jul 24. doi: 10.15585/mmwr.mm6930e1).

Sachin Gupta, MD, FCCP, ATSF, a pulmonologist and member of the CHEST Physician editorial advisory board, has treated patients with COVID-19 and shared some of his thoughts on the problem of prolonged symptoms of COVID-19.
 

Q: Should clinicians expect to see COVID-19 patients who have symptoms persisting weeks after they are diagnosed?

Dr. Gupta: I think clinicians, especially in primary care, are already seeing many patients with lingering symptoms, both respiratory and nonrespiratory related, and debility. A few patients here in the San Francisco Bay Area that I have spoken with 4-6 weeks out from their acute illness have complained of persisting, though improving, fatigue and cough. Early studies are confirming this as a topical issue. There may be other long-lasting sequelae of COVID-19 beyond the common mild lingering symptoms. It will also be important to consider (and get more data on) to what degree asymptomatic patients develop some degree of mild inflammatory and subsequent fibrotic changes in organs like the lungs and heart

Q: How does the recovery phase of COVID-19 compare with recovery from severe influenza or ARDS?

Dr. Gupta: Most prior influenza and acute respiratory distress syndrome (ARDS) studies have provided initial follow-up at 3 months and beyond, so technically speaking, it is a little difficult to compare the symptomatology patterns in the JAMA study of 2 months on follow-up. Nevertheless, the key takeaway is that, even though few patients in the study had ARDS requiring intubation (severe disease), many patients with milder disease had significant lingering symptoms (55% with three or more symptoms) at 2 months.

This fits logically with the premise, which we have some limited data on with ARDS (N Engl J Med. 2003;348:683-93. doi: 10.1056/NEJMoa022450) and severe influenza infection survivors (Nature Sci Rep. 2017;7:17275. doi: 10.1038/s41598-017-17497-6) that varying degrees of the inflammation cascade triggered by certain viruses can lead to changes in important patient-reported outcomes, and objective measures such as pulmonary function over the long term.

Q: What can you do for patients with lingering symptoms of COVID-19 or what can you tell them about their symptoms?

Dr. Gupta: For many patients, there is fear, given the novel nature of the virus/pandemic, that their symptoms may persist long term. Acknowledgment of their symptoms is validating and important for us to recognize as we learn more about the virus. As we are finding, many patients are going online to find answers, after sometimes feeling rushed or dismissed initially in the clinical setting.

In my experience, the bar is fairly high for most patients to reach out to their physicians with complaints of lingering symptoms after acute infection. For the ones who do reach out, they tend to have either a greater constellation of symptoms or higher severity of one or two key symptoms. After assessing and, when appropriate, ruling out secondary infections or newly developed conditions, I shift toward symptom management. I encourage such patients to build up slowly. I suggest they work first on their activities of daily living (bathing, grooming), then their instrumental activities of daily living (cooking, cleaning, checking the mail), and then to engage, based on their tolerance of symptoms, to light purposeful exercise. There are many online resources for at-home exercise activities that I recommend to patients who are more debilitated; some larger centers are beginning to offer some forms of telepulmonary rehab.

Based on what we know about other causes of viral pneumonitis and ARDS, I ask such symptomatic patients to expect a slow, gradual, and in most cases a complete recovery, and depending on the individual case, I recommend pulmonary function tests and imaging that may be helpful to track that progress.

I remind myself, and patients, that our understanding may change as we learn more over time. Checking in at set intervals, even if not in person but through a phone call, can go a long way in a setting where we do not have a specific therapy, other than gradual exercise training, to help these patients recover faster. Reassurance and encouragement are vital for patients who are struggling with the lingering burden of disease and who may find it difficult to return to work or function as usual at home. The final point is to be mindful of our patient’s mental health and, where our reassurance is not enough, to consider appropriate mental health referrals.

Q: Can you handle this kind of problem with telemedicine or which patients with lingering symptoms need to come into the office – or failing that, the ED?

Dr. Gupta: Telemedicine in the outpatient setting provides a helpful tool to assess and manage patients, in my experience, with limited and straightforward complaints. Its scope is limited diagnostically (assessing symptoms and signs) as is its reach (ability to connect with elderly, disabled, or patients without/limited telemedicine access). In many instances, telemedicine limits our ability to connect with patients emotionally and build trust. Many patients who have gone through the acute illness that we see in pulmonary clinic on follow-up are older in age, and for many, video visits are not a practical solution. Telemedicine visits can sometimes present challenges for me as well in terms of thoroughly conveying lifestyle and symptom management strategies. Health literacy is typically easier to gauge and address in person.

For patients with any degree of enduring dyspnea, more so in the acute phase, I recommend home pulse oximetry for monitoring their oxygen saturation if it is financially and technically feasible for them to obtain one. Sending a patient to the ED is an option of last resort, but one that is necessary in some cases. I expect patients with lingering symptoms to tell me that symptoms may be persisting, hopefully gradually improving, and not getting worse. If post–COVID-19 symptoms such as fever, dyspnea, fatigue, or lightheadedness are new or worsening, particularly rapidly, the safest and best option I advise patients is to go to the ED for further assessment and testing. Postviral bacterial pneumonia is something we should consider, and there is some potential for aspergillosis as well.

Q: Do you have any concerns about patients with asthma, chronic obstructive pulmonary disease, or other pulmonary issues having lingering symptoms that may mask exacerbations or may cause exacerbation of their disease?

Dr. Gupta: So far, patients with chronic lung conditions do not appear to have not been disproportionately affected by the pandemic in terms of absolute numbers or percentage wise compared to the general public. I think that sheltering in place has been readily followed by many of these patients, and in addition, I assume better adherence to their maintenance therapies has likely helped. The very few cases of patients with underlying chronic obstructive pulmonary disease and interstitial lung disease that I have seen have fared very poorly when they were diagnosed with COVID-19 in the hospital. There are emerging data about short-term outcomes from severe COVID-19 infection in patients with interstitial lung disease in Europe (medRxiv. 2020 Jul 17. doi: 10.1101/2020.07.15.20152967), and from physicians treating pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (Ann Am Thorac Soc. 2020 Jul 29. doi: 10.1513/AnnalsATS.202005-521OC). But so far, little has been published on the outcomes of mild disease in these patients with chronic lung disease.

Q: It’s still early days to know the significance of lingering symptoms. But at what point do you begin to consider the possibility of some kind of relapse? And what is your next move if the symptoms get worse?

Dr. Gupta: COVID-19 recurrence, whether because of reinfection or relapse, is a potential concern but not one that is very commonly seen so far in my purview. Generally, symptoms of post–COVID-19 infection that are lingering trend toward getting better, even if slowly. If post–COVID-19 infection symptoms are progressing (particularly if rapidly), that would be a strong indication to evaluate that patient in the ED (less likely in clinic), reswab them for SARS-CoV-2, and obtain further testing such as blood work and imaging. A significant challenge from a research perspective will be determining if coinfection with another virus is playing a role as we move closer to the fall season.

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For some patients, a bout of COVID-19 may not be over after hospital discharge, acute symptoms subside, or a couple of tests for SARS-CoV-2 come back negative. Those who have reached these milestones of conquering the disease may find that their recovery journey has only begun. Debilitating symptoms such as fatigue, headache, and dyspnea may linger for weeks or longer. Patients with persistent symptoms, often referred to as “long haulers” in reference to the duration of their recovery, are looking for answers about their condition and when their COVID-19 illness will finally resolve.

Long-haul patients organize

What started as an accumulation of anecdotal evidence in social media, blogs, and the mainstream press about slow recovery and long-lasting symptoms of COVID-19 is now the focus of clinical trials in the population of recovering patients. Projects such as the COVID Symptom Study, initiated by the Massachusetts General Hospital, Boston; the Harvard School of Public Health, Boston; King’s College London; and Stanford (Calif.) University, are collecting data on symptoms from millions of patients and will eventually contribute to a better understanding of prolonged recovery.

Patients looking for answers have created groups on social media such as Facebook to exchange information about their experiences (e.g., Survivor Corps, COVID-19 Support Group, COVID-19 Recovered Survivors). Recovering patients have created patient-led research organizations (Body Politic COVID-19 Support Group) to explore persistent symptoms and begin to create data for research.
 

Some data on lingering symptoms

A small study of 143 previously hospitalized, recovering patients in Italy found that 87.4% of the cohort had at least one persistent symptom 2 months or longer after initial onset and at more than a month after discharge. In this sample, only 5% had been intubated. (JAMA 2020 Jul 9. doi: 10.1001/jama.2020.12603).

One study found that even patients who have had relatively mild symptoms and were not hospitalized can have persistent symptoms. The Centers for Disease Control and Prevention conducted a survey of adults who tested positive for the positive reverse transcription–polymerase chain reaction test for SARS-CoV-2 and found that, among the 292 respondents, 35% were still feeling the impact of the disease 2-3 weeks after testing. Fatigue (71%), cough (61%), and headache (61%) were the most commonly reported symptoms. The survey found that delayed recovery was evident in nearly a quarter of 18- to 34-year-olds and in a third of 35- to 49-year-olds who were not sick enough to require hospitalization (MMWR. 2020 Jul 24. doi: 10.15585/mmwr.mm6930e1).

Sachin Gupta, MD, FCCP, ATSF, a pulmonologist and member of the CHEST Physician editorial advisory board, has treated patients with COVID-19 and shared some of his thoughts on the problem of prolonged symptoms of COVID-19.
 

Q: Should clinicians expect to see COVID-19 patients who have symptoms persisting weeks after they are diagnosed?

Dr. Gupta: I think clinicians, especially in primary care, are already seeing many patients with lingering symptoms, both respiratory and nonrespiratory related, and debility. A few patients here in the San Francisco Bay Area that I have spoken with 4-6 weeks out from their acute illness have complained of persisting, though improving, fatigue and cough. Early studies are confirming this as a topical issue. There may be other long-lasting sequelae of COVID-19 beyond the common mild lingering symptoms. It will also be important to consider (and get more data on) to what degree asymptomatic patients develop some degree of mild inflammatory and subsequent fibrotic changes in organs like the lungs and heart

Q: How does the recovery phase of COVID-19 compare with recovery from severe influenza or ARDS?

Dr. Gupta: Most prior influenza and acute respiratory distress syndrome (ARDS) studies have provided initial follow-up at 3 months and beyond, so technically speaking, it is a little difficult to compare the symptomatology patterns in the JAMA study of 2 months on follow-up. Nevertheless, the key takeaway is that, even though few patients in the study had ARDS requiring intubation (severe disease), many patients with milder disease had significant lingering symptoms (55% with three or more symptoms) at 2 months.

This fits logically with the premise, which we have some limited data on with ARDS (N Engl J Med. 2003;348:683-93. doi: 10.1056/NEJMoa022450) and severe influenza infection survivors (Nature Sci Rep. 2017;7:17275. doi: 10.1038/s41598-017-17497-6) that varying degrees of the inflammation cascade triggered by certain viruses can lead to changes in important patient-reported outcomes, and objective measures such as pulmonary function over the long term.

Q: What can you do for patients with lingering symptoms of COVID-19 or what can you tell them about their symptoms?

Dr. Gupta: For many patients, there is fear, given the novel nature of the virus/pandemic, that their symptoms may persist long term. Acknowledgment of their symptoms is validating and important for us to recognize as we learn more about the virus. As we are finding, many patients are going online to find answers, after sometimes feeling rushed or dismissed initially in the clinical setting.

In my experience, the bar is fairly high for most patients to reach out to their physicians with complaints of lingering symptoms after acute infection. For the ones who do reach out, they tend to have either a greater constellation of symptoms or higher severity of one or two key symptoms. After assessing and, when appropriate, ruling out secondary infections or newly developed conditions, I shift toward symptom management. I encourage such patients to build up slowly. I suggest they work first on their activities of daily living (bathing, grooming), then their instrumental activities of daily living (cooking, cleaning, checking the mail), and then to engage, based on their tolerance of symptoms, to light purposeful exercise. There are many online resources for at-home exercise activities that I recommend to patients who are more debilitated; some larger centers are beginning to offer some forms of telepulmonary rehab.

Based on what we know about other causes of viral pneumonitis and ARDS, I ask such symptomatic patients to expect a slow, gradual, and in most cases a complete recovery, and depending on the individual case, I recommend pulmonary function tests and imaging that may be helpful to track that progress.

I remind myself, and patients, that our understanding may change as we learn more over time. Checking in at set intervals, even if not in person but through a phone call, can go a long way in a setting where we do not have a specific therapy, other than gradual exercise training, to help these patients recover faster. Reassurance and encouragement are vital for patients who are struggling with the lingering burden of disease and who may find it difficult to return to work or function as usual at home. The final point is to be mindful of our patient’s mental health and, where our reassurance is not enough, to consider appropriate mental health referrals.

Q: Can you handle this kind of problem with telemedicine or which patients with lingering symptoms need to come into the office – or failing that, the ED?

Dr. Gupta: Telemedicine in the outpatient setting provides a helpful tool to assess and manage patients, in my experience, with limited and straightforward complaints. Its scope is limited diagnostically (assessing symptoms and signs) as is its reach (ability to connect with elderly, disabled, or patients without/limited telemedicine access). In many instances, telemedicine limits our ability to connect with patients emotionally and build trust. Many patients who have gone through the acute illness that we see in pulmonary clinic on follow-up are older in age, and for many, video visits are not a practical solution. Telemedicine visits can sometimes present challenges for me as well in terms of thoroughly conveying lifestyle and symptom management strategies. Health literacy is typically easier to gauge and address in person.

For patients with any degree of enduring dyspnea, more so in the acute phase, I recommend home pulse oximetry for monitoring their oxygen saturation if it is financially and technically feasible for them to obtain one. Sending a patient to the ED is an option of last resort, but one that is necessary in some cases. I expect patients with lingering symptoms to tell me that symptoms may be persisting, hopefully gradually improving, and not getting worse. If post–COVID-19 symptoms such as fever, dyspnea, fatigue, or lightheadedness are new or worsening, particularly rapidly, the safest and best option I advise patients is to go to the ED for further assessment and testing. Postviral bacterial pneumonia is something we should consider, and there is some potential for aspergillosis as well.

Q: Do you have any concerns about patients with asthma, chronic obstructive pulmonary disease, or other pulmonary issues having lingering symptoms that may mask exacerbations or may cause exacerbation of their disease?

Dr. Gupta: So far, patients with chronic lung conditions do not appear to have not been disproportionately affected by the pandemic in terms of absolute numbers or percentage wise compared to the general public. I think that sheltering in place has been readily followed by many of these patients, and in addition, I assume better adherence to their maintenance therapies has likely helped. The very few cases of patients with underlying chronic obstructive pulmonary disease and interstitial lung disease that I have seen have fared very poorly when they were diagnosed with COVID-19 in the hospital. There are emerging data about short-term outcomes from severe COVID-19 infection in patients with interstitial lung disease in Europe (medRxiv. 2020 Jul 17. doi: 10.1101/2020.07.15.20152967), and from physicians treating pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (Ann Am Thorac Soc. 2020 Jul 29. doi: 10.1513/AnnalsATS.202005-521OC). But so far, little has been published on the outcomes of mild disease in these patients with chronic lung disease.

Q: It’s still early days to know the significance of lingering symptoms. But at what point do you begin to consider the possibility of some kind of relapse? And what is your next move if the symptoms get worse?

Dr. Gupta: COVID-19 recurrence, whether because of reinfection or relapse, is a potential concern but not one that is very commonly seen so far in my purview. Generally, symptoms of post–COVID-19 infection that are lingering trend toward getting better, even if slowly. If post–COVID-19 infection symptoms are progressing (particularly if rapidly), that would be a strong indication to evaluate that patient in the ED (less likely in clinic), reswab them for SARS-CoV-2, and obtain further testing such as blood work and imaging. A significant challenge from a research perspective will be determining if coinfection with another virus is playing a role as we move closer to the fall season.

[email protected]