Since 2019, more than 2,700 individuals have been hospitalized with electronic cigarette- (e-cigarette), or vaping-associated lung injury (EVALI). This entity first reached clinical attention after a series of otherwise healthy young adults presented with dyspnea, severe hypoxia, and diffuse pulmonary infiltrates in the Midwest (Layden J, et al. N Engl J Med. 2020;382[10]:903). Investigation of these cases revealed an association with the use of e-cigarettes, or vaping. As cases continued to mount, the link between vaping and acute lung injury became increasingly apparent.

How it presents

EVALI can present in variable ways, ranging from mild cough or dyspnea without hypoxia to severe acute respiratory distress syndrome (ARDS), requiring advanced life support. Although challenging in the ICU setting, obtaining a detailed history of vaping is crucial to make the diagnosis. Collateral history can be helpful, but if unrevealing, it should not be considered sufficient to exclude vaping as potential etiology, particularly in adolescent e-cigarette users, where parental awareness of substance use history may be limited. If a vaping history is obtained, it is important to assess the substance(s) vaped, how these substances were obtained, and methods of inhalation. While e-cigarettes are the most commonly recognized method of vaping, alternate methods such as “dabbing” and “dripping,” are increasingly popular among vape users, often utilizing modified e-liquid components that may not be reported by patients unless specifically queried.

About 82% of patients hospitalized with EVALI reported vaping tetrahydrocannabinol- (THC) containing fluid. This is important because, unlike nicotine based e-liquids that are primarily purchased over the counter, more than 70% of THC-containing e-liquids are reportedly obtained through informal sources, including illegal distributors. In contrast, only 14% of patients hospitalized with EVALI reported vaping of commercial nicotine products alone. Nicotine-based e-liquids can also be modified, and informal purchasing sources remain a concern, particularly among younger users.

The onset of respiratory symptoms in EVALI is often preceded by several days of a systemic prodrome, including low-grade fevers, myalgia, gastrointestinal complaints, and fatigue (MacMurdo M, et al. Chest. 2020;157[6]:e181). The diagnosis of EVALI is made clinically, and alternative etiologies of lung injury (eg, infections) should be excluded. As there is significant overlap between the presenting symptoms of EVALI and COVID-19 infection, patients should be tested for COVID-19 before a diagnosis of EVALI can be made.

Imaging patterns of EVALI include diffuse alveolar damage (the most common), comprising of diffuse ground-glass opacities, septal thickening, and heterogeneous consolidation (MacMurdo M, et al. Chest. 2020;157[6]:e181). Bilateral ground glass opacities suggestive of organizing pneumonia have also been described. Atypical patterns of nodularity suggestive of hypersensitivity pneumonitis are significantly less common. Given the variety of imaging patterns, EVALI should be considered as a differential diagnosis in all patients presenting with new bilateral pulmonary infiltrates and severe hypoxia.

Early evaluation of these patients revealed lipid-laden macrophages in the bronchoalveolar lavage (BAL) fluid of these patients, raising concern for exogenous lipid inhalation resulting in the development of lipoid pneumonia (Maddock SD, et al. N Engl J Med. 2019;381[15]:1488). Analysis of BAL fluid revealed the presence of vitamin E acetate, a diluent utilized to cut, or dilute, e-liquid (Blount BC, et al. MMWR. 2019;68[45]:1040). This supported the hypothesis that the outbreak of EVALI was being driven, at least in part, by contaminated or self-modified e-liquid. Evaluation of lung biopsies revealed different pathologic patterns of acute lung injury, including diffuse alveolar damage and organizing pneumonia. Importantly, while lipid-laden macrophages were detected, other characteristics of lipoid pneumonia were absent (Mukhopadhyay S, et al. Am J Clin Path. 2019;153[1]30).
 

How to manage EVALI

Approximately half of patients hospitalized with EVALI required ICU admission. However, there is likely a substantial portion of patients with mild disease who may not be represented in the current registry since they did not require hospitalization. The management is primarily supportive and, in patients who require mechanical ventilation, following lung-protective ventilator strategies is of paramount importance. Steroids have been used in some case series, particularly for patients presenting with more severe disease, but data on benefit, optimal dose, and duration are limited.

Vaping cessation is crucial and should be aggressively encouraged. Newer generations of e-cigarettes contain comparatively higher nicotine concentrations, and likely have high potential for nicotine addiction. Treatment for nicotine dependence, including pharmacologic therapy, needs to be considered in all patients following recovery from EVALI.

With supportive care and removal of ongoing exposure, recovery is anticipated in most patients. Long-term outcomes in patients who develop EVALI remain unclear. Although early fibrosis was present in some patients who had transbronchial biopsies, the long-term effects on pulmonary function that may be seen in patients with a history of EVALI are yet to be determined.
 

What about policy?

New regulations related to e-cigarette use have been proposed in response to the increasing prevalence of vaping and the EVALI outbreak. These regulations center primarily on limiting adolescent e-cigarette usage. Tobacco 21, federal legislation passed in 2019, makes it illegal to sell tobacco products to those under the age of 21. The FDA also issued an enforcement policy on unauthorized flavored e-cigarette products. However, this has been criticized for not being comprehensive enough. For example, tobacco and menthol flavors were not included in the ban. Furthermore, THC-containing e-liquid remains largely unregulated at the federal level, and state-level regulation varies significantly by marijuana legalization status.

Policy initiatives that restrict sales without also addressing drivers of e-cigarette use, such as nicotine dependence and aggressive marketing campaigns, are of particular concern and are likely to disproportionately impact younger users. Another unintended effect of e-cigarette sales restrictions may result in a new wave of illegal product distribution and e-liquid modification. Supporting this hypothesis was the finding that the risk of EVALI was higher in states without legalized recreational marijuana, suggesting that users who obtained e-liquid through these informal sources were at greater risk of exposure to contaminated product (Wing C, et al. JAMA Netw Open. 2020;3[4]:e202187). While the CDC is no longer actively tracking EVALI cases, they continue to be reported, and vape use remains common (Armatas C, et al. MMWR. 69[25]:801). As long as e-cigarettes remain in use, another EVALI outbreak remains possible.

It remains important for the intensivist to be familiar with the full spectrum of vaping methods, and to report suspected cases when they arise. While treatable, much remains unknown about the long-term effects on this patient population. Further research is needed to better understand the long-term outcomes in patients with EVALI, in addition to the treatment of nicotine dependence and substance use associated with vaping. Finally, comprehensive regulation to curb e-cigarette usage is needed, particularly among adolescents. However, legislation that is too narrow in scope runs the risk of channeling adolescent e-cigarette users to obtain product through informal sources, further increasing their risk for EVALI. As clinicians, we cannot afford to drop our guard!
 

Dr. Macmurdo and Dr. Choi are with Cleveland Clinic, Respiratory Institute, Cleveland, Ohio.

Since 2019, more than 2,700 individuals have been hospitalized with electronic cigarette- (e-cigarette), or vaping-associated lung injury (EVALI). This entity first reached clinical attention after a series of otherwise healthy young adults presented with dyspnea, severe hypoxia, and diffuse pulmonary infiltrates in the Midwest (Layden J, et al. N Engl J Med. 2020;382[10]:903). Investigation of these cases revealed an association with the use of e-cigarettes, or vaping. As cases continued to mount, the link between vaping and acute lung injury became increasingly apparent.

How it presents

EVALI can present in variable ways, ranging from mild cough or dyspnea without hypoxia to severe acute respiratory distress syndrome (ARDS), requiring advanced life support. Although challenging in the ICU setting, obtaining a detailed history of vaping is crucial to make the diagnosis. Collateral history can be helpful, but if unrevealing, it should not be considered sufficient to exclude vaping as potential etiology, particularly in adolescent e-cigarette users, where parental awareness of substance use history may be limited. If a vaping history is obtained, it is important to assess the substance(s) vaped, how these substances were obtained, and methods of inhalation. While e-cigarettes are the most commonly recognized method of vaping, alternate methods such as “dabbing” and “dripping,” are increasingly popular among vape users, often utilizing modified e-liquid components that may not be reported by patients unless specifically queried.

About 82% of patients hospitalized with EVALI reported vaping tetrahydrocannabinol- (THC) containing fluid. This is important because, unlike nicotine based e-liquids that are primarily purchased over the counter, more than 70% of THC-containing e-liquids are reportedly obtained through informal sources, including illegal distributors. In contrast, only 14% of patients hospitalized with EVALI reported vaping of commercial nicotine products alone. Nicotine-based e-liquids can also be modified, and informal purchasing sources remain a concern, particularly among younger users.

The onset of respiratory symptoms in EVALI is often preceded by several days of a systemic prodrome, including low-grade fevers, myalgia, gastrointestinal complaints, and fatigue (MacMurdo M, et al. Chest. 2020;157[6]:e181). The diagnosis of EVALI is made clinically, and alternative etiologies of lung injury (eg, infections) should be excluded. As there is significant overlap between the presenting symptoms of EVALI and COVID-19 infection, patients should be tested for COVID-19 before a diagnosis of EVALI can be made.

Imaging patterns of EVALI include diffuse alveolar damage (the most common), comprising of diffuse ground-glass opacities, septal thickening, and heterogeneous consolidation (MacMurdo M, et al. Chest. 2020;157[6]:e181). Bilateral ground glass opacities suggestive of organizing pneumonia have also been described. Atypical patterns of nodularity suggestive of hypersensitivity pneumonitis are significantly less common. Given the variety of imaging patterns, EVALI should be considered as a differential diagnosis in all patients presenting with new bilateral pulmonary infiltrates and severe hypoxia.

Early evaluation of these patients revealed lipid-laden macrophages in the bronchoalveolar lavage (BAL) fluid of these patients, raising concern for exogenous lipid inhalation resulting in the development of lipoid pneumonia (Maddock SD, et al. N Engl J Med. 2019;381[15]:1488). Analysis of BAL fluid revealed the presence of vitamin E acetate, a diluent utilized to cut, or dilute, e-liquid (Blount BC, et al. MMWR. 2019;68[45]:1040). This supported the hypothesis that the outbreak of EVALI was being driven, at least in part, by contaminated or self-modified e-liquid. Evaluation of lung biopsies revealed different pathologic patterns of acute lung injury, including diffuse alveolar damage and organizing pneumonia. Importantly, while lipid-laden macrophages were detected, other characteristics of lipoid pneumonia were absent (Mukhopadhyay S, et al. Am J Clin Path. 2019;153[1]30).
 

How to manage EVALI

Approximately half of patients hospitalized with EVALI required ICU admission. However, there is likely a substantial portion of patients with mild disease who may not be represented in the current registry since they did not require hospitalization. The management is primarily supportive and, in patients who require mechanical ventilation, following lung-protective ventilator strategies is of paramount importance. Steroids have been used in some case series, particularly for patients presenting with more severe disease, but data on benefit, optimal dose, and duration are limited.

Vaping cessation is crucial and should be aggressively encouraged. Newer generations of e-cigarettes contain comparatively higher nicotine concentrations, and likely have high potential for nicotine addiction. Treatment for nicotine dependence, including pharmacologic therapy, needs to be considered in all patients following recovery from EVALI.

With supportive care and removal of ongoing exposure, recovery is anticipated in most patients. Long-term outcomes in patients who develop EVALI remain unclear. Although early fibrosis was present in some patients who had transbronchial biopsies, the long-term effects on pulmonary function that may be seen in patients with a history of EVALI are yet to be determined.
 

What about policy?

New regulations related to e-cigarette use have been proposed in response to the increasing prevalence of vaping and the EVALI outbreak. These regulations center primarily on limiting adolescent e-cigarette usage. Tobacco 21, federal legislation passed in 2019, makes it illegal to sell tobacco products to those under the age of 21. The FDA also issued an enforcement policy on unauthorized flavored e-cigarette products. However, this has been criticized for not being comprehensive enough. For example, tobacco and menthol flavors were not included in the ban. Furthermore, THC-containing e-liquid remains largely unregulated at the federal level, and state-level regulation varies significantly by marijuana legalization status.

Policy initiatives that restrict sales without also addressing drivers of e-cigarette use, such as nicotine dependence and aggressive marketing campaigns, are of particular concern and are likely to disproportionately impact younger users. Another unintended effect of e-cigarette sales restrictions may result in a new wave of illegal product distribution and e-liquid modification. Supporting this hypothesis was the finding that the risk of EVALI was higher in states without legalized recreational marijuana, suggesting that users who obtained e-liquid through these informal sources were at greater risk of exposure to contaminated product (Wing C, et al. JAMA Netw Open. 2020;3[4]:e202187). While the CDC is no longer actively tracking EVALI cases, they continue to be reported, and vape use remains common (Armatas C, et al. MMWR. 69[25]:801). As long as e-cigarettes remain in use, another EVALI outbreak remains possible.

It remains important for the intensivist to be familiar with the full spectrum of vaping methods, and to report suspected cases when they arise. While treatable, much remains unknown about the long-term effects on this patient population. Further research is needed to better understand the long-term outcomes in patients with EVALI, in addition to the treatment of nicotine dependence and substance use associated with vaping. Finally, comprehensive regulation to curb e-cigarette usage is needed, particularly among adolescents. However, legislation that is too narrow in scope runs the risk of channeling adolescent e-cigarette users to obtain product through informal sources, further increasing their risk for EVALI. As clinicians, we cannot afford to drop our guard!
 

Dr. Macmurdo and Dr. Choi are with Cleveland Clinic, Respiratory Institute, Cleveland, Ohio.

Since 2019, more than 2,700 individuals have been hospitalized with electronic cigarette- (e-cigarette), or vaping-associated lung injury (EVALI). This entity first reached clinical attention after a series of otherwise healthy young adults presented with dyspnea, severe hypoxia, and diffuse pulmonary infiltrates in the Midwest (Layden J, et al. N Engl J Med. 2020;382[10]:903). Investigation of these cases revealed an association with the use of e-cigarettes, or vaping. As cases continued to mount, the link between vaping and acute lung injury became increasingly apparent.

How it presents

EVALI can present in variable ways, ranging from mild cough or dyspnea without hypoxia to severe acute respiratory distress syndrome (ARDS), requiring advanced life support. Although challenging in the ICU setting, obtaining a detailed history of vaping is crucial to make the diagnosis. Collateral history can be helpful, but if unrevealing, it should not be considered sufficient to exclude vaping as potential etiology, particularly in adolescent e-cigarette users, where parental awareness of substance use history may be limited. If a vaping history is obtained, it is important to assess the substance(s) vaped, how these substances were obtained, and methods of inhalation. While e-cigarettes are the most commonly recognized method of vaping, alternate methods such as “dabbing” and “dripping,” are increasingly popular among vape users, often utilizing modified e-liquid components that may not be reported by patients unless specifically queried.

About 82% of patients hospitalized with EVALI reported vaping tetrahydrocannabinol- (THC) containing fluid. This is important because, unlike nicotine based e-liquids that are primarily purchased over the counter, more than 70% of THC-containing e-liquids are reportedly obtained through informal sources, including illegal distributors. In contrast, only 14% of patients hospitalized with EVALI reported vaping of commercial nicotine products alone. Nicotine-based e-liquids can also be modified, and informal purchasing sources remain a concern, particularly among younger users.

The onset of respiratory symptoms in EVALI is often preceded by several days of a systemic prodrome, including low-grade fevers, myalgia, gastrointestinal complaints, and fatigue (MacMurdo M, et al. Chest. 2020;157[6]:e181). The diagnosis of EVALI is made clinically, and alternative etiologies of lung injury (eg, infections) should be excluded. As there is significant overlap between the presenting symptoms of EVALI and COVID-19 infection, patients should be tested for COVID-19 before a diagnosis of EVALI can be made.

Imaging patterns of EVALI include diffuse alveolar damage (the most common), comprising of diffuse ground-glass opacities, septal thickening, and heterogeneous consolidation (MacMurdo M, et al. Chest. 2020;157[6]:e181). Bilateral ground glass opacities suggestive of organizing pneumonia have also been described. Atypical patterns of nodularity suggestive of hypersensitivity pneumonitis are significantly less common. Given the variety of imaging patterns, EVALI should be considered as a differential diagnosis in all patients presenting with new bilateral pulmonary infiltrates and severe hypoxia.

Early evaluation of these patients revealed lipid-laden macrophages in the bronchoalveolar lavage (BAL) fluid of these patients, raising concern for exogenous lipid inhalation resulting in the development of lipoid pneumonia (Maddock SD, et al. N Engl J Med. 2019;381[15]:1488). Analysis of BAL fluid revealed the presence of vitamin E acetate, a diluent utilized to cut, or dilute, e-liquid (Blount BC, et al. MMWR. 2019;68[45]:1040). This supported the hypothesis that the outbreak of EVALI was being driven, at least in part, by contaminated or self-modified e-liquid. Evaluation of lung biopsies revealed different pathologic patterns of acute lung injury, including diffuse alveolar damage and organizing pneumonia. Importantly, while lipid-laden macrophages were detected, other characteristics of lipoid pneumonia were absent (Mukhopadhyay S, et al. Am J Clin Path. 2019;153[1]30).
 

How to manage EVALI

Approximately half of patients hospitalized with EVALI required ICU admission. However, there is likely a substantial portion of patients with mild disease who may not be represented in the current registry since they did not require hospitalization. The management is primarily supportive and, in patients who require mechanical ventilation, following lung-protective ventilator strategies is of paramount importance. Steroids have been used in some case series, particularly for patients presenting with more severe disease, but data on benefit, optimal dose, and duration are limited.

Vaping cessation is crucial and should be aggressively encouraged. Newer generations of e-cigarettes contain comparatively higher nicotine concentrations, and likely have high potential for nicotine addiction. Treatment for nicotine dependence, including pharmacologic therapy, needs to be considered in all patients following recovery from EVALI.

With supportive care and removal of ongoing exposure, recovery is anticipated in most patients. Long-term outcomes in patients who develop EVALI remain unclear. Although early fibrosis was present in some patients who had transbronchial biopsies, the long-term effects on pulmonary function that may be seen in patients with a history of EVALI are yet to be determined.
 

What about policy?

New regulations related to e-cigarette use have been proposed in response to the increasing prevalence of vaping and the EVALI outbreak. These regulations center primarily on limiting adolescent e-cigarette usage. Tobacco 21, federal legislation passed in 2019, makes it illegal to sell tobacco products to those under the age of 21. The FDA also issued an enforcement policy on unauthorized flavored e-cigarette products. However, this has been criticized for not being comprehensive enough. For example, tobacco and menthol flavors were not included in the ban. Furthermore, THC-containing e-liquid remains largely unregulated at the federal level, and state-level regulation varies significantly by marijuana legalization status.

Policy initiatives that restrict sales without also addressing drivers of e-cigarette use, such as nicotine dependence and aggressive marketing campaigns, are of particular concern and are likely to disproportionately impact younger users. Another unintended effect of e-cigarette sales restrictions may result in a new wave of illegal product distribution and e-liquid modification. Supporting this hypothesis was the finding that the risk of EVALI was higher in states without legalized recreational marijuana, suggesting that users who obtained e-liquid through these informal sources were at greater risk of exposure to contaminated product (Wing C, et al. JAMA Netw Open. 2020;3[4]:e202187). While the CDC is no longer actively tracking EVALI cases, they continue to be reported, and vape use remains common (Armatas C, et al. MMWR. 69[25]:801). As long as e-cigarettes remain in use, another EVALI outbreak remains possible.

It remains important for the intensivist to be familiar with the full spectrum of vaping methods, and to report suspected cases when they arise. While treatable, much remains unknown about the long-term effects on this patient population. Further research is needed to better understand the long-term outcomes in patients with EVALI, in addition to the treatment of nicotine dependence and substance use associated with vaping. Finally, comprehensive regulation to curb e-cigarette usage is needed, particularly among adolescents. However, legislation that is too narrow in scope runs the risk of channeling adolescent e-cigarette users to obtain product through informal sources, further increasing their risk for EVALI. As clinicians, we cannot afford to drop our guard!
 

Dr. Macmurdo and Dr. Choi are with Cleveland Clinic, Respiratory Institute, Cleveland, Ohio.

The CHEST Foundation is excited to announce that the NetWorks Challenge will be reinvented for 2020! Instead of raising funds to support travel grants to CHEST’s Annual Meeting as in previous years, the NetWorks Challenge will focus on raising funds to support COVID-19 community service grants. With so many people suffering due to the pandemic, we believe this change will make a tangible impact on the lives of people who need it most.

To date, the CHEST Foundation has dispersed over $60,000 in payments for patient support groups that provide services to those living with chronic lung disease, and we hope this year’s efforts will enable us to continue this work. For every $2,500 raised by a NetWork, the CHEST Foundation will provide a grant to a community support group in need.

While providing vulnerable populations with funds to purchase essential items (PPE, cleaning supplies, emergency food purchases, etc), each grant will be named in honor of the NetWork raising the funds, and all stories of impact will be shared with NetWorks’ members, once they are available.

The NetWorks Challenge spans from Monday, July 20, to the end of Board Review on August 22, and members can easily designate their donation to their NetWork on the CHEST Foundation’s donor page.

In addition to receiving named recognition of your NetWork, the NetWork that raises the most funds, along with the NetWork with the highest percentage of participation, will receive additional prizes, including two complimentary registrations to CHEST 2020. These registrations are specifically for early-career clinicians and fellows-in-training, which will be selected by each NetWorks’s steering committee.

For every $5,000 raised by a NetWork, that NetWork will receive one complimentary registration to CHEST 2020, which will be awarded to their early-career and fellows-in-training as selected by that NetWorks’s steering committee.

In addition to directly impacting patients across the United States, NetWorks members will have a chance to test their knowledge against their peers by participating in a NetWork Challenge Game Series, where they will be asked a series of hand-selected board review questions each week through the end of Board Review.

For additional Information about the NetWorks Challenge, visit the CHEST Foundation’s website.

The CHEST Foundation is excited to announce that the NetWorks Challenge will be reinvented for 2020! Instead of raising funds to support travel grants to CHEST’s Annual Meeting as in previous years, the NetWorks Challenge will focus on raising funds to support COVID-19 community service grants. With so many people suffering due to the pandemic, we believe this change will make a tangible impact on the lives of people who need it most.

To date, the CHEST Foundation has dispersed over $60,000 in payments for patient support groups that provide services to those living with chronic lung disease, and we hope this year’s efforts will enable us to continue this work. For every $2,500 raised by a NetWork, the CHEST Foundation will provide a grant to a community support group in need.

While providing vulnerable populations with funds to purchase essential items (PPE, cleaning supplies, emergency food purchases, etc), each grant will be named in honor of the NetWork raising the funds, and all stories of impact will be shared with NetWorks’ members, once they are available.

The NetWorks Challenge spans from Monday, July 20, to the end of Board Review on August 22, and members can easily designate their donation to their NetWork on the CHEST Foundation’s donor page.

In addition to receiving named recognition of your NetWork, the NetWork that raises the most funds, along with the NetWork with the highest percentage of participation, will receive additional prizes, including two complimentary registrations to CHEST 2020. These registrations are specifically for early-career clinicians and fellows-in-training, which will be selected by each NetWorks’s steering committee.

For every $5,000 raised by a NetWork, that NetWork will receive one complimentary registration to CHEST 2020, which will be awarded to their early-career and fellows-in-training as selected by that NetWorks’s steering committee.

In addition to directly impacting patients across the United States, NetWorks members will have a chance to test their knowledge against their peers by participating in a NetWork Challenge Game Series, where they will be asked a series of hand-selected board review questions each week through the end of Board Review.

For additional Information about the NetWorks Challenge, visit the CHEST Foundation’s website.

The CHEST Foundation is excited to announce that the NetWorks Challenge will be reinvented for 2020! Instead of raising funds to support travel grants to CHEST’s Annual Meeting as in previous years, the NetWorks Challenge will focus on raising funds to support COVID-19 community service grants. With so many people suffering due to the pandemic, we believe this change will make a tangible impact on the lives of people who need it most.

To date, the CHEST Foundation has dispersed over $60,000 in payments for patient support groups that provide services to those living with chronic lung disease, and we hope this year’s efforts will enable us to continue this work. For every $2,500 raised by a NetWork, the CHEST Foundation will provide a grant to a community support group in need.

While providing vulnerable populations with funds to purchase essential items (PPE, cleaning supplies, emergency food purchases, etc), each grant will be named in honor of the NetWork raising the funds, and all stories of impact will be shared with NetWorks’ members, once they are available.

The NetWorks Challenge spans from Monday, July 20, to the end of Board Review on August 22, and members can easily designate their donation to their NetWork on the CHEST Foundation’s donor page.

In addition to receiving named recognition of your NetWork, the NetWork that raises the most funds, along with the NetWork with the highest percentage of participation, will receive additional prizes, including two complimentary registrations to CHEST 2020. These registrations are specifically for early-career clinicians and fellows-in-training, which will be selected by each NetWorks’s steering committee.

For every $5,000 raised by a NetWork, that NetWork will receive one complimentary registration to CHEST 2020, which will be awarded to their early-career and fellows-in-training as selected by that NetWorks’s steering committee.

In addition to directly impacting patients across the United States, NetWorks members will have a chance to test their knowledge against their peers by participating in a NetWork Challenge Game Series, where they will be asked a series of hand-selected board review questions each week through the end of Board Review.

For additional Information about the NetWorks Challenge, visit the CHEST Foundation’s website.

The Board of Regents met remotely in June because of ongoing travel restrictions and safety concerns for staff and board members.

• The meeting was opened with Stephanie Levine, President; Steve Simpson, President-Elect; and Robert Musacchio, CEO/EVP discussing the impacts of the COVID-19 pandemic and Business Continuity Planning. The COVID-19 Task Force, chaired by Steve Simpson, continues to meet weekly to identify emerging content needs toward supporting membership and their patients through the pandemic, connecting with the Education Committee and Foundation to ensure robust coverage, drawing on the expertise of the NetWorks for content development, and leveraging the Social Media Workgroup for dissemination. Key activities include: a regular Thursday webinar series at 3:00 pm CDT titled: “Advice From the Front Lines”; clinical resources in the form of infographics and guides are posted in the resource center and circulated through social media; Alex Niven, MD FCCP, led a team to develop a wellness curriculum and series; the CHEST Foundation developed patient education videos and guides, a public service announcement in partnership with the American Thoracic Society, and a pilot partnership with AMITA Health enabling access to telehealth.

• The Finance Committee, chaired by John Howington, reported that CHEST is on track to meet its budget and exceed its debt covenants and operating reserve policy for the current fiscal year. The record attendance at the October 2019 annual meeting, along with strong performance from our digital offerings offset the financial impacts of the global pandemic. Bob Musacchio, CEO/EVP, reminded the Board why CHEST is switching from a fiscal year to calendar year budget. A calendar year budget process creates better alignment with budgets of pharma, other clients, and vendors; facilitates various accruals that are based on the calendar year, such as benefits, vacation, sick, and PTO days; provides for greater continuity for doing business throughout the year, and permits more planning time for staff in setting individual goals related to the annual meeting.

• CHEST’S Digital Transformation strategy that kicked off in 2019 was timely considering the pandemic. With education as one of our main foci, CHEST has hired and onboarded a Chief Learning Officer, Jim Young, to actively examine how we develop and deploy our educational products and services. Our first movement toward remote meetings occurred on June 26 with the Virtual Congress originally slated for Bologna, Italy. Here, we piloted a new platform and brought to life the tenets established in the new learning strategy—providing choice, demonstrating responsiveness, and fostering connection.

• CHEST’s Governance Committee reviewed the College bylaws for revisions, as per the group’s practice every 2-3 years, and the Board approved the revisions to the bylaws as proposed by the committee.

• CHEST’s newly formed Health Policy and Advocacy Committee (HPAC), chaired by Neil Freedman, MD, FCCP, is holding monthly meetings with a goal of making a recommendation to the Board of Regents on CHEST’s regulatory and policy priorities during the August meeting. The HPAC assists CHEST leadership and the BOR in developing and implementing health policy positions, setting chest advocacy agendas in the legislative and regulatory arenas, engaging with policymakers as directed by the BOR, and educating CHEST members of government affairs relevant to CHEST’s mission. The HPAC is currently setting its priorities to bring to the BOR for approval later this summer. Areas of focus include home mechanical ventilation and competitive bidding access to in education four home auction therapy, only rehabilitation and tobacco vaping education,

• Peter Mazzone, MD, FCCP; Editor in Chief, CHEST journal, reviewed his editorial team, which now consists of three Deputy Editors, nine Associate Editors, an Assistant Editor, a Statistical Editor, and three Case Series Editors and the publishing staff and partners.

The Board’s next meetings will be a scheduled teleconference in August, followed by their meeting that will occur concomitantly with the CHEST meeting in October.

The Board of Regents met remotely in June because of ongoing travel restrictions and safety concerns for staff and board members.

• The meeting was opened with Stephanie Levine, President; Steve Simpson, President-Elect; and Robert Musacchio, CEO/EVP discussing the impacts of the COVID-19 pandemic and Business Continuity Planning. The COVID-19 Task Force, chaired by Steve Simpson, continues to meet weekly to identify emerging content needs toward supporting membership and their patients through the pandemic, connecting with the Education Committee and Foundation to ensure robust coverage, drawing on the expertise of the NetWorks for content development, and leveraging the Social Media Workgroup for dissemination. Key activities include: a regular Thursday webinar series at 3:00 pm CDT titled: “Advice From the Front Lines”; clinical resources in the form of infographics and guides are posted in the resource center and circulated through social media; Alex Niven, MD FCCP, led a team to develop a wellness curriculum and series; the CHEST Foundation developed patient education videos and guides, a public service announcement in partnership with the American Thoracic Society, and a pilot partnership with AMITA Health enabling access to telehealth.

• The Finance Committee, chaired by John Howington, reported that CHEST is on track to meet its budget and exceed its debt covenants and operating reserve policy for the current fiscal year. The record attendance at the October 2019 annual meeting, along with strong performance from our digital offerings offset the financial impacts of the global pandemic. Bob Musacchio, CEO/EVP, reminded the Board why CHEST is switching from a fiscal year to calendar year budget. A calendar year budget process creates better alignment with budgets of pharma, other clients, and vendors; facilitates various accruals that are based on the calendar year, such as benefits, vacation, sick, and PTO days; provides for greater continuity for doing business throughout the year, and permits more planning time for staff in setting individual goals related to the annual meeting.

• CHEST’S Digital Transformation strategy that kicked off in 2019 was timely considering the pandemic. With education as one of our main foci, CHEST has hired and onboarded a Chief Learning Officer, Jim Young, to actively examine how we develop and deploy our educational products and services. Our first movement toward remote meetings occurred on June 26 with the Virtual Congress originally slated for Bologna, Italy. Here, we piloted a new platform and brought to life the tenets established in the new learning strategy—providing choice, demonstrating responsiveness, and fostering connection.

• CHEST’s Governance Committee reviewed the College bylaws for revisions, as per the group’s practice every 2-3 years, and the Board approved the revisions to the bylaws as proposed by the committee.

• CHEST’s newly formed Health Policy and Advocacy Committee (HPAC), chaired by Neil Freedman, MD, FCCP, is holding monthly meetings with a goal of making a recommendation to the Board of Regents on CHEST’s regulatory and policy priorities during the August meeting. The HPAC assists CHEST leadership and the BOR in developing and implementing health policy positions, setting chest advocacy agendas in the legislative and regulatory arenas, engaging with policymakers as directed by the BOR, and educating CHEST members of government affairs relevant to CHEST’s mission. The HPAC is currently setting its priorities to bring to the BOR for approval later this summer. Areas of focus include home mechanical ventilation and competitive bidding access to in education four home auction therapy, only rehabilitation and tobacco vaping education,

• Peter Mazzone, MD, FCCP; Editor in Chief, CHEST journal, reviewed his editorial team, which now consists of three Deputy Editors, nine Associate Editors, an Assistant Editor, a Statistical Editor, and three Case Series Editors and the publishing staff and partners.

The Board’s next meetings will be a scheduled teleconference in August, followed by their meeting that will occur concomitantly with the CHEST meeting in October.

The Board of Regents met remotely in June because of ongoing travel restrictions and safety concerns for staff and board members.

• The meeting was opened with Stephanie Levine, President; Steve Simpson, President-Elect; and Robert Musacchio, CEO/EVP discussing the impacts of the COVID-19 pandemic and Business Continuity Planning. The COVID-19 Task Force, chaired by Steve Simpson, continues to meet weekly to identify emerging content needs toward supporting membership and their patients through the pandemic, connecting with the Education Committee and Foundation to ensure robust coverage, drawing on the expertise of the NetWorks for content development, and leveraging the Social Media Workgroup for dissemination. Key activities include: a regular Thursday webinar series at 3:00 pm CDT titled: “Advice From the Front Lines”; clinical resources in the form of infographics and guides are posted in the resource center and circulated through social media; Alex Niven, MD FCCP, led a team to develop a wellness curriculum and series; the CHEST Foundation developed patient education videos and guides, a public service announcement in partnership with the American Thoracic Society, and a pilot partnership with AMITA Health enabling access to telehealth.

• The Finance Committee, chaired by John Howington, reported that CHEST is on track to meet its budget and exceed its debt covenants and operating reserve policy for the current fiscal year. The record attendance at the October 2019 annual meeting, along with strong performance from our digital offerings offset the financial impacts of the global pandemic. Bob Musacchio, CEO/EVP, reminded the Board why CHEST is switching from a fiscal year to calendar year budget. A calendar year budget process creates better alignment with budgets of pharma, other clients, and vendors; facilitates various accruals that are based on the calendar year, such as benefits, vacation, sick, and PTO days; provides for greater continuity for doing business throughout the year, and permits more planning time for staff in setting individual goals related to the annual meeting.

• CHEST’S Digital Transformation strategy that kicked off in 2019 was timely considering the pandemic. With education as one of our main foci, CHEST has hired and onboarded a Chief Learning Officer, Jim Young, to actively examine how we develop and deploy our educational products and services. Our first movement toward remote meetings occurred on June 26 with the Virtual Congress originally slated for Bologna, Italy. Here, we piloted a new platform and brought to life the tenets established in the new learning strategy—providing choice, demonstrating responsiveness, and fostering connection.

• CHEST’s Governance Committee reviewed the College bylaws for revisions, as per the group’s practice every 2-3 years, and the Board approved the revisions to the bylaws as proposed by the committee.

• CHEST’s newly formed Health Policy and Advocacy Committee (HPAC), chaired by Neil Freedman, MD, FCCP, is holding monthly meetings with a goal of making a recommendation to the Board of Regents on CHEST’s regulatory and policy priorities during the August meeting. The HPAC assists CHEST leadership and the BOR in developing and implementing health policy positions, setting chest advocacy agendas in the legislative and regulatory arenas, engaging with policymakers as directed by the BOR, and educating CHEST members of government affairs relevant to CHEST’s mission. The HPAC is currently setting its priorities to bring to the BOR for approval later this summer. Areas of focus include home mechanical ventilation and competitive bidding access to in education four home auction therapy, only rehabilitation and tobacco vaping education,

• Peter Mazzone, MD, FCCP; Editor in Chief, CHEST journal, reviewed his editorial team, which now consists of three Deputy Editors, nine Associate Editors, an Assistant Editor, a Statistical Editor, and three Case Series Editors and the publishing staff and partners.

The Board’s next meetings will be a scheduled teleconference in August, followed by their meeting that will occur concomitantly with the CHEST meeting in October.

Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.

AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.

Dr. Elemento described such work during the opening plenary session of the meeting.

Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).

The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.

As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.

Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
 

Application of machine learning

One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.

Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).

The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.

AI and image analysis

Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:

• Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
• Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
• Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
• Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
• Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).

Drug development through applied AI

In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).

The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.

Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.

Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).

With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
 

Challenges to acknowledge

Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.

A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.

If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”

A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.

Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.

At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.

In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.

The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.

Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.

AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.

Dr. Elemento described such work during the opening plenary session of the meeting.

Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).

The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.

As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.

Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
 

Application of machine learning

One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.

Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).

The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.

AI and image analysis

Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:

• Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
• Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
• Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
• Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
• Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).

Drug development through applied AI

In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).

The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.

Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.

Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).

With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
 

Challenges to acknowledge

Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.

A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.

If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”

A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.

Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.

At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.

In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.

The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.

Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Precision medicine is driven by technologies such as rapid genome sequencing and artificial intelligence (AI), according to a presentation at the AACR virtual meeting II.

AI can be applied to the sequencing information derived from advanced cancers to make highly personalized treatment recommendations for patients, said Olivier Elemento, PhD, of Weill Cornell Medicine, New York.

Dr. Elemento described such work during the opening plenary session of the meeting.

Dr. Elemento advocated for whole-genome sequencing (WGS) of metastatic sites, as it can reveal “branched evolution” as tumors progress from localized to metastatic (Nat Genet. 2016 Dec;48[12]:1490-9).

The metastases share common mutations with the primaries from which they arise but also develop their own mutational profiles, which facilitate site-of-origin-agnostic, predictive treatment choices.

As examples, Dr. Elemento mentioned HER2 amplification found in a patient with urothelial cancer (J Natl Compr Canc Netw. 2019 Mar 1;17[3]:194-200) and a patient with uterine serous carcinoma (Gynecol Oncol Rep. 2019 Feb 21;28:54-7), both of whom experienced long-lasting remissions to HER2-targeted therapy.

Dr. Elemento also noted that WGS can reveal complex structural variants in lung adenocarcinomas that lack alterations in the RTK/RAS/RAF pathway (unpublished data).
 

Application of machine learning

One study suggested that microRNA expression and machine learning can be used to identify malignant thyroid lesions (Clin Cancer Res. 2012 Apr 1;18[7]:2032-8). The approach diagnosed malignant lesions with 90% accuracy, 100% sensitivity, and 86% specificity.

Dr. Elemento and colleagues used a similar approach to predict response to immunotherapy in melanoma (unpublished data).

The idea was to mine the cancer genome and transcriptome, allowing for identification of signals from neoantigens, immune gene expression, immune cell composition, and T-cell receptor repertoires, Dr. Elemento said. Integrating these signals with clinical outcome data via machine learning technology enabled the researchers to predict immunotherapy response in malignant melanoma with nearly 90% accuracy.

AI and image analysis

Studies have indicated that AI can be applied to medical images to improve diagnosis and treatment. The approach has been shown to:

• Facilitate correct diagnoses of malignant skin lesions (Nature. 2017 Feb 2;542[7639]:115-8).
• Distinguish lung adenocarcinoma from squamous cell cancer with 100% accuracy (EBioMedicine. 2018 Jan;27:317-28).
• Recognize distinct breast cancer subtypes (ductal, lobular, mucinous, papillary) and biomarkers (bioRxiv 242818. doi: 10.1101/242818; EBioMedicine. 2018 Jan;27:317-28)
• Predict mesothelioma prognosis (Nat Med. 2019 Oct;25[10]:1519-25).
• Predict prostate biopsy results (unpublished data) and calculate Gleason scores that can predict survival in prostate cancer patients (AACR 2020, Abstract 867).

Drug development through applied AI

In another study, Dr. Elemento and colleagues used a Bayesian machine learning approach to predict targets of molecules without a known mechanism of action (Nat Commun. 2019 Nov 19;10[1]:5221).

The method involved using data on gene expression profiles, cell line viability, side effects in animals, and structures of the molecules. The researchers applied this method to a large library of orphan small molecules and found it could predict targets in about 40% of cases.

Of 24 AI-predicted microtubule-targeting molecules, 14 depolymerized microtubules in the lab. Five of these molecules were effective in cell lines that were resistant to other microtubule-targeted drugs.

Dr. Elemento went on to describe how Oncoceutics was developing an antineoplastic agent called ONC201, but the company lacked information about the agent’s target. Using AI, the target was identified as dopamine receptor 2 (DRD2; Clin Cancer Res. 2019 Apr 1;25[7]:2305-13).

With that information, Oncoceutics initiated trials of ONC201 in tumors expressing high levels of DRD2, including a highly resistant glioma (J Neurooncol. 2019 Oct;145[1]:97-105). Responses were seen, and ONC201 is now being tested against other DRD2-expressing cancers.
 

Challenges to acknowledge

Potential benefits of AI in the clinic are exciting, but there are many bench-to-bedside challenges.

A clinically obvious example of AI’s applications is radiographic image analysis. There is no biologic rationale for our RECIST “cut values” for partial response, minimal response, and stable disease.

If AI can measure subtle changes on imaging that correlate with tumor biology (i.e., radiomics), we stand a better chance of predicting treatment outcomes than we can with conventional measurements of shrinkage of arbitrarily selected “target lesions.”

A tremendous amount of work is needed to build the required large image banks. During that time, AI will only improve – and without the human risks of fatigue, inconsistency, or burnout.

Those human frailties notwithstanding, AI cannot substitute for the key discussions between patient and clinician regarding goals of care, trade-offs of risks and benefits, and shared decision-making regarding management options.

At least initially (but painfully), complex technologies like WGS and digital image analysis via AI may further disadvantage patients who are medically disadvantaged by geography or socioeconomic circumstances.

In the discussion period, AACR President Antoni Ribas, MD, of University of California, Los Angeles, asked whether AI can simulate crosstalk between gene pathways so that unique treatment combinations can be identified. Dr. Elemento said those simulations are the subject of ongoing investigation.

The theme of the opening plenary session at the AACR virtual meeting II was “Turning Science into Life-Saving Care.” Applications of AI to optimize personalized use of genomics, digital image analysis, and drug development show great promise for being among the technologies that can help to realize AACR’s thematic vision.

Dr. Elemento disclosed relationships with Volastra Therapeutics, OneThree Biotech, Owkin, Freenome, Genetic Intelligence, Acuamark Diagnostics, Eli Lilly, Janssen, and Sanofi.

Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

A new study of hypertension treatment trends found that uncontrolled high blood pressure along with considerable undertreatment of the condition were prevalent in individuals with a history of both hypertension and stroke. “To our knowledge, the present study is the first to analyze and report national antihypertensive medication trends exclusively among individuals with a history of stroke in the United States,” wrote Daniel Santos, MD, and Mandip S. Dhamoon, MD, DrPH, of the Icahn School of Medicine at Mount Sinai, New York. Their study was published in JAMA Neurology.

To examine blood pressure control and treatment trends among stroke survivors, the researchers examined more than a decade of data from the National Health and Nutrition Examination Survey (NHANES). The cross-sectional survey is conducted in 2-year cycles; the authors analyzed the results from 2005 to 2016 and uncovered a total of 4,971,136 eligible individuals with a history of both stroke and hypertension.

The mean age of the study population was 67.1 (95% confidence interval, 66.1-68.1), and 2,790,518 (56.1%) were women. Their mean blood pressure was 134/68 mm Hg (95% CI, 133/67–136/69), and the average number of antihypertensive medications they were taking was 1.8 (95% CI, 1.7-1.9). Of the 4,971,136 analyzed individuals, 4,721,409 (95%) were aware of their hypertension diagnosis yet more than 10% of that group had not previously been prescribed an antihypertensive medication.

More than 37% (n = 1,846,470) of the participants had uncontrolled high blood pressure upon examination (95% CI, 33.5%-40.8%), and 15.3% (95% CI, 12.5%-18.0%) were not taking any medication for it at all. The most commonly used antihypertensive medications included ACE inhibitors or angiotensin receptor blockers (59.2%; 95% CI, 54.9%-63.4%), beta-blockers (43.8%; 95% CI, 40.3%-47.3%), diuretics (41.6%; 95% CI, 37.3%-45.9%) and calcium-channel blockers (31.5%; 95% CI, 28.2%-34.8%).* Roughly 57% of the sample was taking more than one antihypertensive medication (95% CI, 52.8%-60.6%) while 28% (95% CI, 24.6%-31.5%) were taking only one.
 

Continued surveillance is key

“All the studies that have ever been done show that hypertension is inadequately treated,” Louis Caplan, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston, said in an interview. “One of the reasons is that it can be hard to get some of the patients to seek treatment, particularly Black Americans. Also, a lot of the medicines to treat high blood pressure have side effects, so many patients don’t want to take the pills.

“Treating hypertension really requires continued surveillance,” he added. “It’s not one visit where the doctor gives you a pill. It’s taking the pill, following your blood pressure, and seeing if it works. If it doesn’t, then maybe you change the dose, get another pill, and are followed once again. That doesn’t happen as often as it should.”

In regard to next steps, Dr. Caplan urged that hypertension “be evaluated more seriously. Even as home blood pressure kits and monitoring become increasingly available, many doctors are still going by a casual blood pressure test in the office, which doesn’t tell you how serious the problem is. There needs to be more use of technology and more conditioning of patients to monitor their own blood pressure as a guide, and then we go from there.”

The authors acknowledged their study’s limitations, including the NHANES’s reliance on self-reporting a history of stroke and the inability to distinguish between subtypes of stroke. In addition, they noted that many antihypertensive medications have uses beyond treating hypertension, which introduces “another confounding factor to medication trends.”

The authors and Dr. Caplan reported no conflicts of interest.

SOURCE: Santos D et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2499.

Correction, 8/20/20: An earlier version of this article misstated the confidence interval for diuretics.

A new study of hypertension treatment trends found that uncontrolled high blood pressure along with considerable undertreatment of the condition were prevalent in individuals with a history of both hypertension and stroke. “To our knowledge, the present study is the first to analyze and report national antihypertensive medication trends exclusively among individuals with a history of stroke in the United States,” wrote Daniel Santos, MD, and Mandip S. Dhamoon, MD, DrPH, of the Icahn School of Medicine at Mount Sinai, New York. Their study was published in JAMA Neurology.

To examine blood pressure control and treatment trends among stroke survivors, the researchers examined more than a decade of data from the National Health and Nutrition Examination Survey (NHANES). The cross-sectional survey is conducted in 2-year cycles; the authors analyzed the results from 2005 to 2016 and uncovered a total of 4,971,136 eligible individuals with a history of both stroke and hypertension.

The mean age of the study population was 67.1 (95% confidence interval, 66.1-68.1), and 2,790,518 (56.1%) were women. Their mean blood pressure was 134/68 mm Hg (95% CI, 133/67–136/69), and the average number of antihypertensive medications they were taking was 1.8 (95% CI, 1.7-1.9). Of the 4,971,136 analyzed individuals, 4,721,409 (95%) were aware of their hypertension diagnosis yet more than 10% of that group had not previously been prescribed an antihypertensive medication.

More than 37% (n = 1,846,470) of the participants had uncontrolled high blood pressure upon examination (95% CI, 33.5%-40.8%), and 15.3% (95% CI, 12.5%-18.0%) were not taking any medication for it at all. The most commonly used antihypertensive medications included ACE inhibitors or angiotensin receptor blockers (59.2%; 95% CI, 54.9%-63.4%), beta-blockers (43.8%; 95% CI, 40.3%-47.3%), diuretics (41.6%; 95% CI, 37.3%-45.9%) and calcium-channel blockers (31.5%; 95% CI, 28.2%-34.8%).* Roughly 57% of the sample was taking more than one antihypertensive medication (95% CI, 52.8%-60.6%) while 28% (95% CI, 24.6%-31.5%) were taking only one.
 

Continued surveillance is key

“All the studies that have ever been done show that hypertension is inadequately treated,” Louis Caplan, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston, said in an interview. “One of the reasons is that it can be hard to get some of the patients to seek treatment, particularly Black Americans. Also, a lot of the medicines to treat high blood pressure have side effects, so many patients don’t want to take the pills.

“Treating hypertension really requires continued surveillance,” he added. “It’s not one visit where the doctor gives you a pill. It’s taking the pill, following your blood pressure, and seeing if it works. If it doesn’t, then maybe you change the dose, get another pill, and are followed once again. That doesn’t happen as often as it should.”

In regard to next steps, Dr. Caplan urged that hypertension “be evaluated more seriously. Even as home blood pressure kits and monitoring become increasingly available, many doctors are still going by a casual blood pressure test in the office, which doesn’t tell you how serious the problem is. There needs to be more use of technology and more conditioning of patients to monitor their own blood pressure as a guide, and then we go from there.”

The authors acknowledged their study’s limitations, including the NHANES’s reliance on self-reporting a history of stroke and the inability to distinguish between subtypes of stroke. In addition, they noted that many antihypertensive medications have uses beyond treating hypertension, which introduces “another confounding factor to medication trends.”

The authors and Dr. Caplan reported no conflicts of interest.

SOURCE: Santos D et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2499.

Correction, 8/20/20: An earlier version of this article misstated the confidence interval for diuretics.

A new study of hypertension treatment trends found that uncontrolled high blood pressure along with considerable undertreatment of the condition were prevalent in individuals with a history of both hypertension and stroke. “To our knowledge, the present study is the first to analyze and report national antihypertensive medication trends exclusively among individuals with a history of stroke in the United States,” wrote Daniel Santos, MD, and Mandip S. Dhamoon, MD, DrPH, of the Icahn School of Medicine at Mount Sinai, New York. Their study was published in JAMA Neurology.

To examine blood pressure control and treatment trends among stroke survivors, the researchers examined more than a decade of data from the National Health and Nutrition Examination Survey (NHANES). The cross-sectional survey is conducted in 2-year cycles; the authors analyzed the results from 2005 to 2016 and uncovered a total of 4,971,136 eligible individuals with a history of both stroke and hypertension.

The mean age of the study population was 67.1 (95% confidence interval, 66.1-68.1), and 2,790,518 (56.1%) were women. Their mean blood pressure was 134/68 mm Hg (95% CI, 133/67–136/69), and the average number of antihypertensive medications they were taking was 1.8 (95% CI, 1.7-1.9). Of the 4,971,136 analyzed individuals, 4,721,409 (95%) were aware of their hypertension diagnosis yet more than 10% of that group had not previously been prescribed an antihypertensive medication.

More than 37% (n = 1,846,470) of the participants had uncontrolled high blood pressure upon examination (95% CI, 33.5%-40.8%), and 15.3% (95% CI, 12.5%-18.0%) were not taking any medication for it at all. The most commonly used antihypertensive medications included ACE inhibitors or angiotensin receptor blockers (59.2%; 95% CI, 54.9%-63.4%), beta-blockers (43.8%; 95% CI, 40.3%-47.3%), diuretics (41.6%; 95% CI, 37.3%-45.9%) and calcium-channel blockers (31.5%; 95% CI, 28.2%-34.8%).* Roughly 57% of the sample was taking more than one antihypertensive medication (95% CI, 52.8%-60.6%) while 28% (95% CI, 24.6%-31.5%) were taking only one.
 

Continued surveillance is key

“All the studies that have ever been done show that hypertension is inadequately treated,” Louis Caplan, MD, of Harvard Medical School and Beth Israel Deaconess Medical Center, both in Boston, said in an interview. “One of the reasons is that it can be hard to get some of the patients to seek treatment, particularly Black Americans. Also, a lot of the medicines to treat high blood pressure have side effects, so many patients don’t want to take the pills.

“Treating hypertension really requires continued surveillance,” he added. “It’s not one visit where the doctor gives you a pill. It’s taking the pill, following your blood pressure, and seeing if it works. If it doesn’t, then maybe you change the dose, get another pill, and are followed once again. That doesn’t happen as often as it should.”

In regard to next steps, Dr. Caplan urged that hypertension “be evaluated more seriously. Even as home blood pressure kits and monitoring become increasingly available, many doctors are still going by a casual blood pressure test in the office, which doesn’t tell you how serious the problem is. There needs to be more use of technology and more conditioning of patients to monitor their own blood pressure as a guide, and then we go from there.”

The authors acknowledged their study’s limitations, including the NHANES’s reliance on self-reporting a history of stroke and the inability to distinguish between subtypes of stroke. In addition, they noted that many antihypertensive medications have uses beyond treating hypertension, which introduces “another confounding factor to medication trends.”

The authors and Dr. Caplan reported no conflicts of interest.

SOURCE: Santos D et al. JAMA Neurol. 2020 Jul 27. doi: 10.1001/jamaneurol.2020.2499.

Correction, 8/20/20: An earlier version of this article misstated the confidence interval for diuretics.

In the clinical experience of Libby Edwards, MD, the diagnosis of lichen sclerosus in a young girl often triggers worry from patients and parents alike.

“The parents are worried about the ramifications of genital diseases and they’re worried about scarring,” she said during the virtual annual meeting of the Society for Pediatric Dermatology.

Meanwhile, during the initial assessment, physicians tend to think about sexual abuse or sexually transmitted diseases as the primary culprit. “It’s really important that you consider those issues, but they’re not usually what’s going on,” said Dr. Edwards, a dermatologist who practices in Charlotte, N.C. “Also, for some reason we jump to yeast as a cause of diseases in the genital area. If the child is out of diapers and hasn’t reached puberty, it’s almost never yeast. Do a culture. Try and prove yeast. If it doesn’t respond to treatment for yeast, it’s not going to be yeast. Reassure, and don’t forget to reassure.”

The causes of lichen sclerosus in young girls are not completely understood, she continued, but a main factor is autoimmune-related, which can cause a distinctive rash that usually affects the genital skin around the vulva and anus. Lichen sclerosus presents classically as white, fragile plaques. “Textbooks say that there is cigarette paper-like crinkling of skin,” Dr. Edwards said. “I think of it being more like cellophane paper. In children, we often see it as smooth, kind of waxy and shiny, compared to adults. Children usually present with pruritus and irritation.”

Lichen sclerosus often starts in the clitoral area and on the perineum, and often with an edematous clitoral hood. “It often eventuates into clitoral phimosis, meaning that there is midline adhesion so that the clitoris is buried,” she said. “In adults, seeing this clitoral phimosis is a reliable sign of a scarring dermatosis – most often lichen sclerosus. But you can’t say that in children, because little girls will often have scarring over the clitoris. It’s just physiologic and means nothing, and it will go away at puberty. Certainly, sometimes this white discoloration can have crinkling. Purpura and tearing are common; if you look at lichen sclerosus histologically it looks like a thin epithelium that’s stretched over gelatin. Any rubbing and scratching can cause bleeding in the skin.”

Clinical appearance of well demarcated white skin with texture change drives the diagnosis. “It can be hard to tell from vitiligo at times, but there always should be texture change – whether it’s crinkling, whether it’s waxy, whether it’s smooth – and it’s symptomatic,” she said.

A biopsy is not usually required. “I think a good picture [of the affected area] or some sort of objective description in the chart is important, because most children do so well that in a few months there’s no sign of it, and the next provider [they see] may not believe that they ever had it,” she said.

The recommended initial treatment for lichen sclerosus in girls is a tiny amount of a superpotent topical corticosteroid ointment such as clobetasol or halobetasol one to two times daily until the skin is clear, which usually takes 2-4 months. “You do not treat these children until they’re comfortable, because that may be a week,” Dr. Edwards said. “You treat these children until the skin looks normal. Then you need to keep treating them, because if you don’t, the skin will relapse, even though they might not have symptoms.”

Following initial treatment, she recommends use of a superpotent corticosteroid once per day three times a week, or a midpotency steroid like triamcinolone ointment 0.1% every day. In her clinical experience, if lesions clear and remain clear with long-term treatment through puberty, the chances are good that they’ll stay clear if the medication is stopped.

“There are no studies on what to do after a patient clears,” said Dr. Edwards, chief of dermatology at Carolinas Medical Center, Charlotte, and adjunct clinical professor of dermatology at the University of North Carolina, Chapel Hill. “We have been informed by trial and error. If a child is totally clear after puberty, I will stop their medication and see them back every 3 months for about a year and a half. If they stay clear after a year and a half, I find that they stay clear. I wonder what happens at menopause. We surely don’t know.”

With consistent topical treatment, many patients will have clearing in one area of affected skin after a month or two, and it will take 3 or 4 months for the remaining area to clear. “I tend to see patients back every 6-8 weeks until they’re clear,” she said. “I do not like the idea of sending people out and saying, ‘use this medication twice a day for a month, then once a day for a month, then three times a week, then as needed.’

For patients concerned about the long-term use of topical steroids, the immunosuppressants tacrolimus and pimecrolimus are options. “They are often irritating on the vulva, but can work better than steroids for extragenital disease,” Dr. Edwards said. “Parents sometimes object to the use of a corticosteroid, but because these produce slower benefit and often burn with application, you can remind the parents that tacrolimus and pimecrolimus are not without side effects and are labeled as being associated with cancer. That often will prompt a parent to be willing to use a topical steroid. You can also point to studies that show the safety of topical steroids.”

Intralesional steroids are useful for thick lesions, but Dr. Edwards said that she has never had to use them in a child with lichen sclerosus. “I have found methotrexate to be useful in some people, but there is not one study on genital lichen sclerosus and methotrexate,” she said. “I find that about one in five patients with recalcitrant vulvar lichen sclerosus has had some benefit from methotrexate,” she added, noting that fractional CO₂ laser “is showing promise in these patients.”

Dr. Edwards concluded her remarks by noting that she has never cared for a child with vulvar lichen sclerosus who didn’t respond to topical super potent steroids, “except due to poor compliance.”

She reported having no relevant financial disclosures.

[email protected]

In the clinical experience of Libby Edwards, MD, the diagnosis of lichen sclerosus in a young girl often triggers worry from patients and parents alike.

“The parents are worried about the ramifications of genital diseases and they’re worried about scarring,” she said during the virtual annual meeting of the Society for Pediatric Dermatology.

Meanwhile, during the initial assessment, physicians tend to think about sexual abuse or sexually transmitted diseases as the primary culprit. “It’s really important that you consider those issues, but they’re not usually what’s going on,” said Dr. Edwards, a dermatologist who practices in Charlotte, N.C. “Also, for some reason we jump to yeast as a cause of diseases in the genital area. If the child is out of diapers and hasn’t reached puberty, it’s almost never yeast. Do a culture. Try and prove yeast. If it doesn’t respond to treatment for yeast, it’s not going to be yeast. Reassure, and don’t forget to reassure.”

The causes of lichen sclerosus in young girls are not completely understood, she continued, but a main factor is autoimmune-related, which can cause a distinctive rash that usually affects the genital skin around the vulva and anus. Lichen sclerosus presents classically as white, fragile plaques. “Textbooks say that there is cigarette paper-like crinkling of skin,” Dr. Edwards said. “I think of it being more like cellophane paper. In children, we often see it as smooth, kind of waxy and shiny, compared to adults. Children usually present with pruritus and irritation.”

Lichen sclerosus often starts in the clitoral area and on the perineum, and often with an edematous clitoral hood. “It often eventuates into clitoral phimosis, meaning that there is midline adhesion so that the clitoris is buried,” she said. “In adults, seeing this clitoral phimosis is a reliable sign of a scarring dermatosis – most often lichen sclerosus. But you can’t say that in children, because little girls will often have scarring over the clitoris. It’s just physiologic and means nothing, and it will go away at puberty. Certainly, sometimes this white discoloration can have crinkling. Purpura and tearing are common; if you look at lichen sclerosus histologically it looks like a thin epithelium that’s stretched over gelatin. Any rubbing and scratching can cause bleeding in the skin.”

Clinical appearance of well demarcated white skin with texture change drives the diagnosis. “It can be hard to tell from vitiligo at times, but there always should be texture change – whether it’s crinkling, whether it’s waxy, whether it’s smooth – and it’s symptomatic,” she said.

A biopsy is not usually required. “I think a good picture [of the affected area] or some sort of objective description in the chart is important, because most children do so well that in a few months there’s no sign of it, and the next provider [they see] may not believe that they ever had it,” she said.

The recommended initial treatment for lichen sclerosus in girls is a tiny amount of a superpotent topical corticosteroid ointment such as clobetasol or halobetasol one to two times daily until the skin is clear, which usually takes 2-4 months. “You do not treat these children until they’re comfortable, because that may be a week,” Dr. Edwards said. “You treat these children until the skin looks normal. Then you need to keep treating them, because if you don’t, the skin will relapse, even though they might not have symptoms.”

Following initial treatment, she recommends use of a superpotent corticosteroid once per day three times a week, or a midpotency steroid like triamcinolone ointment 0.1% every day. In her clinical experience, if lesions clear and remain clear with long-term treatment through puberty, the chances are good that they’ll stay clear if the medication is stopped.

“There are no studies on what to do after a patient clears,” said Dr. Edwards, chief of dermatology at Carolinas Medical Center, Charlotte, and adjunct clinical professor of dermatology at the University of North Carolina, Chapel Hill. “We have been informed by trial and error. If a child is totally clear after puberty, I will stop their medication and see them back every 3 months for about a year and a half. If they stay clear after a year and a half, I find that they stay clear. I wonder what happens at menopause. We surely don’t know.”

With consistent topical treatment, many patients will have clearing in one area of affected skin after a month or two, and it will take 3 or 4 months for the remaining area to clear. “I tend to see patients back every 6-8 weeks until they’re clear,” she said. “I do not like the idea of sending people out and saying, ‘use this medication twice a day for a month, then once a day for a month, then three times a week, then as needed.’

For patients concerned about the long-term use of topical steroids, the immunosuppressants tacrolimus and pimecrolimus are options. “They are often irritating on the vulva, but can work better than steroids for extragenital disease,” Dr. Edwards said. “Parents sometimes object to the use of a corticosteroid, but because these produce slower benefit and often burn with application, you can remind the parents that tacrolimus and pimecrolimus are not without side effects and are labeled as being associated with cancer. That often will prompt a parent to be willing to use a topical steroid. You can also point to studies that show the safety of topical steroids.”

Intralesional steroids are useful for thick lesions, but Dr. Edwards said that she has never had to use them in a child with lichen sclerosus. “I have found methotrexate to be useful in some people, but there is not one study on genital lichen sclerosus and methotrexate,” she said. “I find that about one in five patients with recalcitrant vulvar lichen sclerosus has had some benefit from methotrexate,” she added, noting that fractional CO₂ laser “is showing promise in these patients.”

Dr. Edwards concluded her remarks by noting that she has never cared for a child with vulvar lichen sclerosus who didn’t respond to topical super potent steroids, “except due to poor compliance.”

She reported having no relevant financial disclosures.

[email protected]

In the clinical experience of Libby Edwards, MD, the diagnosis of lichen sclerosus in a young girl often triggers worry from patients and parents alike.

“The parents are worried about the ramifications of genital diseases and they’re worried about scarring,” she said during the virtual annual meeting of the Society for Pediatric Dermatology.

Meanwhile, during the initial assessment, physicians tend to think about sexual abuse or sexually transmitted diseases as the primary culprit. “It’s really important that you consider those issues, but they’re not usually what’s going on,” said Dr. Edwards, a dermatologist who practices in Charlotte, N.C. “Also, for some reason we jump to yeast as a cause of diseases in the genital area. If the child is out of diapers and hasn’t reached puberty, it’s almost never yeast. Do a culture. Try and prove yeast. If it doesn’t respond to treatment for yeast, it’s not going to be yeast. Reassure, and don’t forget to reassure.”

The causes of lichen sclerosus in young girls are not completely understood, she continued, but a main factor is autoimmune-related, which can cause a distinctive rash that usually affects the genital skin around the vulva and anus. Lichen sclerosus presents classically as white, fragile plaques. “Textbooks say that there is cigarette paper-like crinkling of skin,” Dr. Edwards said. “I think of it being more like cellophane paper. In children, we often see it as smooth, kind of waxy and shiny, compared to adults. Children usually present with pruritus and irritation.”

Lichen sclerosus often starts in the clitoral area and on the perineum, and often with an edematous clitoral hood. “It often eventuates into clitoral phimosis, meaning that there is midline adhesion so that the clitoris is buried,” she said. “In adults, seeing this clitoral phimosis is a reliable sign of a scarring dermatosis – most often lichen sclerosus. But you can’t say that in children, because little girls will often have scarring over the clitoris. It’s just physiologic and means nothing, and it will go away at puberty. Certainly, sometimes this white discoloration can have crinkling. Purpura and tearing are common; if you look at lichen sclerosus histologically it looks like a thin epithelium that’s stretched over gelatin. Any rubbing and scratching can cause bleeding in the skin.”

Clinical appearance of well demarcated white skin with texture change drives the diagnosis. “It can be hard to tell from vitiligo at times, but there always should be texture change – whether it’s crinkling, whether it’s waxy, whether it’s smooth – and it’s symptomatic,” she said.

A biopsy is not usually required. “I think a good picture [of the affected area] or some sort of objective description in the chart is important, because most children do so well that in a few months there’s no sign of it, and the next provider [they see] may not believe that they ever had it,” she said.

The recommended initial treatment for lichen sclerosus in girls is a tiny amount of a superpotent topical corticosteroid ointment such as clobetasol or halobetasol one to two times daily until the skin is clear, which usually takes 2-4 months. “You do not treat these children until they’re comfortable, because that may be a week,” Dr. Edwards said. “You treat these children until the skin looks normal. Then you need to keep treating them, because if you don’t, the skin will relapse, even though they might not have symptoms.”

Following initial treatment, she recommends use of a superpotent corticosteroid once per day three times a week, or a midpotency steroid like triamcinolone ointment 0.1% every day. In her clinical experience, if lesions clear and remain clear with long-term treatment through puberty, the chances are good that they’ll stay clear if the medication is stopped.

“There are no studies on what to do after a patient clears,” said Dr. Edwards, chief of dermatology at Carolinas Medical Center, Charlotte, and adjunct clinical professor of dermatology at the University of North Carolina, Chapel Hill. “We have been informed by trial and error. If a child is totally clear after puberty, I will stop their medication and see them back every 3 months for about a year and a half. If they stay clear after a year and a half, I find that they stay clear. I wonder what happens at menopause. We surely don’t know.”

With consistent topical treatment, many patients will have clearing in one area of affected skin after a month or two, and it will take 3 or 4 months for the remaining area to clear. “I tend to see patients back every 6-8 weeks until they’re clear,” she said. “I do not like the idea of sending people out and saying, ‘use this medication twice a day for a month, then once a day for a month, then three times a week, then as needed.’

For patients concerned about the long-term use of topical steroids, the immunosuppressants tacrolimus and pimecrolimus are options. “They are often irritating on the vulva, but can work better than steroids for extragenital disease,” Dr. Edwards said. “Parents sometimes object to the use of a corticosteroid, but because these produce slower benefit and often burn with application, you can remind the parents that tacrolimus and pimecrolimus are not without side effects and are labeled as being associated with cancer. That often will prompt a parent to be willing to use a topical steroid. You can also point to studies that show the safety of topical steroids.”

Intralesional steroids are useful for thick lesions, but Dr. Edwards said that she has never had to use them in a child with lichen sclerosus. “I have found methotrexate to be useful in some people, but there is not one study on genital lichen sclerosus and methotrexate,” she said. “I find that about one in five patients with recalcitrant vulvar lichen sclerosus has had some benefit from methotrexate,” she added, noting that fractional CO₂ laser “is showing promise in these patients.”

Dr. Edwards concluded her remarks by noting that she has never cared for a child with vulvar lichen sclerosus who didn’t respond to topical super potent steroids, “except due to poor compliance.”

She reported having no relevant financial disclosures.

[email protected]

Most primary care physicians agree that antibiotic resistance and inappropriate prescribing are problems in the United States, but they are much less inclined to recognize these issues in their own practices, according to the results of a nationwide survey.

“This lack of recognition of physicians’ own contributions to inappropriate prescribing presents a barrier to encouraging widespread stewardship uptake,” Rachel M. Zetts, MPH, of the Pew Charitable Trusts, Washington, D.C., and associates wrote in Open Forum Infectious Diseases.

Almost all (94%) of the 1,550 internists, family physicians, and pediatricians who responded to the survey said that antibiotic resistance is a national problem, and nearly that many (91%) agreed that “inappropriate antibiotic prescribing is a problem in outpatient health care settings,” the investigators acknowledged.

Narrowing the focus to their own practices, however, changed some opinions. At that level, only 55% of the respondents said that resistance was a problem for their practices, and just 37% said that there any sort of inappropriate prescribing going on, based on data from the survey, which was conducted from August to October 2018 by Pew and the American Medical Association.

Antibiotic stewardship, defined as activities meant to ensure appropriate prescribing of antibiotics, should include “staff and patient education, clinician-level antibiotic prescribing feedback, and communications training on how to discuss antibiotic prescribing with patients,” Ms. Zetts and associates explained.

The need for such stewardship in health care settings was acknowledged by 72% of respondents, but 53% of those surveyed also said that all they need to do to support such efforts “is to talk with their patients about the value of an antibiotic for their symptoms,” they noted.

The bacteria, it seems, are not the only ones with some resistance. Half of the primary care physicians believe that it would be difficult to fairly and accurately track the appropriate use of antibiotics, and 52% agreed with the statement that “practice-based reporting requirements for antibiotic use would be too onerous,” the researchers pointed out.

“Antibiotic resistance is an impending public health crisis. We are seeing today, as we respond to the COVID-19 pandemic, what our health system looks like with no or limited treatments available to tackle an outbreak. … We must all remain vigilant in combating the spread of antibiotic resistant bacteria and be prudent when prescribing antibiotics,” AMA President Susan R. Bailey, MD, said in a written statement.

[email protected]

SOURCE: Zetts RM et al. Open Forum Infect Dis. 2020 July;7(7). doi: 10.1093/ofid/ofaa244.

Most primary care physicians agree that antibiotic resistance and inappropriate prescribing are problems in the United States, but they are much less inclined to recognize these issues in their own practices, according to the results of a nationwide survey.

“This lack of recognition of physicians’ own contributions to inappropriate prescribing presents a barrier to encouraging widespread stewardship uptake,” Rachel M. Zetts, MPH, of the Pew Charitable Trusts, Washington, D.C., and associates wrote in Open Forum Infectious Diseases.

Almost all (94%) of the 1,550 internists, family physicians, and pediatricians who responded to the survey said that antibiotic resistance is a national problem, and nearly that many (91%) agreed that “inappropriate antibiotic prescribing is a problem in outpatient health care settings,” the investigators acknowledged.

Narrowing the focus to their own practices, however, changed some opinions. At that level, only 55% of the respondents said that resistance was a problem for their practices, and just 37% said that there any sort of inappropriate prescribing going on, based on data from the survey, which was conducted from August to October 2018 by Pew and the American Medical Association.

Antibiotic stewardship, defined as activities meant to ensure appropriate prescribing of antibiotics, should include “staff and patient education, clinician-level antibiotic prescribing feedback, and communications training on how to discuss antibiotic prescribing with patients,” Ms. Zetts and associates explained.

The need for such stewardship in health care settings was acknowledged by 72% of respondents, but 53% of those surveyed also said that all they need to do to support such efforts “is to talk with their patients about the value of an antibiotic for their symptoms,” they noted.

The bacteria, it seems, are not the only ones with some resistance. Half of the primary care physicians believe that it would be difficult to fairly and accurately track the appropriate use of antibiotics, and 52% agreed with the statement that “practice-based reporting requirements for antibiotic use would be too onerous,” the researchers pointed out.

“Antibiotic resistance is an impending public health crisis. We are seeing today, as we respond to the COVID-19 pandemic, what our health system looks like with no or limited treatments available to tackle an outbreak. … We must all remain vigilant in combating the spread of antibiotic resistant bacteria and be prudent when prescribing antibiotics,” AMA President Susan R. Bailey, MD, said in a written statement.

[email protected]

SOURCE: Zetts RM et al. Open Forum Infect Dis. 2020 July;7(7). doi: 10.1093/ofid/ofaa244.

Most primary care physicians agree that antibiotic resistance and inappropriate prescribing are problems in the United States, but they are much less inclined to recognize these issues in their own practices, according to the results of a nationwide survey.

“This lack of recognition of physicians’ own contributions to inappropriate prescribing presents a barrier to encouraging widespread stewardship uptake,” Rachel M. Zetts, MPH, of the Pew Charitable Trusts, Washington, D.C., and associates wrote in Open Forum Infectious Diseases.

Almost all (94%) of the 1,550 internists, family physicians, and pediatricians who responded to the survey said that antibiotic resistance is a national problem, and nearly that many (91%) agreed that “inappropriate antibiotic prescribing is a problem in outpatient health care settings,” the investigators acknowledged.

Narrowing the focus to their own practices, however, changed some opinions. At that level, only 55% of the respondents said that resistance was a problem for their practices, and just 37% said that there any sort of inappropriate prescribing going on, based on data from the survey, which was conducted from August to October 2018 by Pew and the American Medical Association.

Antibiotic stewardship, defined as activities meant to ensure appropriate prescribing of antibiotics, should include “staff and patient education, clinician-level antibiotic prescribing feedback, and communications training on how to discuss antibiotic prescribing with patients,” Ms. Zetts and associates explained.

The need for such stewardship in health care settings was acknowledged by 72% of respondents, but 53% of those surveyed also said that all they need to do to support such efforts “is to talk with their patients about the value of an antibiotic for their symptoms,” they noted.

The bacteria, it seems, are not the only ones with some resistance. Half of the primary care physicians believe that it would be difficult to fairly and accurately track the appropriate use of antibiotics, and 52% agreed with the statement that “practice-based reporting requirements for antibiotic use would be too onerous,” the researchers pointed out.

“Antibiotic resistance is an impending public health crisis. We are seeing today, as we respond to the COVID-19 pandemic, what our health system looks like with no or limited treatments available to tackle an outbreak. … We must all remain vigilant in combating the spread of antibiotic resistant bacteria and be prudent when prescribing antibiotics,” AMA President Susan R. Bailey, MD, said in a written statement.

[email protected]

SOURCE: Zetts RM et al. Open Forum Infect Dis. 2020 July;7(7). doi: 10.1093/ofid/ofaa244.

Dr. Ira Weintraub, a recently retired orthopedic surgeon who now works at a medical billing consultancy, saw a hip replacement bill for over $400,000 earlier this year.

“The patient stayed in the hospital 17 days, which is only 17 times normal. The bill got paid,” mused Weintraub, chief medical officer of Portland, Oregon-based WellRithms, which helps self-funded employers and workers’ compensation insurers make sense of large, complex medical bills and ensure they pay the fair amount.

Charges like that go a long way toward explaining why hospitals are eager to restore joint replacements to pre-COVID levels as quickly as possible – an eagerness tempered only by safety concerns amid a resurgence of the coronavirus in some regions of the country. Revenue losses at hospitals and outpatient surgery centers may have exceeded $5 billion from canceled knee and hip replacements alone during a roughly two-month hiatus on elective procedures earlier this year.

The cost of joint replacement surgery varies widely – though, on average, it is in the tens, not hundreds, of thousands of dollars. Still, given the high and rapidly growing volume, it’s easy to see why joint replacement operations have become a vital chunk of revenue at most U.S. hospitals.

The rate of knee and hip replacements more than doubled from 2000 to 2015, according to inpatient discharge data from the Agency for Healthcare Research and Quality. And that growth is likely to continue: Knee replacements are expected to triple between now and 2040, with hip replacements not far behind, according to projections published last year in the Journal of Rheumatology.

Joint procedures are usually not emergencies, and they were among the first to be scrubbed or delayed when hospitals froze elective surgeries in March – and again in July in some areas plagued by renewed COVID outbreaks. Loss of the revenue has hit hospitals hard, and regaining it will be crucial to their financial convalescence.

“Without orthopedic volumes returning to something near their pre-pandemic levels, it will make it difficult for health systems to get back to anywhere near break-even from a bottom-line perspective,” said Stephen Thome, a principal in health care consulting at Grant Thornton, an advisory, audit and tax firm.

It’s impossible to know exactly how much knee and hip replacements are worth to hospitals, because no definitive data on total volume or price exists.

But using published estimates of volume, extrapolating average commercial payments from published Medicare rates based on a study, and making an educated guess of patient coinsurance, Thome helped KHN arrive at an annual market value for American hospitals and surgery centers of between $15.5 billion and $21.5 billion for knee replacements alone.

That suggests a revenue loss of $1.3 billion to $1.8 billion per month for the period the surgeries were shut down. These figures include ambulatory surgery centers not owned by hospitals, which also suspended most operations in late March, all of April and into May.

If you add hip replacements, which account for about half the volume of knees and are paid at similar rates, the total annual value rises to a range of $23 billion to $32 billion, with monthly revenue losses from $1.9 billion to $2.7 billion.

The American Hospital Association projects total revenue lost at U.S. hospitals will reach $323 billion by year’s end, not counting additional losses from surgeries canceled during the current coronavirus spike. That amount is partially offset by $69 billion in federal relief dollars hospitals have received so far, according to the association. The California Hospital Association puts the net revenue loss for hospitals in that state at about $10.5 billion, said spokesperson Jan Emerson-Shea.

Hospitals resumed joint replacement surgeries in early to mid-May, with the timing and ramp-up speed varying by region and hospital. Some hospitals restored volume quickly; others took a more cautious route and continue to lose revenue. Still others have had to shut down again.

At the NYU Langone Orthopedic Hospital in New York City, “people are starting to come in and you see the operating rooms full again,” said Dr. Claudette Lajam, chief orthopedic safety officer.

At St. Jude Medical Center in Fullerton, California, where the coronavirus is raging, inpatient joint replacements resumed in the second or third week of May – cautiously at first, but volume is “very close to pre-pandemic levels at this point,” said Dr. Kevin Khajavi, chairman of the hospital’s orthopedic surgery department. However, “we are constantly monitoring the situation to determine if we have to scale back once again,” he said.

In large swaths of Texas, elective surgeries were once again suspended in July because of the COVID-19 resurgence. The same is true at many hospitals in Florida, Alabama, South Carolina and Nevada.

The Mayo Clinic in Phoenix suspended nonemergency joint replacement surgeries in early July. It resumed outpatient replacement procedures the week of July 27, but still has not resumed nonemergency inpatient procedures, said Dr. Mark Spangehl, an orthopedic surgeon there. In terms of medical urgency, joint replacements are “at the bottom of the totem pole,” Spangehl said.

In terms of cash flow, however, joint replacements are decidedly not at the bottom of the totem pole. They have become a cash cow as the number of patients undergoing them has skyrocketed in recent decades.

The volume is being driven by an aging population, an epidemic of obesity and a significant rise in the number of younger people replacing joints worn out by years of sports and exercise.

It’s also being driven by the cash. Once only done in hospitals, the operations are now increasingly performed at ambulatory surgery centers – especially on younger, healthier patients who don’t require hospitalization.

The surgery centers are often physician-owned, but private equity groups such as Bain Capital and KKR & Co. have taken an interest in them, drawn by their high growth potential, robust financial returns and ability to offer competitive prices.

“[G]enerally the savings should be very good – but I do see a lot of outlier surgery centers where they are charging exorbitant amounts of money – $100,000 wouldn’t be too much,” said WellRithm’s Weintraub, who co-owned such a surgery center in Portland.

Fear of catching the coronavirus in a hospital is reinforcing the outpatient trend. Matthew Davis, a 58-year-old resident of Washington, was scheduled for a hip replacement on March 30 but got cold feet because of COVID-19, and canceled just before all elective surgeries were halted. When it came time to reschedule in June, he overcame his reservations in large part because the surgeon planned to perform the procedure at a free-standing surgery center.

“That was key to me – avoiding an overnight hospital stay to minimize my exposure,” Davis said. “These joint replacements are almost industrial-scale. They are cranking out joint replacements 9 to 5. I went in at 6:30 a.m. and I was walking out the door at 11:30.”

Acutely aware of the financial benefits, hospitals and surgery clinics have been marketing joint replacements for years, competing for coveted rankings and running ads that show healthy aging people, all smiles, engaged in vigorous activity.

However, a 2014 study concluded that one-third of knee replacements were not warranted, mainly because the symptoms of the patients were not severe enough to justify the procedures.

“The whole marketing of health care is so manipulative to the consuming public,” said Lisa McGiffert, a longtime consumer advocate and co-founder of the Patient Safety Action Network. “People might be encouraged to get a knee replacement, when in reality something less invasive could have improved their condition.”

McGiffert recounted a conversation with an orthopedic surgeon in Washington state who told her about a patient who requested a knee replacement, even though he had not tried any lower-impact treatments to fix the problem. “I asked the surgeon, ‘You didn’t do it, did you?’ And he said, ‘Of course I did. He would just have gone to somebody else.’ ”

This Kaiser Health News story first published on California Healthline, a service of the California Health Care Foundation.

Dr. Ira Weintraub, a recently retired orthopedic surgeon who now works at a medical billing consultancy, saw a hip replacement bill for over $400,000 earlier this year.

“The patient stayed in the hospital 17 days, which is only 17 times normal. The bill got paid,” mused Weintraub, chief medical officer of Portland, Oregon-based WellRithms, which helps self-funded employers and workers’ compensation insurers make sense of large, complex medical bills and ensure they pay the fair amount.

Charges like that go a long way toward explaining why hospitals are eager to restore joint replacements to pre-COVID levels as quickly as possible – an eagerness tempered only by safety concerns amid a resurgence of the coronavirus in some regions of the country. Revenue losses at hospitals and outpatient surgery centers may have exceeded $5 billion from canceled knee and hip replacements alone during a roughly two-month hiatus on elective procedures earlier this year.

The cost of joint replacement surgery varies widely – though, on average, it is in the tens, not hundreds, of thousands of dollars. Still, given the high and rapidly growing volume, it’s easy to see why joint replacement operations have become a vital chunk of revenue at most U.S. hospitals.

The rate of knee and hip replacements more than doubled from 2000 to 2015, according to inpatient discharge data from the Agency for Healthcare Research and Quality. And that growth is likely to continue: Knee replacements are expected to triple between now and 2040, with hip replacements not far behind, according to projections published last year in the Journal of Rheumatology.

Joint procedures are usually not emergencies, and they were among the first to be scrubbed or delayed when hospitals froze elective surgeries in March – and again in July in some areas plagued by renewed COVID outbreaks. Loss of the revenue has hit hospitals hard, and regaining it will be crucial to their financial convalescence.

“Without orthopedic volumes returning to something near their pre-pandemic levels, it will make it difficult for health systems to get back to anywhere near break-even from a bottom-line perspective,” said Stephen Thome, a principal in health care consulting at Grant Thornton, an advisory, audit and tax firm.

It’s impossible to know exactly how much knee and hip replacements are worth to hospitals, because no definitive data on total volume or price exists.

But using published estimates of volume, extrapolating average commercial payments from published Medicare rates based on a study, and making an educated guess of patient coinsurance, Thome helped KHN arrive at an annual market value for American hospitals and surgery centers of between $15.5 billion and $21.5 billion for knee replacements alone.

That suggests a revenue loss of $1.3 billion to $1.8 billion per month for the period the surgeries were shut down. These figures include ambulatory surgery centers not owned by hospitals, which also suspended most operations in late March, all of April and into May.

If you add hip replacements, which account for about half the volume of knees and are paid at similar rates, the total annual value rises to a range of $23 billion to $32 billion, with monthly revenue losses from $1.9 billion to $2.7 billion.

The American Hospital Association projects total revenue lost at U.S. hospitals will reach $323 billion by year’s end, not counting additional losses from surgeries canceled during the current coronavirus spike. That amount is partially offset by $69 billion in federal relief dollars hospitals have received so far, according to the association. The California Hospital Association puts the net revenue loss for hospitals in that state at about $10.5 billion, said spokesperson Jan Emerson-Shea.

Hospitals resumed joint replacement surgeries in early to mid-May, with the timing and ramp-up speed varying by region and hospital. Some hospitals restored volume quickly; others took a more cautious route and continue to lose revenue. Still others have had to shut down again.

At the NYU Langone Orthopedic Hospital in New York City, “people are starting to come in and you see the operating rooms full again,” said Dr. Claudette Lajam, chief orthopedic safety officer.

At St. Jude Medical Center in Fullerton, California, where the coronavirus is raging, inpatient joint replacements resumed in the second or third week of May – cautiously at first, but volume is “very close to pre-pandemic levels at this point,” said Dr. Kevin Khajavi, chairman of the hospital’s orthopedic surgery department. However, “we are constantly monitoring the situation to determine if we have to scale back once again,” he said.

In large swaths of Texas, elective surgeries were once again suspended in July because of the COVID-19 resurgence. The same is true at many hospitals in Florida, Alabama, South Carolina and Nevada.

The Mayo Clinic in Phoenix suspended nonemergency joint replacement surgeries in early July. It resumed outpatient replacement procedures the week of July 27, but still has not resumed nonemergency inpatient procedures, said Dr. Mark Spangehl, an orthopedic surgeon there. In terms of medical urgency, joint replacements are “at the bottom of the totem pole,” Spangehl said.

In terms of cash flow, however, joint replacements are decidedly not at the bottom of the totem pole. They have become a cash cow as the number of patients undergoing them has skyrocketed in recent decades.

The volume is being driven by an aging population, an epidemic of obesity and a significant rise in the number of younger people replacing joints worn out by years of sports and exercise.

It’s also being driven by the cash. Once only done in hospitals, the operations are now increasingly performed at ambulatory surgery centers – especially on younger, healthier patients who don’t require hospitalization.

The surgery centers are often physician-owned, but private equity groups such as Bain Capital and KKR & Co. have taken an interest in them, drawn by their high growth potential, robust financial returns and ability to offer competitive prices.

“[G]enerally the savings should be very good – but I do see a lot of outlier surgery centers where they are charging exorbitant amounts of money – $100,000 wouldn’t be too much,” said WellRithm’s Weintraub, who co-owned such a surgery center in Portland.

Fear of catching the coronavirus in a hospital is reinforcing the outpatient trend. Matthew Davis, a 58-year-old resident of Washington, was scheduled for a hip replacement on March 30 but got cold feet because of COVID-19, and canceled just before all elective surgeries were halted. When it came time to reschedule in June, he overcame his reservations in large part because the surgeon planned to perform the procedure at a free-standing surgery center.

“That was key to me – avoiding an overnight hospital stay to minimize my exposure,” Davis said. “These joint replacements are almost industrial-scale. They are cranking out joint replacements 9 to 5. I went in at 6:30 a.m. and I was walking out the door at 11:30.”

Acutely aware of the financial benefits, hospitals and surgery clinics have been marketing joint replacements for years, competing for coveted rankings and running ads that show healthy aging people, all smiles, engaged in vigorous activity.

However, a 2014 study concluded that one-third of knee replacements were not warranted, mainly because the symptoms of the patients were not severe enough to justify the procedures.

“The whole marketing of health care is so manipulative to the consuming public,” said Lisa McGiffert, a longtime consumer advocate and co-founder of the Patient Safety Action Network. “People might be encouraged to get a knee replacement, when in reality something less invasive could have improved their condition.”

McGiffert recounted a conversation with an orthopedic surgeon in Washington state who told her about a patient who requested a knee replacement, even though he had not tried any lower-impact treatments to fix the problem. “I asked the surgeon, ‘You didn’t do it, did you?’ And he said, ‘Of course I did. He would just have gone to somebody else.’ ”

This Kaiser Health News story first published on California Healthline, a service of the California Health Care Foundation.

Dr. Ira Weintraub, a recently retired orthopedic surgeon who now works at a medical billing consultancy, saw a hip replacement bill for over $400,000 earlier this year.

“The patient stayed in the hospital 17 days, which is only 17 times normal. The bill got paid,” mused Weintraub, chief medical officer of Portland, Oregon-based WellRithms, which helps self-funded employers and workers’ compensation insurers make sense of large, complex medical bills and ensure they pay the fair amount.

Charges like that go a long way toward explaining why hospitals are eager to restore joint replacements to pre-COVID levels as quickly as possible – an eagerness tempered only by safety concerns amid a resurgence of the coronavirus in some regions of the country. Revenue losses at hospitals and outpatient surgery centers may have exceeded $5 billion from canceled knee and hip replacements alone during a roughly two-month hiatus on elective procedures earlier this year.

The cost of joint replacement surgery varies widely – though, on average, it is in the tens, not hundreds, of thousands of dollars. Still, given the high and rapidly growing volume, it’s easy to see why joint replacement operations have become a vital chunk of revenue at most U.S. hospitals.

The rate of knee and hip replacements more than doubled from 2000 to 2015, according to inpatient discharge data from the Agency for Healthcare Research and Quality. And that growth is likely to continue: Knee replacements are expected to triple between now and 2040, with hip replacements not far behind, according to projections published last year in the Journal of Rheumatology.

Joint procedures are usually not emergencies, and they were among the first to be scrubbed or delayed when hospitals froze elective surgeries in March – and again in July in some areas plagued by renewed COVID outbreaks. Loss of the revenue has hit hospitals hard, and regaining it will be crucial to their financial convalescence.

“Without orthopedic volumes returning to something near their pre-pandemic levels, it will make it difficult for health systems to get back to anywhere near break-even from a bottom-line perspective,” said Stephen Thome, a principal in health care consulting at Grant Thornton, an advisory, audit and tax firm.

It’s impossible to know exactly how much knee and hip replacements are worth to hospitals, because no definitive data on total volume or price exists.

But using published estimates of volume, extrapolating average commercial payments from published Medicare rates based on a study, and making an educated guess of patient coinsurance, Thome helped KHN arrive at an annual market value for American hospitals and surgery centers of between $15.5 billion and $21.5 billion for knee replacements alone.

That suggests a revenue loss of $1.3 billion to $1.8 billion per month for the period the surgeries were shut down. These figures include ambulatory surgery centers not owned by hospitals, which also suspended most operations in late March, all of April and into May.

If you add hip replacements, which account for about half the volume of knees and are paid at similar rates, the total annual value rises to a range of $23 billion to $32 billion, with monthly revenue losses from $1.9 billion to $2.7 billion.

The American Hospital Association projects total revenue lost at U.S. hospitals will reach $323 billion by year’s end, not counting additional losses from surgeries canceled during the current coronavirus spike. That amount is partially offset by $69 billion in federal relief dollars hospitals have received so far, according to the association. The California Hospital Association puts the net revenue loss for hospitals in that state at about $10.5 billion, said spokesperson Jan Emerson-Shea.

Hospitals resumed joint replacement surgeries in early to mid-May, with the timing and ramp-up speed varying by region and hospital. Some hospitals restored volume quickly; others took a more cautious route and continue to lose revenue. Still others have had to shut down again.

At the NYU Langone Orthopedic Hospital in New York City, “people are starting to come in and you see the operating rooms full again,” said Dr. Claudette Lajam, chief orthopedic safety officer.

At St. Jude Medical Center in Fullerton, California, where the coronavirus is raging, inpatient joint replacements resumed in the second or third week of May – cautiously at first, but volume is “very close to pre-pandemic levels at this point,” said Dr. Kevin Khajavi, chairman of the hospital’s orthopedic surgery department. However, “we are constantly monitoring the situation to determine if we have to scale back once again,” he said.

In large swaths of Texas, elective surgeries were once again suspended in July because of the COVID-19 resurgence. The same is true at many hospitals in Florida, Alabama, South Carolina and Nevada.

The Mayo Clinic in Phoenix suspended nonemergency joint replacement surgeries in early July. It resumed outpatient replacement procedures the week of July 27, but still has not resumed nonemergency inpatient procedures, said Dr. Mark Spangehl, an orthopedic surgeon there. In terms of medical urgency, joint replacements are “at the bottom of the totem pole,” Spangehl said.

In terms of cash flow, however, joint replacements are decidedly not at the bottom of the totem pole. They have become a cash cow as the number of patients undergoing them has skyrocketed in recent decades.

The volume is being driven by an aging population, an epidemic of obesity and a significant rise in the number of younger people replacing joints worn out by years of sports and exercise.

It’s also being driven by the cash. Once only done in hospitals, the operations are now increasingly performed at ambulatory surgery centers – especially on younger, healthier patients who don’t require hospitalization.

The surgery centers are often physician-owned, but private equity groups such as Bain Capital and KKR & Co. have taken an interest in them, drawn by their high growth potential, robust financial returns and ability to offer competitive prices.

“[G]enerally the savings should be very good – but I do see a lot of outlier surgery centers where they are charging exorbitant amounts of money – $100,000 wouldn’t be too much,” said WellRithm’s Weintraub, who co-owned such a surgery center in Portland.

Fear of catching the coronavirus in a hospital is reinforcing the outpatient trend. Matthew Davis, a 58-year-old resident of Washington, was scheduled for a hip replacement on March 30 but got cold feet because of COVID-19, and canceled just before all elective surgeries were halted. When it came time to reschedule in June, he overcame his reservations in large part because the surgeon planned to perform the procedure at a free-standing surgery center.

“That was key to me – avoiding an overnight hospital stay to minimize my exposure,” Davis said. “These joint replacements are almost industrial-scale. They are cranking out joint replacements 9 to 5. I went in at 6:30 a.m. and I was walking out the door at 11:30.”

Acutely aware of the financial benefits, hospitals and surgery clinics have been marketing joint replacements for years, competing for coveted rankings and running ads that show healthy aging people, all smiles, engaged in vigorous activity.

However, a 2014 study concluded that one-third of knee replacements were not warranted, mainly because the symptoms of the patients were not severe enough to justify the procedures.

“The whole marketing of health care is so manipulative to the consuming public,” said Lisa McGiffert, a longtime consumer advocate and co-founder of the Patient Safety Action Network. “People might be encouraged to get a knee replacement, when in reality something less invasive could have improved their condition.”

McGiffert recounted a conversation with an orthopedic surgeon in Washington state who told her about a patient who requested a knee replacement, even though he had not tried any lower-impact treatments to fix the problem. “I asked the surgeon, ‘You didn’t do it, did you?’ And he said, ‘Of course I did. He would just have gone to somebody else.’ ”

This Kaiser Health News story first published on California Healthline, a service of the California Health Care Foundation.

A new test, the first to combine liquid biopsy and next-generation sequencing (NGS), has been approved by the US Food and Drug Administration (FDA) for use in patients with metastatic non–small cell lung cancer (NSCLC) to identify tumors with specific mutation types of the epidermal growth factor receptor (EGFR) gene.

The Guardant360 CDx assay (Guardant Health) is the first to combine the two technologies into a diagnostic test to guide treatment decisions.

Liquid biopsy offers the advantage of obtaining genetic information on a tumor from a simple blood draw instead of a tissue biopsy, which requires fine-needle aspiration of the lung. “ It is less invasive and more easily repeatable in comparison to standard tissue biopsies ... and can be used in cases in which standard tissue biopsies are not feasible, for instance, due to the location of the tumor,” the FDA commented.

NGS offers the advantage of simultaneously detecting mutations in 55 tumor genes, as opposed to conducting a separate test for each gene.

However, although the assay can provide information on multiple solid tumor biomarkers, the approval is specific only to identifying EGFR mutations in patients who will benefit from treatment with osimertinib (Tagrisso, AstraZeneca).

The approval does not validate the test for use in detecting other biomarkers, the FDA noted.

As previously reported, the assay has a comprehensive NGS panel that identifies seven guideline-recommended predictive biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET, ERBB2) — known as the G7 biomarkers — and one prognostic marker (KRAS).

But the FDA noted that “genomic findings for other biomarkers evaluated are not validated for choosing a particular corresponding treatment with this approval.

“If the specific NSCLC mutations associated with today’s approval are not detected in the blood, then a tumor biopsy should be performed to determine if the NSCLC mutations are present,” the agency emphasized.

Nevertheless, the FDA announcement highlights the potential of the test to identify these other biomarkers.

“Approval of a companion diagnostic that uses a liquid biopsy and leverages next-generation sequencing marks a new era for mutation testing,” Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, commented in a statement. 

“In addition to benefiting from less invasive testing, patients are provided with a simultaneous mapping of multiple biomarkers of genomic alterations, rather than one biomarker at a time, which can translate to decreased wait times for starting treatment and provide insight into possible resistance mechanisms,” he noted.

The manufacturer also highlighted this potential. “We are confident that our FDA approval will help accelerate wider adoption of guideline-recommended genomic profiling, increase the number of advanced cancer patients who receive potentially life-changing treatments, and pave the way for new companion diagnostic developments for the Guardant360 CDx,” Helmy Eltoukhy, PhD, CEO of Guardant Health, said in a statement.

NILE Study

The FDA did not cite any specific trial of the assay in its announcement of the approval, but Medscape Medical News has previously reported results from the NILE study presented at the 2019 Annual Meeting of the American Association for Cancer Research (AACR).

The NILE trial was conducted in 282 patients with untreated nonsquamous NSCLC who underwent standard-of-care tissue genotyping and had a pretreatment blood sample for cell-free DNA (cfDNA) analysis.

Results showed that a G7 biomarker was identified in a significantly higher proportion of liquid biopsies compared with tissue genotyping (27.3% vs 21.3%; P < .0001).

The lower frequency of G7 biomarkers in tissue genotyping was due to insufficient tissue for sequential sequencing, the authors reported at that time.

Liquid biopsy improved G7 detection frequency by 48%, from 60 to 89 patients, which included samples that were negative by tissue testing (7), not tested (16), or lacked sufficient sample for a tissue-based test (6).

Of 193 patients without a G7 biomarker by tissue or cfDNA, 24 patients (12.4%) had an activating KRAS mutation identified in the tissue alone, and with cfDNA, KRAS-positivity increased from 24 to 92 patients.

The Guardant360 CDx assay has been granted a breakthrough device designation, whereby the FDA provides intensive interaction and guidance on efficient device development to the company.
 

This article first appeared on Medscape.com.

A new test, the first to combine liquid biopsy and next-generation sequencing (NGS), has been approved by the US Food and Drug Administration (FDA) for use in patients with metastatic non–small cell lung cancer (NSCLC) to identify tumors with specific mutation types of the epidermal growth factor receptor (EGFR) gene.

The Guardant360 CDx assay (Guardant Health) is the first to combine the two technologies into a diagnostic test to guide treatment decisions.

Liquid biopsy offers the advantage of obtaining genetic information on a tumor from a simple blood draw instead of a tissue biopsy, which requires fine-needle aspiration of the lung. “ It is less invasive and more easily repeatable in comparison to standard tissue biopsies ... and can be used in cases in which standard tissue biopsies are not feasible, for instance, due to the location of the tumor,” the FDA commented.

NGS offers the advantage of simultaneously detecting mutations in 55 tumor genes, as opposed to conducting a separate test for each gene.

However, although the assay can provide information on multiple solid tumor biomarkers, the approval is specific only to identifying EGFR mutations in patients who will benefit from treatment with osimertinib (Tagrisso, AstraZeneca).

The approval does not validate the test for use in detecting other biomarkers, the FDA noted.

As previously reported, the assay has a comprehensive NGS panel that identifies seven guideline-recommended predictive biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET, ERBB2) — known as the G7 biomarkers — and one prognostic marker (KRAS).

But the FDA noted that “genomic findings for other biomarkers evaluated are not validated for choosing a particular corresponding treatment with this approval.

“If the specific NSCLC mutations associated with today’s approval are not detected in the blood, then a tumor biopsy should be performed to determine if the NSCLC mutations are present,” the agency emphasized.

Nevertheless, the FDA announcement highlights the potential of the test to identify these other biomarkers.

“Approval of a companion diagnostic that uses a liquid biopsy and leverages next-generation sequencing marks a new era for mutation testing,” Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, commented in a statement. 

“In addition to benefiting from less invasive testing, patients are provided with a simultaneous mapping of multiple biomarkers of genomic alterations, rather than one biomarker at a time, which can translate to decreased wait times for starting treatment and provide insight into possible resistance mechanisms,” he noted.

The manufacturer also highlighted this potential. “We are confident that our FDA approval will help accelerate wider adoption of guideline-recommended genomic profiling, increase the number of advanced cancer patients who receive potentially life-changing treatments, and pave the way for new companion diagnostic developments for the Guardant360 CDx,” Helmy Eltoukhy, PhD, CEO of Guardant Health, said in a statement.

NILE Study

The FDA did not cite any specific trial of the assay in its announcement of the approval, but Medscape Medical News has previously reported results from the NILE study presented at the 2019 Annual Meeting of the American Association for Cancer Research (AACR).

The NILE trial was conducted in 282 patients with untreated nonsquamous NSCLC who underwent standard-of-care tissue genotyping and had a pretreatment blood sample for cell-free DNA (cfDNA) analysis.

Results showed that a G7 biomarker was identified in a significantly higher proportion of liquid biopsies compared with tissue genotyping (27.3% vs 21.3%; P < .0001).

The lower frequency of G7 biomarkers in tissue genotyping was due to insufficient tissue for sequential sequencing, the authors reported at that time.

Liquid biopsy improved G7 detection frequency by 48%, from 60 to 89 patients, which included samples that were negative by tissue testing (7), not tested (16), or lacked sufficient sample for a tissue-based test (6).

Of 193 patients without a G7 biomarker by tissue or cfDNA, 24 patients (12.4%) had an activating KRAS mutation identified in the tissue alone, and with cfDNA, KRAS-positivity increased from 24 to 92 patients.

The Guardant360 CDx assay has been granted a breakthrough device designation, whereby the FDA provides intensive interaction and guidance on efficient device development to the company.
 

This article first appeared on Medscape.com.

A new test, the first to combine liquid biopsy and next-generation sequencing (NGS), has been approved by the US Food and Drug Administration (FDA) for use in patients with metastatic non–small cell lung cancer (NSCLC) to identify tumors with specific mutation types of the epidermal growth factor receptor (EGFR) gene.

The Guardant360 CDx assay (Guardant Health) is the first to combine the two technologies into a diagnostic test to guide treatment decisions.

Liquid biopsy offers the advantage of obtaining genetic information on a tumor from a simple blood draw instead of a tissue biopsy, which requires fine-needle aspiration of the lung. “ It is less invasive and more easily repeatable in comparison to standard tissue biopsies ... and can be used in cases in which standard tissue biopsies are not feasible, for instance, due to the location of the tumor,” the FDA commented.

NGS offers the advantage of simultaneously detecting mutations in 55 tumor genes, as opposed to conducting a separate test for each gene.

However, although the assay can provide information on multiple solid tumor biomarkers, the approval is specific only to identifying EGFR mutations in patients who will benefit from treatment with osimertinib (Tagrisso, AstraZeneca).

The approval does not validate the test for use in detecting other biomarkers, the FDA noted.

As previously reported, the assay has a comprehensive NGS panel that identifies seven guideline-recommended predictive biomarkers (EGFR, ALK, ROS1, BRAF, RET, MET, ERBB2) — known as the G7 biomarkers — and one prognostic marker (KRAS).

But the FDA noted that “genomic findings for other biomarkers evaluated are not validated for choosing a particular corresponding treatment with this approval.

“If the specific NSCLC mutations associated with today’s approval are not detected in the blood, then a tumor biopsy should be performed to determine if the NSCLC mutations are present,” the agency emphasized.

Nevertheless, the FDA announcement highlights the potential of the test to identify these other biomarkers.

“Approval of a companion diagnostic that uses a liquid biopsy and leverages next-generation sequencing marks a new era for mutation testing,” Tim Stenzel, MD, PhD, director of the Office of In Vitro Diagnostics and Radiological Health in the FDA’s Center for Devices and Radiological Health, commented in a statement. 

“In addition to benefiting from less invasive testing, patients are provided with a simultaneous mapping of multiple biomarkers of genomic alterations, rather than one biomarker at a time, which can translate to decreased wait times for starting treatment and provide insight into possible resistance mechanisms,” he noted.

The manufacturer also highlighted this potential. “We are confident that our FDA approval will help accelerate wider adoption of guideline-recommended genomic profiling, increase the number of advanced cancer patients who receive potentially life-changing treatments, and pave the way for new companion diagnostic developments for the Guardant360 CDx,” Helmy Eltoukhy, PhD, CEO of Guardant Health, said in a statement.

NILE Study

The FDA did not cite any specific trial of the assay in its announcement of the approval, but Medscape Medical News has previously reported results from the NILE study presented at the 2019 Annual Meeting of the American Association for Cancer Research (AACR).

The NILE trial was conducted in 282 patients with untreated nonsquamous NSCLC who underwent standard-of-care tissue genotyping and had a pretreatment blood sample for cell-free DNA (cfDNA) analysis.

Results showed that a G7 biomarker was identified in a significantly higher proportion of liquid biopsies compared with tissue genotyping (27.3% vs 21.3%; P < .0001).

The lower frequency of G7 biomarkers in tissue genotyping was due to insufficient tissue for sequential sequencing, the authors reported at that time.

Liquid biopsy improved G7 detection frequency by 48%, from 60 to 89 patients, which included samples that were negative by tissue testing (7), not tested (16), or lacked sufficient sample for a tissue-based test (6).

Of 193 patients without a G7 biomarker by tissue or cfDNA, 24 patients (12.4%) had an activating KRAS mutation identified in the tissue alone, and with cfDNA, KRAS-positivity increased from 24 to 92 patients.

The Guardant360 CDx assay has been granted a breakthrough device designation, whereby the FDA provides intensive interaction and guidance on efficient device development to the company.
 

This article first appeared on Medscape.com.

Background: Studies have shown improved hospital outcomes in patients who ambulate regularly. Many assisted mobility protocols aimed at ambulating patients multiple times daily are nurse centered. However, implementation is difficult because of the large number of nursing duties and difficulty finding time away from other competing responsibilities.

Dr. Nelson is a hospitalist at Ochsner Health System, New Orleans.

Background: Studies have shown improved hospital outcomes in patients who ambulate regularly. Many assisted mobility protocols aimed at ambulating patients multiple times daily are nurse centered. However, implementation is difficult because of the large number of nursing duties and difficulty finding time away from other competing responsibilities.

Dr. Nelson is a hospitalist at Ochsner Health System, New Orleans.

Background: Studies have shown improved hospital outcomes in patients who ambulate regularly. Many assisted mobility protocols aimed at ambulating patients multiple times daily are nurse centered. However, implementation is difficult because of the large number of nursing duties and difficulty finding time away from other competing responsibilities.

Dr. Nelson is a hospitalist at Ochsner Health System, New Orleans.