Hypersensitivity to implantable devices, albeit rare, is a growing problem. Cutaneous and noncutaneous reactions can occur secondary to metals and metal alloys, according to a report on biological responses to metal implants released by the Food and Drug Administration in September 2019. Large controlled studies are lacking, and the FDA has initiated extensive postmarketing reviews of certain metal implants in response to safety concerns. Further research is needed on the composition of these implants, the diverse spectrum of metals used, the physical environment in which they are implanted, and the immune response associated with implants.

Local and systemic type IV hypersensitivity reactions can result from exposure to metal ions, which are thought to act as haptens and bind to proteins. The hapten-protein complex acts as the antigen for the T cell. Additionally, both acute and chronic inflammatory responses secondary to wound healing and foreign body reactions can occur. Neutrophils and macrophages elicit a tissue response, which can cause aseptic infection, loosening of joints, and tissue damage. Furthermore, corrosion of metal implants can lead to release of metal ions, which can have genotoxic and carcinogenic effects.

Clinical and subclinical effects of implantable devices depend on the device itself, the composition of the device, the tissue type, and an individual’s immune characteristics. Metal debris released from implants can activate innate and adaptive immune responses through a variety of different mechanisms, depending on the implant type and in what tissues the implant is placed. In the case of orthopedic implants, the most common implants, osteoclasts can sense metal and induce proinflammatory cytokines, which can result in corrosion and uptake of metal particles. Metal devices used in the central nervous system, such as intracerebral electrodes, can cause inflammatory responses leading to tissue encapsulation of electrodes. Corrosion of electrodes and release of metal ions can also impede ion channels in the CNS, blocking critical neuron-signaling pathways. Inflammatory reactions surrounding cardiac and vascular implants containing metal activate coagulation cascades, resulting in endothelial injury and activation of thrombi.

Despite the commonly used term “metal allergy” that delineates a type IV hypersensitivity reaction, reports in the literature supports the existence of both innate and adaptive immune responses to metal implanted in tissues. The recommended terminology is “adverse reactions to metal debris.” The clinical presentation may not be straightforward or easily attributed to the implant. Diagnostic tools are limited and may not detect a causal relationship.

Clinical symptoms can range from local rashes and pruritus to cardiac damage, depression, vertigo, and neurologic symptoms; autoimmune/autoinflammatory reactions including chronic fatigue and autoimmune-like systemic symptoms, such as joint pain, headaches, and hair loss, have also been reported in association with implants containing metal. In addition to pruritus, dermatologic manifestations can include erythema, edema, papules, vesicles, as well as systemic hypersensitivity reactions. Typically, cutaneous reactions usually present within 2 days to 24 months of implantation and may be considered surgical-site infections. Although these reactions can be treated with topical or oral corticosteroids, removal of the device is frequently needed for complete clearance.

In clinical practice, it has been frustrating that potential adverse reactions to metal implants are often overlooked because they are thought to be so rare. There are case series documenting metal implant hypersensitivity, but the actual prevalence of hypersensitivity or autoinflammatory reactions is not known. Testing methods are often inaccurate; therefore, identification of at-risk individuals and management of symptomatic patients with implants is important.

The 2016 American Contact Dermatitis Society guidelines do not recommend preimplantation patch testing unless there is a suspected metal allergy. However, patch testing cannot identify the extent of corrosion, autoinflammatory reactions, and foreign body reactions that can occur.

We must keep an open mind in patients who have implanted devices and have unusual or otherwise undefined symptoms. Often, the symptoms do not directly correspond to the site of implantation and the only way to discern whether the implant is the cause and to treat symptoms is removal of the implanted device.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

 

References

Food and Drug Administration. Biological Responses to Metal Implants. 2019 Sep. https://www.fda.gov/media/131150/download.

Atwater AR, Reeder M. Cutis. 2020 Feb;105(2):68-70.

Schalock PC et al. Dermatitis. Sep-Oct 2016;27(5):241-7.

Hypersensitivity to implantable devices, albeit rare, is a growing problem. Cutaneous and noncutaneous reactions can occur secondary to metals and metal alloys, according to a report on biological responses to metal implants released by the Food and Drug Administration in September 2019. Large controlled studies are lacking, and the FDA has initiated extensive postmarketing reviews of certain metal implants in response to safety concerns. Further research is needed on the composition of these implants, the diverse spectrum of metals used, the physical environment in which they are implanted, and the immune response associated with implants.

Local and systemic type IV hypersensitivity reactions can result from exposure to metal ions, which are thought to act as haptens and bind to proteins. The hapten-protein complex acts as the antigen for the T cell. Additionally, both acute and chronic inflammatory responses secondary to wound healing and foreign body reactions can occur. Neutrophils and macrophages elicit a tissue response, which can cause aseptic infection, loosening of joints, and tissue damage. Furthermore, corrosion of metal implants can lead to release of metal ions, which can have genotoxic and carcinogenic effects.

Clinical and subclinical effects of implantable devices depend on the device itself, the composition of the device, the tissue type, and an individual’s immune characteristics. Metal debris released from implants can activate innate and adaptive immune responses through a variety of different mechanisms, depending on the implant type and in what tissues the implant is placed. In the case of orthopedic implants, the most common implants, osteoclasts can sense metal and induce proinflammatory cytokines, which can result in corrosion and uptake of metal particles. Metal devices used in the central nervous system, such as intracerebral electrodes, can cause inflammatory responses leading to tissue encapsulation of electrodes. Corrosion of electrodes and release of metal ions can also impede ion channels in the CNS, blocking critical neuron-signaling pathways. Inflammatory reactions surrounding cardiac and vascular implants containing metal activate coagulation cascades, resulting in endothelial injury and activation of thrombi.

Despite the commonly used term “metal allergy” that delineates a type IV hypersensitivity reaction, reports in the literature supports the existence of both innate and adaptive immune responses to metal implanted in tissues. The recommended terminology is “adverse reactions to metal debris.” The clinical presentation may not be straightforward or easily attributed to the implant. Diagnostic tools are limited and may not detect a causal relationship.

Clinical symptoms can range from local rashes and pruritus to cardiac damage, depression, vertigo, and neurologic symptoms; autoimmune/autoinflammatory reactions including chronic fatigue and autoimmune-like systemic symptoms, such as joint pain, headaches, and hair loss, have also been reported in association with implants containing metal. In addition to pruritus, dermatologic manifestations can include erythema, edema, papules, vesicles, as well as systemic hypersensitivity reactions. Typically, cutaneous reactions usually present within 2 days to 24 months of implantation and may be considered surgical-site infections. Although these reactions can be treated with topical or oral corticosteroids, removal of the device is frequently needed for complete clearance.

In clinical practice, it has been frustrating that potential adverse reactions to metal implants are often overlooked because they are thought to be so rare. There are case series documenting metal implant hypersensitivity, but the actual prevalence of hypersensitivity or autoinflammatory reactions is not known. Testing methods are often inaccurate; therefore, identification of at-risk individuals and management of symptomatic patients with implants is important.

The 2016 American Contact Dermatitis Society guidelines do not recommend preimplantation patch testing unless there is a suspected metal allergy. However, patch testing cannot identify the extent of corrosion, autoinflammatory reactions, and foreign body reactions that can occur.

We must keep an open mind in patients who have implanted devices and have unusual or otherwise undefined symptoms. Often, the symptoms do not directly correspond to the site of implantation and the only way to discern whether the implant is the cause and to treat symptoms is removal of the implanted device.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

 

References

Food and Drug Administration. Biological Responses to Metal Implants. 2019 Sep. https://www.fda.gov/media/131150/download.

Atwater AR, Reeder M. Cutis. 2020 Feb;105(2):68-70.

Schalock PC et al. Dermatitis. Sep-Oct 2016;27(5):241-7.

Hypersensitivity to implantable devices, albeit rare, is a growing problem. Cutaneous and noncutaneous reactions can occur secondary to metals and metal alloys, according to a report on biological responses to metal implants released by the Food and Drug Administration in September 2019. Large controlled studies are lacking, and the FDA has initiated extensive postmarketing reviews of certain metal implants in response to safety concerns. Further research is needed on the composition of these implants, the diverse spectrum of metals used, the physical environment in which they are implanted, and the immune response associated with implants.

Local and systemic type IV hypersensitivity reactions can result from exposure to metal ions, which are thought to act as haptens and bind to proteins. The hapten-protein complex acts as the antigen for the T cell. Additionally, both acute and chronic inflammatory responses secondary to wound healing and foreign body reactions can occur. Neutrophils and macrophages elicit a tissue response, which can cause aseptic infection, loosening of joints, and tissue damage. Furthermore, corrosion of metal implants can lead to release of metal ions, which can have genotoxic and carcinogenic effects.

Clinical and subclinical effects of implantable devices depend on the device itself, the composition of the device, the tissue type, and an individual’s immune characteristics. Metal debris released from implants can activate innate and adaptive immune responses through a variety of different mechanisms, depending on the implant type and in what tissues the implant is placed. In the case of orthopedic implants, the most common implants, osteoclasts can sense metal and induce proinflammatory cytokines, which can result in corrosion and uptake of metal particles. Metal devices used in the central nervous system, such as intracerebral electrodes, can cause inflammatory responses leading to tissue encapsulation of electrodes. Corrosion of electrodes and release of metal ions can also impede ion channels in the CNS, blocking critical neuron-signaling pathways. Inflammatory reactions surrounding cardiac and vascular implants containing metal activate coagulation cascades, resulting in endothelial injury and activation of thrombi.

Despite the commonly used term “metal allergy” that delineates a type IV hypersensitivity reaction, reports in the literature supports the existence of both innate and adaptive immune responses to metal implanted in tissues. The recommended terminology is “adverse reactions to metal debris.” The clinical presentation may not be straightforward or easily attributed to the implant. Diagnostic tools are limited and may not detect a causal relationship.

Clinical symptoms can range from local rashes and pruritus to cardiac damage, depression, vertigo, and neurologic symptoms; autoimmune/autoinflammatory reactions including chronic fatigue and autoimmune-like systemic symptoms, such as joint pain, headaches, and hair loss, have also been reported in association with implants containing metal. In addition to pruritus, dermatologic manifestations can include erythema, edema, papules, vesicles, as well as systemic hypersensitivity reactions. Typically, cutaneous reactions usually present within 2 days to 24 months of implantation and may be considered surgical-site infections. Although these reactions can be treated with topical or oral corticosteroids, removal of the device is frequently needed for complete clearance.

In clinical practice, it has been frustrating that potential adverse reactions to metal implants are often overlooked because they are thought to be so rare. There are case series documenting metal implant hypersensitivity, but the actual prevalence of hypersensitivity or autoinflammatory reactions is not known. Testing methods are often inaccurate; therefore, identification of at-risk individuals and management of symptomatic patients with implants is important.

The 2016 American Contact Dermatitis Society guidelines do not recommend preimplantation patch testing unless there is a suspected metal allergy. However, patch testing cannot identify the extent of corrosion, autoinflammatory reactions, and foreign body reactions that can occur.

We must keep an open mind in patients who have implanted devices and have unusual or otherwise undefined symptoms. Often, the symptoms do not directly correspond to the site of implantation and the only way to discern whether the implant is the cause and to treat symptoms is removal of the implanted device.

Dr. Wesley and Dr. Talakoub are cocontributors to this column. Dr. Wesley practices dermatology in Beverly Hills, Calif. Dr. Talakoub is in private practice in McLean, Va. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

 

References

Food and Drug Administration. Biological Responses to Metal Implants. 2019 Sep. https://www.fda.gov/media/131150/download.

Atwater AR, Reeder M. Cutis. 2020 Feb;105(2):68-70.

Schalock PC et al. Dermatitis. Sep-Oct 2016;27(5):241-7.

The Food and Drug Administration has approved Kesimpta ofatumumab (Kesimpta) injection for the treatment of adults with relapsing forms of multiple sclerosis, including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.

“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.

Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.

Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.

Twin studies

Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.

The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.

As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.

The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.

Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).

The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.

Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.

The drug is expected to be available in the United States in September.

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

The Food and Drug Administration has approved Kesimpta ofatumumab (Kesimpta) injection for the treatment of adults with relapsing forms of multiple sclerosis, including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.

“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.

Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.

Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.

Twin studies

Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.

The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.

As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.

The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.

Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).

The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.

Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.

The drug is expected to be available in the United States in September.

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

The Food and Drug Administration has approved Kesimpta ofatumumab (Kesimpta) injection for the treatment of adults with relapsing forms of multiple sclerosis, including relapsing-remitting MS, active secondary progressive MS, and clinically isolated syndrome, Novartis announced in a press release. This is the first FDA approval of a self-administered, targeted B-cell therapy for these conditions, and is delivered via an autoinjector pen.

“This approval is wonderful news for patients with relapsing multiple sclerosis,” Stephen Hauser, MD, director of the Weill Institute for Neurosciences at the University of California, San Francisco, said in the press release. “Through its favorable safety profile and well-tolerated monthly injection regimen, patients can self-administer the treatment at home, avoiding visits to the infusion center,” he noted.

Dr. Hauser is cochair of the steering committee for the phase 3 ASCLEPIOS I and II studies that were part of the basis for the FDA’s approval.

Bruce Bebo, PhD, executive vice president of research at the National MS Society, said because response to disease-modifying treatments varies among individuals with MS, it’s important to have a range of treatment options available with differing mechanisms of action. “We are pleased to have an additional option approved for the treatment of relapsing forms of MS,” he said.

Twin studies

Formerly known as OMB157, ofatumumab is a precisely-dosed anti-CD20 monoclonal antibody administered subcutaneously via once-monthly injection. However, Novartis noted that initial doses are given at weeks 0, 1, and 2 – with the first injection occurring with a health care professional present.

The drug “is thought to work by binding to a distinct epitope on the CD20 molecule inducing potent B-cell lysis and depletion,” the manufacturer noted.

As previously reported, results for the ACLEPIOS I and II studies were presented at the 2019 Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), with additional results presented at the 2020 Virtual Annual Meeting of the Consortium of Multiple Sclerosis Centers. In addition, the findings were published in the New England Journal of Medicine.

The twin, identically designed phase 3 studies assessed the safety and efficacy of the drug at a monthly subcutaneous dose of 20 mg versus once daily teriflunomide 14-mg oral tablets. Together, the studies included 1,882 adult patients at more than 350 sites in 37 countries.

Results showed that the study drug reduced the annualized relapse rate (ARR) by 51% in the first study and by 59% in the second versus teriflunomide (P < .001 in both studies), meeting the primary endpoint. Both studies also showed significant reductions of gadolinium-enhancing (Gd+) T1 lesions (by 98% and 94%, respectively) and new or enlarging T2 lesions (by 82% and 85%).

The most commonly observed treatment-related adverse events for ofatumumab were upper respiratory tract infection, headache, and injection-related reactions.

Although the FDA first approved ofatumumab in 2009 for treating chronic lymphocytic leukemia (CLL), it was administered as a high-dose intravenous infusion by a healthcare provider. “This is a different dosing regimen and route of administration than was previously approved for the CLL indication,” the company noted.

The drug is expected to be available in the United States in September.

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

Editor’s Note: This transcript from the August 20 episode of the Blood & Cancer podcast has been edited for clarity. Click this link to listen to the full episode.

David Henry, MD: Welcome to this Blood & Cancer podcast. I’m your host, Dr. David Henry. This podcast airs on Thursday morning each week. This interview and others are archived with show notes from our residents at Pennsylvania Hospital at this link.

Each week we interview key opinion leaders involved in various aspects of blood and cancer. Today, we have a different kind of key opinion leader, as I have the privilege of interviewing Mason Plumlee, a forward with the National Basketball Association’s (NBA) Denver Nuggets. Mason was a first round pick in the NBA, a gold medalist for the U.S. men’s national team, and NBA All-Rookie first team honoree. He’s one of the top playmaking forwards in the country, if not the world, in my opinion. In his four-year college career at Duke University, he helped lead the Blue Devils to a National Collegiate Athletic Association (NCAA) championship and twice earned All-America first team academic honors at Duke. So he’s not just a basketball star, but an academic star as well. Mason, thanks so much for taking some time out from the bubble in Florida to talk with us today.
 

Mason Plumlee: Thanks for having me on. I’m happy to be here.

Henry: Beginning in March, the NBA didn’t know what to do about the COVID pandemic but finally decided to put you professional players in a ‘bubble.’ What did you have to go through to get there? You, your teammates, coaches, trainers, etc. And what’s the ongoing plan to be sure you continue to be safe?

Plumlee: Back to when the season shut down in March, the NBA shut down the practice facilities at the same time. Most people went home. I went back to Indiana. And then, as the idea of this bubble came up and the NBA formalized a plan to start the season again, players started to go back to market. I went back to Denver and was working out there.

About two weeks before we were scheduled to arrive in Orlando, they started testing us every other day. They used the deep nasal swab as well as the throat swab. But they were also taking two to three blood tests in that time period. You needed a certain number of consecutive negative tests before they would allow you to fly on the team plane down to Orlando. So there was an incredible amount of testing in the market. Once you got to Orlando, you went into a 48-hour quarantine. You had to have two negative tests with 48 hours between them before you could leave your hotel room.

Since then, it’s been quite strict down here. And although it’s annoying in a lot of ways, I think it’s one of the reasons our league has been able to pull this off. We’ve had no positive tests within the bubble and we are tested every day. A company called BioReference Laboratories has a setup in one of the meeting rooms here, and it’s like clockwork—we go in, we get our tests. One of my teammates missed a test and they made him stay in his room until he could get another test and get the results, so he missed a game because of that.
 

Henry: During this bubble time, no one has tested positive—players, coaches, staff?

Plumlee: Correct.

Henry: That’s incredible, and it’s allowed those of us who want to watch the NBA and those of you who are in it professionally to continue the sport. It must be a real nuisance for you and your family and friends, because no one can visit you, right?

Plumlee: Right. There’s no visitation. We had one false positive. It was our media relations person and the actions they took when that positive test came in -- they quarantined him in his room and interviewed everybody he had talked to; they tested anyone who had any interaction with him and those people had to go into quarantine. They’re on top of things down here. In addition to the testing, we each have a pulse oximeter and a thermometer, and we use these to check in everyday on an app. So, they’re getting all the insight they need. After the first round of the playoffs, they’re going to open the bubble to friends and family, but those friends and family will be subject to all the same protocols that we were coming in and once they’re here as well.

Henry: I’m sure you’ve heard about the Broadway star [Nick Cordero] who was healthy and suddenly got sick, lost a leg, and then lost his life. There have been some heart attacks that surprised us. Have your colleagues—players, coaches, etc.—been worried? Or are they thinking, what’s the big deal? Has the sense of how serious this is permeated through this sport?

Plumlee: The NBA is one of the groups that has heightened the understanding and awareness of this by shutting down. I think a lot of people were moving forward as is, and then, when the NBA decided to cancel the season, it let the world know, look, this is to be taken seriously.

Henry: A couple of players did test positive early on.

Plumlee: Exactly. A couple of people tested positive. I think at the outset, the unknown is always scarier. As we’ve learned more about the virus, the guys have become more comfortable. You know, I tested positive back in March. At the time, a loss of taste and smell was not a reported symptom.

Henry: And you had that?

Plumlee: I did have that, but I didn’t know what to think. More research has come out and we have a better understanding of that. I think most of the players are comfortable with the virus. We’re at a time in our lives where we’re healthy, we’re active, and we should be able to fight it off. We know the numbers for our age group. Even still, I think nobody wants to get it. Nobody wants to have to go through it. So why chance it?

Henry: Hats off to you and your sport. Other sports such as Major League Baseball haven’t been quite so successful. Of course, they’re wrestling with the players testing positive, and this has stopped games this season.

I was looking over your background prior to the interview and learned that your mother and father have been involved in the medical arena. Can you tell us about that and how it’s rubbed off on you?

Plumlee: Definitely. My mom is a pharmacist, so I spent a lot of time as a kid going to see her at work. And my dad is general counsel for an orthopedic company. My hometown is Warsaw, Ind. Some people refer to it as the “Orthopedic Capital of the World.” Zimmer Biomet is headquartered there. DePuy Synthes is there. Medtronic has offices there, as well as a lot of cottage businesses that support the orthopedic industry. In my hometown, the rock star was Dane Miller, who founded Biomet. I have no formal education in medicine or health care, but I’ve seen the impact of it. From my parents and some cousins, uncles who are doctors and surgeons, it’s been interesting to see their work and learn about what’s the latest and greatest in health care.

Henry: What’s so nice about you in particular is, with that background of interests from your family and your celebrity and accomplishments in professional basketball, you have used that to explore and promote ways to make progress in health care and help others who are less fortunate. For example, you’re involved in a telehealth platform for all-in-one practice management; affordable telehealth for pediatrics; health benefits for small businesses; prior authorization—if you can help with prior authorization, we will be in the stands for you at every game because it’s the bane of our existence; radiotherapy; and probably from mom’s background, pharmacy benefit management. Pick any of those you’d like to talk about, and tell us about your involvement and how it’s going.

Plumlee: My ticket into the arena is investment. Nobody’s calling me, asking for my expertise. But a lot of these visionary founders need financial support, and that’s where I get involved. Then also, with the celebrity angle from being an athlete, sometimes you can open doors for a start-up founder that they may not be able to open themselves.

I’m happy to speak about any of those companies. I am excited about the relaxed regulation that’s come from the pandemic; not that it’s like the Wild West out here, but I think it has allowed companies to implement solutions or think about problems in a way that they couldn’t before the pandemic. Take the prior authorization play, for example, and a company called Banjo Health, with one of my favorite founders, a guy named Saar Mahna. Medicare mandates that you turn around prior authorizations within three days. This company has an artificial intelligence and machine-learning play on prior authorizations that can deliver on that.

So efficiencies, things that increase access or affordability, better outcomes, those are the things that attract me. I lean on other people for the due diligence. The pediatric play that you referenced is a company called Blueberry Pediatrics. You have a monthly subscription for $15 that can be reimbursed by Medicaid. They send two devices to your home—an otoscope and an oximeter. The company is live in Florida right now, and it’s diverting a ton of emergency room (ER) visits. From home, for $15 a month, a mom has an otoscope and an oximeter, and she can chat or video conference with a pediatrician. There’s no additional fee. So that’s saving everyone time and saving the system money. Those are the kinds of things I’m attracted to.

Henry: You’ve touched on a couple of hot button issues for us. In oncology, unfortunately, most of our patients have pain. I am mystified every time I try to get a narcotic or a strong painkiller for a patient on a Friday night and I’m told it requires prior authorization and they’ll open up again on Monday. Well, that’s insane. These patients need something right away. So if you have a special interest in helping all of us with prior authorization, the artificial intelligence is a no brainer. If this kind of computer algorithm could happen overnight, that would be wonderful.

You mentioned the ER. Many people go to the ER as a default. They don’t know what else to do. In the COVID era, we’re trying to dial that down because we want to be able to see the sickest and have the non-sick get care elsewhere. If this particular person or people don’t know what to do, they go to the ER, it costs money, takes a lot of time, and others who may be sick are diverted from care. Families worry terribly about their children, so a device for mom and access to a pediatrician for $15 a month is another wonderful idea. These are both very interesting. Another company is in the pharmacy benefit management (PBM) space. Anything you could say about how that works?
 

Plumlee: I can give an overview of how I look at this as an investor in the PBM space. Three companies control about 75% of a multibillion dollar market. Several initiatives have been pursued politically to provide transparent pricing between these PBMs and pharmaceutical companies, and a lot of people are pointing fingers, but ultimately, drug prices just keep going up. Everybody knows it.

A couple of start-up founders are really set on bringing a competitive marketplace back to the pharmacy benefit manager. As an investor, when you see three people controlling a market, and you have small or medium PBMs that depend on aggregators to get competitive pricing with those big three, you get interested. It’s an interesting industry. My feeling is that somebody is going to disrupt it and bring competition back to that space. Ultimately, drug prices will come down because it’s not sustainable. The insurance companies just accommodate whatever the drug pricing is. If the drug prices go up, your premiums go up. I think these new companies will be level-setting.
 

Henry: In my world of oncology, we’re just a little more than halfway through 2020 and we’ve had five, six, seven new drugs approved. They all will be very expensive. One of the nicer things that’s happening and may help to tamp this down involves biosimilars. When you go to CVS or Rite Aid, you go down the aspirin aisle and see the generics, and they’re identical to the brand name aspirin. Well, these very complex molecules we used to treat cancer are antibodies or proteins, and they’re made in nature’s factories called cells. They’re not identical to the brand name drugs, but they’re called biosimilars. They work exactly the same as the branded drugs with exactly the same safety–our U.S. FDA has done a nice job of vetting that, to be sure. X, Y, Z Company has copied the brand drug after the patent expires. They were hoping for about a 30% discount in price but we’re seeing more like 15%. Nothing’s ever easy. So you make a very good point. This is not sustainable and the competition will be wonderful to tamp down these prices.

Plumlee: My hope is that those biosimilars and generics get placement in these formularies because the formularies are what’s valuable to the drug manufacturers. But they have to accommodate what the Big Three want in the PBM space. To me, making things affordable and accessible is what a lot of these startups are trying to do. And hopefully they will win.

Henry: What have you been going through, in terms of COVID? Have you recovered fully? Have your taste and smell returned, and you’re back to normal?

Plumlee: I’m all good. It caught me off guard but the symptoms weren’t too intense. For me, it was less than a flu, but more than a cold. And I’m all good today.

Henry: We’re so glad and wish you the best of luck.

Dr. Henry is a clinical professor of medicine at the University of Pennsylvania and vice chairman of the department of medicine at Pennsylvania Hospital in Philadelphia and the host of the Blood & Cancer podcast. He has no relevant financial conflicts.

Mr. Plumlee is a board advisor to both Formsense and the Prysm Institute and a board observer with Voiceitt.

Editor’s Note: This transcript from the August 20 episode of the Blood & Cancer podcast has been edited for clarity. Click this link to listen to the full episode.

David Henry, MD: Welcome to this Blood & Cancer podcast. I’m your host, Dr. David Henry. This podcast airs on Thursday morning each week. This interview and others are archived with show notes from our residents at Pennsylvania Hospital at this link.

Each week we interview key opinion leaders involved in various aspects of blood and cancer. Today, we have a different kind of key opinion leader, as I have the privilege of interviewing Mason Plumlee, a forward with the National Basketball Association’s (NBA) Denver Nuggets. Mason was a first round pick in the NBA, a gold medalist for the U.S. men’s national team, and NBA All-Rookie first team honoree. He’s one of the top playmaking forwards in the country, if not the world, in my opinion. In his four-year college career at Duke University, he helped lead the Blue Devils to a National Collegiate Athletic Association (NCAA) championship and twice earned All-America first team academic honors at Duke. So he’s not just a basketball star, but an academic star as well. Mason, thanks so much for taking some time out from the bubble in Florida to talk with us today.
 

Mason Plumlee: Thanks for having me on. I’m happy to be here.

Henry: Beginning in March, the NBA didn’t know what to do about the COVID pandemic but finally decided to put you professional players in a ‘bubble.’ What did you have to go through to get there? You, your teammates, coaches, trainers, etc. And what’s the ongoing plan to be sure you continue to be safe?

Plumlee: Back to when the season shut down in March, the NBA shut down the practice facilities at the same time. Most people went home. I went back to Indiana. And then, as the idea of this bubble came up and the NBA formalized a plan to start the season again, players started to go back to market. I went back to Denver and was working out there.

About two weeks before we were scheduled to arrive in Orlando, they started testing us every other day. They used the deep nasal swab as well as the throat swab. But they were also taking two to three blood tests in that time period. You needed a certain number of consecutive negative tests before they would allow you to fly on the team plane down to Orlando. So there was an incredible amount of testing in the market. Once you got to Orlando, you went into a 48-hour quarantine. You had to have two negative tests with 48 hours between them before you could leave your hotel room.

Since then, it’s been quite strict down here. And although it’s annoying in a lot of ways, I think it’s one of the reasons our league has been able to pull this off. We’ve had no positive tests within the bubble and we are tested every day. A company called BioReference Laboratories has a setup in one of the meeting rooms here, and it’s like clockwork—we go in, we get our tests. One of my teammates missed a test and they made him stay in his room until he could get another test and get the results, so he missed a game because of that.
 

Henry: During this bubble time, no one has tested positive—players, coaches, staff?

Plumlee: Correct.

Henry: That’s incredible, and it’s allowed those of us who want to watch the NBA and those of you who are in it professionally to continue the sport. It must be a real nuisance for you and your family and friends, because no one can visit you, right?

Plumlee: Right. There’s no visitation. We had one false positive. It was our media relations person and the actions they took when that positive test came in -- they quarantined him in his room and interviewed everybody he had talked to; they tested anyone who had any interaction with him and those people had to go into quarantine. They’re on top of things down here. In addition to the testing, we each have a pulse oximeter and a thermometer, and we use these to check in everyday on an app. So, they’re getting all the insight they need. After the first round of the playoffs, they’re going to open the bubble to friends and family, but those friends and family will be subject to all the same protocols that we were coming in and once they’re here as well.

Henry: I’m sure you’ve heard about the Broadway star [Nick Cordero] who was healthy and suddenly got sick, lost a leg, and then lost his life. There have been some heart attacks that surprised us. Have your colleagues—players, coaches, etc.—been worried? Or are they thinking, what’s the big deal? Has the sense of how serious this is permeated through this sport?

Plumlee: The NBA is one of the groups that has heightened the understanding and awareness of this by shutting down. I think a lot of people were moving forward as is, and then, when the NBA decided to cancel the season, it let the world know, look, this is to be taken seriously.

Henry: A couple of players did test positive early on.

Plumlee: Exactly. A couple of people tested positive. I think at the outset, the unknown is always scarier. As we’ve learned more about the virus, the guys have become more comfortable. You know, I tested positive back in March. At the time, a loss of taste and smell was not a reported symptom.

Henry: And you had that?

Plumlee: I did have that, but I didn’t know what to think. More research has come out and we have a better understanding of that. I think most of the players are comfortable with the virus. We’re at a time in our lives where we’re healthy, we’re active, and we should be able to fight it off. We know the numbers for our age group. Even still, I think nobody wants to get it. Nobody wants to have to go through it. So why chance it?

Henry: Hats off to you and your sport. Other sports such as Major League Baseball haven’t been quite so successful. Of course, they’re wrestling with the players testing positive, and this has stopped games this season.

I was looking over your background prior to the interview and learned that your mother and father have been involved in the medical arena. Can you tell us about that and how it’s rubbed off on you?

Plumlee: Definitely. My mom is a pharmacist, so I spent a lot of time as a kid going to see her at work. And my dad is general counsel for an orthopedic company. My hometown is Warsaw, Ind. Some people refer to it as the “Orthopedic Capital of the World.” Zimmer Biomet is headquartered there. DePuy Synthes is there. Medtronic has offices there, as well as a lot of cottage businesses that support the orthopedic industry. In my hometown, the rock star was Dane Miller, who founded Biomet. I have no formal education in medicine or health care, but I’ve seen the impact of it. From my parents and some cousins, uncles who are doctors and surgeons, it’s been interesting to see their work and learn about what’s the latest and greatest in health care.

Henry: What’s so nice about you in particular is, with that background of interests from your family and your celebrity and accomplishments in professional basketball, you have used that to explore and promote ways to make progress in health care and help others who are less fortunate. For example, you’re involved in a telehealth platform for all-in-one practice management; affordable telehealth for pediatrics; health benefits for small businesses; prior authorization—if you can help with prior authorization, we will be in the stands for you at every game because it’s the bane of our existence; radiotherapy; and probably from mom’s background, pharmacy benefit management. Pick any of those you’d like to talk about, and tell us about your involvement and how it’s going.

Plumlee: My ticket into the arena is investment. Nobody’s calling me, asking for my expertise. But a lot of these visionary founders need financial support, and that’s where I get involved. Then also, with the celebrity angle from being an athlete, sometimes you can open doors for a start-up founder that they may not be able to open themselves.

I’m happy to speak about any of those companies. I am excited about the relaxed regulation that’s come from the pandemic; not that it’s like the Wild West out here, but I think it has allowed companies to implement solutions or think about problems in a way that they couldn’t before the pandemic. Take the prior authorization play, for example, and a company called Banjo Health, with one of my favorite founders, a guy named Saar Mahna. Medicare mandates that you turn around prior authorizations within three days. This company has an artificial intelligence and machine-learning play on prior authorizations that can deliver on that.

So efficiencies, things that increase access or affordability, better outcomes, those are the things that attract me. I lean on other people for the due diligence. The pediatric play that you referenced is a company called Blueberry Pediatrics. You have a monthly subscription for $15 that can be reimbursed by Medicaid. They send two devices to your home—an otoscope and an oximeter. The company is live in Florida right now, and it’s diverting a ton of emergency room (ER) visits. From home, for $15 a month, a mom has an otoscope and an oximeter, and she can chat or video conference with a pediatrician. There’s no additional fee. So that’s saving everyone time and saving the system money. Those are the kinds of things I’m attracted to.

Henry: You’ve touched on a couple of hot button issues for us. In oncology, unfortunately, most of our patients have pain. I am mystified every time I try to get a narcotic or a strong painkiller for a patient on a Friday night and I’m told it requires prior authorization and they’ll open up again on Monday. Well, that’s insane. These patients need something right away. So if you have a special interest in helping all of us with prior authorization, the artificial intelligence is a no brainer. If this kind of computer algorithm could happen overnight, that would be wonderful.

You mentioned the ER. Many people go to the ER as a default. They don’t know what else to do. In the COVID era, we’re trying to dial that down because we want to be able to see the sickest and have the non-sick get care elsewhere. If this particular person or people don’t know what to do, they go to the ER, it costs money, takes a lot of time, and others who may be sick are diverted from care. Families worry terribly about their children, so a device for mom and access to a pediatrician for $15 a month is another wonderful idea. These are both very interesting. Another company is in the pharmacy benefit management (PBM) space. Anything you could say about how that works?
 

Plumlee: I can give an overview of how I look at this as an investor in the PBM space. Three companies control about 75% of a multibillion dollar market. Several initiatives have been pursued politically to provide transparent pricing between these PBMs and pharmaceutical companies, and a lot of people are pointing fingers, but ultimately, drug prices just keep going up. Everybody knows it.

A couple of start-up founders are really set on bringing a competitive marketplace back to the pharmacy benefit manager. As an investor, when you see three people controlling a market, and you have small or medium PBMs that depend on aggregators to get competitive pricing with those big three, you get interested. It’s an interesting industry. My feeling is that somebody is going to disrupt it and bring competition back to that space. Ultimately, drug prices will come down because it’s not sustainable. The insurance companies just accommodate whatever the drug pricing is. If the drug prices go up, your premiums go up. I think these new companies will be level-setting.
 

Henry: In my world of oncology, we’re just a little more than halfway through 2020 and we’ve had five, six, seven new drugs approved. They all will be very expensive. One of the nicer things that’s happening and may help to tamp this down involves biosimilars. When you go to CVS or Rite Aid, you go down the aspirin aisle and see the generics, and they’re identical to the brand name aspirin. Well, these very complex molecules we used to treat cancer are antibodies or proteins, and they’re made in nature’s factories called cells. They’re not identical to the brand name drugs, but they’re called biosimilars. They work exactly the same as the branded drugs with exactly the same safety–our U.S. FDA has done a nice job of vetting that, to be sure. X, Y, Z Company has copied the brand drug after the patent expires. They were hoping for about a 30% discount in price but we’re seeing more like 15%. Nothing’s ever easy. So you make a very good point. This is not sustainable and the competition will be wonderful to tamp down these prices.

Plumlee: My hope is that those biosimilars and generics get placement in these formularies because the formularies are what’s valuable to the drug manufacturers. But they have to accommodate what the Big Three want in the PBM space. To me, making things affordable and accessible is what a lot of these startups are trying to do. And hopefully they will win.

Henry: What have you been going through, in terms of COVID? Have you recovered fully? Have your taste and smell returned, and you’re back to normal?

Plumlee: I’m all good. It caught me off guard but the symptoms weren’t too intense. For me, it was less than a flu, but more than a cold. And I’m all good today.

Henry: We’re so glad and wish you the best of luck.

Dr. Henry is a clinical professor of medicine at the University of Pennsylvania and vice chairman of the department of medicine at Pennsylvania Hospital in Philadelphia and the host of the Blood & Cancer podcast. He has no relevant financial conflicts.

Mr. Plumlee is a board advisor to both Formsense and the Prysm Institute and a board observer with Voiceitt.

Editor’s Note: This transcript from the August 20 episode of the Blood & Cancer podcast has been edited for clarity. Click this link to listen to the full episode.

David Henry, MD: Welcome to this Blood & Cancer podcast. I’m your host, Dr. David Henry. This podcast airs on Thursday morning each week. This interview and others are archived with show notes from our residents at Pennsylvania Hospital at this link.

Each week we interview key opinion leaders involved in various aspects of blood and cancer. Today, we have a different kind of key opinion leader, as I have the privilege of interviewing Mason Plumlee, a forward with the National Basketball Association’s (NBA) Denver Nuggets. Mason was a first round pick in the NBA, a gold medalist for the U.S. men’s national team, and NBA All-Rookie first team honoree. He’s one of the top playmaking forwards in the country, if not the world, in my opinion. In his four-year college career at Duke University, he helped lead the Blue Devils to a National Collegiate Athletic Association (NCAA) championship and twice earned All-America first team academic honors at Duke. So he’s not just a basketball star, but an academic star as well. Mason, thanks so much for taking some time out from the bubble in Florida to talk with us today.
 

Mason Plumlee: Thanks for having me on. I’m happy to be here.

Henry: Beginning in March, the NBA didn’t know what to do about the COVID pandemic but finally decided to put you professional players in a ‘bubble.’ What did you have to go through to get there? You, your teammates, coaches, trainers, etc. And what’s the ongoing plan to be sure you continue to be safe?

Plumlee: Back to when the season shut down in March, the NBA shut down the practice facilities at the same time. Most people went home. I went back to Indiana. And then, as the idea of this bubble came up and the NBA formalized a plan to start the season again, players started to go back to market. I went back to Denver and was working out there.

About two weeks before we were scheduled to arrive in Orlando, they started testing us every other day. They used the deep nasal swab as well as the throat swab. But they were also taking two to three blood tests in that time period. You needed a certain number of consecutive negative tests before they would allow you to fly on the team plane down to Orlando. So there was an incredible amount of testing in the market. Once you got to Orlando, you went into a 48-hour quarantine. You had to have two negative tests with 48 hours between them before you could leave your hotel room.

Since then, it’s been quite strict down here. And although it’s annoying in a lot of ways, I think it’s one of the reasons our league has been able to pull this off. We’ve had no positive tests within the bubble and we are tested every day. A company called BioReference Laboratories has a setup in one of the meeting rooms here, and it’s like clockwork—we go in, we get our tests. One of my teammates missed a test and they made him stay in his room until he could get another test and get the results, so he missed a game because of that.
 

Henry: During this bubble time, no one has tested positive—players, coaches, staff?

Plumlee: Correct.

Henry: That’s incredible, and it’s allowed those of us who want to watch the NBA and those of you who are in it professionally to continue the sport. It must be a real nuisance for you and your family and friends, because no one can visit you, right?

Plumlee: Right. There’s no visitation. We had one false positive. It was our media relations person and the actions they took when that positive test came in -- they quarantined him in his room and interviewed everybody he had talked to; they tested anyone who had any interaction with him and those people had to go into quarantine. They’re on top of things down here. In addition to the testing, we each have a pulse oximeter and a thermometer, and we use these to check in everyday on an app. So, they’re getting all the insight they need. After the first round of the playoffs, they’re going to open the bubble to friends and family, but those friends and family will be subject to all the same protocols that we were coming in and once they’re here as well.

Henry: I’m sure you’ve heard about the Broadway star [Nick Cordero] who was healthy and suddenly got sick, lost a leg, and then lost his life. There have been some heart attacks that surprised us. Have your colleagues—players, coaches, etc.—been worried? Or are they thinking, what’s the big deal? Has the sense of how serious this is permeated through this sport?

Plumlee: The NBA is one of the groups that has heightened the understanding and awareness of this by shutting down. I think a lot of people were moving forward as is, and then, when the NBA decided to cancel the season, it let the world know, look, this is to be taken seriously.

Henry: A couple of players did test positive early on.

Plumlee: Exactly. A couple of people tested positive. I think at the outset, the unknown is always scarier. As we’ve learned more about the virus, the guys have become more comfortable. You know, I tested positive back in March. At the time, a loss of taste and smell was not a reported symptom.

Henry: And you had that?

Plumlee: I did have that, but I didn’t know what to think. More research has come out and we have a better understanding of that. I think most of the players are comfortable with the virus. We’re at a time in our lives where we’re healthy, we’re active, and we should be able to fight it off. We know the numbers for our age group. Even still, I think nobody wants to get it. Nobody wants to have to go through it. So why chance it?

Henry: Hats off to you and your sport. Other sports such as Major League Baseball haven’t been quite so successful. Of course, they’re wrestling with the players testing positive, and this has stopped games this season.

I was looking over your background prior to the interview and learned that your mother and father have been involved in the medical arena. Can you tell us about that and how it’s rubbed off on you?

Plumlee: Definitely. My mom is a pharmacist, so I spent a lot of time as a kid going to see her at work. And my dad is general counsel for an orthopedic company. My hometown is Warsaw, Ind. Some people refer to it as the “Orthopedic Capital of the World.” Zimmer Biomet is headquartered there. DePuy Synthes is there. Medtronic has offices there, as well as a lot of cottage businesses that support the orthopedic industry. In my hometown, the rock star was Dane Miller, who founded Biomet. I have no formal education in medicine or health care, but I’ve seen the impact of it. From my parents and some cousins, uncles who are doctors and surgeons, it’s been interesting to see their work and learn about what’s the latest and greatest in health care.

Henry: What’s so nice about you in particular is, with that background of interests from your family and your celebrity and accomplishments in professional basketball, you have used that to explore and promote ways to make progress in health care and help others who are less fortunate. For example, you’re involved in a telehealth platform for all-in-one practice management; affordable telehealth for pediatrics; health benefits for small businesses; prior authorization—if you can help with prior authorization, we will be in the stands for you at every game because it’s the bane of our existence; radiotherapy; and probably from mom’s background, pharmacy benefit management. Pick any of those you’d like to talk about, and tell us about your involvement and how it’s going.

Plumlee: My ticket into the arena is investment. Nobody’s calling me, asking for my expertise. But a lot of these visionary founders need financial support, and that’s where I get involved. Then also, with the celebrity angle from being an athlete, sometimes you can open doors for a start-up founder that they may not be able to open themselves.

I’m happy to speak about any of those companies. I am excited about the relaxed regulation that’s come from the pandemic; not that it’s like the Wild West out here, but I think it has allowed companies to implement solutions or think about problems in a way that they couldn’t before the pandemic. Take the prior authorization play, for example, and a company called Banjo Health, with one of my favorite founders, a guy named Saar Mahna. Medicare mandates that you turn around prior authorizations within three days. This company has an artificial intelligence and machine-learning play on prior authorizations that can deliver on that.

So efficiencies, things that increase access or affordability, better outcomes, those are the things that attract me. I lean on other people for the due diligence. The pediatric play that you referenced is a company called Blueberry Pediatrics. You have a monthly subscription for $15 that can be reimbursed by Medicaid. They send two devices to your home—an otoscope and an oximeter. The company is live in Florida right now, and it’s diverting a ton of emergency room (ER) visits. From home, for $15 a month, a mom has an otoscope and an oximeter, and she can chat or video conference with a pediatrician. There’s no additional fee. So that’s saving everyone time and saving the system money. Those are the kinds of things I’m attracted to.

Henry: You’ve touched on a couple of hot button issues for us. In oncology, unfortunately, most of our patients have pain. I am mystified every time I try to get a narcotic or a strong painkiller for a patient on a Friday night and I’m told it requires prior authorization and they’ll open up again on Monday. Well, that’s insane. These patients need something right away. So if you have a special interest in helping all of us with prior authorization, the artificial intelligence is a no brainer. If this kind of computer algorithm could happen overnight, that would be wonderful.

You mentioned the ER. Many people go to the ER as a default. They don’t know what else to do. In the COVID era, we’re trying to dial that down because we want to be able to see the sickest and have the non-sick get care elsewhere. If this particular person or people don’t know what to do, they go to the ER, it costs money, takes a lot of time, and others who may be sick are diverted from care. Families worry terribly about their children, so a device for mom and access to a pediatrician for $15 a month is another wonderful idea. These are both very interesting. Another company is in the pharmacy benefit management (PBM) space. Anything you could say about how that works?
 

Plumlee: I can give an overview of how I look at this as an investor in the PBM space. Three companies control about 75% of a multibillion dollar market. Several initiatives have been pursued politically to provide transparent pricing between these PBMs and pharmaceutical companies, and a lot of people are pointing fingers, but ultimately, drug prices just keep going up. Everybody knows it.

A couple of start-up founders are really set on bringing a competitive marketplace back to the pharmacy benefit manager. As an investor, when you see three people controlling a market, and you have small or medium PBMs that depend on aggregators to get competitive pricing with those big three, you get interested. It’s an interesting industry. My feeling is that somebody is going to disrupt it and bring competition back to that space. Ultimately, drug prices will come down because it’s not sustainable. The insurance companies just accommodate whatever the drug pricing is. If the drug prices go up, your premiums go up. I think these new companies will be level-setting.
 

Henry: In my world of oncology, we’re just a little more than halfway through 2020 and we’ve had five, six, seven new drugs approved. They all will be very expensive. One of the nicer things that’s happening and may help to tamp this down involves biosimilars. When you go to CVS or Rite Aid, you go down the aspirin aisle and see the generics, and they’re identical to the brand name aspirin. Well, these very complex molecules we used to treat cancer are antibodies or proteins, and they’re made in nature’s factories called cells. They’re not identical to the brand name drugs, but they’re called biosimilars. They work exactly the same as the branded drugs with exactly the same safety–our U.S. FDA has done a nice job of vetting that, to be sure. X, Y, Z Company has copied the brand drug after the patent expires. They were hoping for about a 30% discount in price but we’re seeing more like 15%. Nothing’s ever easy. So you make a very good point. This is not sustainable and the competition will be wonderful to tamp down these prices.

Plumlee: My hope is that those biosimilars and generics get placement in these formularies because the formularies are what’s valuable to the drug manufacturers. But they have to accommodate what the Big Three want in the PBM space. To me, making things affordable and accessible is what a lot of these startups are trying to do. And hopefully they will win.

Henry: What have you been going through, in terms of COVID? Have you recovered fully? Have your taste and smell returned, and you’re back to normal?

Plumlee: I’m all good. It caught me off guard but the symptoms weren’t too intense. For me, it was less than a flu, but more than a cold. And I’m all good today.

Henry: We’re so glad and wish you the best of luck.

Dr. Henry is a clinical professor of medicine at the University of Pennsylvania and vice chairman of the department of medicine at Pennsylvania Hospital in Philadelphia and the host of the Blood & Cancer podcast. He has no relevant financial conflicts.

Mr. Plumlee is a board advisor to both Formsense and the Prysm Institute and a board observer with Voiceitt.

A new study has quantified cancer risk factors in patients with systemic lupus erythematosus, including smoking and the use of certain medications.

“As expected, older age was associated with cancer overall, as well as with the most common cancer subtypes,” wrote Sasha Bernatsky, MD, PhD, of McGill University, Montreal, and coauthors. The study was published in Arthritis Care & Research.

To determine the risk of cancer in people with clinically confirmed incident systemic lupus erythematosus (SLE), the researchers analyzed data from 1,668 newly diagnosed lupus patients with at least one follow-up visit. All patients were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort from across 33 different centers in North America, Europe, and Asia. A total of 89% (n = 1,480) were women, and 49% (n = 824) were white. The average follow-up period was 9 years.

Of the 1,668 SLE patients, 65 developed some type of cancer. The cancers included 15 breast;, 10 nonmelanoma skin; 7 lung; 6 hematologic, 6 prostate; 5 melanoma; 3 cervical; 3 renal; 2 gastric; 2 head and neck; 2 thyroid; and 1 rectal, sarcoma, thymoma, or uterine. No patient had more than one type, and the mean age of the cancer patients at time of SLE diagnosis was 45.6 (standard deviation, 14.5).

Almost half of the 65 cancers occurred in past or current smokers, including all of the lung cancers, while only 33% of patients without cancers smoked prior to baseline. After univariate analysis, characteristics associated with a higher risk of all cancers included older age at SLE diagnosis (adjusted hazard ratio, 1.05; 95% confidence interval, 1.03-1.06), White race/ethnicity (aHR 1.34; 95% CI, 0.76-2.37), and smoking (aHR 1.21; 95% CI, 0.73-2.01).

After multivariate analysis, the two characteristics most associated with increased cancer risk were older age at SLE diagnosis and being male. The analyses also confirmed that older age was a risk factor for breast cancer (aHR 1.06; 95% CI, 1.02-1.10) and nonmelanoma skin cancer (aHR, 1.06; 95% CI, 1.02-1.11), while use of antimalarial drugs was associated with a lower risk of both breast (aHR, 0.28; 95% CI, 0.09-0.90) and nonmelanoma skin (aHR, 0.23; 95% CI, 0.05-0.95) cancers. For lung cancer, the highest risk factor was smoking 15 or more cigarettes a day (aHR, 6.64; 95% CI, 1.43-30.9); for hematologic cancers, it was being in the top quartile of SLE disease activity (aHR, 7.14; 95% CI, 1.13-45.3).

The authors acknowledged their study’s limitations, including the small number of cancers overall and purposefully not comparing cancer risk in SLE patients with risk in the general population. Although their methods – “physicians recording events at annual visits, confirmed by review of charts” – were recognized as very suitable for the current analysis, they noted that a broader comparison would “potentially be problematic due to differential misclassification error” in cancer registry data.

Two of the study’s authors reported potential conflicts of interest, including receiving grants and consulting and personal fees from various pharmaceutical companies. No other potential conflicts were reported.

SOURCE: Bernatsky S et al. Arthritis Care Res. 2020 Aug 19. doi: 10.1002/acr.24425.

A new study has quantified cancer risk factors in patients with systemic lupus erythematosus, including smoking and the use of certain medications.

“As expected, older age was associated with cancer overall, as well as with the most common cancer subtypes,” wrote Sasha Bernatsky, MD, PhD, of McGill University, Montreal, and coauthors. The study was published in Arthritis Care & Research.

To determine the risk of cancer in people with clinically confirmed incident systemic lupus erythematosus (SLE), the researchers analyzed data from 1,668 newly diagnosed lupus patients with at least one follow-up visit. All patients were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort from across 33 different centers in North America, Europe, and Asia. A total of 89% (n = 1,480) were women, and 49% (n = 824) were white. The average follow-up period was 9 years.

Of the 1,668 SLE patients, 65 developed some type of cancer. The cancers included 15 breast;, 10 nonmelanoma skin; 7 lung; 6 hematologic, 6 prostate; 5 melanoma; 3 cervical; 3 renal; 2 gastric; 2 head and neck; 2 thyroid; and 1 rectal, sarcoma, thymoma, or uterine. No patient had more than one type, and the mean age of the cancer patients at time of SLE diagnosis was 45.6 (standard deviation, 14.5).

Almost half of the 65 cancers occurred in past or current smokers, including all of the lung cancers, while only 33% of patients without cancers smoked prior to baseline. After univariate analysis, characteristics associated with a higher risk of all cancers included older age at SLE diagnosis (adjusted hazard ratio, 1.05; 95% confidence interval, 1.03-1.06), White race/ethnicity (aHR 1.34; 95% CI, 0.76-2.37), and smoking (aHR 1.21; 95% CI, 0.73-2.01).

After multivariate analysis, the two characteristics most associated with increased cancer risk were older age at SLE diagnosis and being male. The analyses also confirmed that older age was a risk factor for breast cancer (aHR 1.06; 95% CI, 1.02-1.10) and nonmelanoma skin cancer (aHR, 1.06; 95% CI, 1.02-1.11), while use of antimalarial drugs was associated with a lower risk of both breast (aHR, 0.28; 95% CI, 0.09-0.90) and nonmelanoma skin (aHR, 0.23; 95% CI, 0.05-0.95) cancers. For lung cancer, the highest risk factor was smoking 15 or more cigarettes a day (aHR, 6.64; 95% CI, 1.43-30.9); for hematologic cancers, it was being in the top quartile of SLE disease activity (aHR, 7.14; 95% CI, 1.13-45.3).

The authors acknowledged their study’s limitations, including the small number of cancers overall and purposefully not comparing cancer risk in SLE patients with risk in the general population. Although their methods – “physicians recording events at annual visits, confirmed by review of charts” – were recognized as very suitable for the current analysis, they noted that a broader comparison would “potentially be problematic due to differential misclassification error” in cancer registry data.

Two of the study’s authors reported potential conflicts of interest, including receiving grants and consulting and personal fees from various pharmaceutical companies. No other potential conflicts were reported.

SOURCE: Bernatsky S et al. Arthritis Care Res. 2020 Aug 19. doi: 10.1002/acr.24425.

A new study has quantified cancer risk factors in patients with systemic lupus erythematosus, including smoking and the use of certain medications.

“As expected, older age was associated with cancer overall, as well as with the most common cancer subtypes,” wrote Sasha Bernatsky, MD, PhD, of McGill University, Montreal, and coauthors. The study was published in Arthritis Care & Research.

To determine the risk of cancer in people with clinically confirmed incident systemic lupus erythematosus (SLE), the researchers analyzed data from 1,668 newly diagnosed lupus patients with at least one follow-up visit. All patients were enrolled in the Systemic Lupus International Collaborating Clinics inception cohort from across 33 different centers in North America, Europe, and Asia. A total of 89% (n = 1,480) were women, and 49% (n = 824) were white. The average follow-up period was 9 years.

Of the 1,668 SLE patients, 65 developed some type of cancer. The cancers included 15 breast;, 10 nonmelanoma skin; 7 lung; 6 hematologic, 6 prostate; 5 melanoma; 3 cervical; 3 renal; 2 gastric; 2 head and neck; 2 thyroid; and 1 rectal, sarcoma, thymoma, or uterine. No patient had more than one type, and the mean age of the cancer patients at time of SLE diagnosis was 45.6 (standard deviation, 14.5).

Almost half of the 65 cancers occurred in past or current smokers, including all of the lung cancers, while only 33% of patients without cancers smoked prior to baseline. After univariate analysis, characteristics associated with a higher risk of all cancers included older age at SLE diagnosis (adjusted hazard ratio, 1.05; 95% confidence interval, 1.03-1.06), White race/ethnicity (aHR 1.34; 95% CI, 0.76-2.37), and smoking (aHR 1.21; 95% CI, 0.73-2.01).

After multivariate analysis, the two characteristics most associated with increased cancer risk were older age at SLE diagnosis and being male. The analyses also confirmed that older age was a risk factor for breast cancer (aHR 1.06; 95% CI, 1.02-1.10) and nonmelanoma skin cancer (aHR, 1.06; 95% CI, 1.02-1.11), while use of antimalarial drugs was associated with a lower risk of both breast (aHR, 0.28; 95% CI, 0.09-0.90) and nonmelanoma skin (aHR, 0.23; 95% CI, 0.05-0.95) cancers. For lung cancer, the highest risk factor was smoking 15 or more cigarettes a day (aHR, 6.64; 95% CI, 1.43-30.9); for hematologic cancers, it was being in the top quartile of SLE disease activity (aHR, 7.14; 95% CI, 1.13-45.3).

The authors acknowledged their study’s limitations, including the small number of cancers overall and purposefully not comparing cancer risk in SLE patients with risk in the general population. Although their methods – “physicians recording events at annual visits, confirmed by review of charts” – were recognized as very suitable for the current analysis, they noted that a broader comparison would “potentially be problematic due to differential misclassification error” in cancer registry data.

Two of the study’s authors reported potential conflicts of interest, including receiving grants and consulting and personal fees from various pharmaceutical companies. No other potential conflicts were reported.

SOURCE: Bernatsky S et al. Arthritis Care Res. 2020 Aug 19. doi: 10.1002/acr.24425.

Adjuvant chemoradiotherapy beat radiotherapy alone for treatment of certain patients with World Health Organization (WHO)–defined low-grade glioma (LGG), according to researchers.

Prior results from this trial, NRG Oncology/RTOG 9802 (NCT00003375), demonstrated an increase in progression-free survival (PFS) and overall survival (OS) when procarbazine, lomustine, and vincristine (PCV) chemotherapy was added to radiation in patients with high-risk LGG.

The current results, published in the Journal of Clinical Oncology, displayed highly variable survival outcomes depending on molecular subgroup.

The initial report included only IDH1 R132H immunohistochemistry data because of limited tissue availability. However, retrospective retrieval of additional tissues subsequently enabled rigorous examination of the prognostic and predictive significance of these genetic biomarkers.

Prognostic and predictive

The trial included 251 patients with LGG (grade 2). Among the 106 eligible patients with WHO-defined molecular groups successfully profiled, 26 (24%) were IDH wild-type, 43 (41%) were IDH-mutant/non-codeleted, and 37 (35%) were IDH-mutant/codeleted.

After adjustment for clinical variables and treatment, multivariate analysis confirmed WHO-defined subgroup was a significant predictor of survival. All predictive analyses, however, were considered exploratory because of small sample sizes for patients with specific biomarker features in most cases.

In prognostic multivariable analyses, significantly favorable molecular subgroup associations were observed for OS in the IDH-mutant subgroups versus that in the wild type group (IDH-mutant/codeleted group HR, 0.18; P < .0001; IDH mutant/non-codeleleted group HR, 0.56; P = .048). Individually, the statistical significance was maintained for favorable OS for IDH1/2 mutations and 1p/19q codeletions.

In the predictive analyses, OS was longer for patients harboring IDH mutant/codeleted tumors receiving radiotherapy plus PCV than for those receiving radiotherapy alone (HR, 0.21; P = .029). The  median OS was 13.9 years for radiotherapy and was not reached for PCV and radiotherapy.

PFS in the IDH-mutant/codeleted subgroup also was longer for patients receiving PCV (HR, 0.13; P < .001). The median PFS was 5.8 years for radiotherapy alone and was not reached for added PCV.

In the IDH-mutant/non-codeleted subgroup, OS was longer with PCV (HR, 0.38; P = .013). The median OS was 4.3 years for radiotherapy alone and 11.4 years when PCV was added.

PFS was also longer in the IDH-mutant/non-codeleted subgroup (HR, 0.32; P = .003). The median PFS was 3.3 years for radiotherapy and 10.4 years with PCV added.

IDH–wild type patients displayed no significant clinical benefit from the addition of PCV.

“Historically, many have thought that primarily patients with codeletions received benefit from PCV,” study author Erica H. Bell, PhD, of The Ohio State University in Columbus, said in an interview. “But we showed here that there is benefit in both IDH-mutant groups.”

Primary predictor

“Our evidence suggests that IDH mutation status could serve as the primary predictor of response to PCV in addition to radiotherapy in high-risk, low-grade gliomas and is a more accurate predictor of response than historical histopathological classifications,” Dr. Bell and colleagues wrote. “Consideration should be given for adjuvant PCV in the setting of high-risk, low-grade glioma patients harboring IDH mutations.”

High-risk was defined as being 40 years or older or having a subtotal resection biopsy.

“While both IDH mutant subgroups received benefit from the addition of PCV for both overall survival and PFS, the patients in the wild-type subgroup did not do well," Dr. Bell said. "We need to treat them more aggressively. We need to determine exactly what therapy modality they should receive. This is an active question in our field.”

“Another conclusion from the study,” she added, “is that upfront tissue collection and molecular subtyping are absolutely necessary for moving our field forward.”

Finding novel biomarkers and novel therapeutic targets remain as a further goal.

Dr. Bell commented that results of the CODEL trial of temozolomide in newly diagnosed 1p/19q-codeleted anaplastic glioma are widely anticipated.

“PCV is a very toxic treatment," she said. "If another agent that is less toxic, but just as efficacious, becomes available, we would rather use that. At this point, though, there are no head-to-head trials comparing temozolomide with PCV in codeleted populations.”

The current study was sponsored by the National Cancer Institute and The Ohio State University. The authors disclosed patents, royalties, and other intellectual property.

SOURCE: Bell EH et al. J Clin Oncol. 2020. doi: 10.1200/JCO.19.02983.

Adjuvant chemoradiotherapy beat radiotherapy alone for treatment of certain patients with World Health Organization (WHO)–defined low-grade glioma (LGG), according to researchers.

Prior results from this trial, NRG Oncology/RTOG 9802 (NCT00003375), demonstrated an increase in progression-free survival (PFS) and overall survival (OS) when procarbazine, lomustine, and vincristine (PCV) chemotherapy was added to radiation in patients with high-risk LGG.

The current results, published in the Journal of Clinical Oncology, displayed highly variable survival outcomes depending on molecular subgroup.

The initial report included only IDH1 R132H immunohistochemistry data because of limited tissue availability. However, retrospective retrieval of additional tissues subsequently enabled rigorous examination of the prognostic and predictive significance of these genetic biomarkers.

Prognostic and predictive

The trial included 251 patients with LGG (grade 2). Among the 106 eligible patients with WHO-defined molecular groups successfully profiled, 26 (24%) were IDH wild-type, 43 (41%) were IDH-mutant/non-codeleted, and 37 (35%) were IDH-mutant/codeleted.

After adjustment for clinical variables and treatment, multivariate analysis confirmed WHO-defined subgroup was a significant predictor of survival. All predictive analyses, however, were considered exploratory because of small sample sizes for patients with specific biomarker features in most cases.

In prognostic multivariable analyses, significantly favorable molecular subgroup associations were observed for OS in the IDH-mutant subgroups versus that in the wild type group (IDH-mutant/codeleted group HR, 0.18; P < .0001; IDH mutant/non-codeleleted group HR, 0.56; P = .048). Individually, the statistical significance was maintained for favorable OS for IDH1/2 mutations and 1p/19q codeletions.

In the predictive analyses, OS was longer for patients harboring IDH mutant/codeleted tumors receiving radiotherapy plus PCV than for those receiving radiotherapy alone (HR, 0.21; P = .029). The  median OS was 13.9 years for radiotherapy and was not reached for PCV and radiotherapy.

PFS in the IDH-mutant/codeleted subgroup also was longer for patients receiving PCV (HR, 0.13; P < .001). The median PFS was 5.8 years for radiotherapy alone and was not reached for added PCV.

In the IDH-mutant/non-codeleted subgroup, OS was longer with PCV (HR, 0.38; P = .013). The median OS was 4.3 years for radiotherapy alone and 11.4 years when PCV was added.

PFS was also longer in the IDH-mutant/non-codeleted subgroup (HR, 0.32; P = .003). The median PFS was 3.3 years for radiotherapy and 10.4 years with PCV added.

IDH–wild type patients displayed no significant clinical benefit from the addition of PCV.

“Historically, many have thought that primarily patients with codeletions received benefit from PCV,” study author Erica H. Bell, PhD, of The Ohio State University in Columbus, said in an interview. “But we showed here that there is benefit in both IDH-mutant groups.”

Primary predictor

“Our evidence suggests that IDH mutation status could serve as the primary predictor of response to PCV in addition to radiotherapy in high-risk, low-grade gliomas and is a more accurate predictor of response than historical histopathological classifications,” Dr. Bell and colleagues wrote. “Consideration should be given for adjuvant PCV in the setting of high-risk, low-grade glioma patients harboring IDH mutations.”

High-risk was defined as being 40 years or older or having a subtotal resection biopsy.

“While both IDH mutant subgroups received benefit from the addition of PCV for both overall survival and PFS, the patients in the wild-type subgroup did not do well," Dr. Bell said. "We need to treat them more aggressively. We need to determine exactly what therapy modality they should receive. This is an active question in our field.”

“Another conclusion from the study,” she added, “is that upfront tissue collection and molecular subtyping are absolutely necessary for moving our field forward.”

Finding novel biomarkers and novel therapeutic targets remain as a further goal.

Dr. Bell commented that results of the CODEL trial of temozolomide in newly diagnosed 1p/19q-codeleted anaplastic glioma are widely anticipated.

“PCV is a very toxic treatment," she said. "If another agent that is less toxic, but just as efficacious, becomes available, we would rather use that. At this point, though, there are no head-to-head trials comparing temozolomide with PCV in codeleted populations.”

The current study was sponsored by the National Cancer Institute and The Ohio State University. The authors disclosed patents, royalties, and other intellectual property.

SOURCE: Bell EH et al. J Clin Oncol. 2020. doi: 10.1200/JCO.19.02983.

Adjuvant chemoradiotherapy beat radiotherapy alone for treatment of certain patients with World Health Organization (WHO)–defined low-grade glioma (LGG), according to researchers.

Prior results from this trial, NRG Oncology/RTOG 9802 (NCT00003375), demonstrated an increase in progression-free survival (PFS) and overall survival (OS) when procarbazine, lomustine, and vincristine (PCV) chemotherapy was added to radiation in patients with high-risk LGG.

The current results, published in the Journal of Clinical Oncology, displayed highly variable survival outcomes depending on molecular subgroup.

The initial report included only IDH1 R132H immunohistochemistry data because of limited tissue availability. However, retrospective retrieval of additional tissues subsequently enabled rigorous examination of the prognostic and predictive significance of these genetic biomarkers.

Prognostic and predictive

The trial included 251 patients with LGG (grade 2). Among the 106 eligible patients with WHO-defined molecular groups successfully profiled, 26 (24%) were IDH wild-type, 43 (41%) were IDH-mutant/non-codeleted, and 37 (35%) were IDH-mutant/codeleted.

After adjustment for clinical variables and treatment, multivariate analysis confirmed WHO-defined subgroup was a significant predictor of survival. All predictive analyses, however, were considered exploratory because of small sample sizes for patients with specific biomarker features in most cases.

In prognostic multivariable analyses, significantly favorable molecular subgroup associations were observed for OS in the IDH-mutant subgroups versus that in the wild type group (IDH-mutant/codeleted group HR, 0.18; P < .0001; IDH mutant/non-codeleleted group HR, 0.56; P = .048). Individually, the statistical significance was maintained for favorable OS for IDH1/2 mutations and 1p/19q codeletions.

In the predictive analyses, OS was longer for patients harboring IDH mutant/codeleted tumors receiving radiotherapy plus PCV than for those receiving radiotherapy alone (HR, 0.21; P = .029). The  median OS was 13.9 years for radiotherapy and was not reached for PCV and radiotherapy.

PFS in the IDH-mutant/codeleted subgroup also was longer for patients receiving PCV (HR, 0.13; P < .001). The median PFS was 5.8 years for radiotherapy alone and was not reached for added PCV.

In the IDH-mutant/non-codeleted subgroup, OS was longer with PCV (HR, 0.38; P = .013). The median OS was 4.3 years for radiotherapy alone and 11.4 years when PCV was added.

PFS was also longer in the IDH-mutant/non-codeleted subgroup (HR, 0.32; P = .003). The median PFS was 3.3 years for radiotherapy and 10.4 years with PCV added.

IDH–wild type patients displayed no significant clinical benefit from the addition of PCV.

“Historically, many have thought that primarily patients with codeletions received benefit from PCV,” study author Erica H. Bell, PhD, of The Ohio State University in Columbus, said in an interview. “But we showed here that there is benefit in both IDH-mutant groups.”

Primary predictor

“Our evidence suggests that IDH mutation status could serve as the primary predictor of response to PCV in addition to radiotherapy in high-risk, low-grade gliomas and is a more accurate predictor of response than historical histopathological classifications,” Dr. Bell and colleagues wrote. “Consideration should be given for adjuvant PCV in the setting of high-risk, low-grade glioma patients harboring IDH mutations.”

High-risk was defined as being 40 years or older or having a subtotal resection biopsy.

“While both IDH mutant subgroups received benefit from the addition of PCV for both overall survival and PFS, the patients in the wild-type subgroup did not do well," Dr. Bell said. "We need to treat them more aggressively. We need to determine exactly what therapy modality they should receive. This is an active question in our field.”

“Another conclusion from the study,” she added, “is that upfront tissue collection and molecular subtyping are absolutely necessary for moving our field forward.”

Finding novel biomarkers and novel therapeutic targets remain as a further goal.

Dr. Bell commented that results of the CODEL trial of temozolomide in newly diagnosed 1p/19q-codeleted anaplastic glioma are widely anticipated.

“PCV is a very toxic treatment," she said. "If another agent that is less toxic, but just as efficacious, becomes available, we would rather use that. At this point, though, there are no head-to-head trials comparing temozolomide with PCV in codeleted populations.”

The current study was sponsored by the National Cancer Institute and The Ohio State University. The authors disclosed patents, royalties, and other intellectual property.

SOURCE: Bell EH et al. J Clin Oncol. 2020. doi: 10.1200/JCO.19.02983.

A new study has linked recent-onset diabetes and subsequent weight loss to an increased risk of pancreatic cancer, indicating a distinct group of individuals to screen early for this deadly disease.

“The likelihood of a pancreatic cancer diagnosis was even further elevated among individuals with older age, healthy weight before weight loss, and unintentional weight loss,” wrote Chen Yuan, ScD, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. The study was published in JAMA Oncology.

To determine whether an association exists between diabetes plus weight change and pancreatic cancer, the researchers analyzed decades of medical history data from the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). The study population from the NHS included 112,818 women with a mean age of 59 years; the population from the HPFS included 46,207 men with a mean age of 65 years. Since enrollment – the baseline was 1978 for the NHS and 1988 for the HPFS – participants have provided follow-up information via biennial questionnaires.
 

Recent diabetes onset, weight loss boost cancer risk

From those combined groups, 1,116 incident cases of pancreatic cancer (0.7%) were identified. Compared with patients with no diabetes, patients with recent-onset diabetes had triple the risk of pancreatic cancer (age-adjusted hazard ratio, 2.97; 95% confidence interval, 2.31-3.82) and patients with longstanding diabetes had more than double the risk (HR, 2.16; 95% CI, 1.78-2.60). Patients with longer disease duration also had more than twice the risk of pancreatic cancer, with HRs of 2.25 for those with diabetes for 4-10 years (95% CI, 1.74-2.92) and 2.07 for more than 10 years (95% CI, 1.61-2.66).

Compared with patients who hadn’t lost any weight, patients who reported a 1- to 4-pound weight loss (HR, 1.25; 95% CI, 1.03-1.52), a 5- to 8-pound weight loss (HR, 1.33; 95% CI, 1.06-1.66), and a more than 8-pound weight loss (HR, 1.92; 95% CI, 1.58-2.32) had higher risks of pancreatic cancer. Patients with recent-onset diabetes and a 1- to 8-pound weight loss (91 incident cases per 100,000 person-years; 95% CI, 55-151) or a weight loss of more than 8 pounds (164 incident cases per 100,000 person years; 95% CI, 114-238) had a much higher incidence of pancreatic cancer, compared with patients with neither (16 incident cases per 100,000 person-years; 95% CI, 14-17).

After stratified analyses of patients with both recent-onset diabetes and weight loss, rates of pancreatic cancer were also notably high in those 70 years or older (234 cases per 100,000 person years), those with a body mass index of less than 25 kg/m² before weight loss (400 cases per 100,000 person years), and those with a low likelihood of intentional weight loss (334 cases per 100,000 person years).

“I like the study because it reminds us of the importance of not thinking everyone that presents with type 2 diabetes necessarily has garden-variety diabetes,” Paul Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said in an interview. “I have always been concerned when a new-onset diabetic individual presents with no family history of diabetes or prediabetes, especially if they’re neither overweight nor obese. I have sometimes screened those individuals for pancreatic abnormalities.”
 

A call for screening

“This study highlights the consideration for further screening to those with weight loss at the time of diabetes diagnosis, which is very sensible given how unusual weight loss is as a presenting symptom at the time of diagnosis of typical type 2 diabetes,” Dr. Jellinger added. “The combination of weight loss and no family history of diabetes at the time of diagnosis should be an even stronger signal for pancreatic cancer screening and potential detection at a much earlier stage.”

The authors acknowledged their study’s limitations, including some patients with pancreatic cancer not returning their questionnaires and the timing of the questionnaires meaning that patients could’ve developed diabetes after returning it. In addition, they recognized that the participants were “predominantly White health professionals” and recommended a study of “additional patient populations” in the future.

The authors noted numerous potential conflicts of interest, including receiving grants and personal fees from various initiatives, organizations, and pharmaceutical companies.

Review the “AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review” for best practice advice for clinicians screening and diagnosing pancreatic cancer in high-risk individuals. Learn more at http://ow.ly/vwTR30r4Zwu.  

SOURCE: Yuan C et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.2948.

A new study has linked recent-onset diabetes and subsequent weight loss to an increased risk of pancreatic cancer, indicating a distinct group of individuals to screen early for this deadly disease.

“The likelihood of a pancreatic cancer diagnosis was even further elevated among individuals with older age, healthy weight before weight loss, and unintentional weight loss,” wrote Chen Yuan, ScD, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. The study was published in JAMA Oncology.

To determine whether an association exists between diabetes plus weight change and pancreatic cancer, the researchers analyzed decades of medical history data from the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). The study population from the NHS included 112,818 women with a mean age of 59 years; the population from the HPFS included 46,207 men with a mean age of 65 years. Since enrollment – the baseline was 1978 for the NHS and 1988 for the HPFS – participants have provided follow-up information via biennial questionnaires.
 

Recent diabetes onset, weight loss boost cancer risk

From those combined groups, 1,116 incident cases of pancreatic cancer (0.7%) were identified. Compared with patients with no diabetes, patients with recent-onset diabetes had triple the risk of pancreatic cancer (age-adjusted hazard ratio, 2.97; 95% confidence interval, 2.31-3.82) and patients with longstanding diabetes had more than double the risk (HR, 2.16; 95% CI, 1.78-2.60). Patients with longer disease duration also had more than twice the risk of pancreatic cancer, with HRs of 2.25 for those with diabetes for 4-10 years (95% CI, 1.74-2.92) and 2.07 for more than 10 years (95% CI, 1.61-2.66).

Compared with patients who hadn’t lost any weight, patients who reported a 1- to 4-pound weight loss (HR, 1.25; 95% CI, 1.03-1.52), a 5- to 8-pound weight loss (HR, 1.33; 95% CI, 1.06-1.66), and a more than 8-pound weight loss (HR, 1.92; 95% CI, 1.58-2.32) had higher risks of pancreatic cancer. Patients with recent-onset diabetes and a 1- to 8-pound weight loss (91 incident cases per 100,000 person-years; 95% CI, 55-151) or a weight loss of more than 8 pounds (164 incident cases per 100,000 person years; 95% CI, 114-238) had a much higher incidence of pancreatic cancer, compared with patients with neither (16 incident cases per 100,000 person-years; 95% CI, 14-17).

After stratified analyses of patients with both recent-onset diabetes and weight loss, rates of pancreatic cancer were also notably high in those 70 years or older (234 cases per 100,000 person years), those with a body mass index of less than 25 kg/m² before weight loss (400 cases per 100,000 person years), and those with a low likelihood of intentional weight loss (334 cases per 100,000 person years).

“I like the study because it reminds us of the importance of not thinking everyone that presents with type 2 diabetes necessarily has garden-variety diabetes,” Paul Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said in an interview. “I have always been concerned when a new-onset diabetic individual presents with no family history of diabetes or prediabetes, especially if they’re neither overweight nor obese. I have sometimes screened those individuals for pancreatic abnormalities.”
 

A call for screening

“This study highlights the consideration for further screening to those with weight loss at the time of diabetes diagnosis, which is very sensible given how unusual weight loss is as a presenting symptom at the time of diagnosis of typical type 2 diabetes,” Dr. Jellinger added. “The combination of weight loss and no family history of diabetes at the time of diagnosis should be an even stronger signal for pancreatic cancer screening and potential detection at a much earlier stage.”

The authors acknowledged their study’s limitations, including some patients with pancreatic cancer not returning their questionnaires and the timing of the questionnaires meaning that patients could’ve developed diabetes after returning it. In addition, they recognized that the participants were “predominantly White health professionals” and recommended a study of “additional patient populations” in the future.

The authors noted numerous potential conflicts of interest, including receiving grants and personal fees from various initiatives, organizations, and pharmaceutical companies.

Review the “AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review” for best practice advice for clinicians screening and diagnosing pancreatic cancer in high-risk individuals. Learn more at http://ow.ly/vwTR30r4Zwu.  

SOURCE: Yuan C et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.2948.

A new study has linked recent-onset diabetes and subsequent weight loss to an increased risk of pancreatic cancer, indicating a distinct group of individuals to screen early for this deadly disease.

“The likelihood of a pancreatic cancer diagnosis was even further elevated among individuals with older age, healthy weight before weight loss, and unintentional weight loss,” wrote Chen Yuan, ScD, of the Dana-Farber Cancer Institute and Harvard Medical School, both in Boston. The study was published in JAMA Oncology.

To determine whether an association exists between diabetes plus weight change and pancreatic cancer, the researchers analyzed decades of medical history data from the Nurses’ Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS). The study population from the NHS included 112,818 women with a mean age of 59 years; the population from the HPFS included 46,207 men with a mean age of 65 years. Since enrollment – the baseline was 1978 for the NHS and 1988 for the HPFS – participants have provided follow-up information via biennial questionnaires.
 

Recent diabetes onset, weight loss boost cancer risk

From those combined groups, 1,116 incident cases of pancreatic cancer (0.7%) were identified. Compared with patients with no diabetes, patients with recent-onset diabetes had triple the risk of pancreatic cancer (age-adjusted hazard ratio, 2.97; 95% confidence interval, 2.31-3.82) and patients with longstanding diabetes had more than double the risk (HR, 2.16; 95% CI, 1.78-2.60). Patients with longer disease duration also had more than twice the risk of pancreatic cancer, with HRs of 2.25 for those with diabetes for 4-10 years (95% CI, 1.74-2.92) and 2.07 for more than 10 years (95% CI, 1.61-2.66).

Compared with patients who hadn’t lost any weight, patients who reported a 1- to 4-pound weight loss (HR, 1.25; 95% CI, 1.03-1.52), a 5- to 8-pound weight loss (HR, 1.33; 95% CI, 1.06-1.66), and a more than 8-pound weight loss (HR, 1.92; 95% CI, 1.58-2.32) had higher risks of pancreatic cancer. Patients with recent-onset diabetes and a 1- to 8-pound weight loss (91 incident cases per 100,000 person-years; 95% CI, 55-151) or a weight loss of more than 8 pounds (164 incident cases per 100,000 person years; 95% CI, 114-238) had a much higher incidence of pancreatic cancer, compared with patients with neither (16 incident cases per 100,000 person-years; 95% CI, 14-17).

After stratified analyses of patients with both recent-onset diabetes and weight loss, rates of pancreatic cancer were also notably high in those 70 years or older (234 cases per 100,000 person years), those with a body mass index of less than 25 kg/m² before weight loss (400 cases per 100,000 person years), and those with a low likelihood of intentional weight loss (334 cases per 100,000 person years).

“I like the study because it reminds us of the importance of not thinking everyone that presents with type 2 diabetes necessarily has garden-variety diabetes,” Paul Jellinger, MD, of the Center for Diabetes and Endocrine Care in Hollywood, Fla., said in an interview. “I have always been concerned when a new-onset diabetic individual presents with no family history of diabetes or prediabetes, especially if they’re neither overweight nor obese. I have sometimes screened those individuals for pancreatic abnormalities.”
 

A call for screening

“This study highlights the consideration for further screening to those with weight loss at the time of diabetes diagnosis, which is very sensible given how unusual weight loss is as a presenting symptom at the time of diagnosis of typical type 2 diabetes,” Dr. Jellinger added. “The combination of weight loss and no family history of diabetes at the time of diagnosis should be an even stronger signal for pancreatic cancer screening and potential detection at a much earlier stage.”

The authors acknowledged their study’s limitations, including some patients with pancreatic cancer not returning their questionnaires and the timing of the questionnaires meaning that patients could’ve developed diabetes after returning it. In addition, they recognized that the participants were “predominantly White health professionals” and recommended a study of “additional patient populations” in the future.

The authors noted numerous potential conflicts of interest, including receiving grants and personal fees from various initiatives, organizations, and pharmaceutical companies.

Review the “AGA Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals: Expert Review” for best practice advice for clinicians screening and diagnosing pancreatic cancer in high-risk individuals. Learn more at http://ow.ly/vwTR30r4Zwu.  

SOURCE: Yuan C et al. JAMA Oncol. 2020 Aug 13. doi: 10.1001/jamaoncol.2020.2948.

Increasingly recognized as an independent risk factor for new-onset atrial fibrillation (AFib), new research suggests for the first time that nonalcoholic fatty liver disease (NAFLD) also confers a higher risk for arrhythmia recurrence after AFib ablation.

Over 29 months of postablation follow-up, 56% of patients with NAFLD suffered bouts of arrhythmia, compared with 31% of patients without NAFLD, matched on the basis of age, sex, body mass index (BMI), ejection fraction within 5%, and AFib type (P < .0001).

The presence of NAFLD was an independent predictor of arrhythmia recurrence in multivariable analyses adjusted for several confounders, including hemoglobin A1c, BMI, and AFib type (hazard ratio, 3.0; 95% confidence interval, 1.94-4.68).

The association is concerning given that one in four adults in the United States has NAFLD, and up to 6.1 million Americans are estimated to have Afib. Previous studies, such as ARREST-AF and LEGACY, however, have demonstrated the benefits of aggressive preablation cardiometabolic risk factor modification on long-term AFib ablation success.

Indeed, none of the NAFLD patients in the present study who lost at least 10% of their body weight had recurrent arrhythmia, compared with 31% who lost less than 10%, and 91% who gained weight prior to ablation (P < .0001).

All 22 patients whose A1c increased during the 12 months prior to ablation had recurrent arrhythmia, compared with 36% of patients whose A1c improved (P < .0001).

“I don’t think the findings of the study were particularly surprising, given what we know. It’s just further reinforcement of the essential role of risk-factor modification,” lead author Eoin Donnellan, MD, Cleveland Clinic, said in an interview.

The results were published Augus 12 in JACC Clinical Electrophysiology.

For the study, the researchers examined data from 267 consecutive patients with a mean BMI of 32.7 kg/m² who underwent radiofrequency ablation (98%) or cryoablation (2%) at the Cleveland Clinic between January 2013 and December 2017.

All patients were followed for at least 12 months after ablation and had scheduled clinic visits at 3, 6, and 12 months after pulmonary vein isolation, and annually thereafter.

NAFLD was diagnosed in 89 patients prior to ablation on the basis of CT imaging and abdominal ultrasound or MRI. On the basis of NAFLD-Fibrosis Score (NAFLD-FS), 13 patients had a low probability of liver fibrosis (F0-F2), 54 had an indeterminate probability, and 22 a high probability of fibrosis (F3-F4).

Compared with patients with no or early fibrosis (F0-F2), patients with advanced liver fibrosis (F3-F4) had almost a threefold increase in AFib recurrence (82% vs. 31%; P = .003).

“Cardiologists should make an effort to risk-stratify NAFLD patients either by NAFLD-FS or [an] alternative option, such as transient elastography or MR elastography, given these observations, rather than viewing it as either present or absence [sic] and involve expert multidisciplinary team care early in the clinical course of NAFLD patients with evidence of advanced fibrosis,” Dr. Donnellan and colleagues wrote.

Coauthor Thomas G. Cotter, MD, department of gastroenterology and hepatology, University of Chicago, said in an interview that cardiologists could use just the NAFLD-FS as part of an algorithm for an AFib.

“Because if it shows low risk, then it’s very, very likely the patient will be fine,” he said. “To use more advanced noninvasive testing, there are subtleties in the interpretation that would require referral to a liver doctor or a gastroenterologist and the cost of referring might bulk up the costs. But the NAFLD-FS is freely available and is a validated tool.”

Although it hasn’t specifically been validated in patients with AFib, the NAFLD-FS has been shown to correlate with the development of coronary artery disease  (CAD) and was recommended for clinical use in U.S. multisociety guidelines for NAFLD.

The score is calculated using six readily available clinical variables (age, BMI, hyperglycemia or diabetes, AST/ALT, platelets, and albumin). It does not include family history or alcohol consumption, which should be carefully detailed given the large overlap between NAFLD and alcohol-related liver disease, Dr. Cotter observed.

Of note, the study excluded patients with alcohol consumption of more than 30 g/day in men and more than 20 g/day in women, chronic viral hepatitis, Wilson’s disease, and hereditary hemochromatosis.

Finally, CT imaging revealed that epicardial fat volume (EFV) was greater in patients with NAFLD than in those without NAFLD (248 vs. 223 mL; P = .01).

Although increased amounts of epicardial fat have been associated with CAD, there was no significant difference in EFV between patients who did and did not develop recurrent arrhythmia (238 vs. 229 mL; P = .5). Nor was EFV associated with arrhythmia recurrence on Cox proportional hazards analysis (HR, 1.001; P = .17).

“We hypothesized that the increased risk of arrhythmia recurrence may be mediated in part by an increased epicardial fat volume,” Dr. Donnellan said. “The existing literature exploring the link between epicardial fat volume and A[Fib] burden and recurrence is conflicting. But in both this study and our bariatric surgery study, epicardial fat volume was not a significant predictor of arrhythmia recurrence on multivariable analysis.”

It’s likely that the increased recurrence risk is caused by several mechanisms, including NAFLD’s deleterious impact on cardiac structure and function, the bidirectional relationship between NAFLD and sleep apnea, and transcription of proinflammatory cytokines and low-grade systemic inflammation, he suggested.

“Patients with NAFLD represent a particularly high-risk population for arrhythmia recurrence. NAFLD is a reversible disease, and a multidisciplinary approach incorporating dietary and lifestyle interventions should by instituted prior to ablation,” Dr. Donnellan and colleagues concluded.

They noted that serial abdominal imaging to assess for preablation changes in NAFLD was limited in patients and that only 56% of control subjects underwent dedicated abdominal imaging to rule out hepatic steatosis. Also, the heterogeneity of imaging modalities used to diagnose NAFLD may have influenced the results and the study’s single-center, retrospective design limits their generalizability.

The authors reported having no relevant financial relationships.

Help your patients better understand their risk of NASH and NAFLD by sharing AGA patient education content at http://ow.ly/ZKi930r50am.  

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

Increasingly recognized as an independent risk factor for new-onset atrial fibrillation (AFib), new research suggests for the first time that nonalcoholic fatty liver disease (NAFLD) also confers a higher risk for arrhythmia recurrence after AFib ablation.

Over 29 months of postablation follow-up, 56% of patients with NAFLD suffered bouts of arrhythmia, compared with 31% of patients without NAFLD, matched on the basis of age, sex, body mass index (BMI), ejection fraction within 5%, and AFib type (P < .0001).

The presence of NAFLD was an independent predictor of arrhythmia recurrence in multivariable analyses adjusted for several confounders, including hemoglobin A1c, BMI, and AFib type (hazard ratio, 3.0; 95% confidence interval, 1.94-4.68).

The association is concerning given that one in four adults in the United States has NAFLD, and up to 6.1 million Americans are estimated to have Afib. Previous studies, such as ARREST-AF and LEGACY, however, have demonstrated the benefits of aggressive preablation cardiometabolic risk factor modification on long-term AFib ablation success.

Indeed, none of the NAFLD patients in the present study who lost at least 10% of their body weight had recurrent arrhythmia, compared with 31% who lost less than 10%, and 91% who gained weight prior to ablation (P < .0001).

All 22 patients whose A1c increased during the 12 months prior to ablation had recurrent arrhythmia, compared with 36% of patients whose A1c improved (P < .0001).

“I don’t think the findings of the study were particularly surprising, given what we know. It’s just further reinforcement of the essential role of risk-factor modification,” lead author Eoin Donnellan, MD, Cleveland Clinic, said in an interview.

The results were published Augus 12 in JACC Clinical Electrophysiology.

For the study, the researchers examined data from 267 consecutive patients with a mean BMI of 32.7 kg/m² who underwent radiofrequency ablation (98%) or cryoablation (2%) at the Cleveland Clinic between January 2013 and December 2017.

All patients were followed for at least 12 months after ablation and had scheduled clinic visits at 3, 6, and 12 months after pulmonary vein isolation, and annually thereafter.

NAFLD was diagnosed in 89 patients prior to ablation on the basis of CT imaging and abdominal ultrasound or MRI. On the basis of NAFLD-Fibrosis Score (NAFLD-FS), 13 patients had a low probability of liver fibrosis (F0-F2), 54 had an indeterminate probability, and 22 a high probability of fibrosis (F3-F4).

Compared with patients with no or early fibrosis (F0-F2), patients with advanced liver fibrosis (F3-F4) had almost a threefold increase in AFib recurrence (82% vs. 31%; P = .003).

“Cardiologists should make an effort to risk-stratify NAFLD patients either by NAFLD-FS or [an] alternative option, such as transient elastography or MR elastography, given these observations, rather than viewing it as either present or absence [sic] and involve expert multidisciplinary team care early in the clinical course of NAFLD patients with evidence of advanced fibrosis,” Dr. Donnellan and colleagues wrote.

Coauthor Thomas G. Cotter, MD, department of gastroenterology and hepatology, University of Chicago, said in an interview that cardiologists could use just the NAFLD-FS as part of an algorithm for an AFib.

“Because if it shows low risk, then it’s very, very likely the patient will be fine,” he said. “To use more advanced noninvasive testing, there are subtleties in the interpretation that would require referral to a liver doctor or a gastroenterologist and the cost of referring might bulk up the costs. But the NAFLD-FS is freely available and is a validated tool.”

Although it hasn’t specifically been validated in patients with AFib, the NAFLD-FS has been shown to correlate with the development of coronary artery disease  (CAD) and was recommended for clinical use in U.S. multisociety guidelines for NAFLD.

The score is calculated using six readily available clinical variables (age, BMI, hyperglycemia or diabetes, AST/ALT, platelets, and albumin). It does not include family history or alcohol consumption, which should be carefully detailed given the large overlap between NAFLD and alcohol-related liver disease, Dr. Cotter observed.

Of note, the study excluded patients with alcohol consumption of more than 30 g/day in men and more than 20 g/day in women, chronic viral hepatitis, Wilson’s disease, and hereditary hemochromatosis.

Finally, CT imaging revealed that epicardial fat volume (EFV) was greater in patients with NAFLD than in those without NAFLD (248 vs. 223 mL; P = .01).

Although increased amounts of epicardial fat have been associated with CAD, there was no significant difference in EFV between patients who did and did not develop recurrent arrhythmia (238 vs. 229 mL; P = .5). Nor was EFV associated with arrhythmia recurrence on Cox proportional hazards analysis (HR, 1.001; P = .17).

“We hypothesized that the increased risk of arrhythmia recurrence may be mediated in part by an increased epicardial fat volume,” Dr. Donnellan said. “The existing literature exploring the link between epicardial fat volume and A[Fib] burden and recurrence is conflicting. But in both this study and our bariatric surgery study, epicardial fat volume was not a significant predictor of arrhythmia recurrence on multivariable analysis.”

It’s likely that the increased recurrence risk is caused by several mechanisms, including NAFLD’s deleterious impact on cardiac structure and function, the bidirectional relationship between NAFLD and sleep apnea, and transcription of proinflammatory cytokines and low-grade systemic inflammation, he suggested.

“Patients with NAFLD represent a particularly high-risk population for arrhythmia recurrence. NAFLD is a reversible disease, and a multidisciplinary approach incorporating dietary and lifestyle interventions should by instituted prior to ablation,” Dr. Donnellan and colleagues concluded.

They noted that serial abdominal imaging to assess for preablation changes in NAFLD was limited in patients and that only 56% of control subjects underwent dedicated abdominal imaging to rule out hepatic steatosis. Also, the heterogeneity of imaging modalities used to diagnose NAFLD may have influenced the results and the study’s single-center, retrospective design limits their generalizability.

The authors reported having no relevant financial relationships.

Help your patients better understand their risk of NASH and NAFLD by sharing AGA patient education content at http://ow.ly/ZKi930r50am.  

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

Increasingly recognized as an independent risk factor for new-onset atrial fibrillation (AFib), new research suggests for the first time that nonalcoholic fatty liver disease (NAFLD) also confers a higher risk for arrhythmia recurrence after AFib ablation.

Over 29 months of postablation follow-up, 56% of patients with NAFLD suffered bouts of arrhythmia, compared with 31% of patients without NAFLD, matched on the basis of age, sex, body mass index (BMI), ejection fraction within 5%, and AFib type (P < .0001).

The presence of NAFLD was an independent predictor of arrhythmia recurrence in multivariable analyses adjusted for several confounders, including hemoglobin A1c, BMI, and AFib type (hazard ratio, 3.0; 95% confidence interval, 1.94-4.68).

The association is concerning given that one in four adults in the United States has NAFLD, and up to 6.1 million Americans are estimated to have Afib. Previous studies, such as ARREST-AF and LEGACY, however, have demonstrated the benefits of aggressive preablation cardiometabolic risk factor modification on long-term AFib ablation success.

Indeed, none of the NAFLD patients in the present study who lost at least 10% of their body weight had recurrent arrhythmia, compared with 31% who lost less than 10%, and 91% who gained weight prior to ablation (P < .0001).

All 22 patients whose A1c increased during the 12 months prior to ablation had recurrent arrhythmia, compared with 36% of patients whose A1c improved (P < .0001).

“I don’t think the findings of the study were particularly surprising, given what we know. It’s just further reinforcement of the essential role of risk-factor modification,” lead author Eoin Donnellan, MD, Cleveland Clinic, said in an interview.

The results were published Augus 12 in JACC Clinical Electrophysiology.

For the study, the researchers examined data from 267 consecutive patients with a mean BMI of 32.7 kg/m² who underwent radiofrequency ablation (98%) or cryoablation (2%) at the Cleveland Clinic between January 2013 and December 2017.

All patients were followed for at least 12 months after ablation and had scheduled clinic visits at 3, 6, and 12 months after pulmonary vein isolation, and annually thereafter.

NAFLD was diagnosed in 89 patients prior to ablation on the basis of CT imaging and abdominal ultrasound or MRI. On the basis of NAFLD-Fibrosis Score (NAFLD-FS), 13 patients had a low probability of liver fibrosis (F0-F2), 54 had an indeterminate probability, and 22 a high probability of fibrosis (F3-F4).

Compared with patients with no or early fibrosis (F0-F2), patients with advanced liver fibrosis (F3-F4) had almost a threefold increase in AFib recurrence (82% vs. 31%; P = .003).

“Cardiologists should make an effort to risk-stratify NAFLD patients either by NAFLD-FS or [an] alternative option, such as transient elastography or MR elastography, given these observations, rather than viewing it as either present or absence [sic] and involve expert multidisciplinary team care early in the clinical course of NAFLD patients with evidence of advanced fibrosis,” Dr. Donnellan and colleagues wrote.

Coauthor Thomas G. Cotter, MD, department of gastroenterology and hepatology, University of Chicago, said in an interview that cardiologists could use just the NAFLD-FS as part of an algorithm for an AFib.

“Because if it shows low risk, then it’s very, very likely the patient will be fine,” he said. “To use more advanced noninvasive testing, there are subtleties in the interpretation that would require referral to a liver doctor or a gastroenterologist and the cost of referring might bulk up the costs. But the NAFLD-FS is freely available and is a validated tool.”

Although it hasn’t specifically been validated in patients with AFib, the NAFLD-FS has been shown to correlate with the development of coronary artery disease  (CAD) and was recommended for clinical use in U.S. multisociety guidelines for NAFLD.

The score is calculated using six readily available clinical variables (age, BMI, hyperglycemia or diabetes, AST/ALT, platelets, and albumin). It does not include family history or alcohol consumption, which should be carefully detailed given the large overlap between NAFLD and alcohol-related liver disease, Dr. Cotter observed.

Of note, the study excluded patients with alcohol consumption of more than 30 g/day in men and more than 20 g/day in women, chronic viral hepatitis, Wilson’s disease, and hereditary hemochromatosis.

Finally, CT imaging revealed that epicardial fat volume (EFV) was greater in patients with NAFLD than in those without NAFLD (248 vs. 223 mL; P = .01).

Although increased amounts of epicardial fat have been associated with CAD, there was no significant difference in EFV between patients who did and did not develop recurrent arrhythmia (238 vs. 229 mL; P = .5). Nor was EFV associated with arrhythmia recurrence on Cox proportional hazards analysis (HR, 1.001; P = .17).

“We hypothesized that the increased risk of arrhythmia recurrence may be mediated in part by an increased epicardial fat volume,” Dr. Donnellan said. “The existing literature exploring the link between epicardial fat volume and A[Fib] burden and recurrence is conflicting. But in both this study and our bariatric surgery study, epicardial fat volume was not a significant predictor of arrhythmia recurrence on multivariable analysis.”

It’s likely that the increased recurrence risk is caused by several mechanisms, including NAFLD’s deleterious impact on cardiac structure and function, the bidirectional relationship between NAFLD and sleep apnea, and transcription of proinflammatory cytokines and low-grade systemic inflammation, he suggested.

“Patients with NAFLD represent a particularly high-risk population for arrhythmia recurrence. NAFLD is a reversible disease, and a multidisciplinary approach incorporating dietary and lifestyle interventions should by instituted prior to ablation,” Dr. Donnellan and colleagues concluded.

They noted that serial abdominal imaging to assess for preablation changes in NAFLD was limited in patients and that only 56% of control subjects underwent dedicated abdominal imaging to rule out hepatic steatosis. Also, the heterogeneity of imaging modalities used to diagnose NAFLD may have influenced the results and the study’s single-center, retrospective design limits their generalizability.

The authors reported having no relevant financial relationships.

Help your patients better understand their risk of NASH and NAFLD by sharing AGA patient education content at http://ow.ly/ZKi930r50am.  

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

Jon Paul was leery entering his first wildfire camp of the year late last month to fight three lightning-caused fires scorching parts of a Northern California forest that hadn’t burned in 40 years.

Courtesy of U.S. Forest Service

The 54-year-old engine captain from southern Oregon knew from experience that these crowded, grimy camps can be breeding grounds for norovirus and a respiratory illness that firefighters call the “camp crud” in a normal year. He wondered what the coronavirus would do in the tent cities where hundreds of men and women eat, sleep, wash, and spend their downtime between shifts.

Mr. Paul thought about his immunocompromised wife and his 84-year-old mother back home. Then he joined the approximately 1,300 people spread across the Modoc National Forest who would provide a major test for the COVID-prevention measures that had been developed for wildland firefighters.

“We’re still first responders and we have that responsibility to go and deal with these emergencies,” he said in a recent interview. “I don’t scare easy, but I’m very wary and concerned about my surroundings. I’m still going to work and do my job.”

Mr. Paul is one of thousands of firefighters from across the United States battling dozens of wildfires burning throughout the West. It’s an inherently dangerous job that now carries the additional risk of COVID-19 transmission. Any outbreak that ripples through a camp could easily sideline crews and spread the virus across multiple fires – and back to communities across the country – as personnel transfer in and out of “hot zones” and return home.

Though most firefighters are young and fit, some will inevitably fall ill in these remote makeshift communities of shared showers and portable toilets, where medical care can be limited. The pollutants in the smoke they breathe daily also make them more susceptible to COVID-19 and can worsen the effects of the disease, according to the Centers for Disease Control and Prevention.

Also, one suspected or positive case in a camp will mean many other firefighters will need to be quarantined, unable to work. The worst-case scenario is that multiple outbreaks could hamstring the nation’s ability to respond as wildfire season peaks in August, the hottest and driest month of the year in the western United States.

The number of acres burned so far this year is below the 10-year average, but the fire outlook for August is above average in nine states, according to the National Interagency Fire Center. Twenty-two large fires were ignited on Monday alone after lightning storms passed through the Northwest.

A study published this month by researchers at Colorado State University and the U.S. Forest Service’s Rocky Mountain Research Station concluded that COVID outbreaks “could be a serious threat to the firefighting mission” and urged vigilant social distancing and screening measures in the camps.

“If simultaneous fires incurred outbreaks, the entire wildland response system could be stressed substantially, with a large portion of the workforce quarantined,” the study’s authors wrote.

This spring, the National Wildfire Coordinating Group’s Fire Management Board wrote – and has since been updating – protocols to prevent the spread of COVID-19 in fire camps, based on CDC guidelines. Though they can be adapted by managers at different fires and even by individual team, they center on some key recommendations, including the following:

• Firefighters should be screened for fever and other COVID symptoms when they arrive at camp.
• Every crew should insulate itself as a “module of one” for the fire season and limit interactions with other crews.
• Firefighters should maintain social distancing and wear face coverings when social distancing isn’t possible. Smaller satellite camps, known as spike camps, can be built to ensure enough space.
• Shared areas should be regularly cleaned and disinfected, and sharing tools and radios should be minimized.

The guidance does not include routine testing of newly arrived firefighters – a practice used for athletes at training camps and students returning to college campuses.

The Fire Management Board’s Wildland Fire Medical and Public Health Advisory Team wrote in a July 2 memo that it “does not recommend utilizing universal COVID-19 laboratory testing as a standalone risk mitigation or screening measure among wildland firefighters.” Rather, the group recommends testing an individual and directly exposed coworkers, saying that approach is in line with CDC guidance.

The lack of testing capacity and long turnaround times are factors, according to Forest Service spokesperson Dan Hottle.

The exception is Alaska, where firefighters are tested upon arrival at the airport and are quarantined in a hotel while awaiting results, which come within 24 hours, Mr. Hottle said.

Fire crews responding to early-season fires in the spring had some problems adjusting to the new protocols, according to assessments written by fire leaders and compiled by the Wildland Fire Lessons Learned Center.

Shawn Faiella, superintendent of the interagency “hotshot crew” – so named because they work the most challenging or “hottest” parts of wildfires – based at Montana’s Lolo National Forest, questioned the need to wear masks inside vehicles and the safety of bringing extra vehicles to space out firefighters traveling to a blaze. Parking extra vehicles at the scene of a fire is difficult in tight dirt roads – and would be dangerous if evacuations are necessary, he wrote.

“It’s damn tough to take these practices to the fire line,” Mr. Faiella wrote after his team responded to a 40-acre Montana fire in April.

One recommendation that fire managers say has been particularly effective is the “module of one” concept requiring crews to eat and sleep together in isolation for the entire fire season.

“Whoever came up with it, it is working,” said Mike Goicoechea, the Montana-based incident commander for the Forest Service’s Northern Region Type 1 team, which manages the nation’s largest and most complex wildfires and natural disasters. “Somebody may test positive, and you end up having to take that module out of service for 14 days. But the nice part is you’re not taking out a whole camp. ... It’s just that module.”

The total number of positive COVID cases among wildland firefighters among the various federal, state, local, and tribal agencies is not being tracked. Each fire agency has its own system for tracking and reporting COVID-19, said Jessica Gardetto, a spokesperson for the Bureau of Land Management (BLM) and the National Interagency Fire Center in Idaho.

The largest wildland firefighting agency is the Department of Agriculture’s Forest Service, with 10,000 firefighters. Another major agency is the Department of the Interior, which BLM is part of and which had more than 3,500 full-time fire employees last year. As of the first week of August, 111 Forest Service firefighters and 40 BLM firefighters (who work underneath the broader Interior Department agency) had tested positive for COVID-19, according to officials for the respective agencies.

“Considering we’ve now been experiencing fire activity for several months, this number is surprisingly low if you think about the thousands of fire personnel who’ve been suppressing wildfires this summer,” Ms. Gardetto said.

Mr. Goicoechea and his Montana team traveled north of Tucson, Arizona, on June 22 to manage a rapidly spreading fire in the Santa Catalina Mountains that required 1,200 responders at its peak. Within 2 days of the team’s arrival, his managers were overwhelmed by calls from firefighters worried or with questions about preventing the spread of COVID-19 or carrying the virus home to their families.

In an unusual move, Mr. Goicoechea called upon Montana physician – and former National Park Service ranger with wildfire experience – Harry Sibold, MD, to join the team. Physicians are rarely, if ever, part of a wildfire camp’s medical team, Mr. Goicoechea said.

Dr. Sibold gave regular coronavirus updates during morning briefings, consulted with local health officials, soothed firefighters worried about bringing the virus home to their families, and advised fire managers on how to handle scenarios that might come up.

But Dr. Sibold said he wasn’t optimistic at the beginning about keeping the coronavirus in check in a large camp in Pima County, which has the second-highest number of confirmed cases in Arizona, at the time a national COVID-19 hot spot. “I quite firmly expected that we might have two or three outbreaks,” he said.

There were no positive cases during the team’s 2-week deployment, just three or four cases in which a firefighter showed symptoms but tested negative for the virus. After the Montana team returned home, nine firefighters at the Arizona fire from other units tested positive, Mr. Goicoechea said. Contact tracers notified the Montana team, some of whom were tested. All tests returned negative.

“I can’t say enough about having that doctor to help,” Mr. Goicoechea said, suggesting other teams might consider doing the same. “We’re not the experts in a pandemic. We’re the experts with fire.”

That early success will be tested as the number of fires increases across the West, along with the number of firefighters responding to them. There were more than 15,000 firefighters and support personnel assigned to fires across the nation as of mid-August, and the success of those COVID-19 prevention protocols depend largely on them.

Mr. Paul, the Oregon firefighter, said that the guidelines were followed closely in camp, but less so out on the fire line. It also appeared to him that younger firefighters were less likely to follow the masking and social-distancing rules than the veterans like him. That worried him as he realized it wouldn’t take much to spark an outbreak that could sideline crews and cripple the ability to respond to a fire.

“We’re outside, so it definitely helps with mitigation and makes it simpler to social distance,” Mr. Paul said. “But I think if there’s a mistake made, it could happen.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Jon Paul was leery entering his first wildfire camp of the year late last month to fight three lightning-caused fires scorching parts of a Northern California forest that hadn’t burned in 40 years.

Courtesy of U.S. Forest Service

The 54-year-old engine captain from southern Oregon knew from experience that these crowded, grimy camps can be breeding grounds for norovirus and a respiratory illness that firefighters call the “camp crud” in a normal year. He wondered what the coronavirus would do in the tent cities where hundreds of men and women eat, sleep, wash, and spend their downtime between shifts.

Mr. Paul thought about his immunocompromised wife and his 84-year-old mother back home. Then he joined the approximately 1,300 people spread across the Modoc National Forest who would provide a major test for the COVID-prevention measures that had been developed for wildland firefighters.

“We’re still first responders and we have that responsibility to go and deal with these emergencies,” he said in a recent interview. “I don’t scare easy, but I’m very wary and concerned about my surroundings. I’m still going to work and do my job.”

Mr. Paul is one of thousands of firefighters from across the United States battling dozens of wildfires burning throughout the West. It’s an inherently dangerous job that now carries the additional risk of COVID-19 transmission. Any outbreak that ripples through a camp could easily sideline crews and spread the virus across multiple fires – and back to communities across the country – as personnel transfer in and out of “hot zones” and return home.

Though most firefighters are young and fit, some will inevitably fall ill in these remote makeshift communities of shared showers and portable toilets, where medical care can be limited. The pollutants in the smoke they breathe daily also make them more susceptible to COVID-19 and can worsen the effects of the disease, according to the Centers for Disease Control and Prevention.

Also, one suspected or positive case in a camp will mean many other firefighters will need to be quarantined, unable to work. The worst-case scenario is that multiple outbreaks could hamstring the nation’s ability to respond as wildfire season peaks in August, the hottest and driest month of the year in the western United States.

The number of acres burned so far this year is below the 10-year average, but the fire outlook for August is above average in nine states, according to the National Interagency Fire Center. Twenty-two large fires were ignited on Monday alone after lightning storms passed through the Northwest.

A study published this month by researchers at Colorado State University and the U.S. Forest Service’s Rocky Mountain Research Station concluded that COVID outbreaks “could be a serious threat to the firefighting mission” and urged vigilant social distancing and screening measures in the camps.

“If simultaneous fires incurred outbreaks, the entire wildland response system could be stressed substantially, with a large portion of the workforce quarantined,” the study’s authors wrote.

This spring, the National Wildfire Coordinating Group’s Fire Management Board wrote – and has since been updating – protocols to prevent the spread of COVID-19 in fire camps, based on CDC guidelines. Though they can be adapted by managers at different fires and even by individual team, they center on some key recommendations, including the following:

• Firefighters should be screened for fever and other COVID symptoms when they arrive at camp.
• Every crew should insulate itself as a “module of one” for the fire season and limit interactions with other crews.
• Firefighters should maintain social distancing and wear face coverings when social distancing isn’t possible. Smaller satellite camps, known as spike camps, can be built to ensure enough space.
• Shared areas should be regularly cleaned and disinfected, and sharing tools and radios should be minimized.

The guidance does not include routine testing of newly arrived firefighters – a practice used for athletes at training camps and students returning to college campuses.

The Fire Management Board’s Wildland Fire Medical and Public Health Advisory Team wrote in a July 2 memo that it “does not recommend utilizing universal COVID-19 laboratory testing as a standalone risk mitigation or screening measure among wildland firefighters.” Rather, the group recommends testing an individual and directly exposed coworkers, saying that approach is in line with CDC guidance.

The lack of testing capacity and long turnaround times are factors, according to Forest Service spokesperson Dan Hottle.

The exception is Alaska, where firefighters are tested upon arrival at the airport and are quarantined in a hotel while awaiting results, which come within 24 hours, Mr. Hottle said.

Fire crews responding to early-season fires in the spring had some problems adjusting to the new protocols, according to assessments written by fire leaders and compiled by the Wildland Fire Lessons Learned Center.

Shawn Faiella, superintendent of the interagency “hotshot crew” – so named because they work the most challenging or “hottest” parts of wildfires – based at Montana’s Lolo National Forest, questioned the need to wear masks inside vehicles and the safety of bringing extra vehicles to space out firefighters traveling to a blaze. Parking extra vehicles at the scene of a fire is difficult in tight dirt roads – and would be dangerous if evacuations are necessary, he wrote.

“It’s damn tough to take these practices to the fire line,” Mr. Faiella wrote after his team responded to a 40-acre Montana fire in April.

One recommendation that fire managers say has been particularly effective is the “module of one” concept requiring crews to eat and sleep together in isolation for the entire fire season.

“Whoever came up with it, it is working,” said Mike Goicoechea, the Montana-based incident commander for the Forest Service’s Northern Region Type 1 team, which manages the nation’s largest and most complex wildfires and natural disasters. “Somebody may test positive, and you end up having to take that module out of service for 14 days. But the nice part is you’re not taking out a whole camp. ... It’s just that module.”

The total number of positive COVID cases among wildland firefighters among the various federal, state, local, and tribal agencies is not being tracked. Each fire agency has its own system for tracking and reporting COVID-19, said Jessica Gardetto, a spokesperson for the Bureau of Land Management (BLM) and the National Interagency Fire Center in Idaho.

The largest wildland firefighting agency is the Department of Agriculture’s Forest Service, with 10,000 firefighters. Another major agency is the Department of the Interior, which BLM is part of and which had more than 3,500 full-time fire employees last year. As of the first week of August, 111 Forest Service firefighters and 40 BLM firefighters (who work underneath the broader Interior Department agency) had tested positive for COVID-19, according to officials for the respective agencies.

“Considering we’ve now been experiencing fire activity for several months, this number is surprisingly low if you think about the thousands of fire personnel who’ve been suppressing wildfires this summer,” Ms. Gardetto said.

Mr. Goicoechea and his Montana team traveled north of Tucson, Arizona, on June 22 to manage a rapidly spreading fire in the Santa Catalina Mountains that required 1,200 responders at its peak. Within 2 days of the team’s arrival, his managers were overwhelmed by calls from firefighters worried or with questions about preventing the spread of COVID-19 or carrying the virus home to their families.

In an unusual move, Mr. Goicoechea called upon Montana physician – and former National Park Service ranger with wildfire experience – Harry Sibold, MD, to join the team. Physicians are rarely, if ever, part of a wildfire camp’s medical team, Mr. Goicoechea said.

Dr. Sibold gave regular coronavirus updates during morning briefings, consulted with local health officials, soothed firefighters worried about bringing the virus home to their families, and advised fire managers on how to handle scenarios that might come up.

But Dr. Sibold said he wasn’t optimistic at the beginning about keeping the coronavirus in check in a large camp in Pima County, which has the second-highest number of confirmed cases in Arizona, at the time a national COVID-19 hot spot. “I quite firmly expected that we might have two or three outbreaks,” he said.

There were no positive cases during the team’s 2-week deployment, just three or four cases in which a firefighter showed symptoms but tested negative for the virus. After the Montana team returned home, nine firefighters at the Arizona fire from other units tested positive, Mr. Goicoechea said. Contact tracers notified the Montana team, some of whom were tested. All tests returned negative.

“I can’t say enough about having that doctor to help,” Mr. Goicoechea said, suggesting other teams might consider doing the same. “We’re not the experts in a pandemic. We’re the experts with fire.”

That early success will be tested as the number of fires increases across the West, along with the number of firefighters responding to them. There were more than 15,000 firefighters and support personnel assigned to fires across the nation as of mid-August, and the success of those COVID-19 prevention protocols depend largely on them.

Mr. Paul, the Oregon firefighter, said that the guidelines were followed closely in camp, but less so out on the fire line. It also appeared to him that younger firefighters were less likely to follow the masking and social-distancing rules than the veterans like him. That worried him as he realized it wouldn’t take much to spark an outbreak that could sideline crews and cripple the ability to respond to a fire.

“We’re outside, so it definitely helps with mitigation and makes it simpler to social distance,” Mr. Paul said. “But I think if there’s a mistake made, it could happen.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Jon Paul was leery entering his first wildfire camp of the year late last month to fight three lightning-caused fires scorching parts of a Northern California forest that hadn’t burned in 40 years.

Courtesy of U.S. Forest Service

The 54-year-old engine captain from southern Oregon knew from experience that these crowded, grimy camps can be breeding grounds for norovirus and a respiratory illness that firefighters call the “camp crud” in a normal year. He wondered what the coronavirus would do in the tent cities where hundreds of men and women eat, sleep, wash, and spend their downtime between shifts.

Mr. Paul thought about his immunocompromised wife and his 84-year-old mother back home. Then he joined the approximately 1,300 people spread across the Modoc National Forest who would provide a major test for the COVID-prevention measures that had been developed for wildland firefighters.

“We’re still first responders and we have that responsibility to go and deal with these emergencies,” he said in a recent interview. “I don’t scare easy, but I’m very wary and concerned about my surroundings. I’m still going to work and do my job.”

Mr. Paul is one of thousands of firefighters from across the United States battling dozens of wildfires burning throughout the West. It’s an inherently dangerous job that now carries the additional risk of COVID-19 transmission. Any outbreak that ripples through a camp could easily sideline crews and spread the virus across multiple fires – and back to communities across the country – as personnel transfer in and out of “hot zones” and return home.

Though most firefighters are young and fit, some will inevitably fall ill in these remote makeshift communities of shared showers and portable toilets, where medical care can be limited. The pollutants in the smoke they breathe daily also make them more susceptible to COVID-19 and can worsen the effects of the disease, according to the Centers for Disease Control and Prevention.

Also, one suspected or positive case in a camp will mean many other firefighters will need to be quarantined, unable to work. The worst-case scenario is that multiple outbreaks could hamstring the nation’s ability to respond as wildfire season peaks in August, the hottest and driest month of the year in the western United States.

The number of acres burned so far this year is below the 10-year average, but the fire outlook for August is above average in nine states, according to the National Interagency Fire Center. Twenty-two large fires were ignited on Monday alone after lightning storms passed through the Northwest.

A study published this month by researchers at Colorado State University and the U.S. Forest Service’s Rocky Mountain Research Station concluded that COVID outbreaks “could be a serious threat to the firefighting mission” and urged vigilant social distancing and screening measures in the camps.

“If simultaneous fires incurred outbreaks, the entire wildland response system could be stressed substantially, with a large portion of the workforce quarantined,” the study’s authors wrote.

This spring, the National Wildfire Coordinating Group’s Fire Management Board wrote – and has since been updating – protocols to prevent the spread of COVID-19 in fire camps, based on CDC guidelines. Though they can be adapted by managers at different fires and even by individual team, they center on some key recommendations, including the following:

• Firefighters should be screened for fever and other COVID symptoms when they arrive at camp.
• Every crew should insulate itself as a “module of one” for the fire season and limit interactions with other crews.
• Firefighters should maintain social distancing and wear face coverings when social distancing isn’t possible. Smaller satellite camps, known as spike camps, can be built to ensure enough space.
• Shared areas should be regularly cleaned and disinfected, and sharing tools and radios should be minimized.

The guidance does not include routine testing of newly arrived firefighters – a practice used for athletes at training camps and students returning to college campuses.

The Fire Management Board’s Wildland Fire Medical and Public Health Advisory Team wrote in a July 2 memo that it “does not recommend utilizing universal COVID-19 laboratory testing as a standalone risk mitigation or screening measure among wildland firefighters.” Rather, the group recommends testing an individual and directly exposed coworkers, saying that approach is in line with CDC guidance.

The lack of testing capacity and long turnaround times are factors, according to Forest Service spokesperson Dan Hottle.

The exception is Alaska, where firefighters are tested upon arrival at the airport and are quarantined in a hotel while awaiting results, which come within 24 hours, Mr. Hottle said.

Fire crews responding to early-season fires in the spring had some problems adjusting to the new protocols, according to assessments written by fire leaders and compiled by the Wildland Fire Lessons Learned Center.

Shawn Faiella, superintendent of the interagency “hotshot crew” – so named because they work the most challenging or “hottest” parts of wildfires – based at Montana’s Lolo National Forest, questioned the need to wear masks inside vehicles and the safety of bringing extra vehicles to space out firefighters traveling to a blaze. Parking extra vehicles at the scene of a fire is difficult in tight dirt roads – and would be dangerous if evacuations are necessary, he wrote.

“It’s damn tough to take these practices to the fire line,” Mr. Faiella wrote after his team responded to a 40-acre Montana fire in April.

One recommendation that fire managers say has been particularly effective is the “module of one” concept requiring crews to eat and sleep together in isolation for the entire fire season.

“Whoever came up with it, it is working,” said Mike Goicoechea, the Montana-based incident commander for the Forest Service’s Northern Region Type 1 team, which manages the nation’s largest and most complex wildfires and natural disasters. “Somebody may test positive, and you end up having to take that module out of service for 14 days. But the nice part is you’re not taking out a whole camp. ... It’s just that module.”

The total number of positive COVID cases among wildland firefighters among the various federal, state, local, and tribal agencies is not being tracked. Each fire agency has its own system for tracking and reporting COVID-19, said Jessica Gardetto, a spokesperson for the Bureau of Land Management (BLM) and the National Interagency Fire Center in Idaho.

The largest wildland firefighting agency is the Department of Agriculture’s Forest Service, with 10,000 firefighters. Another major agency is the Department of the Interior, which BLM is part of and which had more than 3,500 full-time fire employees last year. As of the first week of August, 111 Forest Service firefighters and 40 BLM firefighters (who work underneath the broader Interior Department agency) had tested positive for COVID-19, according to officials for the respective agencies.

“Considering we’ve now been experiencing fire activity for several months, this number is surprisingly low if you think about the thousands of fire personnel who’ve been suppressing wildfires this summer,” Ms. Gardetto said.

Mr. Goicoechea and his Montana team traveled north of Tucson, Arizona, on June 22 to manage a rapidly spreading fire in the Santa Catalina Mountains that required 1,200 responders at its peak. Within 2 days of the team’s arrival, his managers were overwhelmed by calls from firefighters worried or with questions about preventing the spread of COVID-19 or carrying the virus home to their families.

In an unusual move, Mr. Goicoechea called upon Montana physician – and former National Park Service ranger with wildfire experience – Harry Sibold, MD, to join the team. Physicians are rarely, if ever, part of a wildfire camp’s medical team, Mr. Goicoechea said.

Dr. Sibold gave regular coronavirus updates during morning briefings, consulted with local health officials, soothed firefighters worried about bringing the virus home to their families, and advised fire managers on how to handle scenarios that might come up.

But Dr. Sibold said he wasn’t optimistic at the beginning about keeping the coronavirus in check in a large camp in Pima County, which has the second-highest number of confirmed cases in Arizona, at the time a national COVID-19 hot spot. “I quite firmly expected that we might have two or three outbreaks,” he said.

There were no positive cases during the team’s 2-week deployment, just three or four cases in which a firefighter showed symptoms but tested negative for the virus. After the Montana team returned home, nine firefighters at the Arizona fire from other units tested positive, Mr. Goicoechea said. Contact tracers notified the Montana team, some of whom were tested. All tests returned negative.

“I can’t say enough about having that doctor to help,” Mr. Goicoechea said, suggesting other teams might consider doing the same. “We’re not the experts in a pandemic. We’re the experts with fire.”

That early success will be tested as the number of fires increases across the West, along with the number of firefighters responding to them. There were more than 15,000 firefighters and support personnel assigned to fires across the nation as of mid-August, and the success of those COVID-19 prevention protocols depend largely on them.

Mr. Paul, the Oregon firefighter, said that the guidelines were followed closely in camp, but less so out on the fire line. It also appeared to him that younger firefighters were less likely to follow the masking and social-distancing rules than the veterans like him. That worried him as he realized it wouldn’t take much to spark an outbreak that could sideline crews and cripple the ability to respond to a fire.

“We’re outside, so it definitely helps with mitigation and makes it simpler to social distance,” Mr. Paul said. “But I think if there’s a mistake made, it could happen.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

Aug. 25, 2020. 12:00 p.m. – 1:00 p.m. ET

Medical Product Theater: Worsening Symptoms and Hospitalization for Heart Failure: Increased Risk of Poor Outcomes and Opportunities to Enhance Care

Objectives

• Discuss hospitalization as a pivotal point in the clinical trajectory of heart failure.
• Highlight strategies for improvement and optimization of the treatment plan for patients with heart failure.
• Provide practical guidance for identifying predictors of worsening heart failure and educating on the importance of patients’ self-management.

Speaker

William T. Abraham, MD, FACP, FACC, FAHA, FESC, FRCPE

Professor of Medicine, Physiology, and Cell Biology

College of Medicine Distinguished Professor

Division of Cardiovascular Medicine

The Ohio State University,

Columbus, Ohio

Sponsored by Novartis Pharmaceuticals, and the faculty will be compensated for time.

Aug. 26, 2020. 12:00 p.m. – 1:00 p.m. ET

Commercial Product Theater: A First Choice Treatment for the Inpatient Management of Stabilized Systolic HF Patients: An Evidence-Based Approach

Description

Patients hospitalized due to heart failure with reduced ejection fraction (HFrEF) are at considerable risk of readmission and mortality. This program will review the benefits and risks of starting therapy in the hospital to help prevent rehospitalization and reduce patient mortality.

Speaker

Hameed Ali, DO, SFHM

Clinical Assistant Professor of Medicine

Baylor Scott and White Health

Dallas, Texas

Sponsored by Novartis Pharmaceuticals, and the faculty will be compensated for time.

Aug. 27, 2020. 12:00 p.m. – 1:00 p.m. ET

Commercial Product Theater: Selecting A First-Choice Therapy for Systolic HF: Meeting the Burden of Proof

Description

What is the burden of proof that needs to be met before a therapy can be selected for the treatment of systolic heart failure? Hear from Dr. Javed Butler, chairman of the Department of Medicine at the University of Mississippi Medical Center, to learn more about selecting a first-choice therapy for your patients with systolic heart failure.

In this program, Dr. Butler will discuss how aligning your therapy selection to pathophysiologic pathways for HFrEF, it is possible to reduce mortality and morbidity while providing a proven safety and tolerability profile.

Regardless of your patients’ previous heart failure treatment history, following this program, you can feel confident selecting your first-choice therapy for your patients with HFrEF.
 

Speaker

Javed Butler, MD, MPH, MBA

Chairman, Department of Medicine

University of Mississippi Medical Center,

Jackson, Mississippi

Sponsored by Novartis Pharmaceuticals, and the faculty will be compensated for time.

Aug. 25, 2020. 12:00 p.m. – 1:00 p.m. ET

Medical Product Theater: Worsening Symptoms and Hospitalization for Heart Failure: Increased Risk of Poor Outcomes and Opportunities to Enhance Care

Objectives

• Discuss hospitalization as a pivotal point in the clinical trajectory of heart failure.
• Highlight strategies for improvement and optimization of the treatment plan for patients with heart failure.
• Provide practical guidance for identifying predictors of worsening heart failure and educating on the importance of patients’ self-management.

Speaker

William T. Abraham, MD, FACP, FACC, FAHA, FESC, FRCPE

Professor of Medicine, Physiology, and Cell Biology

College of Medicine Distinguished Professor

Division of Cardiovascular Medicine

The Ohio State University,

Columbus, Ohio

Sponsored by Novartis Pharmaceuticals, and the faculty will be compensated for time.

Aug. 26, 2020. 12:00 p.m. – 1:00 p.m. ET

Commercial Product Theater: A First Choice Treatment for the Inpatient Management of Stabilized Systolic HF Patients: An Evidence-Based Approach

Description

Patients hospitalized due to heart failure with reduced ejection fraction (HFrEF) are at considerable risk of readmission and mortality. This program will review the benefits and risks of starting therapy in the hospital to help prevent rehospitalization and reduce patient mortality.

Speaker

Hameed Ali, DO, SFHM

Clinical Assistant Professor of Medicine

Baylor Scott and White Health

Dallas, Texas

Sponsored by Novartis Pharmaceuticals, and the faculty will be compensated for time.

Aug. 27, 2020. 12:00 p.m. – 1:00 p.m. ET

Commercial Product Theater: Selecting A First-Choice Therapy for Systolic HF: Meeting the Burden of Proof

Description

What is the burden of proof that needs to be met before a therapy can be selected for the treatment of systolic heart failure? Hear from Dr. Javed Butler, chairman of the Department of Medicine at the University of Mississippi Medical Center, to learn more about selecting a first-choice therapy for your patients with systolic heart failure.

In this program, Dr. Butler will discuss how aligning your therapy selection to pathophysiologic pathways for HFrEF, it is possible to reduce mortality and morbidity while providing a proven safety and tolerability profile.

Regardless of your patients’ previous heart failure treatment history, following this program, you can feel confident selecting your first-choice therapy for your patients with HFrEF.
 

Speaker

Javed Butler, MD, MPH, MBA

Chairman, Department of Medicine

University of Mississippi Medical Center,

Jackson, Mississippi

Sponsored by Novartis Pharmaceuticals, and the faculty will be compensated for time.

Aug. 25, 2020. 12:00 p.m. – 1:00 p.m. ET

Medical Product Theater: Worsening Symptoms and Hospitalization for Heart Failure: Increased Risk of Poor Outcomes and Opportunities to Enhance Care

Objectives

• Discuss hospitalization as a pivotal point in the clinical trajectory of heart failure.
• Highlight strategies for improvement and optimization of the treatment plan for patients with heart failure.
• Provide practical guidance for identifying predictors of worsening heart failure and educating on the importance of patients’ self-management.

Speaker

William T. Abraham, MD, FACP, FACC, FAHA, FESC, FRCPE

Professor of Medicine, Physiology, and Cell Biology

College of Medicine Distinguished Professor

Division of Cardiovascular Medicine

The Ohio State University,

Columbus, Ohio

Sponsored by Novartis Pharmaceuticals, and the faculty will be compensated for time.

Aug. 26, 2020. 12:00 p.m. – 1:00 p.m. ET

Commercial Product Theater: A First Choice Treatment for the Inpatient Management of Stabilized Systolic HF Patients: An Evidence-Based Approach

Description

Patients hospitalized due to heart failure with reduced ejection fraction (HFrEF) are at considerable risk of readmission and mortality. This program will review the benefits and risks of starting therapy in the hospital to help prevent rehospitalization and reduce patient mortality.

Speaker

Hameed Ali, DO, SFHM

Clinical Assistant Professor of Medicine

Baylor Scott and White Health

Dallas, Texas

Sponsored by Novartis Pharmaceuticals, and the faculty will be compensated for time.

Aug. 27, 2020. 12:00 p.m. – 1:00 p.m. ET

Commercial Product Theater: Selecting A First-Choice Therapy for Systolic HF: Meeting the Burden of Proof

Description

What is the burden of proof that needs to be met before a therapy can be selected for the treatment of systolic heart failure? Hear from Dr. Javed Butler, chairman of the Department of Medicine at the University of Mississippi Medical Center, to learn more about selecting a first-choice therapy for your patients with systolic heart failure.

In this program, Dr. Butler will discuss how aligning your therapy selection to pathophysiologic pathways for HFrEF, it is possible to reduce mortality and morbidity while providing a proven safety and tolerability profile.

Regardless of your patients’ previous heart failure treatment history, following this program, you can feel confident selecting your first-choice therapy for your patients with HFrEF.
 

Speaker

Javed Butler, MD, MPH, MBA

Chairman, Department of Medicine

University of Mississippi Medical Center,

Jackson, Mississippi

Sponsored by Novartis Pharmaceuticals, and the faculty will be compensated for time.

Complications from tobacco use are the most common preventable cause of death, disability, and disease in the United States. Tobacco use causes 480,000 premature deaths every year. In pregnancy, tobacco use causes complications such as premature birth, intrauterine growth restriction, and placental abruption. In the perinatal period, it is associated with sudden infant death syndrome. While cigarette smoking is decreasing in adolescents, e-cigarette use in on the rise. Approximately 1,600 children aged 12-17 smoke their first cigarette every day and it is estimated that 5.6 million children and adolescents will die of a tobacco use–related death.¹ For these reasons it is important to address tobacco use and cessation with patients whenever it is possible. Below is a case and recommendations related to a new American Thoracic Society guideline on initiating pharmacologic treatment in tobacco-dependent adults.

A forty-five-year-old male who rarely comes to the office is here today for a physical exam at the urging of his partner. He has been smoking a pack a day since age 17. You have tried at past visits to discuss quitting, but he had been in the precontemplative stage and had been unwilling to consider any change. This visit, however, he is ready to try to quit. What can you offer him?

Core recommendations from ATS guidelines

This patient can be offered varenicline plus nicotine replacement therapy rather than nicotine replacement therapy, bupropion, e-cigarettes, or varenicline alone. His course of therapy should extend beyond 12 weeks instead of the standard 6- to 12-week therapy. Alternatively, he could be offered varenicline alone, rather than nicotine replacement.²

A change from previous guidelines

What makes this recommendation so interesting and new is the emphasis it places on varenicline. The United States Preventive Services Task Force released a recommendation statement in 2015 that stressed a combination of pharmacological and behavioral interventions. It discussed nicotine replacement therapy, bupropion, and varenicline, but did not recommend any one over any of the others.³ The new recommendation from the American Thoracic Society favors varenicline over other pharmacologic interventions. It is based on an independent systematic review of the literature that showed higher rates of tobacco use abstinence at the 6-month follow-up with varenicline alone versus nicotine replacement therapy alone, bupropion alone, or e-cigarette use only.

A review of 14 randomized controlled trials showed that varenicline improves abstinence rates during treatment by approximately 40% compared with nicotine replacement, and by 20% at the end of 6 months of treatment. The review found that varenicline plus nicotine replacement therapy is more effective than varenicline alone. In this comparison, based on three trials, there was a 36% higher abstinence rate at 6 months using varenicline plus nicotine replacement. When varenicline use was compared with use of a nicotine patch, bupropion, or e-cigarettes, there was a reduction in serious adverse events – changes in mood, suicidal ideation, and neurological side effects such as seizures.² Clinicians may remember a black box warning on the varenicline label citing neuropsychiatric effects and it is important to note that the Food and Drug Administration removed this boxed warning in 2016.⁴

Opinion

This recommendation represents an important, evidence-based change from previous guidelines. It presents the opportunity for better outcomes, but will likely take a while to filter into practice, as clinicians need to become more comfortable with the use of varenicline and insurance supports the cost of varenicline.

The average cost of varenicline for 12 weeks is between $1,220 and $1,584. For comparison, nicotine replacement therapy costs $170 to $240 for the same number of weeks. To put those costs in perspective, the 12-week cost of cigarettes for a two-pack-a-day smoker is approximately $1,000.

For some patients, the motivation to quit smoking comes from the realization of how much they are spending on cigarettes each month. That said, if a patient does not have insurance or their insurance does not cover the cost of varenicline, nicotine replacement therapy might be more appealing. It should be noted that better abstinence rates have been seen in patients taking varenicline plus nicotine replacement therapy versus varenicline alone.

Suggested treatment

Based on a systematic review of randomized controlled trials, the American Thoracic Society’s guideline on pharmacological treatment in tobacco-dependent adults concludes that varenicline plus nicotine patch is the preferred pharmacological treatment for tobacco cessation when compared with varenicline alone, bupropion alone, nicotine replacement therapy alone, and e-cigarettes alone. If the patient does not want to start two medicines at once, then varenicline alone would be the preferred choice.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. Dr. Sprogell is a third-year resident in the family medicine residency program at Abington Jefferson Health. They have no conflicts related to the content of this piece. For questions or comments, feel free to contact Dr. Skolnik on Twitter @NeilSkolnik.

References

1. U.S. Preventive Services Task Force. Primary care interventions for prevention and cessation of tobacco use in children and adolescents: U.S. Preventive Services Task Force Recommendation Statement. JAMA.2020;323(16):1590-8. doi: 10.1001/jama.2020.4679.

2. Leone FT et al. Initiating pharmacologic treatment in tobacco-dependent adults: An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202(2):e5–e31.

3. Tobacco smoking cessation in adults, including pregnant women: Behavioral and pharmacotherapy interventions. U.S. Preventive Services Task Force 2015 Sep 21.

4. FDA Drug Safety Communication: FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. 2016 Dec. 16.

Complications from tobacco use are the most common preventable cause of death, disability, and disease in the United States. Tobacco use causes 480,000 premature deaths every year. In pregnancy, tobacco use causes complications such as premature birth, intrauterine growth restriction, and placental abruption. In the perinatal period, it is associated with sudden infant death syndrome. While cigarette smoking is decreasing in adolescents, e-cigarette use in on the rise. Approximately 1,600 children aged 12-17 smoke their first cigarette every day and it is estimated that 5.6 million children and adolescents will die of a tobacco use–related death.¹ For these reasons it is important to address tobacco use and cessation with patients whenever it is possible. Below is a case and recommendations related to a new American Thoracic Society guideline on initiating pharmacologic treatment in tobacco-dependent adults.

A forty-five-year-old male who rarely comes to the office is here today for a physical exam at the urging of his partner. He has been smoking a pack a day since age 17. You have tried at past visits to discuss quitting, but he had been in the precontemplative stage and had been unwilling to consider any change. This visit, however, he is ready to try to quit. What can you offer him?

Core recommendations from ATS guidelines

This patient can be offered varenicline plus nicotine replacement therapy rather than nicotine replacement therapy, bupropion, e-cigarettes, or varenicline alone. His course of therapy should extend beyond 12 weeks instead of the standard 6- to 12-week therapy. Alternatively, he could be offered varenicline alone, rather than nicotine replacement.²

A change from previous guidelines

What makes this recommendation so interesting and new is the emphasis it places on varenicline. The United States Preventive Services Task Force released a recommendation statement in 2015 that stressed a combination of pharmacological and behavioral interventions. It discussed nicotine replacement therapy, bupropion, and varenicline, but did not recommend any one over any of the others.³ The new recommendation from the American Thoracic Society favors varenicline over other pharmacologic interventions. It is based on an independent systematic review of the literature that showed higher rates of tobacco use abstinence at the 6-month follow-up with varenicline alone versus nicotine replacement therapy alone, bupropion alone, or e-cigarette use only.

A review of 14 randomized controlled trials showed that varenicline improves abstinence rates during treatment by approximately 40% compared with nicotine replacement, and by 20% at the end of 6 months of treatment. The review found that varenicline plus nicotine replacement therapy is more effective than varenicline alone. In this comparison, based on three trials, there was a 36% higher abstinence rate at 6 months using varenicline plus nicotine replacement. When varenicline use was compared with use of a nicotine patch, bupropion, or e-cigarettes, there was a reduction in serious adverse events – changes in mood, suicidal ideation, and neurological side effects such as seizures.² Clinicians may remember a black box warning on the varenicline label citing neuropsychiatric effects and it is important to note that the Food and Drug Administration removed this boxed warning in 2016.⁴

Opinion

This recommendation represents an important, evidence-based change from previous guidelines. It presents the opportunity for better outcomes, but will likely take a while to filter into practice, as clinicians need to become more comfortable with the use of varenicline and insurance supports the cost of varenicline.

The average cost of varenicline for 12 weeks is between $1,220 and $1,584. For comparison, nicotine replacement therapy costs $170 to $240 for the same number of weeks. To put those costs in perspective, the 12-week cost of cigarettes for a two-pack-a-day smoker is approximately $1,000.

For some patients, the motivation to quit smoking comes from the realization of how much they are spending on cigarettes each month. That said, if a patient does not have insurance or their insurance does not cover the cost of varenicline, nicotine replacement therapy might be more appealing. It should be noted that better abstinence rates have been seen in patients taking varenicline plus nicotine replacement therapy versus varenicline alone.

Suggested treatment

Based on a systematic review of randomized controlled trials, the American Thoracic Society’s guideline on pharmacological treatment in tobacco-dependent adults concludes that varenicline plus nicotine patch is the preferred pharmacological treatment for tobacco cessation when compared with varenicline alone, bupropion alone, nicotine replacement therapy alone, and e-cigarettes alone. If the patient does not want to start two medicines at once, then varenicline alone would be the preferred choice.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. Dr. Sprogell is a third-year resident in the family medicine residency program at Abington Jefferson Health. They have no conflicts related to the content of this piece. For questions or comments, feel free to contact Dr. Skolnik on Twitter @NeilSkolnik.

References

1. U.S. Preventive Services Task Force. Primary care interventions for prevention and cessation of tobacco use in children and adolescents: U.S. Preventive Services Task Force Recommendation Statement. JAMA.2020;323(16):1590-8. doi: 10.1001/jama.2020.4679.

2. Leone FT et al. Initiating pharmacologic treatment in tobacco-dependent adults: An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202(2):e5–e31.

3. Tobacco smoking cessation in adults, including pregnant women: Behavioral and pharmacotherapy interventions. U.S. Preventive Services Task Force 2015 Sep 21.

4. FDA Drug Safety Communication: FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. 2016 Dec. 16.

Complications from tobacco use are the most common preventable cause of death, disability, and disease in the United States. Tobacco use causes 480,000 premature deaths every year. In pregnancy, tobacco use causes complications such as premature birth, intrauterine growth restriction, and placental abruption. In the perinatal period, it is associated with sudden infant death syndrome. While cigarette smoking is decreasing in adolescents, e-cigarette use in on the rise. Approximately 1,600 children aged 12-17 smoke their first cigarette every day and it is estimated that 5.6 million children and adolescents will die of a tobacco use–related death.¹ For these reasons it is important to address tobacco use and cessation with patients whenever it is possible. Below is a case and recommendations related to a new American Thoracic Society guideline on initiating pharmacologic treatment in tobacco-dependent adults.

A forty-five-year-old male who rarely comes to the office is here today for a physical exam at the urging of his partner. He has been smoking a pack a day since age 17. You have tried at past visits to discuss quitting, but he had been in the precontemplative stage and had been unwilling to consider any change. This visit, however, he is ready to try to quit. What can you offer him?

Core recommendations from ATS guidelines

This patient can be offered varenicline plus nicotine replacement therapy rather than nicotine replacement therapy, bupropion, e-cigarettes, or varenicline alone. His course of therapy should extend beyond 12 weeks instead of the standard 6- to 12-week therapy. Alternatively, he could be offered varenicline alone, rather than nicotine replacement.²

A change from previous guidelines

What makes this recommendation so interesting and new is the emphasis it places on varenicline. The United States Preventive Services Task Force released a recommendation statement in 2015 that stressed a combination of pharmacological and behavioral interventions. It discussed nicotine replacement therapy, bupropion, and varenicline, but did not recommend any one over any of the others.³ The new recommendation from the American Thoracic Society favors varenicline over other pharmacologic interventions. It is based on an independent systematic review of the literature that showed higher rates of tobacco use abstinence at the 6-month follow-up with varenicline alone versus nicotine replacement therapy alone, bupropion alone, or e-cigarette use only.

A review of 14 randomized controlled trials showed that varenicline improves abstinence rates during treatment by approximately 40% compared with nicotine replacement, and by 20% at the end of 6 months of treatment. The review found that varenicline plus nicotine replacement therapy is more effective than varenicline alone. In this comparison, based on three trials, there was a 36% higher abstinence rate at 6 months using varenicline plus nicotine replacement. When varenicline use was compared with use of a nicotine patch, bupropion, or e-cigarettes, there was a reduction in serious adverse events – changes in mood, suicidal ideation, and neurological side effects such as seizures.² Clinicians may remember a black box warning on the varenicline label citing neuropsychiatric effects and it is important to note that the Food and Drug Administration removed this boxed warning in 2016.⁴

Opinion

This recommendation represents an important, evidence-based change from previous guidelines. It presents the opportunity for better outcomes, but will likely take a while to filter into practice, as clinicians need to become more comfortable with the use of varenicline and insurance supports the cost of varenicline.

The average cost of varenicline for 12 weeks is between $1,220 and $1,584. For comparison, nicotine replacement therapy costs $170 to $240 for the same number of weeks. To put those costs in perspective, the 12-week cost of cigarettes for a two-pack-a-day smoker is approximately $1,000.

For some patients, the motivation to quit smoking comes from the realization of how much they are spending on cigarettes each month. That said, if a patient does not have insurance or their insurance does not cover the cost of varenicline, nicotine replacement therapy might be more appealing. It should be noted that better abstinence rates have been seen in patients taking varenicline plus nicotine replacement therapy versus varenicline alone.

Suggested treatment

Based on a systematic review of randomized controlled trials, the American Thoracic Society’s guideline on pharmacological treatment in tobacco-dependent adults concludes that varenicline plus nicotine patch is the preferred pharmacological treatment for tobacco cessation when compared with varenicline alone, bupropion alone, nicotine replacement therapy alone, and e-cigarettes alone. If the patient does not want to start two medicines at once, then varenicline alone would be the preferred choice.

Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health. Dr. Sprogell is a third-year resident in the family medicine residency program at Abington Jefferson Health. They have no conflicts related to the content of this piece. For questions or comments, feel free to contact Dr. Skolnik on Twitter @NeilSkolnik.

References

1. U.S. Preventive Services Task Force. Primary care interventions for prevention and cessation of tobacco use in children and adolescents: U.S. Preventive Services Task Force Recommendation Statement. JAMA.2020;323(16):1590-8. doi: 10.1001/jama.2020.4679.

2. Leone FT et al. Initiating pharmacologic treatment in tobacco-dependent adults: An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020;202(2):e5–e31.

3. Tobacco smoking cessation in adults, including pregnant women: Behavioral and pharmacotherapy interventions. U.S. Preventive Services Task Force 2015 Sep 21.

4. FDA Drug Safety Communication: FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. 2016 Dec. 16.