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MDedge conference coverage features onsite reporting of the latest study results and expert perspectives from leading researchers.
Rosacea and the gut: Looking into SIBO
, according to speakers at the annual Integrative Dermatology Symposium.
“SIBO is definitely something we test for and treat,” Raja Sivamani, MD, said in an interview after the meeting. Dr. Sivamani practices as an integrative dermatologist at the Pacific Skin Institute in Sacramento and is the director of clinical research at the institute’s research unit, Integrative Skin Science and Research. He led a panel discussion on rosacea and acne at the meeting.
Associations between SIBO and several dermatologic conditions, including systemic sclerosis, have been reported, but the strongest evidence to date involves rosacea. “There’s associative epidemiological evidence showing higher rates of SIBO among those with rosacea, and there are prospective studies” showing clearance of rosacea in patients treated for SIBO, said Dr. Sivamani, also adjunct associate professor of clinical dermatology at the University of California, Davis.
Studies are small, but are “well done and well-designed,” he said in the interview. “Do we need more studies? Absolutely. But what we have now is compelling [enough] for us to take a look at it.”
Findings of rosacea clearance
SIBO’s believed contribution to the pathophysiology of rosacea is part of the increasingly described gut microbiome-skin axis. SIBO has been recognized as a medical phenomenon for many decades and has been defined as an excessive bacterial load in the small bowel that causes gastrointestinal symptoms, according to the 2020 American College of Gastroenterology clinical guideline on SIBO.
Symptoms commonly associated with SIBO overlap with the cardinal symptoms of irritable bowel syndrome (IBS): abdominal pain; diarrhea, constipation, or both; bloating; and flatulence. SIBO can be diagnosed with several validated carbohydrate substrate (glucose or lactulose)–based breath tests that measure hydrogen and/or methane.
Hydrogen-positive breath tests suggest bacterial overgrowth, and methane-positive breath tests suggest small intestinal methanogen overgrowth. Methane is increasingly important and recognized, the AGA guideline says, though it creates a “nomenclature problem in the SIBO framework” because methanogens are not bacteria, the authors note.
In conventional practice, SIBO is typically treated with antibiotics such as rifaximin, and often with short-term dietary modification as well. Integrative medicine typically considers the use of supplements and botanicals in addition to or instead of antibiotics, as well as dietary change and increasingly, a close look at SIBO risk factors to prevent recurrence, Dr. Sivamani said. (His research unit is currently studying the use of herbal protocols as an alternative to antibiotics in patients with SIBO and dermatologic conditions.)
During a presentation on rosacea at the meeting, Neal Bhatia, MD, director of clinical dermatology at Therapeutics Clinical Research, a dermatology treatment and research center in San Diego, said that currently available breath tests for SIBO “are very interesting tools for understanding what may be happening in the gut” and that the “rifaximin data are good.”
He referred to a study reported in the Journal of the American Academy of Dermatology showing that patients with rosacea were significantly more likely to have SIBO (41.7% of 48 patients vs. 5.0% of 40 controls; P < .001), and that 64.5% of rosacea patients who completed treatment with rifaximin had remission of rosacea at a 3-year follow-up.
An earlier crossover study is also notable, he said. This study enrolled 113 consecutive patients with rosacea and 60 age- and sex-matched controls, and randomized those with SIBO (52 of the 113 with rosacea vs. 3 of the 60 controls) to rifaximin or placebo. Rosacea cleared in 20 of the 28 patients in the rifaximin group and greatly improved in 6 of the 28. Of 20 patients in the placebo group, rosacea remained unchanged in 18 and worsened in 2. When patients in the placebo group were switched to rifaximin, SIBO was eradicated in 17 of the 20, and rosacea completely resolved in 15 of those patients, Dr. Bhatia said.
In his view, it will take more time, greater awareness of the rosacea-SIBO link, and a willingness “to take chances” for more dermatologists to consider SIBO during rosacea care. “Breath tests are not something used in the [typical dermatology] clinic right now, but they may make their way in,” he said at the meeting.
In a follow-up interview, Dr. Bhatia emphasized that “it’s really a question of uptake, which always takes a while” and of willingness to “think through the disease from another angle ... especially in patients who are recalcitrant.”
Treatment
Dr. Sivamani said in the interview that a third type of SIBO – hydrogen sulfide–dominant SIBO – is now documented and worth considering when glucose and lactulose breath tests are negative in patients with rosacea who have gastrointestinal symptoms.
The use of breath tests to objectively diagnose SIBO is always best, Dr. Sivamani said, but he will consider empiric therapy in some patients. “I always tell patients [about] the benefits of testing, but if they can’t get the test covered or are unable to pay for the test, and they have symptoms consistent with SIBO, I’m okay doing a trial with therapy,” he said.
Rifaximin, one of the suggested antibiotics listed in the AGA guideline, is a nonabsorbable antibiotic that is FDA-approved for IBS with diarrhea (IBS-D); it has been shown to not negatively affect the growth of beneficial bacteria in the colon.
However, herbals are also an attractive option – alone or in combination with rifaximin or other antibiotics – speakers at the meeting said. In a multicenter retrospective chart review led by investigators at the Johns Hopkins Hospital, herbal therapies were at least as effective as rifaximin for treating SIBO, with similar safety profiles. The response rate for normalizing breath hydrogen testing in patients with SIBO was 46% for herbal therapies and 34% for rifaximin.
Dietary change is also part of treatment, with the reduction of fermentable carbohydrates – often through the Low FODMAP Diet and Specific Carbohydrate Diet – being the dominant theme in dietary intervention for SIBO, according to the AGA guideline.
“There are definitely some food choices you can shift,” said Dr. Sivamani. “I’ll work with patients on FODMAP, though it’s hard to sustain over the long-term and can induce psychological issues. You have to provide other options.”
Dr. Sivamani works with patients on using “a restrictive diet for a short amount of time, with the gradual reintroduction of foods to see [what] foods are and aren’t [causing] flares.” He also works to identify and eliminate risk factors and predisposing factors for SIBO so that recurrence will be less likely.
“SIBO is definitely an entity that is not on the fringes anymore ... it adds to inflammation in the body ... and if you have an inflamed gut, there’s a domino effect that will lead to inflammation elsewhere,” Dr. Sivamani said.
“You want to know, do your patients have SIBO? What subset do they have? Do they have risk factors you can eliminate?” he said. “And then what therapies will you use – pharmaceuticals, supplements and botanicals, or a combination? And finally, what will you do with diet?”
Dr. Bhatia disclosed he has affiliations with Abbvie, Almirall, Arcutis, Arena, Biofrontera, BMS, BI, Brickell, Dermavant, EPI Health, Ferndale, Galderma, Genentech, InCyte, ISDIN, Johnson & Johnson, LaRoche-Posay, Leo, Lilly, Novartis, Ortho, Pfizer, Proctor & Gamble, Regeneron, Sanofi, Stemline, SunPharma, and Verrica. Dr. Sivamani did not provide a disclosure statement.
, according to speakers at the annual Integrative Dermatology Symposium.
“SIBO is definitely something we test for and treat,” Raja Sivamani, MD, said in an interview after the meeting. Dr. Sivamani practices as an integrative dermatologist at the Pacific Skin Institute in Sacramento and is the director of clinical research at the institute’s research unit, Integrative Skin Science and Research. He led a panel discussion on rosacea and acne at the meeting.
Associations between SIBO and several dermatologic conditions, including systemic sclerosis, have been reported, but the strongest evidence to date involves rosacea. “There’s associative epidemiological evidence showing higher rates of SIBO among those with rosacea, and there are prospective studies” showing clearance of rosacea in patients treated for SIBO, said Dr. Sivamani, also adjunct associate professor of clinical dermatology at the University of California, Davis.
Studies are small, but are “well done and well-designed,” he said in the interview. “Do we need more studies? Absolutely. But what we have now is compelling [enough] for us to take a look at it.”
Findings of rosacea clearance
SIBO’s believed contribution to the pathophysiology of rosacea is part of the increasingly described gut microbiome-skin axis. SIBO has been recognized as a medical phenomenon for many decades and has been defined as an excessive bacterial load in the small bowel that causes gastrointestinal symptoms, according to the 2020 American College of Gastroenterology clinical guideline on SIBO.
Symptoms commonly associated with SIBO overlap with the cardinal symptoms of irritable bowel syndrome (IBS): abdominal pain; diarrhea, constipation, or both; bloating; and flatulence. SIBO can be diagnosed with several validated carbohydrate substrate (glucose or lactulose)–based breath tests that measure hydrogen and/or methane.
Hydrogen-positive breath tests suggest bacterial overgrowth, and methane-positive breath tests suggest small intestinal methanogen overgrowth. Methane is increasingly important and recognized, the AGA guideline says, though it creates a “nomenclature problem in the SIBO framework” because methanogens are not bacteria, the authors note.
In conventional practice, SIBO is typically treated with antibiotics such as rifaximin, and often with short-term dietary modification as well. Integrative medicine typically considers the use of supplements and botanicals in addition to or instead of antibiotics, as well as dietary change and increasingly, a close look at SIBO risk factors to prevent recurrence, Dr. Sivamani said. (His research unit is currently studying the use of herbal protocols as an alternative to antibiotics in patients with SIBO and dermatologic conditions.)
During a presentation on rosacea at the meeting, Neal Bhatia, MD, director of clinical dermatology at Therapeutics Clinical Research, a dermatology treatment and research center in San Diego, said that currently available breath tests for SIBO “are very interesting tools for understanding what may be happening in the gut” and that the “rifaximin data are good.”
He referred to a study reported in the Journal of the American Academy of Dermatology showing that patients with rosacea were significantly more likely to have SIBO (41.7% of 48 patients vs. 5.0% of 40 controls; P < .001), and that 64.5% of rosacea patients who completed treatment with rifaximin had remission of rosacea at a 3-year follow-up.
An earlier crossover study is also notable, he said. This study enrolled 113 consecutive patients with rosacea and 60 age- and sex-matched controls, and randomized those with SIBO (52 of the 113 with rosacea vs. 3 of the 60 controls) to rifaximin or placebo. Rosacea cleared in 20 of the 28 patients in the rifaximin group and greatly improved in 6 of the 28. Of 20 patients in the placebo group, rosacea remained unchanged in 18 and worsened in 2. When patients in the placebo group were switched to rifaximin, SIBO was eradicated in 17 of the 20, and rosacea completely resolved in 15 of those patients, Dr. Bhatia said.
In his view, it will take more time, greater awareness of the rosacea-SIBO link, and a willingness “to take chances” for more dermatologists to consider SIBO during rosacea care. “Breath tests are not something used in the [typical dermatology] clinic right now, but they may make their way in,” he said at the meeting.
In a follow-up interview, Dr. Bhatia emphasized that “it’s really a question of uptake, which always takes a while” and of willingness to “think through the disease from another angle ... especially in patients who are recalcitrant.”
Treatment
Dr. Sivamani said in the interview that a third type of SIBO – hydrogen sulfide–dominant SIBO – is now documented and worth considering when glucose and lactulose breath tests are negative in patients with rosacea who have gastrointestinal symptoms.
The use of breath tests to objectively diagnose SIBO is always best, Dr. Sivamani said, but he will consider empiric therapy in some patients. “I always tell patients [about] the benefits of testing, but if they can’t get the test covered or are unable to pay for the test, and they have symptoms consistent with SIBO, I’m okay doing a trial with therapy,” he said.
Rifaximin, one of the suggested antibiotics listed in the AGA guideline, is a nonabsorbable antibiotic that is FDA-approved for IBS with diarrhea (IBS-D); it has been shown to not negatively affect the growth of beneficial bacteria in the colon.
However, herbals are also an attractive option – alone or in combination with rifaximin or other antibiotics – speakers at the meeting said. In a multicenter retrospective chart review led by investigators at the Johns Hopkins Hospital, herbal therapies were at least as effective as rifaximin for treating SIBO, with similar safety profiles. The response rate for normalizing breath hydrogen testing in patients with SIBO was 46% for herbal therapies and 34% for rifaximin.
Dietary change is also part of treatment, with the reduction of fermentable carbohydrates – often through the Low FODMAP Diet and Specific Carbohydrate Diet – being the dominant theme in dietary intervention for SIBO, according to the AGA guideline.
“There are definitely some food choices you can shift,” said Dr. Sivamani. “I’ll work with patients on FODMAP, though it’s hard to sustain over the long-term and can induce psychological issues. You have to provide other options.”
Dr. Sivamani works with patients on using “a restrictive diet for a short amount of time, with the gradual reintroduction of foods to see [what] foods are and aren’t [causing] flares.” He also works to identify and eliminate risk factors and predisposing factors for SIBO so that recurrence will be less likely.
“SIBO is definitely an entity that is not on the fringes anymore ... it adds to inflammation in the body ... and if you have an inflamed gut, there’s a domino effect that will lead to inflammation elsewhere,” Dr. Sivamani said.
“You want to know, do your patients have SIBO? What subset do they have? Do they have risk factors you can eliminate?” he said. “And then what therapies will you use – pharmaceuticals, supplements and botanicals, or a combination? And finally, what will you do with diet?”
Dr. Bhatia disclosed he has affiliations with Abbvie, Almirall, Arcutis, Arena, Biofrontera, BMS, BI, Brickell, Dermavant, EPI Health, Ferndale, Galderma, Genentech, InCyte, ISDIN, Johnson & Johnson, LaRoche-Posay, Leo, Lilly, Novartis, Ortho, Pfizer, Proctor & Gamble, Regeneron, Sanofi, Stemline, SunPharma, and Verrica. Dr. Sivamani did not provide a disclosure statement.
, according to speakers at the annual Integrative Dermatology Symposium.
“SIBO is definitely something we test for and treat,” Raja Sivamani, MD, said in an interview after the meeting. Dr. Sivamani practices as an integrative dermatologist at the Pacific Skin Institute in Sacramento and is the director of clinical research at the institute’s research unit, Integrative Skin Science and Research. He led a panel discussion on rosacea and acne at the meeting.
Associations between SIBO and several dermatologic conditions, including systemic sclerosis, have been reported, but the strongest evidence to date involves rosacea. “There’s associative epidemiological evidence showing higher rates of SIBO among those with rosacea, and there are prospective studies” showing clearance of rosacea in patients treated for SIBO, said Dr. Sivamani, also adjunct associate professor of clinical dermatology at the University of California, Davis.
Studies are small, but are “well done and well-designed,” he said in the interview. “Do we need more studies? Absolutely. But what we have now is compelling [enough] for us to take a look at it.”
Findings of rosacea clearance
SIBO’s believed contribution to the pathophysiology of rosacea is part of the increasingly described gut microbiome-skin axis. SIBO has been recognized as a medical phenomenon for many decades and has been defined as an excessive bacterial load in the small bowel that causes gastrointestinal symptoms, according to the 2020 American College of Gastroenterology clinical guideline on SIBO.
Symptoms commonly associated with SIBO overlap with the cardinal symptoms of irritable bowel syndrome (IBS): abdominal pain; diarrhea, constipation, or both; bloating; and flatulence. SIBO can be diagnosed with several validated carbohydrate substrate (glucose or lactulose)–based breath tests that measure hydrogen and/or methane.
Hydrogen-positive breath tests suggest bacterial overgrowth, and methane-positive breath tests suggest small intestinal methanogen overgrowth. Methane is increasingly important and recognized, the AGA guideline says, though it creates a “nomenclature problem in the SIBO framework” because methanogens are not bacteria, the authors note.
In conventional practice, SIBO is typically treated with antibiotics such as rifaximin, and often with short-term dietary modification as well. Integrative medicine typically considers the use of supplements and botanicals in addition to or instead of antibiotics, as well as dietary change and increasingly, a close look at SIBO risk factors to prevent recurrence, Dr. Sivamani said. (His research unit is currently studying the use of herbal protocols as an alternative to antibiotics in patients with SIBO and dermatologic conditions.)
During a presentation on rosacea at the meeting, Neal Bhatia, MD, director of clinical dermatology at Therapeutics Clinical Research, a dermatology treatment and research center in San Diego, said that currently available breath tests for SIBO “are very interesting tools for understanding what may be happening in the gut” and that the “rifaximin data are good.”
He referred to a study reported in the Journal of the American Academy of Dermatology showing that patients with rosacea were significantly more likely to have SIBO (41.7% of 48 patients vs. 5.0% of 40 controls; P < .001), and that 64.5% of rosacea patients who completed treatment with rifaximin had remission of rosacea at a 3-year follow-up.
An earlier crossover study is also notable, he said. This study enrolled 113 consecutive patients with rosacea and 60 age- and sex-matched controls, and randomized those with SIBO (52 of the 113 with rosacea vs. 3 of the 60 controls) to rifaximin or placebo. Rosacea cleared in 20 of the 28 patients in the rifaximin group and greatly improved in 6 of the 28. Of 20 patients in the placebo group, rosacea remained unchanged in 18 and worsened in 2. When patients in the placebo group were switched to rifaximin, SIBO was eradicated in 17 of the 20, and rosacea completely resolved in 15 of those patients, Dr. Bhatia said.
In his view, it will take more time, greater awareness of the rosacea-SIBO link, and a willingness “to take chances” for more dermatologists to consider SIBO during rosacea care. “Breath tests are not something used in the [typical dermatology] clinic right now, but they may make their way in,” he said at the meeting.
In a follow-up interview, Dr. Bhatia emphasized that “it’s really a question of uptake, which always takes a while” and of willingness to “think through the disease from another angle ... especially in patients who are recalcitrant.”
Treatment
Dr. Sivamani said in the interview that a third type of SIBO – hydrogen sulfide–dominant SIBO – is now documented and worth considering when glucose and lactulose breath tests are negative in patients with rosacea who have gastrointestinal symptoms.
The use of breath tests to objectively diagnose SIBO is always best, Dr. Sivamani said, but he will consider empiric therapy in some patients. “I always tell patients [about] the benefits of testing, but if they can’t get the test covered or are unable to pay for the test, and they have symptoms consistent with SIBO, I’m okay doing a trial with therapy,” he said.
Rifaximin, one of the suggested antibiotics listed in the AGA guideline, is a nonabsorbable antibiotic that is FDA-approved for IBS with diarrhea (IBS-D); it has been shown to not negatively affect the growth of beneficial bacteria in the colon.
However, herbals are also an attractive option – alone or in combination with rifaximin or other antibiotics – speakers at the meeting said. In a multicenter retrospective chart review led by investigators at the Johns Hopkins Hospital, herbal therapies were at least as effective as rifaximin for treating SIBO, with similar safety profiles. The response rate for normalizing breath hydrogen testing in patients with SIBO was 46% for herbal therapies and 34% for rifaximin.
Dietary change is also part of treatment, with the reduction of fermentable carbohydrates – often through the Low FODMAP Diet and Specific Carbohydrate Diet – being the dominant theme in dietary intervention for SIBO, according to the AGA guideline.
“There are definitely some food choices you can shift,” said Dr. Sivamani. “I’ll work with patients on FODMAP, though it’s hard to sustain over the long-term and can induce psychological issues. You have to provide other options.”
Dr. Sivamani works with patients on using “a restrictive diet for a short amount of time, with the gradual reintroduction of foods to see [what] foods are and aren’t [causing] flares.” He also works to identify and eliminate risk factors and predisposing factors for SIBO so that recurrence will be less likely.
“SIBO is definitely an entity that is not on the fringes anymore ... it adds to inflammation in the body ... and if you have an inflamed gut, there’s a domino effect that will lead to inflammation elsewhere,” Dr. Sivamani said.
“You want to know, do your patients have SIBO? What subset do they have? Do they have risk factors you can eliminate?” he said. “And then what therapies will you use – pharmaceuticals, supplements and botanicals, or a combination? And finally, what will you do with diet?”
Dr. Bhatia disclosed he has affiliations with Abbvie, Almirall, Arcutis, Arena, Biofrontera, BMS, BI, Brickell, Dermavant, EPI Health, Ferndale, Galderma, Genentech, InCyte, ISDIN, Johnson & Johnson, LaRoche-Posay, Leo, Lilly, Novartis, Ortho, Pfizer, Proctor & Gamble, Regeneron, Sanofi, Stemline, SunPharma, and Verrica. Dr. Sivamani did not provide a disclosure statement.
REPORTING FROM IDS 2022
Applications for laser-assisted drug delivery on the horizon, expert says
For those who view fractional ablative laser–assisted drug delivery as a pie-in-the-sky procedure that will take years to work its way into routine clinical practice, think again.
According to Merete Haedersdal, MD, PhD, DMSc, .
“The groundwork has been established over a decade with more than 100 publications available on PubMed,” Dr. Haedersdal, professor of dermatology at the University of Copenhagen, said during a virtual course on laser and aesthetic skin therapy. “There is no doubt that by drilling tiny little holes or channels with ablative fractional lasers, we enhance drug delivery to the skin, and we also empower different topical treatment regimens. Also, laser-assisted drug delivery holds the potential to bring new innovations into established medicine.”
Many studies have demonstrated that clinicians can enhance drug uptake into the skin with the fractional 10,600 nm CO2 laser, the fractional 2,940 nm erbium:YAG laser, and the 1,927 nm thulium laser, but proper tuning of the devices is key. The lower the density, the better, Dr. Haedersdal said.
“Typically, we use 5% density or 5% coverage, sometimes 10%-15%, but don’t go higher in order to avoid the risk of having a systemic uptake,” she said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “Also, the pulse energy for channel depth needs to be tailored to the specific dermatologic disease being treated,” she said, noting that for melasma, for example, “very low pulse energies” would be used, but they would be higher for treating thicker lesions, such as a hypertrophic scar.
Treatment with ablative fractional lasers enhances drug accumulation in the skin of any drug or substance applied to the skin, and clinical indications are expanding rapidly. Established indications include combining ablative fractional lasers and photodynamic therapy (PDT) for AKs and combining ablative fractional lasers and triamcinolone or 5-FU for scars. “Although we have a good body of evidence, particularly for AKs, it’s still an off-label use,” she emphasized.
Evolving indications include concomitant use of ablative fractional laser and vitamins and cosmeceuticals for rejuvenation; lidocaine for local anesthetics; tranexamic acid and hydroquinone for melasma; antifungals for onychomycosis; Botox for hyperhidrosis; minoxidil for alopecia; and betamethasone for vitiligo. A promising treatment for skin cancer “on the horizon,” she said, is the “combination of ablative fractional laser with PD1 inhibitors and chemotherapy.”
Data on AKs
Evidence supporting laser-assisted drug delivery for AKs comes from more than 10 randomized, controlled trials in the dermatology literature involving 400-plus immunocompetent and immunosuppressed patients. These trials have found ablative fractional laser–assisted PDT to be significantly more efficacious than PDT alone up to 12 months postoperatively and to foster lower rates of AK recurrence.
In a meta-analysis and systematic review, German researchers concluded that PDT combined with ablative laser treatment for AKs is more efficient but not more painful than either therapy alone. They recommended the combined regimen for patients with severe photodamage, field cancerization, and multiple AKs.
In 2020, an international consensus panel of experts, including Dr. Haedersdal, published recommendations regarding laser treatment of traumatic scars and contractures. The panel members determined that laser-assisted delivery of corticosteroids and antimetabolites was recommended for hypertrophic scars and cited triamcinolone acetonide suspension (TAC) as the most common corticosteroid used in combination with ablative fractional lasers. “It can be applied in concentrations of 40 mg/mL or less depending on the degree of hypertrophy,” they wrote.
In addition, they stated that 5-FU solution is “most commonly applied in a concentration of 50 mg/mL alone, or mixed with TAC in ratios of 9:1 or 3:1.”
According to the best available evidence, the clinical approach for hypertrophic scars supports combination treatment with ablative fractional laser and triamcinolone acetonide either alone or in combination with 5-FU. For atrophic scars, laser-assisted delivery of poly-L-lactic acid has been shown to be efficient. “Both of these treatments improve texture and thickness but also dyschromia and scar functionality,” said Dr. Haedersdal, who is also a visiting scientist at the Wellman Center for Photomedicine, Boston.
Commenting on patient safety with laser-assisted drug delivery, “the combination of lasers and topicals can be a powerful cocktail,” she said. “You can expect intensified local skin reactions. When treating larger areas, consider the risk of systemic absorption and the risk of potential toxicity. There is also the potential for infection with pathogens such as Staphylococcus aureus. The take-home message here is that you should only use the type and amount of drug no higher than administered during intradermal injection.”
Dr. Haedersdal disclosed that she has received equipment from Cherry Imaging, Cynosure-Hologic, MiraDry, and PerfAction Technologies. She has also received research grants from Leo Pharma, Lutronic, Mirai Medical, Novoxel, and Venus Concept.
For those who view fractional ablative laser–assisted drug delivery as a pie-in-the-sky procedure that will take years to work its way into routine clinical practice, think again.
According to Merete Haedersdal, MD, PhD, DMSc, .
“The groundwork has been established over a decade with more than 100 publications available on PubMed,” Dr. Haedersdal, professor of dermatology at the University of Copenhagen, said during a virtual course on laser and aesthetic skin therapy. “There is no doubt that by drilling tiny little holes or channels with ablative fractional lasers, we enhance drug delivery to the skin, and we also empower different topical treatment regimens. Also, laser-assisted drug delivery holds the potential to bring new innovations into established medicine.”
Many studies have demonstrated that clinicians can enhance drug uptake into the skin with the fractional 10,600 nm CO2 laser, the fractional 2,940 nm erbium:YAG laser, and the 1,927 nm thulium laser, but proper tuning of the devices is key. The lower the density, the better, Dr. Haedersdal said.
“Typically, we use 5% density or 5% coverage, sometimes 10%-15%, but don’t go higher in order to avoid the risk of having a systemic uptake,” she said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “Also, the pulse energy for channel depth needs to be tailored to the specific dermatologic disease being treated,” she said, noting that for melasma, for example, “very low pulse energies” would be used, but they would be higher for treating thicker lesions, such as a hypertrophic scar.
Treatment with ablative fractional lasers enhances drug accumulation in the skin of any drug or substance applied to the skin, and clinical indications are expanding rapidly. Established indications include combining ablative fractional lasers and photodynamic therapy (PDT) for AKs and combining ablative fractional lasers and triamcinolone or 5-FU for scars. “Although we have a good body of evidence, particularly for AKs, it’s still an off-label use,” she emphasized.
Evolving indications include concomitant use of ablative fractional laser and vitamins and cosmeceuticals for rejuvenation; lidocaine for local anesthetics; tranexamic acid and hydroquinone for melasma; antifungals for onychomycosis; Botox for hyperhidrosis; minoxidil for alopecia; and betamethasone for vitiligo. A promising treatment for skin cancer “on the horizon,” she said, is the “combination of ablative fractional laser with PD1 inhibitors and chemotherapy.”
Data on AKs
Evidence supporting laser-assisted drug delivery for AKs comes from more than 10 randomized, controlled trials in the dermatology literature involving 400-plus immunocompetent and immunosuppressed patients. These trials have found ablative fractional laser–assisted PDT to be significantly more efficacious than PDT alone up to 12 months postoperatively and to foster lower rates of AK recurrence.
In a meta-analysis and systematic review, German researchers concluded that PDT combined with ablative laser treatment for AKs is more efficient but not more painful than either therapy alone. They recommended the combined regimen for patients with severe photodamage, field cancerization, and multiple AKs.
In 2020, an international consensus panel of experts, including Dr. Haedersdal, published recommendations regarding laser treatment of traumatic scars and contractures. The panel members determined that laser-assisted delivery of corticosteroids and antimetabolites was recommended for hypertrophic scars and cited triamcinolone acetonide suspension (TAC) as the most common corticosteroid used in combination with ablative fractional lasers. “It can be applied in concentrations of 40 mg/mL or less depending on the degree of hypertrophy,” they wrote.
In addition, they stated that 5-FU solution is “most commonly applied in a concentration of 50 mg/mL alone, or mixed with TAC in ratios of 9:1 or 3:1.”
According to the best available evidence, the clinical approach for hypertrophic scars supports combination treatment with ablative fractional laser and triamcinolone acetonide either alone or in combination with 5-FU. For atrophic scars, laser-assisted delivery of poly-L-lactic acid has been shown to be efficient. “Both of these treatments improve texture and thickness but also dyschromia and scar functionality,” said Dr. Haedersdal, who is also a visiting scientist at the Wellman Center for Photomedicine, Boston.
Commenting on patient safety with laser-assisted drug delivery, “the combination of lasers and topicals can be a powerful cocktail,” she said. “You can expect intensified local skin reactions. When treating larger areas, consider the risk of systemic absorption and the risk of potential toxicity. There is also the potential for infection with pathogens such as Staphylococcus aureus. The take-home message here is that you should only use the type and amount of drug no higher than administered during intradermal injection.”
Dr. Haedersdal disclosed that she has received equipment from Cherry Imaging, Cynosure-Hologic, MiraDry, and PerfAction Technologies. She has also received research grants from Leo Pharma, Lutronic, Mirai Medical, Novoxel, and Venus Concept.
For those who view fractional ablative laser–assisted drug delivery as a pie-in-the-sky procedure that will take years to work its way into routine clinical practice, think again.
According to Merete Haedersdal, MD, PhD, DMSc, .
“The groundwork has been established over a decade with more than 100 publications available on PubMed,” Dr. Haedersdal, professor of dermatology at the University of Copenhagen, said during a virtual course on laser and aesthetic skin therapy. “There is no doubt that by drilling tiny little holes or channels with ablative fractional lasers, we enhance drug delivery to the skin, and we also empower different topical treatment regimens. Also, laser-assisted drug delivery holds the potential to bring new innovations into established medicine.”
Many studies have demonstrated that clinicians can enhance drug uptake into the skin with the fractional 10,600 nm CO2 laser, the fractional 2,940 nm erbium:YAG laser, and the 1,927 nm thulium laser, but proper tuning of the devices is key. The lower the density, the better, Dr. Haedersdal said.
“Typically, we use 5% density or 5% coverage, sometimes 10%-15%, but don’t go higher in order to avoid the risk of having a systemic uptake,” she said during the meeting, which was sponsored by Harvard Medical School, Massachusetts General Hospital, and the Wellman Center for Photomedicine. “Also, the pulse energy for channel depth needs to be tailored to the specific dermatologic disease being treated,” she said, noting that for melasma, for example, “very low pulse energies” would be used, but they would be higher for treating thicker lesions, such as a hypertrophic scar.
Treatment with ablative fractional lasers enhances drug accumulation in the skin of any drug or substance applied to the skin, and clinical indications are expanding rapidly. Established indications include combining ablative fractional lasers and photodynamic therapy (PDT) for AKs and combining ablative fractional lasers and triamcinolone or 5-FU for scars. “Although we have a good body of evidence, particularly for AKs, it’s still an off-label use,” she emphasized.
Evolving indications include concomitant use of ablative fractional laser and vitamins and cosmeceuticals for rejuvenation; lidocaine for local anesthetics; tranexamic acid and hydroquinone for melasma; antifungals for onychomycosis; Botox for hyperhidrosis; minoxidil for alopecia; and betamethasone for vitiligo. A promising treatment for skin cancer “on the horizon,” she said, is the “combination of ablative fractional laser with PD1 inhibitors and chemotherapy.”
Data on AKs
Evidence supporting laser-assisted drug delivery for AKs comes from more than 10 randomized, controlled trials in the dermatology literature involving 400-plus immunocompetent and immunosuppressed patients. These trials have found ablative fractional laser–assisted PDT to be significantly more efficacious than PDT alone up to 12 months postoperatively and to foster lower rates of AK recurrence.
In a meta-analysis and systematic review, German researchers concluded that PDT combined with ablative laser treatment for AKs is more efficient but not more painful than either therapy alone. They recommended the combined regimen for patients with severe photodamage, field cancerization, and multiple AKs.
In 2020, an international consensus panel of experts, including Dr. Haedersdal, published recommendations regarding laser treatment of traumatic scars and contractures. The panel members determined that laser-assisted delivery of corticosteroids and antimetabolites was recommended for hypertrophic scars and cited triamcinolone acetonide suspension (TAC) as the most common corticosteroid used in combination with ablative fractional lasers. “It can be applied in concentrations of 40 mg/mL or less depending on the degree of hypertrophy,” they wrote.
In addition, they stated that 5-FU solution is “most commonly applied in a concentration of 50 mg/mL alone, or mixed with TAC in ratios of 9:1 or 3:1.”
According to the best available evidence, the clinical approach for hypertrophic scars supports combination treatment with ablative fractional laser and triamcinolone acetonide either alone or in combination with 5-FU. For atrophic scars, laser-assisted delivery of poly-L-lactic acid has been shown to be efficient. “Both of these treatments improve texture and thickness but also dyschromia and scar functionality,” said Dr. Haedersdal, who is also a visiting scientist at the Wellman Center for Photomedicine, Boston.
Commenting on patient safety with laser-assisted drug delivery, “the combination of lasers and topicals can be a powerful cocktail,” she said. “You can expect intensified local skin reactions. When treating larger areas, consider the risk of systemic absorption and the risk of potential toxicity. There is also the potential for infection with pathogens such as Staphylococcus aureus. The take-home message here is that you should only use the type and amount of drug no higher than administered during intradermal injection.”
Dr. Haedersdal disclosed that she has received equipment from Cherry Imaging, Cynosure-Hologic, MiraDry, and PerfAction Technologies. She has also received research grants from Leo Pharma, Lutronic, Mirai Medical, Novoxel, and Venus Concept.
FROM A LASER & AESTHETIC SKIN THERAPY COURSE
CRT boosts heart failure survival in extended follow-up
CHICAGO – Extended follow-up of patients with heart failure enrolled in the RAFT trial strengthens the case for starting treatment early with a cardiac resynchronization therapy plus defibrillation (CRT-D) device in appropriate patients.
RAFT, which compared CRT-D with treatment with an implantable cardioverter defibrillator (ICD) alone, showed that the early survival benefit produced by CRT-D during an average 40-month follow-up in the original trial persisted during an additional mean follow-up of about 5 years. This result strengthens the case for starting treatment early with a CRT-D device in appropriate patients with heart failure.
During extended follow-up of more than half of the enrolled patients, out to an average of 7.6 years overall and to an average of 12.9 years among survivors, patients who received a CRT-D device had a significant 21% relative reduction in their rate of all-cause mortality compared with randomized patients who received an ICD and no cardiac resynchronization, John L. Sapp, MD, reported at the American Heart Association scientific sessions.
The primary results of RAFT were first reported in 2010.
This magnitude of a survival benefit among the patients originally randomized to CRT is “dramatic,” given that many of the comparator patients who initially received no CRT likely crossed over to receive a CRT-D device once the initial, randomized 4 years of the study finished, commented Lynne W. Stevenson, MD, director of cardiomyopathy and the Lisa M. Jacobson Professor of Cardiology at Vanderbilt University Medical Center in Nashville, Tenn., who was not involved with the study.
‘CRT can remap heart failure trajectory’
The new findings “strengthen our conviction that CRT can remap the trajectory” of selected patients with heart failure, and that “candidates for CRT should be vigorously identified,” Dr. Stevenson said in an interview.
She also noted that the benefit with extended follow-up was “strikingly parallel” to that seen at 12 years after the addition of an ACE inhibitor for mild heart failure during the 4 years of the landmark SOLVD trial. The new RAFT extended follow-up, as well as the 12-year follow-up of the SOLVD trial, “support the concept that longer follow-up reveals vital information not provided by the relatively short randomized trial period,” she said.
“The new data say ‘don’t delay starting CRT in appropriate patients with heart failure,’ and ‘don’t think of CRT as just a treatment that makes patients feel better.’
“The totality of these data shows that CRT also treats the underlying heart muscle weakness, which helps patients live longer. Previous data showed that patients with left bundle branch block eligible for CRT are unlikely to respond well to the usual, recommended heart medications so it is important to start treatment with CRT-D early,” declared Dr. Stevenson, who cochaired the session where Dr. Sapp gave his report.
RAFT randomized 1,798 patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of at least 120 msec to receive either a CRT-D or ICD device. The study’s primary endpoint was death from any cause or hospitalization for heart failure. After an average 40 months of randomized follow-up, the primary endpoint occurred in 40% of the patients with an ICD and in 33% of those with a CRT-D device, a significant 25% relative reduction linked with CRT-D use. Both endpoint components contributed to the combined result significantly and to about the same extent, and the incremental benefit from CRT-D was significant for patients with NYHA class II heart failure as well as for those with class III.
However, prespecified subgroup analyses showed that the incremental benefit from CRT-D was significantly limited to patients with an intrinsic QRS duration of at least 150 msec, while in those with a duration of 120-149 msec CRT-D had a neutral effect compared with ICD. The same pattern also appeared when the analysis split patients into those with a left bundle branch block, who significantly benefited from CRT-D, but the initial benefit was not apparent in patients with right bundle branch block.
A study subgroup with extended follow-up
The new, extended follow-up analysis presented by Dr. Sapp included 1,050 of the original 1,798 patients (58%) enrolled at any of eight participating Canadian centers that each enrolled at least 100 patients and followed them through the end of 2021 (the full study cohort came from 34 centers, including 10 centers outside Canada). This subgroup included 520 patients randomized to receive CRT-D and 530 who received an ICD. Although this was a post hoc subgroup analysis, the CRT-D and ICD arms matched closely in all measured baseline characteristics.
The prespecified primary outcome of this follow-up analysis was the rate of all-cause mortality. Because of their longer disease trajectory, this pared-down study cohort included many more patients with NYHA class II function, 803, and in this subgroup CRT-D exerted a significant 23% incremental reduction in mortality compared with ICD treatment. CRT-D also produced a 17% relative reduction in long-term mortality among patients with NYHA class III function at baseline, but this point estimate of relative benefit was not significant in this subgroup of just 247 patients, said Dr. Sapp, a cardiologist and professor at Dalhousie University & Nova Scotia Health in Halifax.
Based on the original RAFT results from 2010, as well as on evidence from several other trials, the current heart failure management guideline from the AHA, the American College of Cardiology, and the Heart Failure Society of America give the highest level of recommendation, level 1, for CRT in patients with a left ventricular ejection fraction of 35% or less, sinus rhythm with left bundle branch block, a QRS duration of at least 150 msec, and NYHA class II, III, or ambulatory IV symptoms while on guideline-directed medical therapy.
The guideline also gives class 2a (“can be useful”) or 2b (“may be considered”) recommendation for certain other heart failure patients, including those with a QRS duration of 120-149 msec, a left ventricular ejection fraction as high as 50%, no left bundle branch block, or NYHA class I symptoms.
Don’t wait to start CRT
Although this 2022 guideline, as well as earlier versions that had roughly similar recommendations for CRT for about a decade, have led to “common” use of CRT in appropriate patients in U.S. practice, “it has not been used as much as it should be, in part because there’s been a feeling that CRT mostly treats symptoms and so perhaps you can wait” to start it, said Dr. Stevenson.
The findings from the new, extended follow-up RAFT analysis give increased urgency to starting CRT “as soon as possible” in appropriate patients with heart failure, even before they stabilize on guideline-directed medical therapy, said Dr. Stevenson. She also downplayed any ambiguity in the RAFT findings about optimal medical therapy, which during the RAFT study included traditional triple therapy at a time before treatment with sacubitril/valsartan (Entresto) and sodium-glucose cotransporter 2 (SGLT2) inhibitors became recommended.
“There is no reason to think that these treatments will negate the benefit of CRT for patients with heart failure with reduced ejection fraction and a wide left bundle branch block,” Dr. Stevenson said.
She also believes that the extended follow-up results, which showed clear efficacy for CRT-D in patients with NYHA class II function, support the case for upgrading the current 2b recommendation for using CRT treatment in patients with NYHA class I function and ischemic heart failure to a 2a recommendation regardless of whether or not patients have coronary artery disease. “The difference between class I and class II depends more on a patient’s lifestyle rather than on the severity of their heart failure,” Dr. Stevenson noted. “The RAFT study results encourage us to reexamine the clinical class and timing for CRT” in the current heart failure guideline.
RAFT received partial sponsorship from Medtronic. Dr. Sapp has been a consultant to Abbott, Biosense Webster, Medtronic, and Varian and has received research funding from Abbott and Biosense Webster. Dr. Stevenson had no disclosures.
CHICAGO – Extended follow-up of patients with heart failure enrolled in the RAFT trial strengthens the case for starting treatment early with a cardiac resynchronization therapy plus defibrillation (CRT-D) device in appropriate patients.
RAFT, which compared CRT-D with treatment with an implantable cardioverter defibrillator (ICD) alone, showed that the early survival benefit produced by CRT-D during an average 40-month follow-up in the original trial persisted during an additional mean follow-up of about 5 years. This result strengthens the case for starting treatment early with a CRT-D device in appropriate patients with heart failure.
During extended follow-up of more than half of the enrolled patients, out to an average of 7.6 years overall and to an average of 12.9 years among survivors, patients who received a CRT-D device had a significant 21% relative reduction in their rate of all-cause mortality compared with randomized patients who received an ICD and no cardiac resynchronization, John L. Sapp, MD, reported at the American Heart Association scientific sessions.
The primary results of RAFT were first reported in 2010.
This magnitude of a survival benefit among the patients originally randomized to CRT is “dramatic,” given that many of the comparator patients who initially received no CRT likely crossed over to receive a CRT-D device once the initial, randomized 4 years of the study finished, commented Lynne W. Stevenson, MD, director of cardiomyopathy and the Lisa M. Jacobson Professor of Cardiology at Vanderbilt University Medical Center in Nashville, Tenn., who was not involved with the study.
‘CRT can remap heart failure trajectory’
The new findings “strengthen our conviction that CRT can remap the trajectory” of selected patients with heart failure, and that “candidates for CRT should be vigorously identified,” Dr. Stevenson said in an interview.
She also noted that the benefit with extended follow-up was “strikingly parallel” to that seen at 12 years after the addition of an ACE inhibitor for mild heart failure during the 4 years of the landmark SOLVD trial. The new RAFT extended follow-up, as well as the 12-year follow-up of the SOLVD trial, “support the concept that longer follow-up reveals vital information not provided by the relatively short randomized trial period,” she said.
“The new data say ‘don’t delay starting CRT in appropriate patients with heart failure,’ and ‘don’t think of CRT as just a treatment that makes patients feel better.’
“The totality of these data shows that CRT also treats the underlying heart muscle weakness, which helps patients live longer. Previous data showed that patients with left bundle branch block eligible for CRT are unlikely to respond well to the usual, recommended heart medications so it is important to start treatment with CRT-D early,” declared Dr. Stevenson, who cochaired the session where Dr. Sapp gave his report.
RAFT randomized 1,798 patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of at least 120 msec to receive either a CRT-D or ICD device. The study’s primary endpoint was death from any cause or hospitalization for heart failure. After an average 40 months of randomized follow-up, the primary endpoint occurred in 40% of the patients with an ICD and in 33% of those with a CRT-D device, a significant 25% relative reduction linked with CRT-D use. Both endpoint components contributed to the combined result significantly and to about the same extent, and the incremental benefit from CRT-D was significant for patients with NYHA class II heart failure as well as for those with class III.
However, prespecified subgroup analyses showed that the incremental benefit from CRT-D was significantly limited to patients with an intrinsic QRS duration of at least 150 msec, while in those with a duration of 120-149 msec CRT-D had a neutral effect compared with ICD. The same pattern also appeared when the analysis split patients into those with a left bundle branch block, who significantly benefited from CRT-D, but the initial benefit was not apparent in patients with right bundle branch block.
A study subgroup with extended follow-up
The new, extended follow-up analysis presented by Dr. Sapp included 1,050 of the original 1,798 patients (58%) enrolled at any of eight participating Canadian centers that each enrolled at least 100 patients and followed them through the end of 2021 (the full study cohort came from 34 centers, including 10 centers outside Canada). This subgroup included 520 patients randomized to receive CRT-D and 530 who received an ICD. Although this was a post hoc subgroup analysis, the CRT-D and ICD arms matched closely in all measured baseline characteristics.
The prespecified primary outcome of this follow-up analysis was the rate of all-cause mortality. Because of their longer disease trajectory, this pared-down study cohort included many more patients with NYHA class II function, 803, and in this subgroup CRT-D exerted a significant 23% incremental reduction in mortality compared with ICD treatment. CRT-D also produced a 17% relative reduction in long-term mortality among patients with NYHA class III function at baseline, but this point estimate of relative benefit was not significant in this subgroup of just 247 patients, said Dr. Sapp, a cardiologist and professor at Dalhousie University & Nova Scotia Health in Halifax.
Based on the original RAFT results from 2010, as well as on evidence from several other trials, the current heart failure management guideline from the AHA, the American College of Cardiology, and the Heart Failure Society of America give the highest level of recommendation, level 1, for CRT in patients with a left ventricular ejection fraction of 35% or less, sinus rhythm with left bundle branch block, a QRS duration of at least 150 msec, and NYHA class II, III, or ambulatory IV symptoms while on guideline-directed medical therapy.
The guideline also gives class 2a (“can be useful”) or 2b (“may be considered”) recommendation for certain other heart failure patients, including those with a QRS duration of 120-149 msec, a left ventricular ejection fraction as high as 50%, no left bundle branch block, or NYHA class I symptoms.
Don’t wait to start CRT
Although this 2022 guideline, as well as earlier versions that had roughly similar recommendations for CRT for about a decade, have led to “common” use of CRT in appropriate patients in U.S. practice, “it has not been used as much as it should be, in part because there’s been a feeling that CRT mostly treats symptoms and so perhaps you can wait” to start it, said Dr. Stevenson.
The findings from the new, extended follow-up RAFT analysis give increased urgency to starting CRT “as soon as possible” in appropriate patients with heart failure, even before they stabilize on guideline-directed medical therapy, said Dr. Stevenson. She also downplayed any ambiguity in the RAFT findings about optimal medical therapy, which during the RAFT study included traditional triple therapy at a time before treatment with sacubitril/valsartan (Entresto) and sodium-glucose cotransporter 2 (SGLT2) inhibitors became recommended.
“There is no reason to think that these treatments will negate the benefit of CRT for patients with heart failure with reduced ejection fraction and a wide left bundle branch block,” Dr. Stevenson said.
She also believes that the extended follow-up results, which showed clear efficacy for CRT-D in patients with NYHA class II function, support the case for upgrading the current 2b recommendation for using CRT treatment in patients with NYHA class I function and ischemic heart failure to a 2a recommendation regardless of whether or not patients have coronary artery disease. “The difference between class I and class II depends more on a patient’s lifestyle rather than on the severity of their heart failure,” Dr. Stevenson noted. “The RAFT study results encourage us to reexamine the clinical class and timing for CRT” in the current heart failure guideline.
RAFT received partial sponsorship from Medtronic. Dr. Sapp has been a consultant to Abbott, Biosense Webster, Medtronic, and Varian and has received research funding from Abbott and Biosense Webster. Dr. Stevenson had no disclosures.
CHICAGO – Extended follow-up of patients with heart failure enrolled in the RAFT trial strengthens the case for starting treatment early with a cardiac resynchronization therapy plus defibrillation (CRT-D) device in appropriate patients.
RAFT, which compared CRT-D with treatment with an implantable cardioverter defibrillator (ICD) alone, showed that the early survival benefit produced by CRT-D during an average 40-month follow-up in the original trial persisted during an additional mean follow-up of about 5 years. This result strengthens the case for starting treatment early with a CRT-D device in appropriate patients with heart failure.
During extended follow-up of more than half of the enrolled patients, out to an average of 7.6 years overall and to an average of 12.9 years among survivors, patients who received a CRT-D device had a significant 21% relative reduction in their rate of all-cause mortality compared with randomized patients who received an ICD and no cardiac resynchronization, John L. Sapp, MD, reported at the American Heart Association scientific sessions.
The primary results of RAFT were first reported in 2010.
This magnitude of a survival benefit among the patients originally randomized to CRT is “dramatic,” given that many of the comparator patients who initially received no CRT likely crossed over to receive a CRT-D device once the initial, randomized 4 years of the study finished, commented Lynne W. Stevenson, MD, director of cardiomyopathy and the Lisa M. Jacobson Professor of Cardiology at Vanderbilt University Medical Center in Nashville, Tenn., who was not involved with the study.
‘CRT can remap heart failure trajectory’
The new findings “strengthen our conviction that CRT can remap the trajectory” of selected patients with heart failure, and that “candidates for CRT should be vigorously identified,” Dr. Stevenson said in an interview.
She also noted that the benefit with extended follow-up was “strikingly parallel” to that seen at 12 years after the addition of an ACE inhibitor for mild heart failure during the 4 years of the landmark SOLVD trial. The new RAFT extended follow-up, as well as the 12-year follow-up of the SOLVD trial, “support the concept that longer follow-up reveals vital information not provided by the relatively short randomized trial period,” she said.
“The new data say ‘don’t delay starting CRT in appropriate patients with heart failure,’ and ‘don’t think of CRT as just a treatment that makes patients feel better.’
“The totality of these data shows that CRT also treats the underlying heart muscle weakness, which helps patients live longer. Previous data showed that patients with left bundle branch block eligible for CRT are unlikely to respond well to the usual, recommended heart medications so it is important to start treatment with CRT-D early,” declared Dr. Stevenson, who cochaired the session where Dr. Sapp gave his report.
RAFT randomized 1,798 patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of at least 120 msec to receive either a CRT-D or ICD device. The study’s primary endpoint was death from any cause or hospitalization for heart failure. After an average 40 months of randomized follow-up, the primary endpoint occurred in 40% of the patients with an ICD and in 33% of those with a CRT-D device, a significant 25% relative reduction linked with CRT-D use. Both endpoint components contributed to the combined result significantly and to about the same extent, and the incremental benefit from CRT-D was significant for patients with NYHA class II heart failure as well as for those with class III.
However, prespecified subgroup analyses showed that the incremental benefit from CRT-D was significantly limited to patients with an intrinsic QRS duration of at least 150 msec, while in those with a duration of 120-149 msec CRT-D had a neutral effect compared with ICD. The same pattern also appeared when the analysis split patients into those with a left bundle branch block, who significantly benefited from CRT-D, but the initial benefit was not apparent in patients with right bundle branch block.
A study subgroup with extended follow-up
The new, extended follow-up analysis presented by Dr. Sapp included 1,050 of the original 1,798 patients (58%) enrolled at any of eight participating Canadian centers that each enrolled at least 100 patients and followed them through the end of 2021 (the full study cohort came from 34 centers, including 10 centers outside Canada). This subgroup included 520 patients randomized to receive CRT-D and 530 who received an ICD. Although this was a post hoc subgroup analysis, the CRT-D and ICD arms matched closely in all measured baseline characteristics.
The prespecified primary outcome of this follow-up analysis was the rate of all-cause mortality. Because of their longer disease trajectory, this pared-down study cohort included many more patients with NYHA class II function, 803, and in this subgroup CRT-D exerted a significant 23% incremental reduction in mortality compared with ICD treatment. CRT-D also produced a 17% relative reduction in long-term mortality among patients with NYHA class III function at baseline, but this point estimate of relative benefit was not significant in this subgroup of just 247 patients, said Dr. Sapp, a cardiologist and professor at Dalhousie University & Nova Scotia Health in Halifax.
Based on the original RAFT results from 2010, as well as on evidence from several other trials, the current heart failure management guideline from the AHA, the American College of Cardiology, and the Heart Failure Society of America give the highest level of recommendation, level 1, for CRT in patients with a left ventricular ejection fraction of 35% or less, sinus rhythm with left bundle branch block, a QRS duration of at least 150 msec, and NYHA class II, III, or ambulatory IV symptoms while on guideline-directed medical therapy.
The guideline also gives class 2a (“can be useful”) or 2b (“may be considered”) recommendation for certain other heart failure patients, including those with a QRS duration of 120-149 msec, a left ventricular ejection fraction as high as 50%, no left bundle branch block, or NYHA class I symptoms.
Don’t wait to start CRT
Although this 2022 guideline, as well as earlier versions that had roughly similar recommendations for CRT for about a decade, have led to “common” use of CRT in appropriate patients in U.S. practice, “it has not been used as much as it should be, in part because there’s been a feeling that CRT mostly treats symptoms and so perhaps you can wait” to start it, said Dr. Stevenson.
The findings from the new, extended follow-up RAFT analysis give increased urgency to starting CRT “as soon as possible” in appropriate patients with heart failure, even before they stabilize on guideline-directed medical therapy, said Dr. Stevenson. She also downplayed any ambiguity in the RAFT findings about optimal medical therapy, which during the RAFT study included traditional triple therapy at a time before treatment with sacubitril/valsartan (Entresto) and sodium-glucose cotransporter 2 (SGLT2) inhibitors became recommended.
“There is no reason to think that these treatments will negate the benefit of CRT for patients with heart failure with reduced ejection fraction and a wide left bundle branch block,” Dr. Stevenson said.
She also believes that the extended follow-up results, which showed clear efficacy for CRT-D in patients with NYHA class II function, support the case for upgrading the current 2b recommendation for using CRT treatment in patients with NYHA class I function and ischemic heart failure to a 2a recommendation regardless of whether or not patients have coronary artery disease. “The difference between class I and class II depends more on a patient’s lifestyle rather than on the severity of their heart failure,” Dr. Stevenson noted. “The RAFT study results encourage us to reexamine the clinical class and timing for CRT” in the current heart failure guideline.
RAFT received partial sponsorship from Medtronic. Dr. Sapp has been a consultant to Abbott, Biosense Webster, Medtronic, and Varian and has received research funding from Abbott and Biosense Webster. Dr. Stevenson had no disclosures.
AT AHA 2022
ASH 2022: New clinical data challenge long-held assumptions
The conference starts in New Orleans on Saturday, Dec. 10, , but a sample of what is to come was given last week in a preview media briefing, moderated by Mikkael A. Sekeres, MD, from the University of Miami. Dr. Sekeres, who recently authored a book on the FDA and how it regulates drug approvals, also serves as chair of the ASH Committee on Communications.
“Feeding Our Patients Gruel”
Dr. Sekeres expressed particular excitement about a multicenter randomized trial done in Italy. It showed that patients who have neutropenia after a stem cell transplant need not be required to eat a bland diet (Abstract 169).
“We for years have been essentially feeding our patients gruel in the hospital, and these are folks who have to be hospitalized for a stem cell transplant or in my case – I’m a leukemia specialist – for acute leukemia, for 4-6 weeks. The neutropenic diet consists of the blandest food you can imagine, with nothing to really spice it up.”
He noted that a neutropenic diet is so unpalatable that family members often sneak food into patient rooms, and “for years we’ve never seen adverse outcomes in any of those folks who instead of having mashed potatoes and oatmeal ate a corned beef sandwich for dinner.”
Now, the results from this trial “actually give us license to finally allow patients to eat whatever they want,” Dr. Sekeres said.
Practice-changing data
ASH experts pointed to two more presentations that are expected to change clinical practice. These include the finding that high-dose methotrexate does not reduce the risk for central nervous system relapse in children with acute lymphoblastic leukemia and lymphoblastic lymphoma (Abstract 214).
Another new study that seems to defy conventional wisdom showed that in adults with relapsed or refractory acute myeloid leukemia, intensive chemotherapy in an effort to achieve remission before a stem cell transplant did not result in better outcomes, compared with sequential conditioning and immediate transplant (Abstract 4).
Premature aging in HL survivors
ASH President Jane N. Winter, MD, from Northwestern University, Chicago, who also spoke at the briefing, highlighted a study that followed adult survivors of pediatric Hodgkin lymphoma. This study, from St. Jude Children’s Research Hospital in Memphis and the Wilmot Cancer Institute at the University of Rochester (N.Y), found that these adult survivors are at significantly elevated risk for epigenetic age acceleration accompanied by neurocognitive deficits when compared with controls (Abstract 902).
“This is an area that is very near and dear to my heart,” she said. “Much of my career has focused on reducing the therapy to reduce the long-term consequences of treatments. Pediatricians have been very much wedded to very intensive therapies and tend to incorporate radiation more commonly in their treatment strategies for children than we do in adults.”
Dr. Winter noted that, although clinicians focus primarily on the link between mediastinal radiation and long-term adverse events such as breast cancer, “now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated. Being able to screen for this impact of our treatment, and perhaps then develop strategies to deal with it or prevent it, will have very wide-ranging impact.”
Inherited thrombophilia and miscarriage
Cynthia E. Dunbar, MD, chief of the translational stem cell biology branch at the National Heart, Lung, and Blood Institute in Bethesda, Md., who also spoke at the briefing, said that one of the abstracts most important to her practice is a study concerning pregnancy. It showed that low-molecular-weight heparin did not prevent miscarriage in pregnant women with confirmed inherited thrombophilia who had two or more prior pregnancy losses, compared with standard surveillance (Abstract LBA-5).
“This is not my field at all; on the other hand, as a hematologist and a woman, that’s what my emails in the middle of the night and my panicked phone calls are often about. Once somebody has one miscarriage, especially if they feel like they’re already over 30 and the clock is ticking, there’s a huge emphasis and a huge amount of pressure on obstetricians to basically work up for everything, kind of a shotgun [approach],” she said.
Those workups may reveal genetic mutations that are associated with mild elevations in risk for clotting. As a result, some pregnant women are put on anticoagulation therapy, which can cause complications for both pregnancy and delivery. These study findings don’t solve the problem of spontaneous pregnancy loss, but they at least rule out inherited thrombophilia as a preventable cause of miscarriages, Dr. Dunbar said.
Another potentially practice-changing abstract is a study showing that, in younger adults with mantle cell lymphoma, the addition of the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica) to induction therapy and as maintenance with or without autologous stem cell transplant had strong efficacy and acceptable toxicity (Abstract 1).
“The results show that the ibrutinib-containing regimen without transplant is at least as good as the current standard of care with transplant.” Dr. Winter said. “Additional follow-up will be required to show definitively that an autotransplant is unnecessary if ibrutinib is included in this treatment regimen.”
A version of this article first appeared on Medscape.com.
The conference starts in New Orleans on Saturday, Dec. 10, , but a sample of what is to come was given last week in a preview media briefing, moderated by Mikkael A. Sekeres, MD, from the University of Miami. Dr. Sekeres, who recently authored a book on the FDA and how it regulates drug approvals, also serves as chair of the ASH Committee on Communications.
“Feeding Our Patients Gruel”
Dr. Sekeres expressed particular excitement about a multicenter randomized trial done in Italy. It showed that patients who have neutropenia after a stem cell transplant need not be required to eat a bland diet (Abstract 169).
“We for years have been essentially feeding our patients gruel in the hospital, and these are folks who have to be hospitalized for a stem cell transplant or in my case – I’m a leukemia specialist – for acute leukemia, for 4-6 weeks. The neutropenic diet consists of the blandest food you can imagine, with nothing to really spice it up.”
He noted that a neutropenic diet is so unpalatable that family members often sneak food into patient rooms, and “for years we’ve never seen adverse outcomes in any of those folks who instead of having mashed potatoes and oatmeal ate a corned beef sandwich for dinner.”
Now, the results from this trial “actually give us license to finally allow patients to eat whatever they want,” Dr. Sekeres said.
Practice-changing data
ASH experts pointed to two more presentations that are expected to change clinical practice. These include the finding that high-dose methotrexate does not reduce the risk for central nervous system relapse in children with acute lymphoblastic leukemia and lymphoblastic lymphoma (Abstract 214).
Another new study that seems to defy conventional wisdom showed that in adults with relapsed or refractory acute myeloid leukemia, intensive chemotherapy in an effort to achieve remission before a stem cell transplant did not result in better outcomes, compared with sequential conditioning and immediate transplant (Abstract 4).
Premature aging in HL survivors
ASH President Jane N. Winter, MD, from Northwestern University, Chicago, who also spoke at the briefing, highlighted a study that followed adult survivors of pediatric Hodgkin lymphoma. This study, from St. Jude Children’s Research Hospital in Memphis and the Wilmot Cancer Institute at the University of Rochester (N.Y), found that these adult survivors are at significantly elevated risk for epigenetic age acceleration accompanied by neurocognitive deficits when compared with controls (Abstract 902).
“This is an area that is very near and dear to my heart,” she said. “Much of my career has focused on reducing the therapy to reduce the long-term consequences of treatments. Pediatricians have been very much wedded to very intensive therapies and tend to incorporate radiation more commonly in their treatment strategies for children than we do in adults.”
Dr. Winter noted that, although clinicians focus primarily on the link between mediastinal radiation and long-term adverse events such as breast cancer, “now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated. Being able to screen for this impact of our treatment, and perhaps then develop strategies to deal with it or prevent it, will have very wide-ranging impact.”
Inherited thrombophilia and miscarriage
Cynthia E. Dunbar, MD, chief of the translational stem cell biology branch at the National Heart, Lung, and Blood Institute in Bethesda, Md., who also spoke at the briefing, said that one of the abstracts most important to her practice is a study concerning pregnancy. It showed that low-molecular-weight heparin did not prevent miscarriage in pregnant women with confirmed inherited thrombophilia who had two or more prior pregnancy losses, compared with standard surveillance (Abstract LBA-5).
“This is not my field at all; on the other hand, as a hematologist and a woman, that’s what my emails in the middle of the night and my panicked phone calls are often about. Once somebody has one miscarriage, especially if they feel like they’re already over 30 and the clock is ticking, there’s a huge emphasis and a huge amount of pressure on obstetricians to basically work up for everything, kind of a shotgun [approach],” she said.
Those workups may reveal genetic mutations that are associated with mild elevations in risk for clotting. As a result, some pregnant women are put on anticoagulation therapy, which can cause complications for both pregnancy and delivery. These study findings don’t solve the problem of spontaneous pregnancy loss, but they at least rule out inherited thrombophilia as a preventable cause of miscarriages, Dr. Dunbar said.
Another potentially practice-changing abstract is a study showing that, in younger adults with mantle cell lymphoma, the addition of the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica) to induction therapy and as maintenance with or without autologous stem cell transplant had strong efficacy and acceptable toxicity (Abstract 1).
“The results show that the ibrutinib-containing regimen without transplant is at least as good as the current standard of care with transplant.” Dr. Winter said. “Additional follow-up will be required to show definitively that an autotransplant is unnecessary if ibrutinib is included in this treatment regimen.”
A version of this article first appeared on Medscape.com.
The conference starts in New Orleans on Saturday, Dec. 10, , but a sample of what is to come was given last week in a preview media briefing, moderated by Mikkael A. Sekeres, MD, from the University of Miami. Dr. Sekeres, who recently authored a book on the FDA and how it regulates drug approvals, also serves as chair of the ASH Committee on Communications.
“Feeding Our Patients Gruel”
Dr. Sekeres expressed particular excitement about a multicenter randomized trial done in Italy. It showed that patients who have neutropenia after a stem cell transplant need not be required to eat a bland diet (Abstract 169).
“We for years have been essentially feeding our patients gruel in the hospital, and these are folks who have to be hospitalized for a stem cell transplant or in my case – I’m a leukemia specialist – for acute leukemia, for 4-6 weeks. The neutropenic diet consists of the blandest food you can imagine, with nothing to really spice it up.”
He noted that a neutropenic diet is so unpalatable that family members often sneak food into patient rooms, and “for years we’ve never seen adverse outcomes in any of those folks who instead of having mashed potatoes and oatmeal ate a corned beef sandwich for dinner.”
Now, the results from this trial “actually give us license to finally allow patients to eat whatever they want,” Dr. Sekeres said.
Practice-changing data
ASH experts pointed to two more presentations that are expected to change clinical practice. These include the finding that high-dose methotrexate does not reduce the risk for central nervous system relapse in children with acute lymphoblastic leukemia and lymphoblastic lymphoma (Abstract 214).
Another new study that seems to defy conventional wisdom showed that in adults with relapsed or refractory acute myeloid leukemia, intensive chemotherapy in an effort to achieve remission before a stem cell transplant did not result in better outcomes, compared with sequential conditioning and immediate transplant (Abstract 4).
Premature aging in HL survivors
ASH President Jane N. Winter, MD, from Northwestern University, Chicago, who also spoke at the briefing, highlighted a study that followed adult survivors of pediatric Hodgkin lymphoma. This study, from St. Jude Children’s Research Hospital in Memphis and the Wilmot Cancer Institute at the University of Rochester (N.Y), found that these adult survivors are at significantly elevated risk for epigenetic age acceleration accompanied by neurocognitive deficits when compared with controls (Abstract 902).
“This is an area that is very near and dear to my heart,” she said. “Much of my career has focused on reducing the therapy to reduce the long-term consequences of treatments. Pediatricians have been very much wedded to very intensive therapies and tend to incorporate radiation more commonly in their treatment strategies for children than we do in adults.”
Dr. Winter noted that, although clinicians focus primarily on the link between mediastinal radiation and long-term adverse events such as breast cancer, “now we’re shedding a light on the neurocognitive deficits, which I think are underappreciated. Being able to screen for this impact of our treatment, and perhaps then develop strategies to deal with it or prevent it, will have very wide-ranging impact.”
Inherited thrombophilia and miscarriage
Cynthia E. Dunbar, MD, chief of the translational stem cell biology branch at the National Heart, Lung, and Blood Institute in Bethesda, Md., who also spoke at the briefing, said that one of the abstracts most important to her practice is a study concerning pregnancy. It showed that low-molecular-weight heparin did not prevent miscarriage in pregnant women with confirmed inherited thrombophilia who had two or more prior pregnancy losses, compared with standard surveillance (Abstract LBA-5).
“This is not my field at all; on the other hand, as a hematologist and a woman, that’s what my emails in the middle of the night and my panicked phone calls are often about. Once somebody has one miscarriage, especially if they feel like they’re already over 30 and the clock is ticking, there’s a huge emphasis and a huge amount of pressure on obstetricians to basically work up for everything, kind of a shotgun [approach],” she said.
Those workups may reveal genetic mutations that are associated with mild elevations in risk for clotting. As a result, some pregnant women are put on anticoagulation therapy, which can cause complications for both pregnancy and delivery. These study findings don’t solve the problem of spontaneous pregnancy loss, but they at least rule out inherited thrombophilia as a preventable cause of miscarriages, Dr. Dunbar said.
Another potentially practice-changing abstract is a study showing that, in younger adults with mantle cell lymphoma, the addition of the Bruton’s tyrosine kinase inhibitor ibrutinib (Imbruvica) to induction therapy and as maintenance with or without autologous stem cell transplant had strong efficacy and acceptable toxicity (Abstract 1).
“The results show that the ibrutinib-containing regimen without transplant is at least as good as the current standard of care with transplant.” Dr. Winter said. “Additional follow-up will be required to show definitively that an autotransplant is unnecessary if ibrutinib is included in this treatment regimen.”
A version of this article first appeared on Medscape.com.
FROM ASH 2022
Ask knee OA patients about stair climbing difficulty
Asking knee osteoarthritis patients a simple question – do you have difficulty climbing stairs? – may predict the risk of future functional limitation, according to research presented at the annual meeting of the American College of Rheumatology. Finding out that the patient has difficulty also opens avenues for further evaluation and intervention, said Jason Jakiela, a PhD candidate at the University of Delaware, Newark, who led the study. “We like to view it as a kind of yellow flag,” Mr. Jakiela said in an interview.
Another expert agreed. “I think this is useful for clinical rheumatologists,” said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson, and director of the University of Arizona Arthritis Center. He commented on the study findings but was not involved in the study. Another common question asked of OA patients, about pain, may not be as useful as asking about difficulty climbing stairs, he said. “Their pain level can go up and down and can be quite varied.”
Osteoarthritis affects more than 32.5 million adults, according to the CDC, and the knee is a common site.
Study details, results
Mr. Jakiela and his team, including Daniel White, PT, ScD, MSC, associate professor of physical therapy at the University of Delaware, Newark, used data from the Osteoarthritis Initiative (OAI). They assessed stair climbing difficulty at baseline with the question: Does your health now limit you in climbing several flights of stairs? Respondents could answer that they were limited a lot, a little, or not at all.
The researchers evaluated functional limitation using two measures: Walking speed and Western Ontario and McMaster Universities Osteoarthritis Index physical function (WOMAC-PF) scores. A walking speed of < 1.22 m/s over 20 meters, the speed needed to safely cross a timed intersection, represented poor function. A WOMAC-PF score of 28/68 or more was also used to define low functioning.
The analyses included only people free of functional limitations at baseline. Each measure was conducted at the start and then at 12, 24, 36, 48, 72, and 96 months’ follow-up visits.
While 2,952 participants (mean age 60.1, 54% female, mean body mass index 27.9) were in the walking speed sample, 3,983 participants (mean age 61.2, 57% female, mean BMI 28.2) were in the WOMAC-PF sample.
When compared with people who had no limitations, those limited a little had a 47% greater risk of gait speed functional limitation and those limited a lot had a 61% greater risk at follow-up. There was a 70% greater risk for functional limitation defined by WOMAC-PF score at follow-up among people who were limited a little in stair climbing when compared with those not limited at all, and people with a lot of limitations had 161% greater risk. Slow gait speed has been linked with mortality.
Over the 8-year follow-up, 973 in the walking speed sample and 578 in the WOMAC-PF sample developed functional limitation.
Starting the conversation
The question about stair climbing difficulty is a good “jumping-off point,” Mr. Jakiela said. “It opens up a line of questioning.” With knee OA, stair climbing difficulty is often the first reported limitation. That difficulty could capture a variety of issues, he said. Patients could be struggling with strength issues, cardiovascular problems, or balance deficits, for instance.
It signals there may be a trajectory of slow decline coming in this patient, Mr. Jakiela said.
“It’s a signal that something is not right,” Dr. White said in an interview. “We don’t know what is wrong.” While questions about stairs have routinely been asked of OA patients, the study findings suggest the answer to the question about having difficulty could help predict a patient’s future course, he said.
After patients reported a little or a lot of difficulty with stair climbing, the average time to reach functional limitation status was about 3 years, Mr. Jakiela said. That gives health care providers time to ask more questions about the patient’s condition and potentially intervene, depending on the details of the difficulty. If it’s a balance issue, physical therapy might help, for example.
While gait speed is a tried-and-true indication, collecting answers about stair climbing difficulty is easier and quicker for clinicians than assessing gait speed, which requires more time as well as office space, Mr. Jakiela said. It’s also intuitive for the patients to recall, the researchers said.
More practical takeaways
Finding out whether functional limitation is likely, based on the stair question, can help health care providers consider nonpharmacologic interventions, Dr. Kwoh agreed, such as physical therapy or braces. “It doesn’t have to be drugs. We have limited drugs for OA at the moment. We don’t have a so-called DMARD drug [for OA].”
NSAIDs have side effects, and people are very familiar with the issues of opioids, he said. It’s important, he added, for the health care provider, if referring to a physical therapist, to find the right one. To help those dealing with knee OA, a PT in sports medicine might be a good choice, he said.
Mr. Jakiela has no disclosures. Dr. Kwoh and Dr. White have no relevant disclosures.
Asking knee osteoarthritis patients a simple question – do you have difficulty climbing stairs? – may predict the risk of future functional limitation, according to research presented at the annual meeting of the American College of Rheumatology. Finding out that the patient has difficulty also opens avenues for further evaluation and intervention, said Jason Jakiela, a PhD candidate at the University of Delaware, Newark, who led the study. “We like to view it as a kind of yellow flag,” Mr. Jakiela said in an interview.
Another expert agreed. “I think this is useful for clinical rheumatologists,” said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson, and director of the University of Arizona Arthritis Center. He commented on the study findings but was not involved in the study. Another common question asked of OA patients, about pain, may not be as useful as asking about difficulty climbing stairs, he said. “Their pain level can go up and down and can be quite varied.”
Osteoarthritis affects more than 32.5 million adults, according to the CDC, and the knee is a common site.
Study details, results
Mr. Jakiela and his team, including Daniel White, PT, ScD, MSC, associate professor of physical therapy at the University of Delaware, Newark, used data from the Osteoarthritis Initiative (OAI). They assessed stair climbing difficulty at baseline with the question: Does your health now limit you in climbing several flights of stairs? Respondents could answer that they were limited a lot, a little, or not at all.
The researchers evaluated functional limitation using two measures: Walking speed and Western Ontario and McMaster Universities Osteoarthritis Index physical function (WOMAC-PF) scores. A walking speed of < 1.22 m/s over 20 meters, the speed needed to safely cross a timed intersection, represented poor function. A WOMAC-PF score of 28/68 or more was also used to define low functioning.
The analyses included only people free of functional limitations at baseline. Each measure was conducted at the start and then at 12, 24, 36, 48, 72, and 96 months’ follow-up visits.
While 2,952 participants (mean age 60.1, 54% female, mean body mass index 27.9) were in the walking speed sample, 3,983 participants (mean age 61.2, 57% female, mean BMI 28.2) were in the WOMAC-PF sample.
When compared with people who had no limitations, those limited a little had a 47% greater risk of gait speed functional limitation and those limited a lot had a 61% greater risk at follow-up. There was a 70% greater risk for functional limitation defined by WOMAC-PF score at follow-up among people who were limited a little in stair climbing when compared with those not limited at all, and people with a lot of limitations had 161% greater risk. Slow gait speed has been linked with mortality.
Over the 8-year follow-up, 973 in the walking speed sample and 578 in the WOMAC-PF sample developed functional limitation.
Starting the conversation
The question about stair climbing difficulty is a good “jumping-off point,” Mr. Jakiela said. “It opens up a line of questioning.” With knee OA, stair climbing difficulty is often the first reported limitation. That difficulty could capture a variety of issues, he said. Patients could be struggling with strength issues, cardiovascular problems, or balance deficits, for instance.
It signals there may be a trajectory of slow decline coming in this patient, Mr. Jakiela said.
“It’s a signal that something is not right,” Dr. White said in an interview. “We don’t know what is wrong.” While questions about stairs have routinely been asked of OA patients, the study findings suggest the answer to the question about having difficulty could help predict a patient’s future course, he said.
After patients reported a little or a lot of difficulty with stair climbing, the average time to reach functional limitation status was about 3 years, Mr. Jakiela said. That gives health care providers time to ask more questions about the patient’s condition and potentially intervene, depending on the details of the difficulty. If it’s a balance issue, physical therapy might help, for example.
While gait speed is a tried-and-true indication, collecting answers about stair climbing difficulty is easier and quicker for clinicians than assessing gait speed, which requires more time as well as office space, Mr. Jakiela said. It’s also intuitive for the patients to recall, the researchers said.
More practical takeaways
Finding out whether functional limitation is likely, based on the stair question, can help health care providers consider nonpharmacologic interventions, Dr. Kwoh agreed, such as physical therapy or braces. “It doesn’t have to be drugs. We have limited drugs for OA at the moment. We don’t have a so-called DMARD drug [for OA].”
NSAIDs have side effects, and people are very familiar with the issues of opioids, he said. It’s important, he added, for the health care provider, if referring to a physical therapist, to find the right one. To help those dealing with knee OA, a PT in sports medicine might be a good choice, he said.
Mr. Jakiela has no disclosures. Dr. Kwoh and Dr. White have no relevant disclosures.
Asking knee osteoarthritis patients a simple question – do you have difficulty climbing stairs? – may predict the risk of future functional limitation, according to research presented at the annual meeting of the American College of Rheumatology. Finding out that the patient has difficulty also opens avenues for further evaluation and intervention, said Jason Jakiela, a PhD candidate at the University of Delaware, Newark, who led the study. “We like to view it as a kind of yellow flag,” Mr. Jakiela said in an interview.
Another expert agreed. “I think this is useful for clinical rheumatologists,” said C. Kent Kwoh, MD, professor of medicine and medical imaging at the University of Arizona, Tucson, and director of the University of Arizona Arthritis Center. He commented on the study findings but was not involved in the study. Another common question asked of OA patients, about pain, may not be as useful as asking about difficulty climbing stairs, he said. “Their pain level can go up and down and can be quite varied.”
Osteoarthritis affects more than 32.5 million adults, according to the CDC, and the knee is a common site.
Study details, results
Mr. Jakiela and his team, including Daniel White, PT, ScD, MSC, associate professor of physical therapy at the University of Delaware, Newark, used data from the Osteoarthritis Initiative (OAI). They assessed stair climbing difficulty at baseline with the question: Does your health now limit you in climbing several flights of stairs? Respondents could answer that they were limited a lot, a little, or not at all.
The researchers evaluated functional limitation using two measures: Walking speed and Western Ontario and McMaster Universities Osteoarthritis Index physical function (WOMAC-PF) scores. A walking speed of < 1.22 m/s over 20 meters, the speed needed to safely cross a timed intersection, represented poor function. A WOMAC-PF score of 28/68 or more was also used to define low functioning.
The analyses included only people free of functional limitations at baseline. Each measure was conducted at the start and then at 12, 24, 36, 48, 72, and 96 months’ follow-up visits.
While 2,952 participants (mean age 60.1, 54% female, mean body mass index 27.9) were in the walking speed sample, 3,983 participants (mean age 61.2, 57% female, mean BMI 28.2) were in the WOMAC-PF sample.
When compared with people who had no limitations, those limited a little had a 47% greater risk of gait speed functional limitation and those limited a lot had a 61% greater risk at follow-up. There was a 70% greater risk for functional limitation defined by WOMAC-PF score at follow-up among people who were limited a little in stair climbing when compared with those not limited at all, and people with a lot of limitations had 161% greater risk. Slow gait speed has been linked with mortality.
Over the 8-year follow-up, 973 in the walking speed sample and 578 in the WOMAC-PF sample developed functional limitation.
Starting the conversation
The question about stair climbing difficulty is a good “jumping-off point,” Mr. Jakiela said. “It opens up a line of questioning.” With knee OA, stair climbing difficulty is often the first reported limitation. That difficulty could capture a variety of issues, he said. Patients could be struggling with strength issues, cardiovascular problems, or balance deficits, for instance.
It signals there may be a trajectory of slow decline coming in this patient, Mr. Jakiela said.
“It’s a signal that something is not right,” Dr. White said in an interview. “We don’t know what is wrong.” While questions about stairs have routinely been asked of OA patients, the study findings suggest the answer to the question about having difficulty could help predict a patient’s future course, he said.
After patients reported a little or a lot of difficulty with stair climbing, the average time to reach functional limitation status was about 3 years, Mr. Jakiela said. That gives health care providers time to ask more questions about the patient’s condition and potentially intervene, depending on the details of the difficulty. If it’s a balance issue, physical therapy might help, for example.
While gait speed is a tried-and-true indication, collecting answers about stair climbing difficulty is easier and quicker for clinicians than assessing gait speed, which requires more time as well as office space, Mr. Jakiela said. It’s also intuitive for the patients to recall, the researchers said.
More practical takeaways
Finding out whether functional limitation is likely, based on the stair question, can help health care providers consider nonpharmacologic interventions, Dr. Kwoh agreed, such as physical therapy or braces. “It doesn’t have to be drugs. We have limited drugs for OA at the moment. We don’t have a so-called DMARD drug [for OA].”
NSAIDs have side effects, and people are very familiar with the issues of opioids, he said. It’s important, he added, for the health care provider, if referring to a physical therapist, to find the right one. To help those dealing with knee OA, a PT in sports medicine might be a good choice, he said.
Mr. Jakiela has no disclosures. Dr. Kwoh and Dr. White have no relevant disclosures.
FROM ACR 2022
Deductibles a threat to more imaging after abnormal mammogram
CHICAGO – One in five women will skip further imaging after an abnormal mammogram if they have to pay out of pocket before their deductible is met, new data indicate.
“The ACA [Affordable Care Act] removed out-of-pocket costs for screening mammograms under most health plans to encourage women to partake in this important preventative health care measure,” Michael Ngo, MD, a radiology resident at Boston Medical Center and Boston University, said in a statement.
However, the screening mammogram is only the first step. If it’s abnormal, additional tests and a biopsy help determine whether the patient has cancer. The ACA does not mandate coverage for those, Dr. Ngo noted.
Dr. Ngo was lead author of the study presented at the annual meeting of the Radiological Society of North America.
Researchers collected 932 surveys. Asked whether they would skip follow-up imaging if they knew that they would have to pay a deductible, 151 of 714 (21.2%) said that they would skip the imaging; 424 (59.4%) said that they would not skip further imaging; and 139 (19.5%) were undecided. Responses differed by race, education level, household income, and insurance payer.
Groups most likely to forgo further tests
The groups with the highest percentage of persons who would skip additional imaging were Hispanic persons (33%); persons whose level of education was high school or less (31.0%); persons with a household income of less than $35,000 (27%); and those covered by Medicaid or who were uninsured (31.5%).
Wendie Berg, MD, PhD, professor of radiology at the University of Pittsburgh, who was not part of the study, said that because insurance companies had to cover initial mammograms fully under the ACA, “they generally increased deductibles. That resulted in more charges to patients when they came in for additional testing.
“It caught a lot of women by surprise,” she told this news organization.
The out-of-pocket charges can escalate with each step – more images, a biopsy, then more if they do have cancer, she said. This puts patients on the hook for hundreds, if not thousands, of dollars in medical bills.
However, Dr. Berg said, “The vast majority of women – 95% – who are called back for additional testing don’t have cancer. It is a problem that a lot of women will experience the cost and don’t have any benefit.”
Reducing false-positive recalls
The study highlights several things, she said. One is that “it’s incumbent on all of us to reduce false-positive recalls, which is one of the benefits of 3-D mammogram.”
Physicians who order additional tests must also consider the financial burden for patients, she said.
Some states have tackled the issue, she said. “Seven states do require insurance to cover diagnostic testing.” But those states differ in the extent of the coverage. DenseBreast-info.org, a website she helps with on a volunteer basis, explains the benefits by state.
Further compounding the problem is that not every insurer is subject to state law, she said.
Many states have programs that cover the cost for those who meet income requirements, although, she noted, some women make too much to qualify.
“It would be great to have a federal law that is inclusive,” she said.
Education efforts may help
Brian N. Dontchos, MD, with the University of Washington in Seattle, who was not part of the study, views the data another way. He told this news organization, “It is encouraging from the study that the majority of women would pursue additional imaging after an abnormal screening mammogram despite incurring more cost.”
He said that since direct patient education “has been shown to be effective in improving patient participation in screening programs, it is possible that, with more education of patients and providers, that advocacy could influence payers to support downstream imaging and biopsies that result from screening programs.”
Dr. Ngo, Dr. Berg, and Dr. Dontchos report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – One in five women will skip further imaging after an abnormal mammogram if they have to pay out of pocket before their deductible is met, new data indicate.
“The ACA [Affordable Care Act] removed out-of-pocket costs for screening mammograms under most health plans to encourage women to partake in this important preventative health care measure,” Michael Ngo, MD, a radiology resident at Boston Medical Center and Boston University, said in a statement.
However, the screening mammogram is only the first step. If it’s abnormal, additional tests and a biopsy help determine whether the patient has cancer. The ACA does not mandate coverage for those, Dr. Ngo noted.
Dr. Ngo was lead author of the study presented at the annual meeting of the Radiological Society of North America.
Researchers collected 932 surveys. Asked whether they would skip follow-up imaging if they knew that they would have to pay a deductible, 151 of 714 (21.2%) said that they would skip the imaging; 424 (59.4%) said that they would not skip further imaging; and 139 (19.5%) were undecided. Responses differed by race, education level, household income, and insurance payer.
Groups most likely to forgo further tests
The groups with the highest percentage of persons who would skip additional imaging were Hispanic persons (33%); persons whose level of education was high school or less (31.0%); persons with a household income of less than $35,000 (27%); and those covered by Medicaid or who were uninsured (31.5%).
Wendie Berg, MD, PhD, professor of radiology at the University of Pittsburgh, who was not part of the study, said that because insurance companies had to cover initial mammograms fully under the ACA, “they generally increased deductibles. That resulted in more charges to patients when they came in for additional testing.
“It caught a lot of women by surprise,” she told this news organization.
The out-of-pocket charges can escalate with each step – more images, a biopsy, then more if they do have cancer, she said. This puts patients on the hook for hundreds, if not thousands, of dollars in medical bills.
However, Dr. Berg said, “The vast majority of women – 95% – who are called back for additional testing don’t have cancer. It is a problem that a lot of women will experience the cost and don’t have any benefit.”
Reducing false-positive recalls
The study highlights several things, she said. One is that “it’s incumbent on all of us to reduce false-positive recalls, which is one of the benefits of 3-D mammogram.”
Physicians who order additional tests must also consider the financial burden for patients, she said.
Some states have tackled the issue, she said. “Seven states do require insurance to cover diagnostic testing.” But those states differ in the extent of the coverage. DenseBreast-info.org, a website she helps with on a volunteer basis, explains the benefits by state.
Further compounding the problem is that not every insurer is subject to state law, she said.
Many states have programs that cover the cost for those who meet income requirements, although, she noted, some women make too much to qualify.
“It would be great to have a federal law that is inclusive,” she said.
Education efforts may help
Brian N. Dontchos, MD, with the University of Washington in Seattle, who was not part of the study, views the data another way. He told this news organization, “It is encouraging from the study that the majority of women would pursue additional imaging after an abnormal screening mammogram despite incurring more cost.”
He said that since direct patient education “has been shown to be effective in improving patient participation in screening programs, it is possible that, with more education of patients and providers, that advocacy could influence payers to support downstream imaging and biopsies that result from screening programs.”
Dr. Ngo, Dr. Berg, and Dr. Dontchos report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – One in five women will skip further imaging after an abnormal mammogram if they have to pay out of pocket before their deductible is met, new data indicate.
“The ACA [Affordable Care Act] removed out-of-pocket costs for screening mammograms under most health plans to encourage women to partake in this important preventative health care measure,” Michael Ngo, MD, a radiology resident at Boston Medical Center and Boston University, said in a statement.
However, the screening mammogram is only the first step. If it’s abnormal, additional tests and a biopsy help determine whether the patient has cancer. The ACA does not mandate coverage for those, Dr. Ngo noted.
Dr. Ngo was lead author of the study presented at the annual meeting of the Radiological Society of North America.
Researchers collected 932 surveys. Asked whether they would skip follow-up imaging if they knew that they would have to pay a deductible, 151 of 714 (21.2%) said that they would skip the imaging; 424 (59.4%) said that they would not skip further imaging; and 139 (19.5%) were undecided. Responses differed by race, education level, household income, and insurance payer.
Groups most likely to forgo further tests
The groups with the highest percentage of persons who would skip additional imaging were Hispanic persons (33%); persons whose level of education was high school or less (31.0%); persons with a household income of less than $35,000 (27%); and those covered by Medicaid or who were uninsured (31.5%).
Wendie Berg, MD, PhD, professor of radiology at the University of Pittsburgh, who was not part of the study, said that because insurance companies had to cover initial mammograms fully under the ACA, “they generally increased deductibles. That resulted in more charges to patients when they came in for additional testing.
“It caught a lot of women by surprise,” she told this news organization.
The out-of-pocket charges can escalate with each step – more images, a biopsy, then more if they do have cancer, she said. This puts patients on the hook for hundreds, if not thousands, of dollars in medical bills.
However, Dr. Berg said, “The vast majority of women – 95% – who are called back for additional testing don’t have cancer. It is a problem that a lot of women will experience the cost and don’t have any benefit.”
Reducing false-positive recalls
The study highlights several things, she said. One is that “it’s incumbent on all of us to reduce false-positive recalls, which is one of the benefits of 3-D mammogram.”
Physicians who order additional tests must also consider the financial burden for patients, she said.
Some states have tackled the issue, she said. “Seven states do require insurance to cover diagnostic testing.” But those states differ in the extent of the coverage. DenseBreast-info.org, a website she helps with on a volunteer basis, explains the benefits by state.
Further compounding the problem is that not every insurer is subject to state law, she said.
Many states have programs that cover the cost for those who meet income requirements, although, she noted, some women make too much to qualify.
“It would be great to have a federal law that is inclusive,” she said.
Education efforts may help
Brian N. Dontchos, MD, with the University of Washington in Seattle, who was not part of the study, views the data another way. He told this news organization, “It is encouraging from the study that the majority of women would pursue additional imaging after an abnormal screening mammogram despite incurring more cost.”
He said that since direct patient education “has been shown to be effective in improving patient participation in screening programs, it is possible that, with more education of patients and providers, that advocacy could influence payers to support downstream imaging and biopsies that result from screening programs.”
Dr. Ngo, Dr. Berg, and Dr. Dontchos report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT RSNA 2022
Consider quality of life, comorbidities in hidradenitis suppurativa
LAS VEGAS – , Robert G. Micheletti, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
For patients with HS, “the quality-of-life impact is profound, greater than any other systematically studied dermatologic condition,” said Dr. Micheletti, associate professor of dermatology at the Hospital of the University of Pennsylavnia, and chief of hospital dermatology, and chief of dermatology at Pennsylvania Hospital, Philadelphia.
Two key aspects of quality of life that affect HS patients are sexual health and overall pain, he said. The female-to-male ratio of HS is approximately 3:1, and data show that approximately 40% of female HS patients experience fertility issues and have unaddressed questions about HS and pregnancy, said Dr. Micheletti. Additionally, data from a systematic review showed that 50%-60% of patients with HS reported sexual dysfunction. Impaired sexual function is also associated with both overall impaired quality of life ratings and the presence of mood disorders, he noted.
Pain also has a significant impact on quality of life for HS patients. When these patients present in an emergency department, 70% report severe pain, and approximately 60% receive opioids, said Dr. Micheletti.
Data from a 2021 study showed that HS patients are significantly more likely to receive opioids compared with controls, and also more likely to be diagnosed with opioid use disorder than controls, especially if they are seen by nondermatologists, he noted.
For acute pain, Dr. Micheletti recommended starting with acetaminophen 500 mg every 4 to 6 hours as needed, and topical nonsteroidal anti-inflammatory drugs (NSAIDs). “It still makes sense to do topical care,” said Dr. Micheletti, but he added that he also prescribes medications for anxiety for these patients.
Patients with increased pain severity or refractory disease may benefit from systemic NSAIDs, or intralesional triamcinolone, he noted. Incision and draining of abscesses may provide temporary symptomatic relief, but keep in mind that lesions will recur, he noted.
For the most severe cases, Dr. Micheletti advised adding tramadol as a first-line opioid, or another short-acting opioid for breakthrough pain.
To manage patients with HS who have chronic pain, Dr. Micheletti recommended starting with HS disease–directed therapy, but also screening for pain severity and psychological comorbidities.
His strategies in these cases include nonpharmacological pain management in the form of physical therapy, wound care, and behavioral health. His algorithm for nociceptive pain is NSAIDs with or without acetaminophen; duloxetine or nortriptyline are other options. For neuropathic pain, gabapentin and/or duloxetine are top choices, but pregabalin, venlafaxine, and nortriptyline are on the list as well.
Topical NSAIDs or topical lidocaine may serve as add-ons to systemic therapy in more severe cases, or as first-line therapy for milder chronic pain, Dr. Micheletti noted. Patients who have failed treatment with at least two pharmacologic agents, suffer medically refractory HS with debilitating pain, or use opioids on an ongoing basis should be referred to a pain management specialist, he said.
Don’t forget lifestyle
Although data on the impact of diet on patients with HS are limited, “we know anecdotally that dairy and refined carbohydrates are associated with exacerbations,” said Dr. Micheletti.
In addition, many patients use complementary medicine “and they aren’t always telling us,” he emphasized. Smoking is prevalent among patients with HS, and is a risk factor for the disease in general, and for more severe and refractory disease, he added. Consequently, screening for tobacco smoking is recommended for patients with HS not only because of the impact on disease, but because it is a potentially modifiable cardiovascular risk factor, he explained.
Consider comorbidities
Cardiovascular disease is among several comorbidities associated with HS, said Dr. Micheletti. HS foundations in the United States and Canada recently published evidence-based recommendations for comorbidity screening. The recommendations included screening for 19 specific comorbidities: acne, dissecting cellulitis, pilonidal disease, pyoderma gangrenosum, depression, anxiety, suicide, smoking, substance abuse, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction.
Dr. Micheletti highlighted cardiovascular comorbidities, and noted the association between HS and modifiable cardiovascular risk factors: smoking, obesity, diabetes mellitus, and dyslipidemia. “HS is also independently associated with cardiovascular disease leading to myocardial infarction, stroke, cardiovascular-associated death, and all-cause mortality compared to controls,” he said. Studies show an incidence rate ratio of 1.53 for major adverse cardiovascular events in patients with HS compared with controls, with the highest relative risk among those aged 18-29 years, he added.
Medical management
Depending on the patient, medical management of HS may involve antibiotics, hormonal agents, and biologics, said Dr. Micheletti. Some of the most commonly used antibiotic regimens for HS are those recommended in treatment guidelines, including doxycycline and a clindamycin/rifampin combination, he said. However, the use of trimethoprim-sulfamethoxazole or ciprofloxacin has been associated with increased antibiotic resistance and is not supported by available evidence, he noted.
Hormonal therapies may help some women with HS, said Dr. Micheletti. Options include spironolactone, metformin, or estrogen-containing hormonal contraceptives, he said.
When it comes to biologics, only 33% of HS patients meet criteria for their use (Hurley stage II or III, moderate or severe HS), he noted. However, research suggests “a huge gap” in the use of anti-TNF therapy even among patients for whom it is recommended, he said.
Of the TNF-alpha inhibitors, data on adalimumab, which is FDA-approved for HS, are the most recent. Adalimumab “is our gold standard biologic and our gateway biologic, for HS at this time,” Dr. Micheletti said.
However, those who respond to adalimumab “can continue to do better, but they can wax and wane and flare,” he cautioned. Infliximab, while not approved for HS, has been studied in patients with HS and is prescribed by some providers. Although no comparative studies have been done for infliximab versus adalimumab, “anecdotally, response to infliximab tends to be better, and it is the most effective biologic in common use for severe HS,” he noted.
Dr. Micheletti’s top treatment recommendations for using biologics start with considering biosimilars. Most patients on biosimilars do fine, but some patients who previously responded to infliximab will unpredictably lose efficacy or have reactions when switched to a biosimilar, he said.
Patients on biologics also may experience waning efficacy in the wake of an immune response stimulated by foreign antibodies, said Dr. Micheletti. “Anti-drug antibody formation is more likely to occur when treatment is interrupted,” he noted. Minimize the risk of antibody formation by paying attention to adherence issues and dosing frequency, he advised.
If patients fail both adalimumab and infliximab, Dr. Micheletti tells them not to lose hope, and that treatment is a trial-and-error process that may involve more than one therapy. Other biologics in active use for HS include ustekinumab, anakinra, secukinumab, brodalumab, golimumab, and JAK inhibitors, any of which might be effective in any given patient, he said.
Surgical solutions
For HS patients with chronic, recurring inflammation and drainage associated with a sinus tract, surgical deroofing may the best treatment option, Dr. Micheletti said. “Deroofing involves the use of a probe to trace the extent of the subcutaneous tract, followed by incision and removal of the tract ‘roof,’ ’’ he explained. The deroofing procedure involves local anesthesia and has a low morbidity rate, as well as a low recurrence rate and high levels of patient satisfaction, he said.
“The acute role for surgery is to remove active foci of inflammation and relieve pain,” which is achieved more effectively with deroofing, said Dr. Micheletti. By contrast, incision and drainage is associated with an almost 100% recurrence rate, he added.
When planning elective surgery for HS, Dr. Micheletti noted that holding infliximab for less than 4 weeks does not affect postoperative infection rates in patients with rheumatoid arthritis, and a recent randomized, controlled trial showed that adalimumab can be continued safely through HS surgeries.
In fact, “continuing TNF inhibitors through elective surgery does not increase infection risk and results in better disease control,” and dermatologists should work with surgery to balance infection and disease flare concerns in HS patients, he said.
Dr. Micheletti disclosed serving as a consultant or advisor for Adaptimmune and Vertex, and research funding from Amgen and Cabaletta Bio. MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – , Robert G. Micheletti, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
For patients with HS, “the quality-of-life impact is profound, greater than any other systematically studied dermatologic condition,” said Dr. Micheletti, associate professor of dermatology at the Hospital of the University of Pennsylavnia, and chief of hospital dermatology, and chief of dermatology at Pennsylvania Hospital, Philadelphia.
Two key aspects of quality of life that affect HS patients are sexual health and overall pain, he said. The female-to-male ratio of HS is approximately 3:1, and data show that approximately 40% of female HS patients experience fertility issues and have unaddressed questions about HS and pregnancy, said Dr. Micheletti. Additionally, data from a systematic review showed that 50%-60% of patients with HS reported sexual dysfunction. Impaired sexual function is also associated with both overall impaired quality of life ratings and the presence of mood disorders, he noted.
Pain also has a significant impact on quality of life for HS patients. When these patients present in an emergency department, 70% report severe pain, and approximately 60% receive opioids, said Dr. Micheletti.
Data from a 2021 study showed that HS patients are significantly more likely to receive opioids compared with controls, and also more likely to be diagnosed with opioid use disorder than controls, especially if they are seen by nondermatologists, he noted.
For acute pain, Dr. Micheletti recommended starting with acetaminophen 500 mg every 4 to 6 hours as needed, and topical nonsteroidal anti-inflammatory drugs (NSAIDs). “It still makes sense to do topical care,” said Dr. Micheletti, but he added that he also prescribes medications for anxiety for these patients.
Patients with increased pain severity or refractory disease may benefit from systemic NSAIDs, or intralesional triamcinolone, he noted. Incision and draining of abscesses may provide temporary symptomatic relief, but keep in mind that lesions will recur, he noted.
For the most severe cases, Dr. Micheletti advised adding tramadol as a first-line opioid, or another short-acting opioid for breakthrough pain.
To manage patients with HS who have chronic pain, Dr. Micheletti recommended starting with HS disease–directed therapy, but also screening for pain severity and psychological comorbidities.
His strategies in these cases include nonpharmacological pain management in the form of physical therapy, wound care, and behavioral health. His algorithm for nociceptive pain is NSAIDs with or without acetaminophen; duloxetine or nortriptyline are other options. For neuropathic pain, gabapentin and/or duloxetine are top choices, but pregabalin, venlafaxine, and nortriptyline are on the list as well.
Topical NSAIDs or topical lidocaine may serve as add-ons to systemic therapy in more severe cases, or as first-line therapy for milder chronic pain, Dr. Micheletti noted. Patients who have failed treatment with at least two pharmacologic agents, suffer medically refractory HS with debilitating pain, or use opioids on an ongoing basis should be referred to a pain management specialist, he said.
Don’t forget lifestyle
Although data on the impact of diet on patients with HS are limited, “we know anecdotally that dairy and refined carbohydrates are associated with exacerbations,” said Dr. Micheletti.
In addition, many patients use complementary medicine “and they aren’t always telling us,” he emphasized. Smoking is prevalent among patients with HS, and is a risk factor for the disease in general, and for more severe and refractory disease, he added. Consequently, screening for tobacco smoking is recommended for patients with HS not only because of the impact on disease, but because it is a potentially modifiable cardiovascular risk factor, he explained.
Consider comorbidities
Cardiovascular disease is among several comorbidities associated with HS, said Dr. Micheletti. HS foundations in the United States and Canada recently published evidence-based recommendations for comorbidity screening. The recommendations included screening for 19 specific comorbidities: acne, dissecting cellulitis, pilonidal disease, pyoderma gangrenosum, depression, anxiety, suicide, smoking, substance abuse, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction.
Dr. Micheletti highlighted cardiovascular comorbidities, and noted the association between HS and modifiable cardiovascular risk factors: smoking, obesity, diabetes mellitus, and dyslipidemia. “HS is also independently associated with cardiovascular disease leading to myocardial infarction, stroke, cardiovascular-associated death, and all-cause mortality compared to controls,” he said. Studies show an incidence rate ratio of 1.53 for major adverse cardiovascular events in patients with HS compared with controls, with the highest relative risk among those aged 18-29 years, he added.
Medical management
Depending on the patient, medical management of HS may involve antibiotics, hormonal agents, and biologics, said Dr. Micheletti. Some of the most commonly used antibiotic regimens for HS are those recommended in treatment guidelines, including doxycycline and a clindamycin/rifampin combination, he said. However, the use of trimethoprim-sulfamethoxazole or ciprofloxacin has been associated with increased antibiotic resistance and is not supported by available evidence, he noted.
Hormonal therapies may help some women with HS, said Dr. Micheletti. Options include spironolactone, metformin, or estrogen-containing hormonal contraceptives, he said.
When it comes to biologics, only 33% of HS patients meet criteria for their use (Hurley stage II or III, moderate or severe HS), he noted. However, research suggests “a huge gap” in the use of anti-TNF therapy even among patients for whom it is recommended, he said.
Of the TNF-alpha inhibitors, data on adalimumab, which is FDA-approved for HS, are the most recent. Adalimumab “is our gold standard biologic and our gateway biologic, for HS at this time,” Dr. Micheletti said.
However, those who respond to adalimumab “can continue to do better, but they can wax and wane and flare,” he cautioned. Infliximab, while not approved for HS, has been studied in patients with HS and is prescribed by some providers. Although no comparative studies have been done for infliximab versus adalimumab, “anecdotally, response to infliximab tends to be better, and it is the most effective biologic in common use for severe HS,” he noted.
Dr. Micheletti’s top treatment recommendations for using biologics start with considering biosimilars. Most patients on biosimilars do fine, but some patients who previously responded to infliximab will unpredictably lose efficacy or have reactions when switched to a biosimilar, he said.
Patients on biologics also may experience waning efficacy in the wake of an immune response stimulated by foreign antibodies, said Dr. Micheletti. “Anti-drug antibody formation is more likely to occur when treatment is interrupted,” he noted. Minimize the risk of antibody formation by paying attention to adherence issues and dosing frequency, he advised.
If patients fail both adalimumab and infliximab, Dr. Micheletti tells them not to lose hope, and that treatment is a trial-and-error process that may involve more than one therapy. Other biologics in active use for HS include ustekinumab, anakinra, secukinumab, brodalumab, golimumab, and JAK inhibitors, any of which might be effective in any given patient, he said.
Surgical solutions
For HS patients with chronic, recurring inflammation and drainage associated with a sinus tract, surgical deroofing may the best treatment option, Dr. Micheletti said. “Deroofing involves the use of a probe to trace the extent of the subcutaneous tract, followed by incision and removal of the tract ‘roof,’ ’’ he explained. The deroofing procedure involves local anesthesia and has a low morbidity rate, as well as a low recurrence rate and high levels of patient satisfaction, he said.
“The acute role for surgery is to remove active foci of inflammation and relieve pain,” which is achieved more effectively with deroofing, said Dr. Micheletti. By contrast, incision and drainage is associated with an almost 100% recurrence rate, he added.
When planning elective surgery for HS, Dr. Micheletti noted that holding infliximab for less than 4 weeks does not affect postoperative infection rates in patients with rheumatoid arthritis, and a recent randomized, controlled trial showed that adalimumab can be continued safely through HS surgeries.
In fact, “continuing TNF inhibitors through elective surgery does not increase infection risk and results in better disease control,” and dermatologists should work with surgery to balance infection and disease flare concerns in HS patients, he said.
Dr. Micheletti disclosed serving as a consultant or advisor for Adaptimmune and Vertex, and research funding from Amgen and Cabaletta Bio. MedscapeLive and this news organization are owned by the same parent company.
LAS VEGAS – , Robert G. Micheletti, MD, said in a presentation at MedscapeLive’s annual Las Vegas Dermatology Seminar.
For patients with HS, “the quality-of-life impact is profound, greater than any other systematically studied dermatologic condition,” said Dr. Micheletti, associate professor of dermatology at the Hospital of the University of Pennsylavnia, and chief of hospital dermatology, and chief of dermatology at Pennsylvania Hospital, Philadelphia.
Two key aspects of quality of life that affect HS patients are sexual health and overall pain, he said. The female-to-male ratio of HS is approximately 3:1, and data show that approximately 40% of female HS patients experience fertility issues and have unaddressed questions about HS and pregnancy, said Dr. Micheletti. Additionally, data from a systematic review showed that 50%-60% of patients with HS reported sexual dysfunction. Impaired sexual function is also associated with both overall impaired quality of life ratings and the presence of mood disorders, he noted.
Pain also has a significant impact on quality of life for HS patients. When these patients present in an emergency department, 70% report severe pain, and approximately 60% receive opioids, said Dr. Micheletti.
Data from a 2021 study showed that HS patients are significantly more likely to receive opioids compared with controls, and also more likely to be diagnosed with opioid use disorder than controls, especially if they are seen by nondermatologists, he noted.
For acute pain, Dr. Micheletti recommended starting with acetaminophen 500 mg every 4 to 6 hours as needed, and topical nonsteroidal anti-inflammatory drugs (NSAIDs). “It still makes sense to do topical care,” said Dr. Micheletti, but he added that he also prescribes medications for anxiety for these patients.
Patients with increased pain severity or refractory disease may benefit from systemic NSAIDs, or intralesional triamcinolone, he noted. Incision and draining of abscesses may provide temporary symptomatic relief, but keep in mind that lesions will recur, he noted.
For the most severe cases, Dr. Micheletti advised adding tramadol as a first-line opioid, or another short-acting opioid for breakthrough pain.
To manage patients with HS who have chronic pain, Dr. Micheletti recommended starting with HS disease–directed therapy, but also screening for pain severity and psychological comorbidities.
His strategies in these cases include nonpharmacological pain management in the form of physical therapy, wound care, and behavioral health. His algorithm for nociceptive pain is NSAIDs with or without acetaminophen; duloxetine or nortriptyline are other options. For neuropathic pain, gabapentin and/or duloxetine are top choices, but pregabalin, venlafaxine, and nortriptyline are on the list as well.
Topical NSAIDs or topical lidocaine may serve as add-ons to systemic therapy in more severe cases, or as first-line therapy for milder chronic pain, Dr. Micheletti noted. Patients who have failed treatment with at least two pharmacologic agents, suffer medically refractory HS with debilitating pain, or use opioids on an ongoing basis should be referred to a pain management specialist, he said.
Don’t forget lifestyle
Although data on the impact of diet on patients with HS are limited, “we know anecdotally that dairy and refined carbohydrates are associated with exacerbations,” said Dr. Micheletti.
In addition, many patients use complementary medicine “and they aren’t always telling us,” he emphasized. Smoking is prevalent among patients with HS, and is a risk factor for the disease in general, and for more severe and refractory disease, he added. Consequently, screening for tobacco smoking is recommended for patients with HS not only because of the impact on disease, but because it is a potentially modifiable cardiovascular risk factor, he explained.
Consider comorbidities
Cardiovascular disease is among several comorbidities associated with HS, said Dr. Micheletti. HS foundations in the United States and Canada recently published evidence-based recommendations for comorbidity screening. The recommendations included screening for 19 specific comorbidities: acne, dissecting cellulitis, pilonidal disease, pyoderma gangrenosum, depression, anxiety, suicide, smoking, substance abuse, polycystic ovary syndrome, obesity, dyslipidemia, diabetes mellitus, metabolic syndrome, hypertension, cardiovascular disease, inflammatory bowel disease, spondyloarthritis, and sexual dysfunction.
Dr. Micheletti highlighted cardiovascular comorbidities, and noted the association between HS and modifiable cardiovascular risk factors: smoking, obesity, diabetes mellitus, and dyslipidemia. “HS is also independently associated with cardiovascular disease leading to myocardial infarction, stroke, cardiovascular-associated death, and all-cause mortality compared to controls,” he said. Studies show an incidence rate ratio of 1.53 for major adverse cardiovascular events in patients with HS compared with controls, with the highest relative risk among those aged 18-29 years, he added.
Medical management
Depending on the patient, medical management of HS may involve antibiotics, hormonal agents, and biologics, said Dr. Micheletti. Some of the most commonly used antibiotic regimens for HS are those recommended in treatment guidelines, including doxycycline and a clindamycin/rifampin combination, he said. However, the use of trimethoprim-sulfamethoxazole or ciprofloxacin has been associated with increased antibiotic resistance and is not supported by available evidence, he noted.
Hormonal therapies may help some women with HS, said Dr. Micheletti. Options include spironolactone, metformin, or estrogen-containing hormonal contraceptives, he said.
When it comes to biologics, only 33% of HS patients meet criteria for their use (Hurley stage II or III, moderate or severe HS), he noted. However, research suggests “a huge gap” in the use of anti-TNF therapy even among patients for whom it is recommended, he said.
Of the TNF-alpha inhibitors, data on adalimumab, which is FDA-approved for HS, are the most recent. Adalimumab “is our gold standard biologic and our gateway biologic, for HS at this time,” Dr. Micheletti said.
However, those who respond to adalimumab “can continue to do better, but they can wax and wane and flare,” he cautioned. Infliximab, while not approved for HS, has been studied in patients with HS and is prescribed by some providers. Although no comparative studies have been done for infliximab versus adalimumab, “anecdotally, response to infliximab tends to be better, and it is the most effective biologic in common use for severe HS,” he noted.
Dr. Micheletti’s top treatment recommendations for using biologics start with considering biosimilars. Most patients on biosimilars do fine, but some patients who previously responded to infliximab will unpredictably lose efficacy or have reactions when switched to a biosimilar, he said.
Patients on biologics also may experience waning efficacy in the wake of an immune response stimulated by foreign antibodies, said Dr. Micheletti. “Anti-drug antibody formation is more likely to occur when treatment is interrupted,” he noted. Minimize the risk of antibody formation by paying attention to adherence issues and dosing frequency, he advised.
If patients fail both adalimumab and infliximab, Dr. Micheletti tells them not to lose hope, and that treatment is a trial-and-error process that may involve more than one therapy. Other biologics in active use for HS include ustekinumab, anakinra, secukinumab, brodalumab, golimumab, and JAK inhibitors, any of which might be effective in any given patient, he said.
Surgical solutions
For HS patients with chronic, recurring inflammation and drainage associated with a sinus tract, surgical deroofing may the best treatment option, Dr. Micheletti said. “Deroofing involves the use of a probe to trace the extent of the subcutaneous tract, followed by incision and removal of the tract ‘roof,’ ’’ he explained. The deroofing procedure involves local anesthesia and has a low morbidity rate, as well as a low recurrence rate and high levels of patient satisfaction, he said.
“The acute role for surgery is to remove active foci of inflammation and relieve pain,” which is achieved more effectively with deroofing, said Dr. Micheletti. By contrast, incision and drainage is associated with an almost 100% recurrence rate, he added.
When planning elective surgery for HS, Dr. Micheletti noted that holding infliximab for less than 4 weeks does not affect postoperative infection rates in patients with rheumatoid arthritis, and a recent randomized, controlled trial showed that adalimumab can be continued safely through HS surgeries.
In fact, “continuing TNF inhibitors through elective surgery does not increase infection risk and results in better disease control,” and dermatologists should work with surgery to balance infection and disease flare concerns in HS patients, he said.
Dr. Micheletti disclosed serving as a consultant or advisor for Adaptimmune and Vertex, and research funding from Amgen and Cabaletta Bio. MedscapeLive and this news organization are owned by the same parent company.
AT INNOVATIONS IN DERMATOLOGY
Single chest x-ray could predict 10-year CVD risk
who presented the results of their deep-learning model at the annual meeting of the Radiological Society of North America.
Current American College of Cardiologists and American Heart Association guidelines recommend estimating 10-year risk of major adverse cardiovascular events (MACE) to determine whether a patient should receive statins to help prevent atherosclerotic cardiovascular disease (ASCVD). Statins are recommended for patients with a 10-year risk of 7.5% or higher, the authors noted.
The current ASCVD risk score is determined with nine factors: age, sex, race, systolic blood pressure, hypertension treatment, smoking, type 2 diabetes, and a lipid panel.
Not all data points available in EHR
But not all of those data points may be available through the electronic health record, “which makes novel and easier approaches for population-wide screening desirable,” said lead researcher Jakob Weiss, MD, a radiologist affiliated with the Cardiovascular Imaging Research Center at Massachusetts General Hospital and the AI in medicine program at the Brigham and Women’s Hospital in Boston.
Chest x-ray images, on the other hand, are commonly available. The images carry rich information beyond diagnostic data but have not been used in this type of prediction model because AI models have been lacking, Dr. Weiss said.
The researchers trained a deep-learning model with single chest x-rays only.
They used 147,497 chest x-rays from 40,643 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial, a multicenter, randomized controlled trial designed and sponsored by the National Cancer Institute.
Dr. Weiss acknowledged that the population used to train the model was heavily White and that should be a consideration in validating the model.
They compared their model’s ability to predict 10-year ASCVD risk with the standard ACC/AHA model.
“Based on a single chest radiograph image, deep learning can predict the risk of future cardiovascular events independent of cardiovascular risk factors and with similar performance to the established and guideline-recommended ASCVD risk score,” Dr. Weiss said.
Tested against independent group
They tested the model against an independent group of 11,430 outpatients (average age, 60 years; 42.9% male) who underwent a routine outpatient chest x-ray at Mass General Brigham and were potentially eligible to receive statins.
Of those 11,430 patients, 1,096 (9.6%) had a major adverse cardiac event over the median follow-up of 10.3 years.
There was a significant association of CXR-CVD risk and MACE among patients eligible to receive statins, the researchers found (hazard ratio, 2.03; 95% confidence interval, 1.81-2.30; P < .001), which remained significant after adjusting for cardiovascular risk factors (adjusted HR, 1.63; 95% CI, 1.43-1.86; P < .001).
Some of the variables were missing in the standard model, but in a subgroup of 2,401 patients, all the variables were available.
They calculated ASCVD risk in that subgroup using the standard model and the CXR model and found that the performance was similar (c-statistic, 0.64 vs. 0.65; P = .48) to the ASCVD risk score (aHR, 1.58; 95% CI, 1.20-2.09; P = .001).
Ritu R. Gill MD, MPH, associate professor of radiology at Harvard Medical School in Boston, who was not part of the study, said in an interview that “the predictive algorithm is promising and potentially translatable and could enhance the annual medical checkup in a select population.
“The algorithm was developed using the PLCO cohort with radiographs, which are likely subjects in the lung cancer screening arm,” she said. “This cohort would be at high risk of cardiovascular diseases, as smoking is a known risk factor for atherosclerotic disease, and therefore the results are expected.
“The algorithm needs to be validated in an independent database with inclusion of subjects with younger age groups and adjusted for gender and racial diversity,” Gill said.
David Cho, MD, a cardiologist at the University of California, Los Angeles, who also was not part of the study, said in an interview that “this work is a great example of AI being able to detect clinically relevant outcomes with a widely used and low-cost screening test.
“The volume of data needed to train these models is already out there,” Dr. Cho said. “It just needs to be mined.”
He noted that this tool, if validated in randomized trials, could help determine risk among patients living in places where access to specialized cardiac care is limited.
Dr. Weiss and Dr. Cho disclosed no relevant financial relationships. Dr. Gill has received research support from Cannon Inc and consultant fees from Imbio and WorldCare.
A version of this article first appeared on Medscape.com.
who presented the results of their deep-learning model at the annual meeting of the Radiological Society of North America.
Current American College of Cardiologists and American Heart Association guidelines recommend estimating 10-year risk of major adverse cardiovascular events (MACE) to determine whether a patient should receive statins to help prevent atherosclerotic cardiovascular disease (ASCVD). Statins are recommended for patients with a 10-year risk of 7.5% or higher, the authors noted.
The current ASCVD risk score is determined with nine factors: age, sex, race, systolic blood pressure, hypertension treatment, smoking, type 2 diabetes, and a lipid panel.
Not all data points available in EHR
But not all of those data points may be available through the electronic health record, “which makes novel and easier approaches for population-wide screening desirable,” said lead researcher Jakob Weiss, MD, a radiologist affiliated with the Cardiovascular Imaging Research Center at Massachusetts General Hospital and the AI in medicine program at the Brigham and Women’s Hospital in Boston.
Chest x-ray images, on the other hand, are commonly available. The images carry rich information beyond diagnostic data but have not been used in this type of prediction model because AI models have been lacking, Dr. Weiss said.
The researchers trained a deep-learning model with single chest x-rays only.
They used 147,497 chest x-rays from 40,643 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial, a multicenter, randomized controlled trial designed and sponsored by the National Cancer Institute.
Dr. Weiss acknowledged that the population used to train the model was heavily White and that should be a consideration in validating the model.
They compared their model’s ability to predict 10-year ASCVD risk with the standard ACC/AHA model.
“Based on a single chest radiograph image, deep learning can predict the risk of future cardiovascular events independent of cardiovascular risk factors and with similar performance to the established and guideline-recommended ASCVD risk score,” Dr. Weiss said.
Tested against independent group
They tested the model against an independent group of 11,430 outpatients (average age, 60 years; 42.9% male) who underwent a routine outpatient chest x-ray at Mass General Brigham and were potentially eligible to receive statins.
Of those 11,430 patients, 1,096 (9.6%) had a major adverse cardiac event over the median follow-up of 10.3 years.
There was a significant association of CXR-CVD risk and MACE among patients eligible to receive statins, the researchers found (hazard ratio, 2.03; 95% confidence interval, 1.81-2.30; P < .001), which remained significant after adjusting for cardiovascular risk factors (adjusted HR, 1.63; 95% CI, 1.43-1.86; P < .001).
Some of the variables were missing in the standard model, but in a subgroup of 2,401 patients, all the variables were available.
They calculated ASCVD risk in that subgroup using the standard model and the CXR model and found that the performance was similar (c-statistic, 0.64 vs. 0.65; P = .48) to the ASCVD risk score (aHR, 1.58; 95% CI, 1.20-2.09; P = .001).
Ritu R. Gill MD, MPH, associate professor of radiology at Harvard Medical School in Boston, who was not part of the study, said in an interview that “the predictive algorithm is promising and potentially translatable and could enhance the annual medical checkup in a select population.
“The algorithm was developed using the PLCO cohort with radiographs, which are likely subjects in the lung cancer screening arm,” she said. “This cohort would be at high risk of cardiovascular diseases, as smoking is a known risk factor for atherosclerotic disease, and therefore the results are expected.
“The algorithm needs to be validated in an independent database with inclusion of subjects with younger age groups and adjusted for gender and racial diversity,” Gill said.
David Cho, MD, a cardiologist at the University of California, Los Angeles, who also was not part of the study, said in an interview that “this work is a great example of AI being able to detect clinically relevant outcomes with a widely used and low-cost screening test.
“The volume of data needed to train these models is already out there,” Dr. Cho said. “It just needs to be mined.”
He noted that this tool, if validated in randomized trials, could help determine risk among patients living in places where access to specialized cardiac care is limited.
Dr. Weiss and Dr. Cho disclosed no relevant financial relationships. Dr. Gill has received research support from Cannon Inc and consultant fees from Imbio and WorldCare.
A version of this article first appeared on Medscape.com.
who presented the results of their deep-learning model at the annual meeting of the Radiological Society of North America.
Current American College of Cardiologists and American Heart Association guidelines recommend estimating 10-year risk of major adverse cardiovascular events (MACE) to determine whether a patient should receive statins to help prevent atherosclerotic cardiovascular disease (ASCVD). Statins are recommended for patients with a 10-year risk of 7.5% or higher, the authors noted.
The current ASCVD risk score is determined with nine factors: age, sex, race, systolic blood pressure, hypertension treatment, smoking, type 2 diabetes, and a lipid panel.
Not all data points available in EHR
But not all of those data points may be available through the electronic health record, “which makes novel and easier approaches for population-wide screening desirable,” said lead researcher Jakob Weiss, MD, a radiologist affiliated with the Cardiovascular Imaging Research Center at Massachusetts General Hospital and the AI in medicine program at the Brigham and Women’s Hospital in Boston.
Chest x-ray images, on the other hand, are commonly available. The images carry rich information beyond diagnostic data but have not been used in this type of prediction model because AI models have been lacking, Dr. Weiss said.
The researchers trained a deep-learning model with single chest x-rays only.
They used 147,497 chest x-rays from 40,643 participants in the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial, a multicenter, randomized controlled trial designed and sponsored by the National Cancer Institute.
Dr. Weiss acknowledged that the population used to train the model was heavily White and that should be a consideration in validating the model.
They compared their model’s ability to predict 10-year ASCVD risk with the standard ACC/AHA model.
“Based on a single chest radiograph image, deep learning can predict the risk of future cardiovascular events independent of cardiovascular risk factors and with similar performance to the established and guideline-recommended ASCVD risk score,” Dr. Weiss said.
Tested against independent group
They tested the model against an independent group of 11,430 outpatients (average age, 60 years; 42.9% male) who underwent a routine outpatient chest x-ray at Mass General Brigham and were potentially eligible to receive statins.
Of those 11,430 patients, 1,096 (9.6%) had a major adverse cardiac event over the median follow-up of 10.3 years.
There was a significant association of CXR-CVD risk and MACE among patients eligible to receive statins, the researchers found (hazard ratio, 2.03; 95% confidence interval, 1.81-2.30; P < .001), which remained significant after adjusting for cardiovascular risk factors (adjusted HR, 1.63; 95% CI, 1.43-1.86; P < .001).
Some of the variables were missing in the standard model, but in a subgroup of 2,401 patients, all the variables were available.
They calculated ASCVD risk in that subgroup using the standard model and the CXR model and found that the performance was similar (c-statistic, 0.64 vs. 0.65; P = .48) to the ASCVD risk score (aHR, 1.58; 95% CI, 1.20-2.09; P = .001).
Ritu R. Gill MD, MPH, associate professor of radiology at Harvard Medical School in Boston, who was not part of the study, said in an interview that “the predictive algorithm is promising and potentially translatable and could enhance the annual medical checkup in a select population.
“The algorithm was developed using the PLCO cohort with radiographs, which are likely subjects in the lung cancer screening arm,” she said. “This cohort would be at high risk of cardiovascular diseases, as smoking is a known risk factor for atherosclerotic disease, and therefore the results are expected.
“The algorithm needs to be validated in an independent database with inclusion of subjects with younger age groups and adjusted for gender and racial diversity,” Gill said.
David Cho, MD, a cardiologist at the University of California, Los Angeles, who also was not part of the study, said in an interview that “this work is a great example of AI being able to detect clinically relevant outcomes with a widely used and low-cost screening test.
“The volume of data needed to train these models is already out there,” Dr. Cho said. “It just needs to be mined.”
He noted that this tool, if validated in randomized trials, could help determine risk among patients living in places where access to specialized cardiac care is limited.
Dr. Weiss and Dr. Cho disclosed no relevant financial relationships. Dr. Gill has received research support from Cannon Inc and consultant fees from Imbio and WorldCare.
A version of this article first appeared on Medscape.com.
AT RSNA 2022
Higher potency of fentanyl affects addiction treatment, screening
As fentanyl-related overdose deaths continue to increase, clinicians should take note of important differences that set the drug apart from the other drugs of misuse – and the troubling reality that fentanyl now contaminates most of them.
“It would be fair to tell patients, if you’re buying any illicit drugs – pills, powder, liquid, whatever it is, you’ve got to assume it’s either contaminated with or replaced by fentanyl,” said Edwin Salsitz, MD, an associate clinical professor at the Icahn School of Medicine at Mount Sinai, New York, during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In many if not most cases, he noted, patients become addicted to fentanyl unknowingly. They assume they are ingesting oxycodone, cocaine, or another drug, and have no realization that they are even exposed to fentanyl until they test positive for it – or overdose.
Meanwhile, the high potency of fentanyl can overcome the opioid blockade of addiction treatment therapies – methadone and buprenorphine – that take away the high that users get from less potent drugs such as heroin.
“Fentanyl is overcoming this blockade that methadone and buprenorphine used to provide,” Dr. Salsitz said. “With fentanyl having such a higher potency, patients are saying ‘no, I still feel the fentanyl effects,’ and they continue feeling it even with 200 milligrams of methadone or 24 milligrams of buprenorphine.”
‘Wooden chest syndrome’
Among the lesser-known dangers of fentanyl is the possibility that some overdose deaths may occur as the result of a syndrome previously reported as a rare complication following the medical use of fentanyl in critically ill patients – fentanyl-induced chest-wall rigidity, or “wooden chest syndrome,” Dr. Salsitz explained.
In such cases, the muscles of respiration become rigid and paralyzed, causing suffocation within a matter of minutes – too soon to benefit from the overdose rescue medication naloxone.
In one recent study published in Clinical Toxicology , nearly half of fentanyl overdose deaths were found to have occurred even before the body had a chance to produce norfentanyl, a metabolite of fentanyl that takes only about 2-3 minutes to appear in the system, suggesting the deaths occurred rapidly.
In the study of 48 fentanyl deaths, no appreciable concentrations of norfentanyl could be detected in 20 of the 48 overdose deaths (42%), and concentrations were less than 1 ng/mL in 25 cases (52%).
“The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity,” the authors reported.
“In several cases fentanyl concentrations were strikingly high (22 ng/mL and 20 ng/mL) with no norfentanyl detected,” they said.
Dr. Salsitz noted that the syndrome is not well known among the addiction treatment community.
“This is different than the usual respiratory opioid overdose where there’s a gradual decrease in the breathing rate and a gradual decrease in how much air is going in and out of the lungs,” Dr. Salsitz explained.
“With those cases, some may survive for an hour or longer, allowing time for someone to administer naloxone or to get the patient to the emergency room,” he said. “But with this, breathing stops and people can die within minutes.
“I think that this is one of the reasons that fentanyl deaths keep going up despite more and more naloxone availability out there,” he said.
Clearance may take longer
In toxicology testing for fentanyl, clinicians should also note the important difference between fentanyl and other opioids – that fentanyl, because of its high lipophilicity, may be detected in urine toxicology testing up to 3 weeks after last use. This is much longer than the 2- to 4-day clearance observed with other opioids, possibly causing patients to continue to test positive for the drug weeks after cessation.
This effect was observed in one recent study of 12 opioid use disorder patients in a residential treatment program who had previously been exposed to daily fentanyl.
The study showed the mean amount of time of fentanyl clearance was 2 weeks, with a range of 4-26 days after last use.
The authors pointed out that the findings “might explain recent reports of difficulty in buprenorphine inductions for persons who use fentanyl, and point to a need to better understand the pharmacokinetics of fentanyl in the context of opioid withdrawal in persons who regularly use fentanyl.”
Though the study was small, Dr. Salsitz said “that’s not a stumbling block to the important finding that, with regular use of fentanyl, the drug may stay in the urine for a long time.”
Dr. Salsitz noted that similar observations have been made at his center, with clinicians logically assuming that patients were still somehow getting fentanyl.
“When we initially found this in patients, we thought that they were using on the unit, perhaps that they brought in the fentanyl, because otherwise how could it stay in the urine that long,” he noted. “But fentanyl appears to be more lipophilic and gets into the fat; it’s then excreted very slowly and then stays in the urine.”
Dr. Salsitz said most practitioners think of fentanyl as a short-acting drug, so “it’s important to realize that people may continue to test positive and it should be thought of as a long-acting opioid.”
Opiate screening tests don’t work
Dr. Salsitz warned of another misconception in fentanyl testing – the common mistake of assuming that fentanyl should show up in a test for opiates – when in fact fentanyl is not, technically, an opiate.
“The word opiate only refers to morphine, codeine, heroin and sometimes hydrocodone,” he explained. “Other opioids are classified as semisynthetic, such as oxycodone, or synthetics, such as fentanyl and methadone, buprenorphine.”
“In order to detect the synthetics, you must have a separate strip for each one of those drugs. They will not show up positive on a screen for opiates,” he noted.
The belief that fentanyl and other synthetic and semisynthetic opioids will show positive on an opiate screen is a common misconception, he said. “The misunderstanding in toxicology interpretation is a problem for many practitioners, [but] it’s essential to understand because otherwise false assumptions about the patient will be considered.”
Another important testing misreading can occur with the antidepressant drug trazodone, which Dr. Salsitz cautioned may falsely test as positive for fentanyl on immunoassays.
“Trazodone is very commonly used in addiction treatment centers, but it can give a false positive on the fentanyl immunoassay and we’ve had a number of those cases,” he said.
Dr. Salsitz had no disclosures to report.
The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.
As fentanyl-related overdose deaths continue to increase, clinicians should take note of important differences that set the drug apart from the other drugs of misuse – and the troubling reality that fentanyl now contaminates most of them.
“It would be fair to tell patients, if you’re buying any illicit drugs – pills, powder, liquid, whatever it is, you’ve got to assume it’s either contaminated with or replaced by fentanyl,” said Edwin Salsitz, MD, an associate clinical professor at the Icahn School of Medicine at Mount Sinai, New York, during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In many if not most cases, he noted, patients become addicted to fentanyl unknowingly. They assume they are ingesting oxycodone, cocaine, or another drug, and have no realization that they are even exposed to fentanyl until they test positive for it – or overdose.
Meanwhile, the high potency of fentanyl can overcome the opioid blockade of addiction treatment therapies – methadone and buprenorphine – that take away the high that users get from less potent drugs such as heroin.
“Fentanyl is overcoming this blockade that methadone and buprenorphine used to provide,” Dr. Salsitz said. “With fentanyl having such a higher potency, patients are saying ‘no, I still feel the fentanyl effects,’ and they continue feeling it even with 200 milligrams of methadone or 24 milligrams of buprenorphine.”
‘Wooden chest syndrome’
Among the lesser-known dangers of fentanyl is the possibility that some overdose deaths may occur as the result of a syndrome previously reported as a rare complication following the medical use of fentanyl in critically ill patients – fentanyl-induced chest-wall rigidity, or “wooden chest syndrome,” Dr. Salsitz explained.
In such cases, the muscles of respiration become rigid and paralyzed, causing suffocation within a matter of minutes – too soon to benefit from the overdose rescue medication naloxone.
In one recent study published in Clinical Toxicology , nearly half of fentanyl overdose deaths were found to have occurred even before the body had a chance to produce norfentanyl, a metabolite of fentanyl that takes only about 2-3 minutes to appear in the system, suggesting the deaths occurred rapidly.
In the study of 48 fentanyl deaths, no appreciable concentrations of norfentanyl could be detected in 20 of the 48 overdose deaths (42%), and concentrations were less than 1 ng/mL in 25 cases (52%).
“The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity,” the authors reported.
“In several cases fentanyl concentrations were strikingly high (22 ng/mL and 20 ng/mL) with no norfentanyl detected,” they said.
Dr. Salsitz noted that the syndrome is not well known among the addiction treatment community.
“This is different than the usual respiratory opioid overdose where there’s a gradual decrease in the breathing rate and a gradual decrease in how much air is going in and out of the lungs,” Dr. Salsitz explained.
“With those cases, some may survive for an hour or longer, allowing time for someone to administer naloxone or to get the patient to the emergency room,” he said. “But with this, breathing stops and people can die within minutes.
“I think that this is one of the reasons that fentanyl deaths keep going up despite more and more naloxone availability out there,” he said.
Clearance may take longer
In toxicology testing for fentanyl, clinicians should also note the important difference between fentanyl and other opioids – that fentanyl, because of its high lipophilicity, may be detected in urine toxicology testing up to 3 weeks after last use. This is much longer than the 2- to 4-day clearance observed with other opioids, possibly causing patients to continue to test positive for the drug weeks after cessation.
This effect was observed in one recent study of 12 opioid use disorder patients in a residential treatment program who had previously been exposed to daily fentanyl.
The study showed the mean amount of time of fentanyl clearance was 2 weeks, with a range of 4-26 days after last use.
The authors pointed out that the findings “might explain recent reports of difficulty in buprenorphine inductions for persons who use fentanyl, and point to a need to better understand the pharmacokinetics of fentanyl in the context of opioid withdrawal in persons who regularly use fentanyl.”
Though the study was small, Dr. Salsitz said “that’s not a stumbling block to the important finding that, with regular use of fentanyl, the drug may stay in the urine for a long time.”
Dr. Salsitz noted that similar observations have been made at his center, with clinicians logically assuming that patients were still somehow getting fentanyl.
“When we initially found this in patients, we thought that they were using on the unit, perhaps that they brought in the fentanyl, because otherwise how could it stay in the urine that long,” he noted. “But fentanyl appears to be more lipophilic and gets into the fat; it’s then excreted very slowly and then stays in the urine.”
Dr. Salsitz said most practitioners think of fentanyl as a short-acting drug, so “it’s important to realize that people may continue to test positive and it should be thought of as a long-acting opioid.”
Opiate screening tests don’t work
Dr. Salsitz warned of another misconception in fentanyl testing – the common mistake of assuming that fentanyl should show up in a test for opiates – when in fact fentanyl is not, technically, an opiate.
“The word opiate only refers to morphine, codeine, heroin and sometimes hydrocodone,” he explained. “Other opioids are classified as semisynthetic, such as oxycodone, or synthetics, such as fentanyl and methadone, buprenorphine.”
“In order to detect the synthetics, you must have a separate strip for each one of those drugs. They will not show up positive on a screen for opiates,” he noted.
The belief that fentanyl and other synthetic and semisynthetic opioids will show positive on an opiate screen is a common misconception, he said. “The misunderstanding in toxicology interpretation is a problem for many practitioners, [but] it’s essential to understand because otherwise false assumptions about the patient will be considered.”
Another important testing misreading can occur with the antidepressant drug trazodone, which Dr. Salsitz cautioned may falsely test as positive for fentanyl on immunoassays.
“Trazodone is very commonly used in addiction treatment centers, but it can give a false positive on the fentanyl immunoassay and we’ve had a number of those cases,” he said.
Dr. Salsitz had no disclosures to report.
The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.
As fentanyl-related overdose deaths continue to increase, clinicians should take note of important differences that set the drug apart from the other drugs of misuse – and the troubling reality that fentanyl now contaminates most of them.
“It would be fair to tell patients, if you’re buying any illicit drugs – pills, powder, liquid, whatever it is, you’ve got to assume it’s either contaminated with or replaced by fentanyl,” said Edwin Salsitz, MD, an associate clinical professor at the Icahn School of Medicine at Mount Sinai, New York, during a presentation on the subject at the 21st Annual Psychopharmacology Update presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.
In many if not most cases, he noted, patients become addicted to fentanyl unknowingly. They assume they are ingesting oxycodone, cocaine, or another drug, and have no realization that they are even exposed to fentanyl until they test positive for it – or overdose.
Meanwhile, the high potency of fentanyl can overcome the opioid blockade of addiction treatment therapies – methadone and buprenorphine – that take away the high that users get from less potent drugs such as heroin.
“Fentanyl is overcoming this blockade that methadone and buprenorphine used to provide,” Dr. Salsitz said. “With fentanyl having such a higher potency, patients are saying ‘no, I still feel the fentanyl effects,’ and they continue feeling it even with 200 milligrams of methadone or 24 milligrams of buprenorphine.”
‘Wooden chest syndrome’
Among the lesser-known dangers of fentanyl is the possibility that some overdose deaths may occur as the result of a syndrome previously reported as a rare complication following the medical use of fentanyl in critically ill patients – fentanyl-induced chest-wall rigidity, or “wooden chest syndrome,” Dr. Salsitz explained.
In such cases, the muscles of respiration become rigid and paralyzed, causing suffocation within a matter of minutes – too soon to benefit from the overdose rescue medication naloxone.
In one recent study published in Clinical Toxicology , nearly half of fentanyl overdose deaths were found to have occurred even before the body had a chance to produce norfentanyl, a metabolite of fentanyl that takes only about 2-3 minutes to appear in the system, suggesting the deaths occurred rapidly.
In the study of 48 fentanyl deaths, no appreciable concentrations of norfentanyl could be detected in 20 of the 48 overdose deaths (42%), and concentrations were less than 1 ng/mL in 25 cases (52%).
“The lack of any measurable norfentanyl in half of our cases suggests a very rapid death, consistent with acute chest rigidity,” the authors reported.
“In several cases fentanyl concentrations were strikingly high (22 ng/mL and 20 ng/mL) with no norfentanyl detected,” they said.
Dr. Salsitz noted that the syndrome is not well known among the addiction treatment community.
“This is different than the usual respiratory opioid overdose where there’s a gradual decrease in the breathing rate and a gradual decrease in how much air is going in and out of the lungs,” Dr. Salsitz explained.
“With those cases, some may survive for an hour or longer, allowing time for someone to administer naloxone or to get the patient to the emergency room,” he said. “But with this, breathing stops and people can die within minutes.
“I think that this is one of the reasons that fentanyl deaths keep going up despite more and more naloxone availability out there,” he said.
Clearance may take longer
In toxicology testing for fentanyl, clinicians should also note the important difference between fentanyl and other opioids – that fentanyl, because of its high lipophilicity, may be detected in urine toxicology testing up to 3 weeks after last use. This is much longer than the 2- to 4-day clearance observed with other opioids, possibly causing patients to continue to test positive for the drug weeks after cessation.
This effect was observed in one recent study of 12 opioid use disorder patients in a residential treatment program who had previously been exposed to daily fentanyl.
The study showed the mean amount of time of fentanyl clearance was 2 weeks, with a range of 4-26 days after last use.
The authors pointed out that the findings “might explain recent reports of difficulty in buprenorphine inductions for persons who use fentanyl, and point to a need to better understand the pharmacokinetics of fentanyl in the context of opioid withdrawal in persons who regularly use fentanyl.”
Though the study was small, Dr. Salsitz said “that’s not a stumbling block to the important finding that, with regular use of fentanyl, the drug may stay in the urine for a long time.”
Dr. Salsitz noted that similar observations have been made at his center, with clinicians logically assuming that patients were still somehow getting fentanyl.
“When we initially found this in patients, we thought that they were using on the unit, perhaps that they brought in the fentanyl, because otherwise how could it stay in the urine that long,” he noted. “But fentanyl appears to be more lipophilic and gets into the fat; it’s then excreted very slowly and then stays in the urine.”
Dr. Salsitz said most practitioners think of fentanyl as a short-acting drug, so “it’s important to realize that people may continue to test positive and it should be thought of as a long-acting opioid.”
Opiate screening tests don’t work
Dr. Salsitz warned of another misconception in fentanyl testing – the common mistake of assuming that fentanyl should show up in a test for opiates – when in fact fentanyl is not, technically, an opiate.
“The word opiate only refers to morphine, codeine, heroin and sometimes hydrocodone,” he explained. “Other opioids are classified as semisynthetic, such as oxycodone, or synthetics, such as fentanyl and methadone, buprenorphine.”
“In order to detect the synthetics, you must have a separate strip for each one of those drugs. They will not show up positive on a screen for opiates,” he noted.
The belief that fentanyl and other synthetic and semisynthetic opioids will show positive on an opiate screen is a common misconception, he said. “The misunderstanding in toxicology interpretation is a problem for many practitioners, [but] it’s essential to understand because otherwise false assumptions about the patient will be considered.”
Another important testing misreading can occur with the antidepressant drug trazodone, which Dr. Salsitz cautioned may falsely test as positive for fentanyl on immunoassays.
“Trazodone is very commonly used in addiction treatment centers, but it can give a false positive on the fentanyl immunoassay and we’ve had a number of those cases,” he said.
Dr. Salsitz had no disclosures to report.
The Psychopharmacology Update was sponsored by Medscape Live. Medscape Live and this news organization are owned by the same parent company.
FROM PSYCHOPHARMACOLOGY UPDATE
Lung cancer screening pushes 20-year survival rate to 80%
CHICAGO – , findings from a 20-year international study indicate.
Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.
The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.
Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
Participants’ 20-year survival rate 80%
Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.
Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.
For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).
No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.
These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.
At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.
Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.
When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.
“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.
“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
Findings “very promising”
Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.
“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.
“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.
Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.
So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.
“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.
Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.
Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – , findings from a 20-year international study indicate.
Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.
The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.
Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
Participants’ 20-year survival rate 80%
Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.
Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.
For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).
No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.
These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.
At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.
Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.
When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.
“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.
“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
Findings “very promising”
Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.
“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.
“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.
Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.
So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.
“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.
Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.
Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
CHICAGO – , findings from a 20-year international study indicate.
Claudia Henschke, MD, PhD, professor of radiology and director of the Early Lung and Cardiac Action Program at the Icahn School of Medicine at Mount Sinai, New York, presented research results at the annual meeting of the Radiological Society of North America.
The researchers studied lung-cancer–specific survival (LCS) of 87,416 participants enrolled in an international, prospective study named the International Early Lung Cancer Action Program.
Lung cancer is the leading cause of cancer death. The American Lung Association states the average 5-year survival rate is 18.6%. Only 16% of the cancers are caught early and more than half of people with lung cancer die within a year of diagnosis.
Participants’ 20-year survival rate 80%
Results of this large international study showed the overall 20-year survival rate for the 1,285 screening participants diagnosed with early-stage cancer was 80% (95% confidence interval, 77%-83%). Among the 1,285 diagnosed, 83% had stage 1 cancer, Dr. Henschke said.
Lung cancer survival (LCS) was 100% for the 139 participants with nonsolid nodule consistency and for the 155 participants with part-solid consistency. LCS was 73% (95% CI, 69%-77%) for the 991 with solid consistency, and for clinical stage IA participants LCS was 86% (95% CI, 83%-89%), regardless of consistency.
For participants with pathologic stage IA lung cancer 10 mm or less in average diameter, the 20-year survival rate with identification and resection was 92% (95% CI, 87%-96%).
No lung cancer deaths were identified in the part-solid and nonsolid cancers, the researchers report.
These results show the 10-year findings from 2006 published in the New England Journal of Medicine, which also showed 80% survival rates with low-dose CT, have persisted, she said.
At the time of the 2006 paper, 95% of Americans diagnosed with lung cancer died from it, Dr. Henschke said.
Dr. Henschke notes that by the time symptoms appear, lung cancer is often advanced, so the best tool for detecting early-stage lung cancer is enrolling in an annual screening program.
When cancer is small enough and can be surgically removed, patients can be effectively cured long-term, she said.
“In the future, perhaps blood markers will allow us to detect it in the first half of the life cycle of lung cancer instead of CT at the beginning of the second half of the life cycle,” Dr. Henschke said.
“The study raises the power of prospective data collection in the context of clinical care as recommended by the Institute of Medicine long ago,” she said.
Findings “very promising”
Ernest Hawk, MD, MPH, head of the division of cancer prevention and population sciences at the University of Texas MD Anderson Cancer, Houston, told this news organization the findings look “very promising.” Dr. Hawk was not involved in the study.
“This was one of the earliest studies to evaluate low-dose CT scanning. Their report that the initial benefits seem to be holding up over a longer period of observation is great,” he said.
“This bolsters the data that lung cancer screening is beneficial over a longer period of observation,” he said, noting that most of the randomized controlled trials have been shorter.
Lung cancer screening is now recommended for high-risk individuals – those with at least a 20-pack-year history of tobacco use who are between 50 and 80 years old.
So far, screening is still limited to people at high risk, Dr. Hawk said, though there’s discussion about whether benefit would extend to people exposed to asbestos, for instance, or secondhand smoke.
“The biggest challenge right now is getting the screening to those who actually meet the criteria,” Dr. Hawk said.
Medscape reported earlier this month that less than 6% of high-risk smokers have the recommended annual lung cancer screening, according to a new report from the American Lung Association.
Dr. Henschke is on the Advisory Board for LungLifeAI and is on the board for the Early Diagnosis and Treatment Research Foundation. Dr. Hawk reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT RSNA 2022