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Nivolumab Wins First-Line Indication in Metastatic Urothelial Carcinoma
Approval was based on the CHECKMATE-901 trial in 608 patients randomized equally to either cisplatin and gemcitabine for ≤ six cycles or nivolumab plus cisplatin and gemcitabine for ≤ six cycles, followed by nivolumab alone for ≤ 2 years.
Median overall survival was 21.7 months with nivolumab add-on vs 18.9 months with cisplatin/gemcitabine alone (hazard ratio [HR], 0.78; P = .0171). The nivolumab group had a slightly higher median progression-free survival of 7.9 months vs 7.6 months in the cisplatin and gemcitabine group (HR, 0.72; P = .0012).
The most common adverse events, occurring in ≥ 15% of nivolumab patients, were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritus.
Among numerous other oncology indications, nivolumab was previously approved for adjuvant treatment following urothelial carcinoma resection and for locally advanced or metastatic urothelial carcinoma that progresses during or following platinum-containing chemotherapy.
A version of this article appeared on Medscape.com .
Approval was based on the CHECKMATE-901 trial in 608 patients randomized equally to either cisplatin and gemcitabine for ≤ six cycles or nivolumab plus cisplatin and gemcitabine for ≤ six cycles, followed by nivolumab alone for ≤ 2 years.
Median overall survival was 21.7 months with nivolumab add-on vs 18.9 months with cisplatin/gemcitabine alone (hazard ratio [HR], 0.78; P = .0171). The nivolumab group had a slightly higher median progression-free survival of 7.9 months vs 7.6 months in the cisplatin and gemcitabine group (HR, 0.72; P = .0012).
The most common adverse events, occurring in ≥ 15% of nivolumab patients, were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritus.
Among numerous other oncology indications, nivolumab was previously approved for adjuvant treatment following urothelial carcinoma resection and for locally advanced or metastatic urothelial carcinoma that progresses during or following platinum-containing chemotherapy.
A version of this article appeared on Medscape.com .
Approval was based on the CHECKMATE-901 trial in 608 patients randomized equally to either cisplatin and gemcitabine for ≤ six cycles or nivolumab plus cisplatin and gemcitabine for ≤ six cycles, followed by nivolumab alone for ≤ 2 years.
Median overall survival was 21.7 months with nivolumab add-on vs 18.9 months with cisplatin/gemcitabine alone (hazard ratio [HR], 0.78; P = .0171). The nivolumab group had a slightly higher median progression-free survival of 7.9 months vs 7.6 months in the cisplatin and gemcitabine group (HR, 0.72; P = .0012).
The most common adverse events, occurring in ≥ 15% of nivolumab patients, were nausea, fatigue, musculoskeletal pain, constipation, decreased appetite, rash, vomiting, peripheral neuropathy, urinary tract infection, diarrhea, edema, hypothyroidism, and pruritus.
Among numerous other oncology indications, nivolumab was previously approved for adjuvant treatment following urothelial carcinoma resection and for locally advanced or metastatic urothelial carcinoma that progresses during or following platinum-containing chemotherapy.
A version of this article appeared on Medscape.com .
Leflunomide: A Fresh Look at an Old Drug
The Food and Drug Administration’s approval of leflunomide in September 1998 as a treatment for rheumatoid arthritis was sandwiched between the debuts of infliximab (Remicade and biosimilars) and etanercept (Enbrel) in August and November of that year, the latter of which was so exciting that “within 2 months you couldn’t get [it],” recalled Eric M. Ruderman, MD. And “like every middle child, [leflunomide] was underloved, underappreciated, and largely dismissed.”
Yet should it have been? Is it worth another look today?
At the 2024 Rheumatology Winter Clinical Symposium, Dr. Ruderman reflected on some of the clinical trial data published after leflunomide’s approval that “got lost in the shuffle” of the rightful embrace of biologics in United States practice, and urged reconsideration of the loading strategy still advised in the drug’s labeling.
“I’m not telling you that you should be using [leflunomide] in place of biologics, instead of biologics, or before biologics … but it should be in your toolkit,” said Dr. Ruderman, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago. The drug “still has a role in RA, including in combination with methotrexate, and a potential role in other rheumatic diseases.”
“In our PsA clinic,” he noted, “we’ve actually not infrequently added leflunomide to some of the other agents we’ve been using.”
Key Findings Over the Years in RA
Leflunomide showed efficacy similar to that of sulfasalazine in a randomized trial published in 1999 that used primary endpoints of tender/swollen joints and physician and patient global scores. Then, against methotrexate, it proved just as efficacious in achieving at least 20% improvement in American College of Rheumatology composite response criteria (ACR20) over 52 weeks, and in meeting endpoints similar to those of the sulfasalazine trial, in two trials, one published in 1999 and another in 2000.
“So here were two big trials [comparing it with methotrexate] that suggested the drug was just as good as what had become our standard of care by that point,” Dr. Ruderman said.
Each of these three trials used a loading dose of 100 mg leflunomide for 3 days, followed by 20 mg daily. Sulfasalazine was initiated at 2 g and escalated over 4 weeks. Methotrexate was initiated in one of the trials at a dose of 7.5 mg, then increased to 15 mg in almost two-thirds of patients; in the other methotrexate trial the initial dose was 15 mg escalated over 3 months.
Side effects of leflunomide — GI issues, rash, alopecia (reversible), and elevated liver function tests — were similar across the trials, and represented “about the same toxicities as methotrexate,” he said.
Researchers then tested leflunomide as an add-on to methotrexate in patients who had inadequate response, which “was a little bit daunting since we were still concerned about the toxicity of methotrexate at this point,” Dr. Ruderman said. “The idea that we’d take another drug with similar toxicities and add it on to the methotrexate was a little scary.”
But it worked. Patients on a mean background dose of 16.5 mg methotrexate were randomized to placebo or to a 2-day leflunomide loading dose followed by 10 mg/day that could be escalated at 8 weeks to 20 mg if needed. At 6 months, 19.5% and 46.2%, respectively, met ACR20 (P < .001), and “interestingly,” he said, “adverse events were pretty similar” between combination therapy and methotrexate monotherapy.
“This was very much like all the studies we’ve seen over the years with new biologics — they were all added to background methotrexate,” he said. “And the truth is, the [46%] response seen when adding leflunomide to background methotrexate wasn’t very different from the 50% [ACR20] response you tend to see when you add a biologic.”
However, despite the study’s conclusion that combination therapy provided significant benefit to patients with inadequate response to methotrexate alone, “the drug got lost, because everyone was prescribing the biologics,” Dr. Ruderman said.
He said he found only one study comparing leflunomide with a biologic. In a notably small but well-designed study from Sri Lanka published in 2017, 40 patients with an inadequate response to methotrexate were randomized to low-dose rituximab (500 mg x 2) or 20 mg/day leflunomide (no loading dose). At week 24, ACR20 was nearly identical (85% vs 84%), with a similar rate of adverse events.
The researchers pointed out “that there’s a potential cost benefit in developing countries where biologics aren’t as accessible,” he said, agreeing that “the big opportunity for a drug like leflunomide is outside the US, where you don’t have access to the drugs we take advantage of all the time.”
A meeting participant from Canada pointed out that rheumatologists there are “mandated to use it for PsA in combination with methotrexate before we can get a biologic, and for RA we can use it with Plaquenil [hydroxychloroquine] and methotrexate before we get a biologic, so we’re using it all the time.”
Asked about efficacy, the physician said the combination with methotrexate is “absolutely” efficacious. “It works really well” he said. “The problem is, you really have to watch the white cell count and liver function … and the half-life is long.”
Indeed, Dr. Ruderman said during his talk, the plasma half-life of teriflunomide, its active metabolite, is 15.5 days, which is challenging when adverse events occur. “And it’s a terrible drug in young women thinking about pregnancy because it’s teratogenic and stays around,” he said.
Leflunomide, which, notably, was “developed specifically for RA from the get-go” and not borrowed from another specialty, works by blocking de novo pyrimidine synthesis, Dr. Ruderman said. T-cell activation requires the upregulation of pyrimidine production (salvage pathways are insufficient); the “drug prevents that” by inhibiting an enzyme that catalyzes conversion of dihydroorotate to orotate, which, in turn, is converted to pyrimidine ribonucleotides, he explained.
Other potential mechanisms of action have been proposed — mainly, inhibition of tumor necrosis factor signaling and inhibition of kinase activity, including the JAK/STAT pathway — but “there’s not great data for any of them,” he said.
Loading vs Not Loading, and Its Role in PsA and Other Diseases
“We stopped loading years ago because at 100 mg for 3 days in a row, everyone has GI issues,” Dr. Ruderman said. “It may have made sense from a pharmacokinetic standpoint because [based on the long half-life] you could get to a higher drug level quicker, but not a practical standpoint, because patients would stop the drug — they couldn’t take it.” The first study to examine the necessity of loading leflunomide in a “prospective, careful way” was published in 2013. It randomized 120 patients to 100 mg or 20 mg for 3 days, followed by a 3-month open-label period of 20 mg, and found no clinical benefit with loading but more diarrhea and elevated liver enzymes.
“It tells us something about how we need to think about half-lives,” he said. “Maybe [loading is] not necessary because the biological effects are different than the drug levels.”
In the PsA space, in 2004, researchers reported a double-blind randomized trial in which 190 patients with active PsA and cutaneous psoriasis with at least 3% body surface area involvement were randomized to receive leflunomide (a loading dose followed by 20 mg/day) or placebo for 24 weeks. Almost 60% of leflunomide-treated patients, compared with 30% of placebo-treated patients, were classified as responders by the Psoriatic Arthritis Response criteria (P < .0001), “which is a soft endpoint” but was utilized at the time, Dr. Ruderman said. The researchers noted improvements in ACR20 and skin responses as well, and toxicity was similar to that reported in the RA studies.
However, approval was never sought, and the drug was infrequently prescribed, “because etanercept came out for this disease, and then adalimumab … and then the world changed,” he said.
More recently, a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA tested leflunomide plus methotrexate vs methotrexate monotherapy and was published in The Lancet Rheumatology. After 16 weeks, mean Psoriatic Arthritis Disease Activity Score (PASDAS) had improved for patients in the combination therapy group in comparison with the monotherapy group (3.1 [standard deviation (SD), 1.4] vs 3.7 [SD, 1.3]; treatment difference, -0.6; 90% CI, -1.0 to -0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than that of the monotherapy group (34%; P = .019). Three patients in the combination therapy group experienced serious adverse events, two of which were deemed unrelated to leflunomide. The most frequently occurring adverse events were nausea or vomiting, tiredness, and elevated alanine aminotransferase. Mild adverse events were more common in the methotrexate plus leflunomide group.
In an interview after the meeting, Dr. Ruderman explained that in his practice, about 15 years ago, leflunomide was sometimes prescribed as an alternative to a biologic change for patients whose skin disease improved significantly with ustekinumab (Stelara) but who “suddenly had more joint symptoms that they didn’t have before.”
And “we’ve found ourselves a bit recently with the same sort of story, where patients are prescribed IL-23 inhibitors like Skyrizi [risankizumab] and Tremfya [guselkumab] and their skin does really well but now they’re having more joint symptoms than previously,” he said. “Our choices are to switch to a whole different biologic, or to think about adding something as an adjunct — and maybe leflunomide is a reasonable option.”
In the last 5 years, Dr. Ruderman noted, randomized trial data has been published on leflunomide in lupus nephritis induction, and in lupus nephritis maintenance, as well as in IgG4-related disease.
Dr. Ruderman disclosed consulting and/or drug safety monitoring board work for AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Lilly, Merck, Novartis, NS Pharma, and UCB.
The Food and Drug Administration’s approval of leflunomide in September 1998 as a treatment for rheumatoid arthritis was sandwiched between the debuts of infliximab (Remicade and biosimilars) and etanercept (Enbrel) in August and November of that year, the latter of which was so exciting that “within 2 months you couldn’t get [it],” recalled Eric M. Ruderman, MD. And “like every middle child, [leflunomide] was underloved, underappreciated, and largely dismissed.”
Yet should it have been? Is it worth another look today?
At the 2024 Rheumatology Winter Clinical Symposium, Dr. Ruderman reflected on some of the clinical trial data published after leflunomide’s approval that “got lost in the shuffle” of the rightful embrace of biologics in United States practice, and urged reconsideration of the loading strategy still advised in the drug’s labeling.
“I’m not telling you that you should be using [leflunomide] in place of biologics, instead of biologics, or before biologics … but it should be in your toolkit,” said Dr. Ruderman, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago. The drug “still has a role in RA, including in combination with methotrexate, and a potential role in other rheumatic diseases.”
“In our PsA clinic,” he noted, “we’ve actually not infrequently added leflunomide to some of the other agents we’ve been using.”
Key Findings Over the Years in RA
Leflunomide showed efficacy similar to that of sulfasalazine in a randomized trial published in 1999 that used primary endpoints of tender/swollen joints and physician and patient global scores. Then, against methotrexate, it proved just as efficacious in achieving at least 20% improvement in American College of Rheumatology composite response criteria (ACR20) over 52 weeks, and in meeting endpoints similar to those of the sulfasalazine trial, in two trials, one published in 1999 and another in 2000.
“So here were two big trials [comparing it with methotrexate] that suggested the drug was just as good as what had become our standard of care by that point,” Dr. Ruderman said.
Each of these three trials used a loading dose of 100 mg leflunomide for 3 days, followed by 20 mg daily. Sulfasalazine was initiated at 2 g and escalated over 4 weeks. Methotrexate was initiated in one of the trials at a dose of 7.5 mg, then increased to 15 mg in almost two-thirds of patients; in the other methotrexate trial the initial dose was 15 mg escalated over 3 months.
Side effects of leflunomide — GI issues, rash, alopecia (reversible), and elevated liver function tests — were similar across the trials, and represented “about the same toxicities as methotrexate,” he said.
Researchers then tested leflunomide as an add-on to methotrexate in patients who had inadequate response, which “was a little bit daunting since we were still concerned about the toxicity of methotrexate at this point,” Dr. Ruderman said. “The idea that we’d take another drug with similar toxicities and add it on to the methotrexate was a little scary.”
But it worked. Patients on a mean background dose of 16.5 mg methotrexate were randomized to placebo or to a 2-day leflunomide loading dose followed by 10 mg/day that could be escalated at 8 weeks to 20 mg if needed. At 6 months, 19.5% and 46.2%, respectively, met ACR20 (P < .001), and “interestingly,” he said, “adverse events were pretty similar” between combination therapy and methotrexate monotherapy.
“This was very much like all the studies we’ve seen over the years with new biologics — they were all added to background methotrexate,” he said. “And the truth is, the [46%] response seen when adding leflunomide to background methotrexate wasn’t very different from the 50% [ACR20] response you tend to see when you add a biologic.”
However, despite the study’s conclusion that combination therapy provided significant benefit to patients with inadequate response to methotrexate alone, “the drug got lost, because everyone was prescribing the biologics,” Dr. Ruderman said.
He said he found only one study comparing leflunomide with a biologic. In a notably small but well-designed study from Sri Lanka published in 2017, 40 patients with an inadequate response to methotrexate were randomized to low-dose rituximab (500 mg x 2) or 20 mg/day leflunomide (no loading dose). At week 24, ACR20 was nearly identical (85% vs 84%), with a similar rate of adverse events.
The researchers pointed out “that there’s a potential cost benefit in developing countries where biologics aren’t as accessible,” he said, agreeing that “the big opportunity for a drug like leflunomide is outside the US, where you don’t have access to the drugs we take advantage of all the time.”
A meeting participant from Canada pointed out that rheumatologists there are “mandated to use it for PsA in combination with methotrexate before we can get a biologic, and for RA we can use it with Plaquenil [hydroxychloroquine] and methotrexate before we get a biologic, so we’re using it all the time.”
Asked about efficacy, the physician said the combination with methotrexate is “absolutely” efficacious. “It works really well” he said. “The problem is, you really have to watch the white cell count and liver function … and the half-life is long.”
Indeed, Dr. Ruderman said during his talk, the plasma half-life of teriflunomide, its active metabolite, is 15.5 days, which is challenging when adverse events occur. “And it’s a terrible drug in young women thinking about pregnancy because it’s teratogenic and stays around,” he said.
Leflunomide, which, notably, was “developed specifically for RA from the get-go” and not borrowed from another specialty, works by blocking de novo pyrimidine synthesis, Dr. Ruderman said. T-cell activation requires the upregulation of pyrimidine production (salvage pathways are insufficient); the “drug prevents that” by inhibiting an enzyme that catalyzes conversion of dihydroorotate to orotate, which, in turn, is converted to pyrimidine ribonucleotides, he explained.
Other potential mechanisms of action have been proposed — mainly, inhibition of tumor necrosis factor signaling and inhibition of kinase activity, including the JAK/STAT pathway — but “there’s not great data for any of them,” he said.
Loading vs Not Loading, and Its Role in PsA and Other Diseases
“We stopped loading years ago because at 100 mg for 3 days in a row, everyone has GI issues,” Dr. Ruderman said. “It may have made sense from a pharmacokinetic standpoint because [based on the long half-life] you could get to a higher drug level quicker, but not a practical standpoint, because patients would stop the drug — they couldn’t take it.” The first study to examine the necessity of loading leflunomide in a “prospective, careful way” was published in 2013. It randomized 120 patients to 100 mg or 20 mg for 3 days, followed by a 3-month open-label period of 20 mg, and found no clinical benefit with loading but more diarrhea and elevated liver enzymes.
“It tells us something about how we need to think about half-lives,” he said. “Maybe [loading is] not necessary because the biological effects are different than the drug levels.”
In the PsA space, in 2004, researchers reported a double-blind randomized trial in which 190 patients with active PsA and cutaneous psoriasis with at least 3% body surface area involvement were randomized to receive leflunomide (a loading dose followed by 20 mg/day) or placebo for 24 weeks. Almost 60% of leflunomide-treated patients, compared with 30% of placebo-treated patients, were classified as responders by the Psoriatic Arthritis Response criteria (P < .0001), “which is a soft endpoint” but was utilized at the time, Dr. Ruderman said. The researchers noted improvements in ACR20 and skin responses as well, and toxicity was similar to that reported in the RA studies.
However, approval was never sought, and the drug was infrequently prescribed, “because etanercept came out for this disease, and then adalimumab … and then the world changed,” he said.
More recently, a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA tested leflunomide plus methotrexate vs methotrexate monotherapy and was published in The Lancet Rheumatology. After 16 weeks, mean Psoriatic Arthritis Disease Activity Score (PASDAS) had improved for patients in the combination therapy group in comparison with the monotherapy group (3.1 [standard deviation (SD), 1.4] vs 3.7 [SD, 1.3]; treatment difference, -0.6; 90% CI, -1.0 to -0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than that of the monotherapy group (34%; P = .019). Three patients in the combination therapy group experienced serious adverse events, two of which were deemed unrelated to leflunomide. The most frequently occurring adverse events were nausea or vomiting, tiredness, and elevated alanine aminotransferase. Mild adverse events were more common in the methotrexate plus leflunomide group.
In an interview after the meeting, Dr. Ruderman explained that in his practice, about 15 years ago, leflunomide was sometimes prescribed as an alternative to a biologic change for patients whose skin disease improved significantly with ustekinumab (Stelara) but who “suddenly had more joint symptoms that they didn’t have before.”
And “we’ve found ourselves a bit recently with the same sort of story, where patients are prescribed IL-23 inhibitors like Skyrizi [risankizumab] and Tremfya [guselkumab] and their skin does really well but now they’re having more joint symptoms than previously,” he said. “Our choices are to switch to a whole different biologic, or to think about adding something as an adjunct — and maybe leflunomide is a reasonable option.”
In the last 5 years, Dr. Ruderman noted, randomized trial data has been published on leflunomide in lupus nephritis induction, and in lupus nephritis maintenance, as well as in IgG4-related disease.
Dr. Ruderman disclosed consulting and/or drug safety monitoring board work for AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Lilly, Merck, Novartis, NS Pharma, and UCB.
The Food and Drug Administration’s approval of leflunomide in September 1998 as a treatment for rheumatoid arthritis was sandwiched between the debuts of infliximab (Remicade and biosimilars) and etanercept (Enbrel) in August and November of that year, the latter of which was so exciting that “within 2 months you couldn’t get [it],” recalled Eric M. Ruderman, MD. And “like every middle child, [leflunomide] was underloved, underappreciated, and largely dismissed.”
Yet should it have been? Is it worth another look today?
At the 2024 Rheumatology Winter Clinical Symposium, Dr. Ruderman reflected on some of the clinical trial data published after leflunomide’s approval that “got lost in the shuffle” of the rightful embrace of biologics in United States practice, and urged reconsideration of the loading strategy still advised in the drug’s labeling.
“I’m not telling you that you should be using [leflunomide] in place of biologics, instead of biologics, or before biologics … but it should be in your toolkit,” said Dr. Ruderman, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago. The drug “still has a role in RA, including in combination with methotrexate, and a potential role in other rheumatic diseases.”
“In our PsA clinic,” he noted, “we’ve actually not infrequently added leflunomide to some of the other agents we’ve been using.”
Key Findings Over the Years in RA
Leflunomide showed efficacy similar to that of sulfasalazine in a randomized trial published in 1999 that used primary endpoints of tender/swollen joints and physician and patient global scores. Then, against methotrexate, it proved just as efficacious in achieving at least 20% improvement in American College of Rheumatology composite response criteria (ACR20) over 52 weeks, and in meeting endpoints similar to those of the sulfasalazine trial, in two trials, one published in 1999 and another in 2000.
“So here were two big trials [comparing it with methotrexate] that suggested the drug was just as good as what had become our standard of care by that point,” Dr. Ruderman said.
Each of these three trials used a loading dose of 100 mg leflunomide for 3 days, followed by 20 mg daily. Sulfasalazine was initiated at 2 g and escalated over 4 weeks. Methotrexate was initiated in one of the trials at a dose of 7.5 mg, then increased to 15 mg in almost two-thirds of patients; in the other methotrexate trial the initial dose was 15 mg escalated over 3 months.
Side effects of leflunomide — GI issues, rash, alopecia (reversible), and elevated liver function tests — were similar across the trials, and represented “about the same toxicities as methotrexate,” he said.
Researchers then tested leflunomide as an add-on to methotrexate in patients who had inadequate response, which “was a little bit daunting since we were still concerned about the toxicity of methotrexate at this point,” Dr. Ruderman said. “The idea that we’d take another drug with similar toxicities and add it on to the methotrexate was a little scary.”
But it worked. Patients on a mean background dose of 16.5 mg methotrexate were randomized to placebo or to a 2-day leflunomide loading dose followed by 10 mg/day that could be escalated at 8 weeks to 20 mg if needed. At 6 months, 19.5% and 46.2%, respectively, met ACR20 (P < .001), and “interestingly,” he said, “adverse events were pretty similar” between combination therapy and methotrexate monotherapy.
“This was very much like all the studies we’ve seen over the years with new biologics — they were all added to background methotrexate,” he said. “And the truth is, the [46%] response seen when adding leflunomide to background methotrexate wasn’t very different from the 50% [ACR20] response you tend to see when you add a biologic.”
However, despite the study’s conclusion that combination therapy provided significant benefit to patients with inadequate response to methotrexate alone, “the drug got lost, because everyone was prescribing the biologics,” Dr. Ruderman said.
He said he found only one study comparing leflunomide with a biologic. In a notably small but well-designed study from Sri Lanka published in 2017, 40 patients with an inadequate response to methotrexate were randomized to low-dose rituximab (500 mg x 2) or 20 mg/day leflunomide (no loading dose). At week 24, ACR20 was nearly identical (85% vs 84%), with a similar rate of adverse events.
The researchers pointed out “that there’s a potential cost benefit in developing countries where biologics aren’t as accessible,” he said, agreeing that “the big opportunity for a drug like leflunomide is outside the US, where you don’t have access to the drugs we take advantage of all the time.”
A meeting participant from Canada pointed out that rheumatologists there are “mandated to use it for PsA in combination with methotrexate before we can get a biologic, and for RA we can use it with Plaquenil [hydroxychloroquine] and methotrexate before we get a biologic, so we’re using it all the time.”
Asked about efficacy, the physician said the combination with methotrexate is “absolutely” efficacious. “It works really well” he said. “The problem is, you really have to watch the white cell count and liver function … and the half-life is long.”
Indeed, Dr. Ruderman said during his talk, the plasma half-life of teriflunomide, its active metabolite, is 15.5 days, which is challenging when adverse events occur. “And it’s a terrible drug in young women thinking about pregnancy because it’s teratogenic and stays around,” he said.
Leflunomide, which, notably, was “developed specifically for RA from the get-go” and not borrowed from another specialty, works by blocking de novo pyrimidine synthesis, Dr. Ruderman said. T-cell activation requires the upregulation of pyrimidine production (salvage pathways are insufficient); the “drug prevents that” by inhibiting an enzyme that catalyzes conversion of dihydroorotate to orotate, which, in turn, is converted to pyrimidine ribonucleotides, he explained.
Other potential mechanisms of action have been proposed — mainly, inhibition of tumor necrosis factor signaling and inhibition of kinase activity, including the JAK/STAT pathway — but “there’s not great data for any of them,” he said.
Loading vs Not Loading, and Its Role in PsA and Other Diseases
“We stopped loading years ago because at 100 mg for 3 days in a row, everyone has GI issues,” Dr. Ruderman said. “It may have made sense from a pharmacokinetic standpoint because [based on the long half-life] you could get to a higher drug level quicker, but not a practical standpoint, because patients would stop the drug — they couldn’t take it.” The first study to examine the necessity of loading leflunomide in a “prospective, careful way” was published in 2013. It randomized 120 patients to 100 mg or 20 mg for 3 days, followed by a 3-month open-label period of 20 mg, and found no clinical benefit with loading but more diarrhea and elevated liver enzymes.
“It tells us something about how we need to think about half-lives,” he said. “Maybe [loading is] not necessary because the biological effects are different than the drug levels.”
In the PsA space, in 2004, researchers reported a double-blind randomized trial in which 190 patients with active PsA and cutaneous psoriasis with at least 3% body surface area involvement were randomized to receive leflunomide (a loading dose followed by 20 mg/day) or placebo for 24 weeks. Almost 60% of leflunomide-treated patients, compared with 30% of placebo-treated patients, were classified as responders by the Psoriatic Arthritis Response criteria (P < .0001), “which is a soft endpoint” but was utilized at the time, Dr. Ruderman said. The researchers noted improvements in ACR20 and skin responses as well, and toxicity was similar to that reported in the RA studies.
However, approval was never sought, and the drug was infrequently prescribed, “because etanercept came out for this disease, and then adalimumab … and then the world changed,” he said.
More recently, a single-center, double-blind, randomized trial that included 78 Dutch patients with PsA tested leflunomide plus methotrexate vs methotrexate monotherapy and was published in The Lancet Rheumatology. After 16 weeks, mean Psoriatic Arthritis Disease Activity Score (PASDAS) had improved for patients in the combination therapy group in comparison with the monotherapy group (3.1 [standard deviation (SD), 1.4] vs 3.7 [SD, 1.3]; treatment difference, -0.6; 90% CI, -1.0 to -0.1; P = .025). The combination therapy group also achieved PASDAS low disease activity at a higher rate (59%) than that of the monotherapy group (34%; P = .019). Three patients in the combination therapy group experienced serious adverse events, two of which were deemed unrelated to leflunomide. The most frequently occurring adverse events were nausea or vomiting, tiredness, and elevated alanine aminotransferase. Mild adverse events were more common in the methotrexate plus leflunomide group.
In an interview after the meeting, Dr. Ruderman explained that in his practice, about 15 years ago, leflunomide was sometimes prescribed as an alternative to a biologic change for patients whose skin disease improved significantly with ustekinumab (Stelara) but who “suddenly had more joint symptoms that they didn’t have before.”
And “we’ve found ourselves a bit recently with the same sort of story, where patients are prescribed IL-23 inhibitors like Skyrizi [risankizumab] and Tremfya [guselkumab] and their skin does really well but now they’re having more joint symptoms than previously,” he said. “Our choices are to switch to a whole different biologic, or to think about adding something as an adjunct — and maybe leflunomide is a reasonable option.”
In the last 5 years, Dr. Ruderman noted, randomized trial data has been published on leflunomide in lupus nephritis induction, and in lupus nephritis maintenance, as well as in IgG4-related disease.
Dr. Ruderman disclosed consulting and/or drug safety monitoring board work for AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Lilly, Merck, Novartis, NS Pharma, and UCB.
FROM RWCS 2024
TIL for Melanoma: What Are the Costs and Other Challenges to Getting It to Patients?
The US Food and Drug Administration (FDA) recently approved the tumor-infiltrating lymphocyte cell therapy (TIL) for use in certain adults with unresectable or metastatic melanoma. This marks the first time the FDA has allowed a cellular therapy to be marketed for a solid tumor cancer.
Lifileucel is made from a patient’s surgically removed tumor. Tissue from that tumor is then sent to a manufacturing center. Turnaround time to when the drug is ready to be sent back to the cancer center for use is approximately 34 days, according to the drug’s manufacturer, Iovance.
Insurance Adjustments
The cost of the one-time lifileucel treatment is $515,000, according to the manufacturer.
Two investigators in the clinical trials of lifileucel, Allison Betof Warner, MD, of Stanford University, Stanford, California, and Igor Puzanov, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, shared their expectations regarding factors that would contribute to how much a patient paid for the drug.
Given the drug’s recent approval, the logistical details are still being worked out between cancer centers and insurers regarding how much patients will pay out of pocket for lifileucel, said Dr. Betof Warner, who is assistant professor in the Department of Medicine, Division of Medical Oncology at Stanford University.
The associated costs, including the surgery that is needed to procure the TIL cells for expansion into the final drug product, will be different for each patient, she told this publication.
Patients’ costs for lifileucel will vary based on their insurance, explained Dr. Puzanov, chief of melanoma and professor of oncology at Roswell Park Comprehensive Cancer Center.
At Roswell Park, “we will work with our regionally-based payers on a case-by-case basis to seek approval for those patients we believe can most benefit from lifileucel,” he said in an interview. Preauthorization will be required, as is standard for many cancer treatments, he added.
Once payer approval is in place, Dr. Puzanov said, he did not anticipate significant delays in access for patients.
Certified centers such as the multidisciplinary team at Roswell Park are ready to treat patients now. Other centers are similarly prepared, especially those involved in the clinical trials of lifileucel, he said.
Logistics and Infrastructure
A position article and guidelines on the management of and best practices for TIL was published in the Journal for ImmunoTherapy of Cancer on February 29. The paper, of which both Dr. Betof Warner and Dr. Puzanov served as authors, noted that one of the barriers to the use of TIL cell therapy in clinical practice is the need for state-of-the art infrastructure at centers that want to offer the treatment. Scheduling, patient referrals, and surgery, as well as the production and infusion of TIL, must be organized and streamlined for successful treatment, the authors wrote.
The two supply chains involved in TIL — the transportation of the tumor tissue from the treatment center to the manufacturer and transport of the TIL infusion product back to the treatment center — must be timely and precise, they emphasized.
Docs Hope TIL Improves in Several Ways
Although the TIL technology is a breakthrough, “we hope to see even better efficacy and lower toxicity as further research looks at ways to improve on the current TIL standard,” Dr. Puzanov said.
More research and dose adjustments may impact patient costs and side effects, he noted. “I am looking to see TILs used in the front line, with or without checkpoint inhibitors.”
Research is needed to explore how to lower the chemotherapy doses and possibly the associated toxicity, he added. Finally, researchers must consider whether high-dose IL-2 therapy — given as part of the TIL cell therapy — could be replaced with other cytokines, or whether the number of doses could be lowered. Another avenue of exploration is engineering genes for cytokines into TILs, he said.
“The key is to think about TIL therapy before you need it — ideally, when the patient is still doing well on their frontline checkpoint inhibition immunotherapy,” Dr. Puzanov said in an interview. That is the time for evaluation, and specialty centers can provide an expert assessment, he said.
“We are constantly working to improve TIL therapy,” Dr. Betof Warner told this publication. More research is needed optimize the regimen to reduce side effects, which would not only make treatment easier for currently eligible patients, but might allow treatment for patients not currently eligible.
“For example, we are looking for ways to reduce the dose of preparative chemotherapy, which prepares the body for the cells to maximize their longevity and efficacy, and to reduce or eliminate the need to give IL-2 after the cell administration,” continued Dr. Betof Warner, who is also Director of Melanoma Medical Oncology, Director of Solid Tumor Cellular Therapy, and Codirector of the Pigmented Lesion and Melanoma Program at Stanford University. “We are also actively studying next-generation TIL therapies to try to increase the efficacy.”
“Lifileucel has about a 30% success rate for melanoma that has progressed after standard therapy; we are working hard to do better than that,” she noted.
In a press release, Iovance summarized the results of the trial that supported the FDA’s accelerated approval of lifileucel. In an open-label single-arm study, including multiple sites worldwide, 73 adults with unresectable or metastatic melanoma who had received at least one previous systemic therapy underwent a lymphodepleting regimen followed by treatments with fludarabine and aldesleukin. Patients then received lifileucel at a median dose of 21.1 x 109 viable cells; the recommended dose ranges from 7.5 x 109 to 72 x 109 cells.
The primary efficacy outcome was objective response rate (ORR). The ORR in the study was 31.5%, and the median time to initial lifileucel response was 1.5 months.
The clinical trials of lifileucel for which Dr. Betof Warner and Dr. Puzanov served as investigators were sponsored by Iovance.
The US Food and Drug Administration (FDA) recently approved the tumor-infiltrating lymphocyte cell therapy (TIL) for use in certain adults with unresectable or metastatic melanoma. This marks the first time the FDA has allowed a cellular therapy to be marketed for a solid tumor cancer.
Lifileucel is made from a patient’s surgically removed tumor. Tissue from that tumor is then sent to a manufacturing center. Turnaround time to when the drug is ready to be sent back to the cancer center for use is approximately 34 days, according to the drug’s manufacturer, Iovance.
Insurance Adjustments
The cost of the one-time lifileucel treatment is $515,000, according to the manufacturer.
Two investigators in the clinical trials of lifileucel, Allison Betof Warner, MD, of Stanford University, Stanford, California, and Igor Puzanov, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, shared their expectations regarding factors that would contribute to how much a patient paid for the drug.
Given the drug’s recent approval, the logistical details are still being worked out between cancer centers and insurers regarding how much patients will pay out of pocket for lifileucel, said Dr. Betof Warner, who is assistant professor in the Department of Medicine, Division of Medical Oncology at Stanford University.
The associated costs, including the surgery that is needed to procure the TIL cells for expansion into the final drug product, will be different for each patient, she told this publication.
Patients’ costs for lifileucel will vary based on their insurance, explained Dr. Puzanov, chief of melanoma and professor of oncology at Roswell Park Comprehensive Cancer Center.
At Roswell Park, “we will work with our regionally-based payers on a case-by-case basis to seek approval for those patients we believe can most benefit from lifileucel,” he said in an interview. Preauthorization will be required, as is standard for many cancer treatments, he added.
Once payer approval is in place, Dr. Puzanov said, he did not anticipate significant delays in access for patients.
Certified centers such as the multidisciplinary team at Roswell Park are ready to treat patients now. Other centers are similarly prepared, especially those involved in the clinical trials of lifileucel, he said.
Logistics and Infrastructure
A position article and guidelines on the management of and best practices for TIL was published in the Journal for ImmunoTherapy of Cancer on February 29. The paper, of which both Dr. Betof Warner and Dr. Puzanov served as authors, noted that one of the barriers to the use of TIL cell therapy in clinical practice is the need for state-of-the art infrastructure at centers that want to offer the treatment. Scheduling, patient referrals, and surgery, as well as the production and infusion of TIL, must be organized and streamlined for successful treatment, the authors wrote.
The two supply chains involved in TIL — the transportation of the tumor tissue from the treatment center to the manufacturer and transport of the TIL infusion product back to the treatment center — must be timely and precise, they emphasized.
Docs Hope TIL Improves in Several Ways
Although the TIL technology is a breakthrough, “we hope to see even better efficacy and lower toxicity as further research looks at ways to improve on the current TIL standard,” Dr. Puzanov said.
More research and dose adjustments may impact patient costs and side effects, he noted. “I am looking to see TILs used in the front line, with or without checkpoint inhibitors.”
Research is needed to explore how to lower the chemotherapy doses and possibly the associated toxicity, he added. Finally, researchers must consider whether high-dose IL-2 therapy — given as part of the TIL cell therapy — could be replaced with other cytokines, or whether the number of doses could be lowered. Another avenue of exploration is engineering genes for cytokines into TILs, he said.
“The key is to think about TIL therapy before you need it — ideally, when the patient is still doing well on their frontline checkpoint inhibition immunotherapy,” Dr. Puzanov said in an interview. That is the time for evaluation, and specialty centers can provide an expert assessment, he said.
“We are constantly working to improve TIL therapy,” Dr. Betof Warner told this publication. More research is needed optimize the regimen to reduce side effects, which would not only make treatment easier for currently eligible patients, but might allow treatment for patients not currently eligible.
“For example, we are looking for ways to reduce the dose of preparative chemotherapy, which prepares the body for the cells to maximize their longevity and efficacy, and to reduce or eliminate the need to give IL-2 after the cell administration,” continued Dr. Betof Warner, who is also Director of Melanoma Medical Oncology, Director of Solid Tumor Cellular Therapy, and Codirector of the Pigmented Lesion and Melanoma Program at Stanford University. “We are also actively studying next-generation TIL therapies to try to increase the efficacy.”
“Lifileucel has about a 30% success rate for melanoma that has progressed after standard therapy; we are working hard to do better than that,” she noted.
In a press release, Iovance summarized the results of the trial that supported the FDA’s accelerated approval of lifileucel. In an open-label single-arm study, including multiple sites worldwide, 73 adults with unresectable or metastatic melanoma who had received at least one previous systemic therapy underwent a lymphodepleting regimen followed by treatments with fludarabine and aldesleukin. Patients then received lifileucel at a median dose of 21.1 x 109 viable cells; the recommended dose ranges from 7.5 x 109 to 72 x 109 cells.
The primary efficacy outcome was objective response rate (ORR). The ORR in the study was 31.5%, and the median time to initial lifileucel response was 1.5 months.
The clinical trials of lifileucel for which Dr. Betof Warner and Dr. Puzanov served as investigators were sponsored by Iovance.
The US Food and Drug Administration (FDA) recently approved the tumor-infiltrating lymphocyte cell therapy (TIL) for use in certain adults with unresectable or metastatic melanoma. This marks the first time the FDA has allowed a cellular therapy to be marketed for a solid tumor cancer.
Lifileucel is made from a patient’s surgically removed tumor. Tissue from that tumor is then sent to a manufacturing center. Turnaround time to when the drug is ready to be sent back to the cancer center for use is approximately 34 days, according to the drug’s manufacturer, Iovance.
Insurance Adjustments
The cost of the one-time lifileucel treatment is $515,000, according to the manufacturer.
Two investigators in the clinical trials of lifileucel, Allison Betof Warner, MD, of Stanford University, Stanford, California, and Igor Puzanov, MD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, shared their expectations regarding factors that would contribute to how much a patient paid for the drug.
Given the drug’s recent approval, the logistical details are still being worked out between cancer centers and insurers regarding how much patients will pay out of pocket for lifileucel, said Dr. Betof Warner, who is assistant professor in the Department of Medicine, Division of Medical Oncology at Stanford University.
The associated costs, including the surgery that is needed to procure the TIL cells for expansion into the final drug product, will be different for each patient, she told this publication.
Patients’ costs for lifileucel will vary based on their insurance, explained Dr. Puzanov, chief of melanoma and professor of oncology at Roswell Park Comprehensive Cancer Center.
At Roswell Park, “we will work with our regionally-based payers on a case-by-case basis to seek approval for those patients we believe can most benefit from lifileucel,” he said in an interview. Preauthorization will be required, as is standard for many cancer treatments, he added.
Once payer approval is in place, Dr. Puzanov said, he did not anticipate significant delays in access for patients.
Certified centers such as the multidisciplinary team at Roswell Park are ready to treat patients now. Other centers are similarly prepared, especially those involved in the clinical trials of lifileucel, he said.
Logistics and Infrastructure
A position article and guidelines on the management of and best practices for TIL was published in the Journal for ImmunoTherapy of Cancer on February 29. The paper, of which both Dr. Betof Warner and Dr. Puzanov served as authors, noted that one of the barriers to the use of TIL cell therapy in clinical practice is the need for state-of-the art infrastructure at centers that want to offer the treatment. Scheduling, patient referrals, and surgery, as well as the production and infusion of TIL, must be organized and streamlined for successful treatment, the authors wrote.
The two supply chains involved in TIL — the transportation of the tumor tissue from the treatment center to the manufacturer and transport of the TIL infusion product back to the treatment center — must be timely and precise, they emphasized.
Docs Hope TIL Improves in Several Ways
Although the TIL technology is a breakthrough, “we hope to see even better efficacy and lower toxicity as further research looks at ways to improve on the current TIL standard,” Dr. Puzanov said.
More research and dose adjustments may impact patient costs and side effects, he noted. “I am looking to see TILs used in the front line, with or without checkpoint inhibitors.”
Research is needed to explore how to lower the chemotherapy doses and possibly the associated toxicity, he added. Finally, researchers must consider whether high-dose IL-2 therapy — given as part of the TIL cell therapy — could be replaced with other cytokines, or whether the number of doses could be lowered. Another avenue of exploration is engineering genes for cytokines into TILs, he said.
“The key is to think about TIL therapy before you need it — ideally, when the patient is still doing well on their frontline checkpoint inhibition immunotherapy,” Dr. Puzanov said in an interview. That is the time for evaluation, and specialty centers can provide an expert assessment, he said.
“We are constantly working to improve TIL therapy,” Dr. Betof Warner told this publication. More research is needed optimize the regimen to reduce side effects, which would not only make treatment easier for currently eligible patients, but might allow treatment for patients not currently eligible.
“For example, we are looking for ways to reduce the dose of preparative chemotherapy, which prepares the body for the cells to maximize their longevity and efficacy, and to reduce or eliminate the need to give IL-2 after the cell administration,” continued Dr. Betof Warner, who is also Director of Melanoma Medical Oncology, Director of Solid Tumor Cellular Therapy, and Codirector of the Pigmented Lesion and Melanoma Program at Stanford University. “We are also actively studying next-generation TIL therapies to try to increase the efficacy.”
“Lifileucel has about a 30% success rate for melanoma that has progressed after standard therapy; we are working hard to do better than that,” she noted.
In a press release, Iovance summarized the results of the trial that supported the FDA’s accelerated approval of lifileucel. In an open-label single-arm study, including multiple sites worldwide, 73 adults with unresectable or metastatic melanoma who had received at least one previous systemic therapy underwent a lymphodepleting regimen followed by treatments with fludarabine and aldesleukin. Patients then received lifileucel at a median dose of 21.1 x 109 viable cells; the recommended dose ranges from 7.5 x 109 to 72 x 109 cells.
The primary efficacy outcome was objective response rate (ORR). The ORR in the study was 31.5%, and the median time to initial lifileucel response was 1.5 months.
The clinical trials of lifileucel for which Dr. Betof Warner and Dr. Puzanov served as investigators were sponsored by Iovance.
Air Pollution Tied to Greater Amyloid Burden in the Brain
TOPLINE:
, a new postmortem study showed.
METHODOLOGY:
- Investigators examined the brain tissue of 224 people living in the Atlanta area who agreed to donate their brains after death (average age of death, 76 years) for the presence of amyloid plaques and tau tangles.
- They also studied the amount of fine particulate matter < 2.5 microns (PM2.5) from traffic-related air pollution at participants’ home addresses at 1, 3, and 5 years before death.
- The presence of the APOE e4 gene was examined for evidence of any effect on the relationship between air pollution and evidence of Alzheimer’s disease (AD).
TAKEAWAY:
The average level of exposure in the year before death was 1.32 µg/m3 and 1.35 µg/m3 in the 3 years before death.
People with 1 µg/m3 higher PM2.5 exposure in the year before death were nearly twice as likely to have higher levels of plaques (odds ratio [OR], 1.92; 95% CI, 1.12-3.30), while those with higher exposure in the 3 years before death were 87% more likely to have higher levels of plaques (OR, 1.87; 95% CI, 1.01-3.17).
A little more than half (56%) of the sample were positive for the APOE e4 genotype, but the strongest association between pollution and neuropathology markers was for noncarriers of the genotype, although this relationship did not reach statistical significance.
IN PRACTICE:
“More research is needed to establish causality for the association between PM2.5 and AD, including epidemiologic and mechanistic studies. Future studies should also investigate the association between PM2.5 and other dementia-related pathologies, including cerebrovascular pathology,” the study authors wrote.
SOURCE:
Anke Hüls, PhD, of Emory University in Atlanta, led the study, which was published online on February 21, 2024, in Neurology.
LIMITATIONS:
The sample was not population-based but a convenience sample composed mostly of highly educated White participants.
DISCLOSURES:
The study was funded by the National Institute of Environmental Health Sciences, the Goizueta Alzheimer’s Disease Research Center, the National Institute on Aging, and the National Institutes of Health. There were no relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
, a new postmortem study showed.
METHODOLOGY:
- Investigators examined the brain tissue of 224 people living in the Atlanta area who agreed to donate their brains after death (average age of death, 76 years) for the presence of amyloid plaques and tau tangles.
- They also studied the amount of fine particulate matter < 2.5 microns (PM2.5) from traffic-related air pollution at participants’ home addresses at 1, 3, and 5 years before death.
- The presence of the APOE e4 gene was examined for evidence of any effect on the relationship between air pollution and evidence of Alzheimer’s disease (AD).
TAKEAWAY:
The average level of exposure in the year before death was 1.32 µg/m3 and 1.35 µg/m3 in the 3 years before death.
People with 1 µg/m3 higher PM2.5 exposure in the year before death were nearly twice as likely to have higher levels of plaques (odds ratio [OR], 1.92; 95% CI, 1.12-3.30), while those with higher exposure in the 3 years before death were 87% more likely to have higher levels of plaques (OR, 1.87; 95% CI, 1.01-3.17).
A little more than half (56%) of the sample were positive for the APOE e4 genotype, but the strongest association between pollution and neuropathology markers was for noncarriers of the genotype, although this relationship did not reach statistical significance.
IN PRACTICE:
“More research is needed to establish causality for the association between PM2.5 and AD, including epidemiologic and mechanistic studies. Future studies should also investigate the association between PM2.5 and other dementia-related pathologies, including cerebrovascular pathology,” the study authors wrote.
SOURCE:
Anke Hüls, PhD, of Emory University in Atlanta, led the study, which was published online on February 21, 2024, in Neurology.
LIMITATIONS:
The sample was not population-based but a convenience sample composed mostly of highly educated White participants.
DISCLOSURES:
The study was funded by the National Institute of Environmental Health Sciences, the Goizueta Alzheimer’s Disease Research Center, the National Institute on Aging, and the National Institutes of Health. There were no relevant disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
, a new postmortem study showed.
METHODOLOGY:
- Investigators examined the brain tissue of 224 people living in the Atlanta area who agreed to donate their brains after death (average age of death, 76 years) for the presence of amyloid plaques and tau tangles.
- They also studied the amount of fine particulate matter < 2.5 microns (PM2.5) from traffic-related air pollution at participants’ home addresses at 1, 3, and 5 years before death.
- The presence of the APOE e4 gene was examined for evidence of any effect on the relationship between air pollution and evidence of Alzheimer’s disease (AD).
TAKEAWAY:
The average level of exposure in the year before death was 1.32 µg/m3 and 1.35 µg/m3 in the 3 years before death.
People with 1 µg/m3 higher PM2.5 exposure in the year before death were nearly twice as likely to have higher levels of plaques (odds ratio [OR], 1.92; 95% CI, 1.12-3.30), while those with higher exposure in the 3 years before death were 87% more likely to have higher levels of plaques (OR, 1.87; 95% CI, 1.01-3.17).
A little more than half (56%) of the sample were positive for the APOE e4 genotype, but the strongest association between pollution and neuropathology markers was for noncarriers of the genotype, although this relationship did not reach statistical significance.
IN PRACTICE:
“More research is needed to establish causality for the association between PM2.5 and AD, including epidemiologic and mechanistic studies. Future studies should also investigate the association between PM2.5 and other dementia-related pathologies, including cerebrovascular pathology,” the study authors wrote.
SOURCE:
Anke Hüls, PhD, of Emory University in Atlanta, led the study, which was published online on February 21, 2024, in Neurology.
LIMITATIONS:
The sample was not population-based but a convenience sample composed mostly of highly educated White participants.
DISCLOSURES:
The study was funded by the National Institute of Environmental Health Sciences, the Goizueta Alzheimer’s Disease Research Center, the National Institute on Aging, and the National Institutes of Health. There were no relevant disclosures.
A version of this article appeared on Medscape.com.
AGA Guides Usage of GLP-1 Receptor Agonists Before Endoscopy
The American Gastroenterological Association (AGA) has issued a rapid clinical practice update on the use of glucagon-like peptide 1 (GLP-1) receptor agonists prior to endoscopy.
The update was partly prompted by consensus-based perioperative guidance issued by the American Society of Anesthesiologists in June 2023, which advises withholding GLP-1 receptor agonists before endoscopy. This recommendation has caused some anesthesia providers to cancel or postpone endoscopic procedures, or even elect general endotracheal intubation over standard sedation.
“Many facilities and medical centers are now struggling to revise preprocedural protocols for patients taking this class of medications despite the lack of high-level evidence regarding how to proceed,” the panelists wrote in Clinical Gastroenterology and Hepatology. “Important questions include whether these preprocedural changes are necessary, if they truly mitigate periprocedural aspiration, or if the delays instituted by following this guidance might further compound the major problem currently faced nationwide: that of large numbers of patients awaiting endoscopic procedures because of delays from the COVID-19 pandemic, reduction in the recommended age threshold to start colorectal cancer screening in 2018, and workforce challenges.”
The rapid clinical practice update, commissioned and approved by the AGA, includes background on the relationship between GLP-1 receptor agonists and endoscopic procedures, followed by clinical strategies for patients taking these medications.
Lead panelist Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues began by noting that GLP-1 receptor agonists have been associated with increased gastric residue in patients with diabetes, and among nondiabetic patients, increased gastric retention of solids but not liquids. Delayed gastric emptying and increased residual gastric contents may be more common among patients on GLP-1 agonists who have vomiting, nausea, dyspepsia, or abdominal bloating, they added.
The above findings “imply an increased risk of aspiration in patients receiving GLP-1 receptor agonist medications who present for procedures that require sedation,” the panelists wrote, but more data is needed to support this hypothesis.
Yet the implications for endoscopic risk are still unclear.
Residual liquid in the stomach, at least, is “less of an issue,” according to the update, since “it is easily removed during an esophagogastroduodenoscopy, and this is the first maneuver performed by endoscopists on entering the stomach.”
While residual solids in the stomach could theoretically increase risk of aspiration, other patients with gastroparesis, such as those taking opioids, are not routinely given “special dietary precautions or medication adjustments” prior to endoscopy, Dr. Al Hashash and colleagues wrote. Even patients with severe gastroparesis who are undergoing gastric peroral endoscopic myotomy (which depends upon an empty stomach), are only required to stop ingesting solid foods the day before the procedure, they noted.
“It is appropriate that the ASA’s perioperative suggestions for patients on GLP-1 [receptor agonists] are labeled ‘consensus-based guidance on perioperative management,’ because there is clearly insufficient published evidence for a robust systematic review and guideline,” they wrote. “As such, the ASA’s suggestions are expert opinions, which may inform but should not replace clinical judgment.”
, for whom withholding these medications “might provide more risk than benefit.”
Withholding GLP-1 receptor agonists may be safe and reasonable for patients taking them solely for weight loss, but “this should not be considered mandatory or evidence-based,” as it remains unclear whether withholding one dose is enough to restore normal gastric motility.
“Generally, in patients on GLP-1 receptor agonists who have followed standard perioperative procedures (typically an 8-hour solid-food fast and a 2-hour liquid fast) and who do not have symptoms of nausea, vomiting, dyspepsia, or abdominal distention, we advise proceeding with upper and/or lower endoscopy,” the panelists concluded.
The rapid clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Apollo Endosurgery, Medtronic, Boston Scientific, and others.
The American Gastroenterological Association (AGA) has issued a rapid clinical practice update on the use of glucagon-like peptide 1 (GLP-1) receptor agonists prior to endoscopy.
The update was partly prompted by consensus-based perioperative guidance issued by the American Society of Anesthesiologists in June 2023, which advises withholding GLP-1 receptor agonists before endoscopy. This recommendation has caused some anesthesia providers to cancel or postpone endoscopic procedures, or even elect general endotracheal intubation over standard sedation.
“Many facilities and medical centers are now struggling to revise preprocedural protocols for patients taking this class of medications despite the lack of high-level evidence regarding how to proceed,” the panelists wrote in Clinical Gastroenterology and Hepatology. “Important questions include whether these preprocedural changes are necessary, if they truly mitigate periprocedural aspiration, or if the delays instituted by following this guidance might further compound the major problem currently faced nationwide: that of large numbers of patients awaiting endoscopic procedures because of delays from the COVID-19 pandemic, reduction in the recommended age threshold to start colorectal cancer screening in 2018, and workforce challenges.”
The rapid clinical practice update, commissioned and approved by the AGA, includes background on the relationship between GLP-1 receptor agonists and endoscopic procedures, followed by clinical strategies for patients taking these medications.
Lead panelist Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues began by noting that GLP-1 receptor agonists have been associated with increased gastric residue in patients with diabetes, and among nondiabetic patients, increased gastric retention of solids but not liquids. Delayed gastric emptying and increased residual gastric contents may be more common among patients on GLP-1 agonists who have vomiting, nausea, dyspepsia, or abdominal bloating, they added.
The above findings “imply an increased risk of aspiration in patients receiving GLP-1 receptor agonist medications who present for procedures that require sedation,” the panelists wrote, but more data is needed to support this hypothesis.
Yet the implications for endoscopic risk are still unclear.
Residual liquid in the stomach, at least, is “less of an issue,” according to the update, since “it is easily removed during an esophagogastroduodenoscopy, and this is the first maneuver performed by endoscopists on entering the stomach.”
While residual solids in the stomach could theoretically increase risk of aspiration, other patients with gastroparesis, such as those taking opioids, are not routinely given “special dietary precautions or medication adjustments” prior to endoscopy, Dr. Al Hashash and colleagues wrote. Even patients with severe gastroparesis who are undergoing gastric peroral endoscopic myotomy (which depends upon an empty stomach), are only required to stop ingesting solid foods the day before the procedure, they noted.
“It is appropriate that the ASA’s perioperative suggestions for patients on GLP-1 [receptor agonists] are labeled ‘consensus-based guidance on perioperative management,’ because there is clearly insufficient published evidence for a robust systematic review and guideline,” they wrote. “As such, the ASA’s suggestions are expert opinions, which may inform but should not replace clinical judgment.”
, for whom withholding these medications “might provide more risk than benefit.”
Withholding GLP-1 receptor agonists may be safe and reasonable for patients taking them solely for weight loss, but “this should not be considered mandatory or evidence-based,” as it remains unclear whether withholding one dose is enough to restore normal gastric motility.
“Generally, in patients on GLP-1 receptor agonists who have followed standard perioperative procedures (typically an 8-hour solid-food fast and a 2-hour liquid fast) and who do not have symptoms of nausea, vomiting, dyspepsia, or abdominal distention, we advise proceeding with upper and/or lower endoscopy,” the panelists concluded.
The rapid clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Apollo Endosurgery, Medtronic, Boston Scientific, and others.
The American Gastroenterological Association (AGA) has issued a rapid clinical practice update on the use of glucagon-like peptide 1 (GLP-1) receptor agonists prior to endoscopy.
The update was partly prompted by consensus-based perioperative guidance issued by the American Society of Anesthesiologists in June 2023, which advises withholding GLP-1 receptor agonists before endoscopy. This recommendation has caused some anesthesia providers to cancel or postpone endoscopic procedures, or even elect general endotracheal intubation over standard sedation.
“Many facilities and medical centers are now struggling to revise preprocedural protocols for patients taking this class of medications despite the lack of high-level evidence regarding how to proceed,” the panelists wrote in Clinical Gastroenterology and Hepatology. “Important questions include whether these preprocedural changes are necessary, if they truly mitigate periprocedural aspiration, or if the delays instituted by following this guidance might further compound the major problem currently faced nationwide: that of large numbers of patients awaiting endoscopic procedures because of delays from the COVID-19 pandemic, reduction in the recommended age threshold to start colorectal cancer screening in 2018, and workforce challenges.”
The rapid clinical practice update, commissioned and approved by the AGA, includes background on the relationship between GLP-1 receptor agonists and endoscopic procedures, followed by clinical strategies for patients taking these medications.
Lead panelist Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues began by noting that GLP-1 receptor agonists have been associated with increased gastric residue in patients with diabetes, and among nondiabetic patients, increased gastric retention of solids but not liquids. Delayed gastric emptying and increased residual gastric contents may be more common among patients on GLP-1 agonists who have vomiting, nausea, dyspepsia, or abdominal bloating, they added.
The above findings “imply an increased risk of aspiration in patients receiving GLP-1 receptor agonist medications who present for procedures that require sedation,” the panelists wrote, but more data is needed to support this hypothesis.
Yet the implications for endoscopic risk are still unclear.
Residual liquid in the stomach, at least, is “less of an issue,” according to the update, since “it is easily removed during an esophagogastroduodenoscopy, and this is the first maneuver performed by endoscopists on entering the stomach.”
While residual solids in the stomach could theoretically increase risk of aspiration, other patients with gastroparesis, such as those taking opioids, are not routinely given “special dietary precautions or medication adjustments” prior to endoscopy, Dr. Al Hashash and colleagues wrote. Even patients with severe gastroparesis who are undergoing gastric peroral endoscopic myotomy (which depends upon an empty stomach), are only required to stop ingesting solid foods the day before the procedure, they noted.
“It is appropriate that the ASA’s perioperative suggestions for patients on GLP-1 [receptor agonists] are labeled ‘consensus-based guidance on perioperative management,’ because there is clearly insufficient published evidence for a robust systematic review and guideline,” they wrote. “As such, the ASA’s suggestions are expert opinions, which may inform but should not replace clinical judgment.”
, for whom withholding these medications “might provide more risk than benefit.”
Withholding GLP-1 receptor agonists may be safe and reasonable for patients taking them solely for weight loss, but “this should not be considered mandatory or evidence-based,” as it remains unclear whether withholding one dose is enough to restore normal gastric motility.
“Generally, in patients on GLP-1 receptor agonists who have followed standard perioperative procedures (typically an 8-hour solid-food fast and a 2-hour liquid fast) and who do not have symptoms of nausea, vomiting, dyspepsia, or abdominal distention, we advise proceeding with upper and/or lower endoscopy,” the panelists concluded.
The rapid clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Apollo Endosurgery, Medtronic, Boston Scientific, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
AGA Offers Practical Advice on IBD Diets
.
The new guidance, authored by Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues, includes 12 best practices that address dietary options, enteral and parenteral nutrition, patient monitoring, and the need for multidisciplinary care.
“There is growing recognition of the role of diet in the care of patients with IBD, as both an etiopathogenic risk factor and, more recently, as a disease-modifying modality,” the update panelists wrote in Gastroenterology.
Historically, they noted, patients with IBD had been advised to avoid many different foods including fiber, but this strategy may result in unintended consequences.
“[T]hese approaches frequently led patients with IBD to avoid what are traditionally considered healthy foods, even after achieving clinical remission,” Dr. Al Hashash and colleagues wrote.
With an increasing body of data available for dietary interventions in both Crohn’s disease and ulcerative colitis, they wrote the present clinical practice update to offer some needed clarity.
A Starting Point
First, the panelists advise that, unless contraindicated, all patients with IBD follow a Mediterranean diet while minimizing salt, sugar, and ultraprocessed foods.
Patients with symptomatic intestinal strictures may struggle to digest raw fruits and vegetables due to their fibrous nature, they added, so these patients should first soften these foods through cooking, steaming, or “careful chewing” before consumption.
“No diet has consistently been found to decrease the rate of flares in adults with IBD,” the update panelists noted. “A diet low in red and processed meat may reduce ulcerative colitis flares, but has not been found to reduce relapse in Crohn’s disease.”
Beyond these dietary suggestions for adults, the update advises breastfeeding for newborns and a Mediterranean diet for children, as both may reduce risk of developing IBD.
Enteral Nutrition
The update suggests that exclusive enteral nutrition is a reasonable option to induce clinical remission and endoscopic response, or as a steroid-sparing bridge, in Crohn’s disease, although this may be more effective in children than adults.
Malnourished patients may also benefit from exclusive enteral nutrition prior to elective surgery for Crohn’s disease, Dr. Al Hashash and colleagues added, as this strategy can “optimize nutritional status and reduce postoperative complications.”
A Crohn’s disease exclusion diet, which involves partial enteral nutrition therapy, may be considered in mild or moderate cases, according to the update.
“Data on the use of enteral nutrition in the treatment of active ulcerative colitis are limited,” the panelists wrote, although early data suggest it is safe and well tolerated, and can improve prealbumin levels.
Parenteral Nutrition
The update recommends short-term parenteral nutrition for patients with phlegmonous inflammation and/or an intra-abdominal abscess, as this can act as a bridge to surgical intervention.
Patients with prolonged ileus, short bowel syndrome, or high-output gastrointestinal fistula may also be candidates for parenteral nutrition, as well as those who have tried and failed both oral and enteral nutrition.
Lastly, the update encourages transition from long-term parenteral nutrition to oral intake and customized hydration management “whenever possible.”
Monitoring and Multidisciplinary Care
Dr. Al Hashash and colleagues concluded by advising that all patients with complicated IBD be comanaged by a gastroenterologist and a registered dietitian, both of whom should remain watchful for signs of malnutrition.
Using serum protein as a surrogate marker of malnutrition is no longer recommended and there are different criteria that should be utilized to identify malnutrition. Routine iron and vitamin D testing are warranted, as well as B12 testing for patients with extensive ileal disease or a history of ileal surgery.
This clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Merck, Celgene, Janssen, and others.
.
The new guidance, authored by Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues, includes 12 best practices that address dietary options, enteral and parenteral nutrition, patient monitoring, and the need for multidisciplinary care.
“There is growing recognition of the role of diet in the care of patients with IBD, as both an etiopathogenic risk factor and, more recently, as a disease-modifying modality,” the update panelists wrote in Gastroenterology.
Historically, they noted, patients with IBD had been advised to avoid many different foods including fiber, but this strategy may result in unintended consequences.
“[T]hese approaches frequently led patients with IBD to avoid what are traditionally considered healthy foods, even after achieving clinical remission,” Dr. Al Hashash and colleagues wrote.
With an increasing body of data available for dietary interventions in both Crohn’s disease and ulcerative colitis, they wrote the present clinical practice update to offer some needed clarity.
A Starting Point
First, the panelists advise that, unless contraindicated, all patients with IBD follow a Mediterranean diet while minimizing salt, sugar, and ultraprocessed foods.
Patients with symptomatic intestinal strictures may struggle to digest raw fruits and vegetables due to their fibrous nature, they added, so these patients should first soften these foods through cooking, steaming, or “careful chewing” before consumption.
“No diet has consistently been found to decrease the rate of flares in adults with IBD,” the update panelists noted. “A diet low in red and processed meat may reduce ulcerative colitis flares, but has not been found to reduce relapse in Crohn’s disease.”
Beyond these dietary suggestions for adults, the update advises breastfeeding for newborns and a Mediterranean diet for children, as both may reduce risk of developing IBD.
Enteral Nutrition
The update suggests that exclusive enteral nutrition is a reasonable option to induce clinical remission and endoscopic response, or as a steroid-sparing bridge, in Crohn’s disease, although this may be more effective in children than adults.
Malnourished patients may also benefit from exclusive enteral nutrition prior to elective surgery for Crohn’s disease, Dr. Al Hashash and colleagues added, as this strategy can “optimize nutritional status and reduce postoperative complications.”
A Crohn’s disease exclusion diet, which involves partial enteral nutrition therapy, may be considered in mild or moderate cases, according to the update.
“Data on the use of enteral nutrition in the treatment of active ulcerative colitis are limited,” the panelists wrote, although early data suggest it is safe and well tolerated, and can improve prealbumin levels.
Parenteral Nutrition
The update recommends short-term parenteral nutrition for patients with phlegmonous inflammation and/or an intra-abdominal abscess, as this can act as a bridge to surgical intervention.
Patients with prolonged ileus, short bowel syndrome, or high-output gastrointestinal fistula may also be candidates for parenteral nutrition, as well as those who have tried and failed both oral and enteral nutrition.
Lastly, the update encourages transition from long-term parenteral nutrition to oral intake and customized hydration management “whenever possible.”
Monitoring and Multidisciplinary Care
Dr. Al Hashash and colleagues concluded by advising that all patients with complicated IBD be comanaged by a gastroenterologist and a registered dietitian, both of whom should remain watchful for signs of malnutrition.
Using serum protein as a surrogate marker of malnutrition is no longer recommended and there are different criteria that should be utilized to identify malnutrition. Routine iron and vitamin D testing are warranted, as well as B12 testing for patients with extensive ileal disease or a history of ileal surgery.
This clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Merck, Celgene, Janssen, and others.
.
The new guidance, authored by Jana G. Al Hashash, MD, MSc, AGAF, of Mayo Clinic, Jacksonville, Florida, and colleagues, includes 12 best practices that address dietary options, enteral and parenteral nutrition, patient monitoring, and the need for multidisciplinary care.
“There is growing recognition of the role of diet in the care of patients with IBD, as both an etiopathogenic risk factor and, more recently, as a disease-modifying modality,” the update panelists wrote in Gastroenterology.
Historically, they noted, patients with IBD had been advised to avoid many different foods including fiber, but this strategy may result in unintended consequences.
“[T]hese approaches frequently led patients with IBD to avoid what are traditionally considered healthy foods, even after achieving clinical remission,” Dr. Al Hashash and colleagues wrote.
With an increasing body of data available for dietary interventions in both Crohn’s disease and ulcerative colitis, they wrote the present clinical practice update to offer some needed clarity.
A Starting Point
First, the panelists advise that, unless contraindicated, all patients with IBD follow a Mediterranean diet while minimizing salt, sugar, and ultraprocessed foods.
Patients with symptomatic intestinal strictures may struggle to digest raw fruits and vegetables due to their fibrous nature, they added, so these patients should first soften these foods through cooking, steaming, or “careful chewing” before consumption.
“No diet has consistently been found to decrease the rate of flares in adults with IBD,” the update panelists noted. “A diet low in red and processed meat may reduce ulcerative colitis flares, but has not been found to reduce relapse in Crohn’s disease.”
Beyond these dietary suggestions for adults, the update advises breastfeeding for newborns and a Mediterranean diet for children, as both may reduce risk of developing IBD.
Enteral Nutrition
The update suggests that exclusive enteral nutrition is a reasonable option to induce clinical remission and endoscopic response, or as a steroid-sparing bridge, in Crohn’s disease, although this may be more effective in children than adults.
Malnourished patients may also benefit from exclusive enteral nutrition prior to elective surgery for Crohn’s disease, Dr. Al Hashash and colleagues added, as this strategy can “optimize nutritional status and reduce postoperative complications.”
A Crohn’s disease exclusion diet, which involves partial enteral nutrition therapy, may be considered in mild or moderate cases, according to the update.
“Data on the use of enteral nutrition in the treatment of active ulcerative colitis are limited,” the panelists wrote, although early data suggest it is safe and well tolerated, and can improve prealbumin levels.
Parenteral Nutrition
The update recommends short-term parenteral nutrition for patients with phlegmonous inflammation and/or an intra-abdominal abscess, as this can act as a bridge to surgical intervention.
Patients with prolonged ileus, short bowel syndrome, or high-output gastrointestinal fistula may also be candidates for parenteral nutrition, as well as those who have tried and failed both oral and enteral nutrition.
Lastly, the update encourages transition from long-term parenteral nutrition to oral intake and customized hydration management “whenever possible.”
Monitoring and Multidisciplinary Care
Dr. Al Hashash and colleagues concluded by advising that all patients with complicated IBD be comanaged by a gastroenterologist and a registered dietitian, both of whom should remain watchful for signs of malnutrition.
Using serum protein as a surrogate marker of malnutrition is no longer recommended and there are different criteria that should be utilized to identify malnutrition. Routine iron and vitamin D testing are warranted, as well as B12 testing for patients with extensive ileal disease or a history of ileal surgery.
This clinical practice update was commissioned and approved by the AGA. The update panelists disclosed relationships with Merck, Celgene, Janssen, and others.
FROM GASTROENTEROLOGY
Home Insulin Pumps Safe for In-Hospital Pediatric Care
TOPLINE:
METHODOLOGY:
- Clinical guidelines support the use of home insulin pumps in adults hospitalized for noncritical illnesses, but it has been unclear if adult safety data translate to pediatric inpatients.
- The study evaluated if insulin can be safely and precisely delivered using home insulin pumps managed by patients or caregivers in 2738 patients (0.5-25 years old; median age about 16) with insulin-dependent diabetes admitted to non–intensive care units of a tertiary children’s hospital between January 2016 and December 2021.
- Insulin was delivered either using home insulin pumps managed by patients or caregivers or using hospital insulin pumps or subcutaneous injections managed by hospital staff.
- Safety was measured by hyperglycemia (glucose level > 250 mg/dL), hypoglycemia (moderate: glucose level, 45-59 mg/dL or severe: glucose level, < 45 mg/dL), glucose variability, and the incidence of diabetic ketoacidosis for each delivery method.
- Results were calculated by the number of days a patient had one or more glucose levels meeting the definition of hyperglycemia or hypoglycemia and divided by the number of days a patient receive any insulin dose.
TAKEAWAY:
The number of hyperglycemic days was lower in patients using a hospital (15.7%) or a home (27.0%) insulin pump than in those receiving subcutaneous insulin injections (45.2%; P < .001).
At least one moderate hypoglycemic day was noted in patients receiving insulin through subcutaneous injections (5.1%) compared with those receiving it through hospital (3.1%) or home insulin pumps (4.5%; P = .02).
The proportion of days within the desired blood glucose range and glucose variability were similar in patients using hospital or home insulin pumps and worse in patients managed with injections (P < .001).
No patients using home or hospital pumps developed diabetic ketoacidosis, but two cases of diabetic ketoacidosis were noted among patients using injections.
IN PRACTICE:
“Safety is not sacrificed when patients or caregivers use home pumps during pediatric non–intensive care unit admissions,” the authors wrote.
SOURCE:
The investigation, led by Jodi Owens, MSN, RN, Division of Endocrinology, Cincinnati Children’s Hospital Medical Center, was published along with an invited commentary in JAMA Network Open.
LIMITATIONS:
The strategies employed for insulin safety and awareness by the institution may have led to improved rates of hypoglycemia and hyperglycemia. Moreover, the study did not assess changes in glycemic levels during transition in the insulin delivery method. The study was limited to non–intensive care units and hence cannot be generalized to intensive care unit settings or in patients with diabetic ketoacidosis. The study did not include patients using hybrid-closed loop insulin pumps.
DISCLOSURES:
The study did not disclose any source of funding. The authors did not report any conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Clinical guidelines support the use of home insulin pumps in adults hospitalized for noncritical illnesses, but it has been unclear if adult safety data translate to pediatric inpatients.
- The study evaluated if insulin can be safely and precisely delivered using home insulin pumps managed by patients or caregivers in 2738 patients (0.5-25 years old; median age about 16) with insulin-dependent diabetes admitted to non–intensive care units of a tertiary children’s hospital between January 2016 and December 2021.
- Insulin was delivered either using home insulin pumps managed by patients or caregivers or using hospital insulin pumps or subcutaneous injections managed by hospital staff.
- Safety was measured by hyperglycemia (glucose level > 250 mg/dL), hypoglycemia (moderate: glucose level, 45-59 mg/dL or severe: glucose level, < 45 mg/dL), glucose variability, and the incidence of diabetic ketoacidosis for each delivery method.
- Results were calculated by the number of days a patient had one or more glucose levels meeting the definition of hyperglycemia or hypoglycemia and divided by the number of days a patient receive any insulin dose.
TAKEAWAY:
The number of hyperglycemic days was lower in patients using a hospital (15.7%) or a home (27.0%) insulin pump than in those receiving subcutaneous insulin injections (45.2%; P < .001).
At least one moderate hypoglycemic day was noted in patients receiving insulin through subcutaneous injections (5.1%) compared with those receiving it through hospital (3.1%) or home insulin pumps (4.5%; P = .02).
The proportion of days within the desired blood glucose range and glucose variability were similar in patients using hospital or home insulin pumps and worse in patients managed with injections (P < .001).
No patients using home or hospital pumps developed diabetic ketoacidosis, but two cases of diabetic ketoacidosis were noted among patients using injections.
IN PRACTICE:
“Safety is not sacrificed when patients or caregivers use home pumps during pediatric non–intensive care unit admissions,” the authors wrote.
SOURCE:
The investigation, led by Jodi Owens, MSN, RN, Division of Endocrinology, Cincinnati Children’s Hospital Medical Center, was published along with an invited commentary in JAMA Network Open.
LIMITATIONS:
The strategies employed for insulin safety and awareness by the institution may have led to improved rates of hypoglycemia and hyperglycemia. Moreover, the study did not assess changes in glycemic levels during transition in the insulin delivery method. The study was limited to non–intensive care units and hence cannot be generalized to intensive care unit settings or in patients with diabetic ketoacidosis. The study did not include patients using hybrid-closed loop insulin pumps.
DISCLOSURES:
The study did not disclose any source of funding. The authors did not report any conflicts of interest.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Clinical guidelines support the use of home insulin pumps in adults hospitalized for noncritical illnesses, but it has been unclear if adult safety data translate to pediatric inpatients.
- The study evaluated if insulin can be safely and precisely delivered using home insulin pumps managed by patients or caregivers in 2738 patients (0.5-25 years old; median age about 16) with insulin-dependent diabetes admitted to non–intensive care units of a tertiary children’s hospital between January 2016 and December 2021.
- Insulin was delivered either using home insulin pumps managed by patients or caregivers or using hospital insulin pumps or subcutaneous injections managed by hospital staff.
- Safety was measured by hyperglycemia (glucose level > 250 mg/dL), hypoglycemia (moderate: glucose level, 45-59 mg/dL or severe: glucose level, < 45 mg/dL), glucose variability, and the incidence of diabetic ketoacidosis for each delivery method.
- Results were calculated by the number of days a patient had one or more glucose levels meeting the definition of hyperglycemia or hypoglycemia and divided by the number of days a patient receive any insulin dose.
TAKEAWAY:
The number of hyperglycemic days was lower in patients using a hospital (15.7%) or a home (27.0%) insulin pump than in those receiving subcutaneous insulin injections (45.2%; P < .001).
At least one moderate hypoglycemic day was noted in patients receiving insulin through subcutaneous injections (5.1%) compared with those receiving it through hospital (3.1%) or home insulin pumps (4.5%; P = .02).
The proportion of days within the desired blood glucose range and glucose variability were similar in patients using hospital or home insulin pumps and worse in patients managed with injections (P < .001).
No patients using home or hospital pumps developed diabetic ketoacidosis, but two cases of diabetic ketoacidosis were noted among patients using injections.
IN PRACTICE:
“Safety is not sacrificed when patients or caregivers use home pumps during pediatric non–intensive care unit admissions,” the authors wrote.
SOURCE:
The investigation, led by Jodi Owens, MSN, RN, Division of Endocrinology, Cincinnati Children’s Hospital Medical Center, was published along with an invited commentary in JAMA Network Open.
LIMITATIONS:
The strategies employed for insulin safety and awareness by the institution may have led to improved rates of hypoglycemia and hyperglycemia. Moreover, the study did not assess changes in glycemic levels during transition in the insulin delivery method. The study was limited to non–intensive care units and hence cannot be generalized to intensive care unit settings or in patients with diabetic ketoacidosis. The study did not include patients using hybrid-closed loop insulin pumps.
DISCLOSURES:
The study did not disclose any source of funding. The authors did not report any conflicts of interest.
A version of this article appeared on Medscape.com.
Patients haunted by fears of living with and dying from severe lung disease
Many patients with chronic progressive pulmonary disease feel anxious and depressed as their conditions advance, as breathing becomes increasingly labored and difficult, and as performing even small daily tasks leaves them exhausted.
Disease-related mental distress can lead to increased disability, more frequent use of costly healthcare resources, higher morbidity, and elevated risk of death, investigators say.
“Individuals with severe COPD are twice as likely to develop depression than patients with mild COPD. Prevalence rates for clinical anxiety in COPD range from 13% to 46% in outpatients and 10% to 55% among inpatients,” wrote Abebaw Mengitsu Yohannes, PhD, then from Azusa Pacific University in Azusa, California, and colleagues in an article published jointly by The Journal of Family Practice and The Cleveland Clinic Journal of Medicine.
Patients with COPD may experience major depressive disorders, chronic mild depression (dysthymias), and minor depression, as well as generalized anxiety disorder, phobias, and panic disorders, the investigators say.
“Growing evidence suggests that the relationship between mood disorders — particularly depression — and COPD is bidirectional, meaning that mood disorders adversely impact prognosis in COPD, whereas COPD increases the risk of developing depression,” Yohannes et al. wrote.
Jamie Garfield, MD, professor of thoracic medicine and surgery at Temple University’s Lewis Katz School of Medicine in Philadelphia, Pennsylvania, told Chest Physician that the association between severe chronic diseases and mood disorders is well known.
“I don’t think that it’s specific to chronic lung diseases; in people with chronic heart disease or malignancies we see that coexistence of depression and anxiety will worsen the course of disease,” she said.
Dr. Johannes, who is currently a professor of physical therapy at the University of Alabama School of Health Professionals in Birmingham, said that depression and anxiety are often underdiagnosed and undertreated in patients with obstructive pulmonary diseases because the conditions can share symptoms such as dyspnea (for example, in anxiety) or fatigue (in depression).
“Therefore, unless one begins to explore further, it’s hard for physicians to be able to identify these conditions,” he said in an interview with Chest Physician.
Fears of dying (and living)
The causes of depression and anxiety among patients with obstructive pulmonary disorders are multifactorial, and may require a variety of treatment and coping strategies, according to Susann Strang, RN, PhD, and colleagues from the University of Gothenburg, Gothenburg, Sweden.
They conducted qualitative in-depth interviews with 31 men and women with stage III or IV COPD, and found that the majority of patients had anxiety associated with their disease.
“Analyses revealed three major themes: death anxiety, life anxiety, and counterweights to anxiety,” the investigators wrote in a study published in the journal Palliative and Supportive Care in 2014.
Factors contributing to anxiety surrounding death included fear of suffocation, awareness of impending death, fear of the process of death, and anxiety about being separated from loved ones.
In contrast, some patients expressed dread of living with the limitations and loneliness imposed on them by their disease — so-called “life anxiety.”
The patients also reported “counterweights” to anxiety as a way of coping. For some this involved trust in their healthcare professionals and adherence to medication, inhalers, and supplemental oxygen.
“The patients also placed hope in new treatments, better medication, surgery, stem cell treatment, or lung transplants,” Dr. Strang and colleagues reported.
Others reported avoiding talking about death, sleeping more, or using humor to “laugh off this difficult subject.”
Screening and diagnosis
Primary care practitioners are often the first health professionals that patients with COPD see, but these clinicians often don’t have the time to add screening to their already crammed schedules. In addition, “the lack of a standardized approach in diagnosis, and inadequate knowledge or confidence in assessing psychological status (particularly given the number of strategies available for screening patients for mood disorders),” can make it difficult for PCPs to detect and manage anxiety and depression in their patients with significant healthcare burdens from COPD and other obstructive lung diseases, Dr. Yohannes and colleagues noted.
In addition to commonly used screening tools for anxiety and depression such as the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire (PHQ-9), there are at least two designed to evaluate patients with lung disease: the Anxiety Inventory for Respiratory (AIR) Disease scale, developed by Dr. Yohannes and colleagues, and the COPD Anxiety Questionnaire.
The COPD Assessment Test and Clinical COPD Questionnaire, while not specifically designed to screen for mental disorders, include questions that can point to symptoms of distress in patients with COPD, Dr. Yohannes said.
“In truth I think that there are few providers who will routinely do this on all their patients in terms of quantifying the severity or the presence or absence of depression, but in my own practice I very much ask questions that align with the questions in these tools to determine whether my patient appears to have high levels of anxiety and depression,” Dr. Garfield said.
Listen to patients and families
Among the most powerful tools that clinicians have at their disposal for treating anxiety and depression in patients with chronic lung disease are their ears and their minds, said Anthony Saleh, MD, a pulmonologist at New York-Presbyterian Brooklyn Methodist Hospital in Brooklyn, New York.
“I think just listening to the patient, that’s a little bit forgotten yet so important,” he said in an interview with CHEST Physician.
“When I have someone with advanced lung disease, like idiopathic pulmonary fibrosis, like advanced emphysema, one of the most important things I think is to listen to the patient, and not just to listen to the answers of your perfunctory ‘how’s your breathing? Any chest pain?’ and those sort of rote medical questions, but listen to their thoughts, and it will given them a safe space to say ‘Hey, I’m nervous, hey I’m worried about my family, hey I’m worried if I die what’s going to happen to my wife and kids,’ and that’s something I think is invaluable.”
It’s also vital to listen to the concerns of the patients family members, who may be the primary caregivers and may share the patient’s stresses and anxieties, he said.
Pulmonary Rehabilitation
All of the experts interviewed for this article agreed that a combination of medical, social and mental health support services is important for treatment for patients with chronic obstructive lung diseases.
One of the most effective means of helping patients with both acute breathing problems and with disease-related anxiety and depression is pulmonary rehabilitation. Depending on disease severity, this multidisciplinary approach may involve exercise, patient education, psychological and nutrition counseling, and training patients how to conserve energy and adopt breathing strategies to help them better manage their symptoms.
“I think that pulmonary rehabilitation is one of the first interventions that we should be recommending for our patients,” Dr. Garfield said. “It’s physical therapy for patients with chronic lung diseases, backed by respiratory therapists, and it offers not only physical rehabilitation — improving strength and coordination, but also it helps our patients get as much as possible out of what they’ve got.”
For example, patients can be taught how to decrease their respiratory rate when they’re feeling a sense of urgency or panic. Patients can also learn how to change body positions to help them breathe more effectively when they feel that their breath is limited or restricted, she said.
“Once you’re into medical interventions, pulmonary rehab is phenomenal,” Dr. Saleh said.
Pulmonary rehabilitation helps patients to feel better about themselves and about their abilities, but “unfortunately it’s not as available as we like,” he said.
Many patients don’t live near a pulmonary rehabilitation center, and the typical two to three weekly sessions for 4-12 weeks or longer can be a significant burden for patients and caregivers, he acknowledged.
“You have to sit [with the patient] and be honest and tell them it’s a lot of diligence involved and you have to be really motivated,” he said.
Other treatment options include pharmacological therapy with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and anxiolytic agents.
“SSRIs are the current first-line drug treatment for depression, and have been shown to significantly improve depression and anxiety in patients with COPD in some, but not all, trials published to date. However, it is important to note that a diagnosis of bipolar disorder must be ruled out before initiating standard antidepressant therapy,” Dr. Johannes and colleagues wrote.
Defiant joy
Importantly, even with the burden of life with COPD, many patients found ways to experience what Strang et al. called “a defiant joy.”
“It was remarkable that when the patients were asked about what gave their lives meaning today, many talked about what had given their life meaning in the past, prior to becoming ill. In the light of the things they had lost because of the disease, many felt that their previous sources of joy no longer existed. Despite this, many still hoped to be able to get out into the fresh air, to be able to do errands, or that tomorrow might be better,” the investigators wrote.
Dr. Yohannes, Dr. Garfield, and Dr. Saleh all reported having no relevant conflicts of interest to report.
Many patients with chronic progressive pulmonary disease feel anxious and depressed as their conditions advance, as breathing becomes increasingly labored and difficult, and as performing even small daily tasks leaves them exhausted.
Disease-related mental distress can lead to increased disability, more frequent use of costly healthcare resources, higher morbidity, and elevated risk of death, investigators say.
“Individuals with severe COPD are twice as likely to develop depression than patients with mild COPD. Prevalence rates for clinical anxiety in COPD range from 13% to 46% in outpatients and 10% to 55% among inpatients,” wrote Abebaw Mengitsu Yohannes, PhD, then from Azusa Pacific University in Azusa, California, and colleagues in an article published jointly by The Journal of Family Practice and The Cleveland Clinic Journal of Medicine.
Patients with COPD may experience major depressive disorders, chronic mild depression (dysthymias), and minor depression, as well as generalized anxiety disorder, phobias, and panic disorders, the investigators say.
“Growing evidence suggests that the relationship between mood disorders — particularly depression — and COPD is bidirectional, meaning that mood disorders adversely impact prognosis in COPD, whereas COPD increases the risk of developing depression,” Yohannes et al. wrote.
Jamie Garfield, MD, professor of thoracic medicine and surgery at Temple University’s Lewis Katz School of Medicine in Philadelphia, Pennsylvania, told Chest Physician that the association between severe chronic diseases and mood disorders is well known.
“I don’t think that it’s specific to chronic lung diseases; in people with chronic heart disease or malignancies we see that coexistence of depression and anxiety will worsen the course of disease,” she said.
Dr. Johannes, who is currently a professor of physical therapy at the University of Alabama School of Health Professionals in Birmingham, said that depression and anxiety are often underdiagnosed and undertreated in patients with obstructive pulmonary diseases because the conditions can share symptoms such as dyspnea (for example, in anxiety) or fatigue (in depression).
“Therefore, unless one begins to explore further, it’s hard for physicians to be able to identify these conditions,” he said in an interview with Chest Physician.
Fears of dying (and living)
The causes of depression and anxiety among patients with obstructive pulmonary disorders are multifactorial, and may require a variety of treatment and coping strategies, according to Susann Strang, RN, PhD, and colleagues from the University of Gothenburg, Gothenburg, Sweden.
They conducted qualitative in-depth interviews with 31 men and women with stage III or IV COPD, and found that the majority of patients had anxiety associated with their disease.
“Analyses revealed three major themes: death anxiety, life anxiety, and counterweights to anxiety,” the investigators wrote in a study published in the journal Palliative and Supportive Care in 2014.
Factors contributing to anxiety surrounding death included fear of suffocation, awareness of impending death, fear of the process of death, and anxiety about being separated from loved ones.
In contrast, some patients expressed dread of living with the limitations and loneliness imposed on them by their disease — so-called “life anxiety.”
The patients also reported “counterweights” to anxiety as a way of coping. For some this involved trust in their healthcare professionals and adherence to medication, inhalers, and supplemental oxygen.
“The patients also placed hope in new treatments, better medication, surgery, stem cell treatment, or lung transplants,” Dr. Strang and colleagues reported.
Others reported avoiding talking about death, sleeping more, or using humor to “laugh off this difficult subject.”
Screening and diagnosis
Primary care practitioners are often the first health professionals that patients with COPD see, but these clinicians often don’t have the time to add screening to their already crammed schedules. In addition, “the lack of a standardized approach in diagnosis, and inadequate knowledge or confidence in assessing psychological status (particularly given the number of strategies available for screening patients for mood disorders),” can make it difficult for PCPs to detect and manage anxiety and depression in their patients with significant healthcare burdens from COPD and other obstructive lung diseases, Dr. Yohannes and colleagues noted.
In addition to commonly used screening tools for anxiety and depression such as the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire (PHQ-9), there are at least two designed to evaluate patients with lung disease: the Anxiety Inventory for Respiratory (AIR) Disease scale, developed by Dr. Yohannes and colleagues, and the COPD Anxiety Questionnaire.
The COPD Assessment Test and Clinical COPD Questionnaire, while not specifically designed to screen for mental disorders, include questions that can point to symptoms of distress in patients with COPD, Dr. Yohannes said.
“In truth I think that there are few providers who will routinely do this on all their patients in terms of quantifying the severity or the presence or absence of depression, but in my own practice I very much ask questions that align with the questions in these tools to determine whether my patient appears to have high levels of anxiety and depression,” Dr. Garfield said.
Listen to patients and families
Among the most powerful tools that clinicians have at their disposal for treating anxiety and depression in patients with chronic lung disease are their ears and their minds, said Anthony Saleh, MD, a pulmonologist at New York-Presbyterian Brooklyn Methodist Hospital in Brooklyn, New York.
“I think just listening to the patient, that’s a little bit forgotten yet so important,” he said in an interview with CHEST Physician.
“When I have someone with advanced lung disease, like idiopathic pulmonary fibrosis, like advanced emphysema, one of the most important things I think is to listen to the patient, and not just to listen to the answers of your perfunctory ‘how’s your breathing? Any chest pain?’ and those sort of rote medical questions, but listen to their thoughts, and it will given them a safe space to say ‘Hey, I’m nervous, hey I’m worried about my family, hey I’m worried if I die what’s going to happen to my wife and kids,’ and that’s something I think is invaluable.”
It’s also vital to listen to the concerns of the patients family members, who may be the primary caregivers and may share the patient’s stresses and anxieties, he said.
Pulmonary Rehabilitation
All of the experts interviewed for this article agreed that a combination of medical, social and mental health support services is important for treatment for patients with chronic obstructive lung diseases.
One of the most effective means of helping patients with both acute breathing problems and with disease-related anxiety and depression is pulmonary rehabilitation. Depending on disease severity, this multidisciplinary approach may involve exercise, patient education, psychological and nutrition counseling, and training patients how to conserve energy and adopt breathing strategies to help them better manage their symptoms.
“I think that pulmonary rehabilitation is one of the first interventions that we should be recommending for our patients,” Dr. Garfield said. “It’s physical therapy for patients with chronic lung diseases, backed by respiratory therapists, and it offers not only physical rehabilitation — improving strength and coordination, but also it helps our patients get as much as possible out of what they’ve got.”
For example, patients can be taught how to decrease their respiratory rate when they’re feeling a sense of urgency or panic. Patients can also learn how to change body positions to help them breathe more effectively when they feel that their breath is limited or restricted, she said.
“Once you’re into medical interventions, pulmonary rehab is phenomenal,” Dr. Saleh said.
Pulmonary rehabilitation helps patients to feel better about themselves and about their abilities, but “unfortunately it’s not as available as we like,” he said.
Many patients don’t live near a pulmonary rehabilitation center, and the typical two to three weekly sessions for 4-12 weeks or longer can be a significant burden for patients and caregivers, he acknowledged.
“You have to sit [with the patient] and be honest and tell them it’s a lot of diligence involved and you have to be really motivated,” he said.
Other treatment options include pharmacological therapy with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and anxiolytic agents.
“SSRIs are the current first-line drug treatment for depression, and have been shown to significantly improve depression and anxiety in patients with COPD in some, but not all, trials published to date. However, it is important to note that a diagnosis of bipolar disorder must be ruled out before initiating standard antidepressant therapy,” Dr. Johannes and colleagues wrote.
Defiant joy
Importantly, even with the burden of life with COPD, many patients found ways to experience what Strang et al. called “a defiant joy.”
“It was remarkable that when the patients were asked about what gave their lives meaning today, many talked about what had given their life meaning in the past, prior to becoming ill. In the light of the things they had lost because of the disease, many felt that their previous sources of joy no longer existed. Despite this, many still hoped to be able to get out into the fresh air, to be able to do errands, or that tomorrow might be better,” the investigators wrote.
Dr. Yohannes, Dr. Garfield, and Dr. Saleh all reported having no relevant conflicts of interest to report.
Many patients with chronic progressive pulmonary disease feel anxious and depressed as their conditions advance, as breathing becomes increasingly labored and difficult, and as performing even small daily tasks leaves them exhausted.
Disease-related mental distress can lead to increased disability, more frequent use of costly healthcare resources, higher morbidity, and elevated risk of death, investigators say.
“Individuals with severe COPD are twice as likely to develop depression than patients with mild COPD. Prevalence rates for clinical anxiety in COPD range from 13% to 46% in outpatients and 10% to 55% among inpatients,” wrote Abebaw Mengitsu Yohannes, PhD, then from Azusa Pacific University in Azusa, California, and colleagues in an article published jointly by The Journal of Family Practice and The Cleveland Clinic Journal of Medicine.
Patients with COPD may experience major depressive disorders, chronic mild depression (dysthymias), and minor depression, as well as generalized anxiety disorder, phobias, and panic disorders, the investigators say.
“Growing evidence suggests that the relationship between mood disorders — particularly depression — and COPD is bidirectional, meaning that mood disorders adversely impact prognosis in COPD, whereas COPD increases the risk of developing depression,” Yohannes et al. wrote.
Jamie Garfield, MD, professor of thoracic medicine and surgery at Temple University’s Lewis Katz School of Medicine in Philadelphia, Pennsylvania, told Chest Physician that the association between severe chronic diseases and mood disorders is well known.
“I don’t think that it’s specific to chronic lung diseases; in people with chronic heart disease or malignancies we see that coexistence of depression and anxiety will worsen the course of disease,” she said.
Dr. Johannes, who is currently a professor of physical therapy at the University of Alabama School of Health Professionals in Birmingham, said that depression and anxiety are often underdiagnosed and undertreated in patients with obstructive pulmonary diseases because the conditions can share symptoms such as dyspnea (for example, in anxiety) or fatigue (in depression).
“Therefore, unless one begins to explore further, it’s hard for physicians to be able to identify these conditions,” he said in an interview with Chest Physician.
Fears of dying (and living)
The causes of depression and anxiety among patients with obstructive pulmonary disorders are multifactorial, and may require a variety of treatment and coping strategies, according to Susann Strang, RN, PhD, and colleagues from the University of Gothenburg, Gothenburg, Sweden.
They conducted qualitative in-depth interviews with 31 men and women with stage III or IV COPD, and found that the majority of patients had anxiety associated with their disease.
“Analyses revealed three major themes: death anxiety, life anxiety, and counterweights to anxiety,” the investigators wrote in a study published in the journal Palliative and Supportive Care in 2014.
Factors contributing to anxiety surrounding death included fear of suffocation, awareness of impending death, fear of the process of death, and anxiety about being separated from loved ones.
In contrast, some patients expressed dread of living with the limitations and loneliness imposed on them by their disease — so-called “life anxiety.”
The patients also reported “counterweights” to anxiety as a way of coping. For some this involved trust in their healthcare professionals and adherence to medication, inhalers, and supplemental oxygen.
“The patients also placed hope in new treatments, better medication, surgery, stem cell treatment, or lung transplants,” Dr. Strang and colleagues reported.
Others reported avoiding talking about death, sleeping more, or using humor to “laugh off this difficult subject.”
Screening and diagnosis
Primary care practitioners are often the first health professionals that patients with COPD see, but these clinicians often don’t have the time to add screening to their already crammed schedules. In addition, “the lack of a standardized approach in diagnosis, and inadequate knowledge or confidence in assessing psychological status (particularly given the number of strategies available for screening patients for mood disorders),” can make it difficult for PCPs to detect and manage anxiety and depression in their patients with significant healthcare burdens from COPD and other obstructive lung diseases, Dr. Yohannes and colleagues noted.
In addition to commonly used screening tools for anxiety and depression such as the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire (PHQ-9), there are at least two designed to evaluate patients with lung disease: the Anxiety Inventory for Respiratory (AIR) Disease scale, developed by Dr. Yohannes and colleagues, and the COPD Anxiety Questionnaire.
The COPD Assessment Test and Clinical COPD Questionnaire, while not specifically designed to screen for mental disorders, include questions that can point to symptoms of distress in patients with COPD, Dr. Yohannes said.
“In truth I think that there are few providers who will routinely do this on all their patients in terms of quantifying the severity or the presence or absence of depression, but in my own practice I very much ask questions that align with the questions in these tools to determine whether my patient appears to have high levels of anxiety and depression,” Dr. Garfield said.
Listen to patients and families
Among the most powerful tools that clinicians have at their disposal for treating anxiety and depression in patients with chronic lung disease are their ears and their minds, said Anthony Saleh, MD, a pulmonologist at New York-Presbyterian Brooklyn Methodist Hospital in Brooklyn, New York.
“I think just listening to the patient, that’s a little bit forgotten yet so important,” he said in an interview with CHEST Physician.
“When I have someone with advanced lung disease, like idiopathic pulmonary fibrosis, like advanced emphysema, one of the most important things I think is to listen to the patient, and not just to listen to the answers of your perfunctory ‘how’s your breathing? Any chest pain?’ and those sort of rote medical questions, but listen to their thoughts, and it will given them a safe space to say ‘Hey, I’m nervous, hey I’m worried about my family, hey I’m worried if I die what’s going to happen to my wife and kids,’ and that’s something I think is invaluable.”
It’s also vital to listen to the concerns of the patients family members, who may be the primary caregivers and may share the patient’s stresses and anxieties, he said.
Pulmonary Rehabilitation
All of the experts interviewed for this article agreed that a combination of medical, social and mental health support services is important for treatment for patients with chronic obstructive lung diseases.
One of the most effective means of helping patients with both acute breathing problems and with disease-related anxiety and depression is pulmonary rehabilitation. Depending on disease severity, this multidisciplinary approach may involve exercise, patient education, psychological and nutrition counseling, and training patients how to conserve energy and adopt breathing strategies to help them better manage their symptoms.
“I think that pulmonary rehabilitation is one of the first interventions that we should be recommending for our patients,” Dr. Garfield said. “It’s physical therapy for patients with chronic lung diseases, backed by respiratory therapists, and it offers not only physical rehabilitation — improving strength and coordination, but also it helps our patients get as much as possible out of what they’ve got.”
For example, patients can be taught how to decrease their respiratory rate when they’re feeling a sense of urgency or panic. Patients can also learn how to change body positions to help them breathe more effectively when they feel that their breath is limited or restricted, she said.
“Once you’re into medical interventions, pulmonary rehab is phenomenal,” Dr. Saleh said.
Pulmonary rehabilitation helps patients to feel better about themselves and about their abilities, but “unfortunately it’s not as available as we like,” he said.
Many patients don’t live near a pulmonary rehabilitation center, and the typical two to three weekly sessions for 4-12 weeks or longer can be a significant burden for patients and caregivers, he acknowledged.
“You have to sit [with the patient] and be honest and tell them it’s a lot of diligence involved and you have to be really motivated,” he said.
Other treatment options include pharmacological therapy with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and anxiolytic agents.
“SSRIs are the current first-line drug treatment for depression, and have been shown to significantly improve depression and anxiety in patients with COPD in some, but not all, trials published to date. However, it is important to note that a diagnosis of bipolar disorder must be ruled out before initiating standard antidepressant therapy,” Dr. Johannes and colleagues wrote.
Defiant joy
Importantly, even with the burden of life with COPD, many patients found ways to experience what Strang et al. called “a defiant joy.”
“It was remarkable that when the patients were asked about what gave their lives meaning today, many talked about what had given their life meaning in the past, prior to becoming ill. In the light of the things they had lost because of the disease, many felt that their previous sources of joy no longer existed. Despite this, many still hoped to be able to get out into the fresh air, to be able to do errands, or that tomorrow might be better,” the investigators wrote.
Dr. Yohannes, Dr. Garfield, and Dr. Saleh all reported having no relevant conflicts of interest to report.
Largest US Independent Primary Care Network Accused of Medicare Fraud
A Maryland firm that oversees the nation’s largest independent network of primary care medical practices is facing a whistleblower lawsuit alleging it cheated Medicare out of millions of dollars using billing software “rigged” to make patients appear sicker than they were.
“Aledade did whatever it took to make patients appear sicker than they were,” according to the suit.
For example, the suit alleges that Aledade “conflated” anxiety into depression, which could boost payments by $3300 a year per patient. And Aledade decided that patients over 65 years old who said they had more than one drink per day had substance use issues, which could bring in $3680 extra per patient, the suit says.
The whistleblower case was filed by Khushwinder Singh in federal court in Seattle in 2021 but remained under seal until January of this year. Singh, a “senior medical director of risk and wellness product” at Aledade from January 2021 through May 2021, alleges the company fired him after he objected to its “fraudulent course of conduct,” according to the suit. He declined to comment on the suit.
The case is pending, and Aledade has yet to file a legal response in court. Julie Bataille, Aledade’s senior vice president for communications, denied the allegations, saying in an interview that “the whole case is totally baseless and meritless.”
Based in Bethesda, Maryland, Aledade helps manage independent primary care clinics and medical offices in more than 40 states, serving some 2 million people.
Aledade is one of hundreds of groups known as accountable care organizations. ACOs enjoy strong support from federal health officials who hope they can keep people healthier and achieve measurable cost savings.
Aledade was co-founded in 2014 by Farzad Mostashari, a former health information technology chief in the Obama administration, and has welcomed other ex-government health figures into its ranks. In June 2023, President Joe Biden appointed Mandy Cohen, then executive vice president at Aledade, to head the Centers for Disease Control and Prevention in Atlanta.
Aledade has grown rapidly behind hundreds of millions of dollars in venture capital financing and was valued at $3.5 billion in 2023.
Mostashari, Aledade’s chief executive officer, declined to be interviewed on the record.
“As this is an active legal matter, we will not respond to individual allegations in the complaint,” Aledade said in a statement to KFF Health News. “We remain focused on our top priority of delivering high-quality, value-based care with our physician partners and will defend ourselves vigorously if needed in a court of law.”
The lawsuit also names as defendants 19 independent physician practices, many in small cities in Delaware, Kansas, Louisiana, North Carolina, Pennsylvania, and West Virginia. According to the suit, the doctors knowingly used Aledade software to trigger illegal billings, a practice known in the medical industry as “upcoding.” None has filed an answer in court.
More than two dozen whistleblower lawsuits, some dating back more than a decade, have accused Medicare health plans of overcharging the government by billing for medical conditions not supported by patient medical records. These cases have resulted in hundreds of millions of dollars in penalties. In September 2023, Cigna agreed to pay $37 million to settle one such case, for instance.
But the whistleblower suit filed against Aledade appears to be the first to allege upcoding within accountable care organizations, which describe part of their mission as foiling wasteful spending. ACOs including Aledade made headlines recently for helping to expose an alleged massive Medicare fraud involving urinary catheters, for instance.
Finding the ‘Gravy’
Singh’s suit targets Aledade’s use of coding software and guidance to medical practices that joined its network. Some doctors treated patients on standard Medicare through the ACO networks, while others cared for seniors enrolled in Medicare Advantage plans, according to the suit.
Medicare Advantage is a privately run alternative to standard Medicare that has surged in popularity and now cares for more than 30 million people. Aledade has sought to expand its services to Medicare Advantage enrollees.
The lawsuit alleges Aledade encouraged doctors to tack on suspect medical diagnoses that paid extra money. Aledade called it finding “the gravy sitting in the [patient’s] chart,” according to the suit.
The company “instructed” providers to diagnose diabetes with complications, “even if the patient’s diabetes was under control or the complicating factor no longer existed,” according to the suit.
Some medical practices in Delaware, North Carolina, and West Virginia billed the inflated code for more than 90% of their Medicare Advantage patients with diabetes, according to the suit.
The lawsuit also alleges that Aledade “rigged” the software to change a diagnosis of overweight to “morbid obesity,” which could pay about $2500 more per patient. Some providers coded morbid obesity for patients on traditional Medicare at 10 times the national average, according to the suit.
“This fraudulent coding guidance was known as ‘Aledade gospel,’ ” according to the suit, and following it “paid dividends in the form of millions of dollars in increased revenue.”
These tactics “usurped” the clinical judgment of doctors, according to the suit.
‘No Diagnosis Left Behind’
In its statement to KFF Health News, Aledade said its software offers doctors a range of data and guidance that helps them evaluate and treat patients.
“Aledade’s independent physicians remain solely responsible for all medical decision-making for their patients,” the statement read.
The company said it will “continue to advocate for changes to improve Medicare’s risk adjustment process to promote accuracy while also reducing unnecessary administrative burdens.”
In a message to employees and partner practices sent on Feb. 29, Mostashari noted that the Justice Department had declined to take over the False Claims Act case.
“We recently learned that the federal government has declined to join the case U.S. ex rel. Khushwinder Singh v. Aledade, Inc., et al. That’s good news, and a decision we wholeheartedly applaud given the baseless allegations about improper coding practices and wrongful termination brought by a former Aledade employee 3 years ago. We do not yet know how the full legal situation will play out but will defend ourselves vigorously if needed in a court of law,” the statement said.
The Justice Department advised the Seattle court on Jan. 9 that it would not intervene in the case “at this time,” which prompted an order to unseal it, court records show. Under the false claims law, whistleblowers can proceed with the case on their own. The Justice Department does not state a reason for declining a case but has said in other court cases that doing so has no bearing on its merits.
Singh argues in his complaint that many “unsupported” diagnosis codes were added during annual “wellness visits” and that they did not result in the patients receiving any additional medical care.
Aledade maintained Slack channels in which doctors could discuss the financial incentives for adding higher-paying diagnostic codes, according to the suit.
The company also closely monitored how doctors coded as part of an initiative dubbed “no diagnosis left behind,” according to the suit.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism.
A Maryland firm that oversees the nation’s largest independent network of primary care medical practices is facing a whistleblower lawsuit alleging it cheated Medicare out of millions of dollars using billing software “rigged” to make patients appear sicker than they were.
“Aledade did whatever it took to make patients appear sicker than they were,” according to the suit.
For example, the suit alleges that Aledade “conflated” anxiety into depression, which could boost payments by $3300 a year per patient. And Aledade decided that patients over 65 years old who said they had more than one drink per day had substance use issues, which could bring in $3680 extra per patient, the suit says.
The whistleblower case was filed by Khushwinder Singh in federal court in Seattle in 2021 but remained under seal until January of this year. Singh, a “senior medical director of risk and wellness product” at Aledade from January 2021 through May 2021, alleges the company fired him after he objected to its “fraudulent course of conduct,” according to the suit. He declined to comment on the suit.
The case is pending, and Aledade has yet to file a legal response in court. Julie Bataille, Aledade’s senior vice president for communications, denied the allegations, saying in an interview that “the whole case is totally baseless and meritless.”
Based in Bethesda, Maryland, Aledade helps manage independent primary care clinics and medical offices in more than 40 states, serving some 2 million people.
Aledade is one of hundreds of groups known as accountable care organizations. ACOs enjoy strong support from federal health officials who hope they can keep people healthier and achieve measurable cost savings.
Aledade was co-founded in 2014 by Farzad Mostashari, a former health information technology chief in the Obama administration, and has welcomed other ex-government health figures into its ranks. In June 2023, President Joe Biden appointed Mandy Cohen, then executive vice president at Aledade, to head the Centers for Disease Control and Prevention in Atlanta.
Aledade has grown rapidly behind hundreds of millions of dollars in venture capital financing and was valued at $3.5 billion in 2023.
Mostashari, Aledade’s chief executive officer, declined to be interviewed on the record.
“As this is an active legal matter, we will not respond to individual allegations in the complaint,” Aledade said in a statement to KFF Health News. “We remain focused on our top priority of delivering high-quality, value-based care with our physician partners and will defend ourselves vigorously if needed in a court of law.”
The lawsuit also names as defendants 19 independent physician practices, many in small cities in Delaware, Kansas, Louisiana, North Carolina, Pennsylvania, and West Virginia. According to the suit, the doctors knowingly used Aledade software to trigger illegal billings, a practice known in the medical industry as “upcoding.” None has filed an answer in court.
More than two dozen whistleblower lawsuits, some dating back more than a decade, have accused Medicare health plans of overcharging the government by billing for medical conditions not supported by patient medical records. These cases have resulted in hundreds of millions of dollars in penalties. In September 2023, Cigna agreed to pay $37 million to settle one such case, for instance.
But the whistleblower suit filed against Aledade appears to be the first to allege upcoding within accountable care organizations, which describe part of their mission as foiling wasteful spending. ACOs including Aledade made headlines recently for helping to expose an alleged massive Medicare fraud involving urinary catheters, for instance.
Finding the ‘Gravy’
Singh’s suit targets Aledade’s use of coding software and guidance to medical practices that joined its network. Some doctors treated patients on standard Medicare through the ACO networks, while others cared for seniors enrolled in Medicare Advantage plans, according to the suit.
Medicare Advantage is a privately run alternative to standard Medicare that has surged in popularity and now cares for more than 30 million people. Aledade has sought to expand its services to Medicare Advantage enrollees.
The lawsuit alleges Aledade encouraged doctors to tack on suspect medical diagnoses that paid extra money. Aledade called it finding “the gravy sitting in the [patient’s] chart,” according to the suit.
The company “instructed” providers to diagnose diabetes with complications, “even if the patient’s diabetes was under control or the complicating factor no longer existed,” according to the suit.
Some medical practices in Delaware, North Carolina, and West Virginia billed the inflated code for more than 90% of their Medicare Advantage patients with diabetes, according to the suit.
The lawsuit also alleges that Aledade “rigged” the software to change a diagnosis of overweight to “morbid obesity,” which could pay about $2500 more per patient. Some providers coded morbid obesity for patients on traditional Medicare at 10 times the national average, according to the suit.
“This fraudulent coding guidance was known as ‘Aledade gospel,’ ” according to the suit, and following it “paid dividends in the form of millions of dollars in increased revenue.”
These tactics “usurped” the clinical judgment of doctors, according to the suit.
‘No Diagnosis Left Behind’
In its statement to KFF Health News, Aledade said its software offers doctors a range of data and guidance that helps them evaluate and treat patients.
“Aledade’s independent physicians remain solely responsible for all medical decision-making for their patients,” the statement read.
The company said it will “continue to advocate for changes to improve Medicare’s risk adjustment process to promote accuracy while also reducing unnecessary administrative burdens.”
In a message to employees and partner practices sent on Feb. 29, Mostashari noted that the Justice Department had declined to take over the False Claims Act case.
“We recently learned that the federal government has declined to join the case U.S. ex rel. Khushwinder Singh v. Aledade, Inc., et al. That’s good news, and a decision we wholeheartedly applaud given the baseless allegations about improper coding practices and wrongful termination brought by a former Aledade employee 3 years ago. We do not yet know how the full legal situation will play out but will defend ourselves vigorously if needed in a court of law,” the statement said.
The Justice Department advised the Seattle court on Jan. 9 that it would not intervene in the case “at this time,” which prompted an order to unseal it, court records show. Under the false claims law, whistleblowers can proceed with the case on their own. The Justice Department does not state a reason for declining a case but has said in other court cases that doing so has no bearing on its merits.
Singh argues in his complaint that many “unsupported” diagnosis codes were added during annual “wellness visits” and that they did not result in the patients receiving any additional medical care.
Aledade maintained Slack channels in which doctors could discuss the financial incentives for adding higher-paying diagnostic codes, according to the suit.
The company also closely monitored how doctors coded as part of an initiative dubbed “no diagnosis left behind,” according to the suit.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism.
A Maryland firm that oversees the nation’s largest independent network of primary care medical practices is facing a whistleblower lawsuit alleging it cheated Medicare out of millions of dollars using billing software “rigged” to make patients appear sicker than they were.
“Aledade did whatever it took to make patients appear sicker than they were,” according to the suit.
For example, the suit alleges that Aledade “conflated” anxiety into depression, which could boost payments by $3300 a year per patient. And Aledade decided that patients over 65 years old who said they had more than one drink per day had substance use issues, which could bring in $3680 extra per patient, the suit says.
The whistleblower case was filed by Khushwinder Singh in federal court in Seattle in 2021 but remained under seal until January of this year. Singh, a “senior medical director of risk and wellness product” at Aledade from January 2021 through May 2021, alleges the company fired him after he objected to its “fraudulent course of conduct,” according to the suit. He declined to comment on the suit.
The case is pending, and Aledade has yet to file a legal response in court. Julie Bataille, Aledade’s senior vice president for communications, denied the allegations, saying in an interview that “the whole case is totally baseless and meritless.”
Based in Bethesda, Maryland, Aledade helps manage independent primary care clinics and medical offices in more than 40 states, serving some 2 million people.
Aledade is one of hundreds of groups known as accountable care organizations. ACOs enjoy strong support from federal health officials who hope they can keep people healthier and achieve measurable cost savings.
Aledade was co-founded in 2014 by Farzad Mostashari, a former health information technology chief in the Obama administration, and has welcomed other ex-government health figures into its ranks. In June 2023, President Joe Biden appointed Mandy Cohen, then executive vice president at Aledade, to head the Centers for Disease Control and Prevention in Atlanta.
Aledade has grown rapidly behind hundreds of millions of dollars in venture capital financing and was valued at $3.5 billion in 2023.
Mostashari, Aledade’s chief executive officer, declined to be interviewed on the record.
“As this is an active legal matter, we will not respond to individual allegations in the complaint,” Aledade said in a statement to KFF Health News. “We remain focused on our top priority of delivering high-quality, value-based care with our physician partners and will defend ourselves vigorously if needed in a court of law.”
The lawsuit also names as defendants 19 independent physician practices, many in small cities in Delaware, Kansas, Louisiana, North Carolina, Pennsylvania, and West Virginia. According to the suit, the doctors knowingly used Aledade software to trigger illegal billings, a practice known in the medical industry as “upcoding.” None has filed an answer in court.
More than two dozen whistleblower lawsuits, some dating back more than a decade, have accused Medicare health plans of overcharging the government by billing for medical conditions not supported by patient medical records. These cases have resulted in hundreds of millions of dollars in penalties. In September 2023, Cigna agreed to pay $37 million to settle one such case, for instance.
But the whistleblower suit filed against Aledade appears to be the first to allege upcoding within accountable care organizations, which describe part of their mission as foiling wasteful spending. ACOs including Aledade made headlines recently for helping to expose an alleged massive Medicare fraud involving urinary catheters, for instance.
Finding the ‘Gravy’
Singh’s suit targets Aledade’s use of coding software and guidance to medical practices that joined its network. Some doctors treated patients on standard Medicare through the ACO networks, while others cared for seniors enrolled in Medicare Advantage plans, according to the suit.
Medicare Advantage is a privately run alternative to standard Medicare that has surged in popularity and now cares for more than 30 million people. Aledade has sought to expand its services to Medicare Advantage enrollees.
The lawsuit alleges Aledade encouraged doctors to tack on suspect medical diagnoses that paid extra money. Aledade called it finding “the gravy sitting in the [patient’s] chart,” according to the suit.
The company “instructed” providers to diagnose diabetes with complications, “even if the patient’s diabetes was under control or the complicating factor no longer existed,” according to the suit.
Some medical practices in Delaware, North Carolina, and West Virginia billed the inflated code for more than 90% of their Medicare Advantage patients with diabetes, according to the suit.
The lawsuit also alleges that Aledade “rigged” the software to change a diagnosis of overweight to “morbid obesity,” which could pay about $2500 more per patient. Some providers coded morbid obesity for patients on traditional Medicare at 10 times the national average, according to the suit.
“This fraudulent coding guidance was known as ‘Aledade gospel,’ ” according to the suit, and following it “paid dividends in the form of millions of dollars in increased revenue.”
These tactics “usurped” the clinical judgment of doctors, according to the suit.
‘No Diagnosis Left Behind’
In its statement to KFF Health News, Aledade said its software offers doctors a range of data and guidance that helps them evaluate and treat patients.
“Aledade’s independent physicians remain solely responsible for all medical decision-making for their patients,” the statement read.
The company said it will “continue to advocate for changes to improve Medicare’s risk adjustment process to promote accuracy while also reducing unnecessary administrative burdens.”
In a message to employees and partner practices sent on Feb. 29, Mostashari noted that the Justice Department had declined to take over the False Claims Act case.
“We recently learned that the federal government has declined to join the case U.S. ex rel. Khushwinder Singh v. Aledade, Inc., et al. That’s good news, and a decision we wholeheartedly applaud given the baseless allegations about improper coding practices and wrongful termination brought by a former Aledade employee 3 years ago. We do not yet know how the full legal situation will play out but will defend ourselves vigorously if needed in a court of law,” the statement said.
The Justice Department advised the Seattle court on Jan. 9 that it would not intervene in the case “at this time,” which prompted an order to unseal it, court records show. Under the false claims law, whistleblowers can proceed with the case on their own. The Justice Department does not state a reason for declining a case but has said in other court cases that doing so has no bearing on its merits.
Singh argues in his complaint that many “unsupported” diagnosis codes were added during annual “wellness visits” and that they did not result in the patients receiving any additional medical care.
Aledade maintained Slack channels in which doctors could discuss the financial incentives for adding higher-paying diagnostic codes, according to the suit.
The company also closely monitored how doctors coded as part of an initiative dubbed “no diagnosis left behind,” according to the suit.
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Residents Unionizing: What Are the Benefits, the Downsides?
This transcript has been edited for clarity.
Hospital administrators and some department heads have been vocal about the potential for unions to affect both the attending-resident relationship and the ability for residents to directly discuss concerns and educational plans.
Sometimes, there are institution-specific issues as well. One example was at Loma Linda. They argued that unionization would go against their religious principles. They filed a lawsuit. That didn’t go through, and the residents won a few months later.
I know there’s always that one senior, older doctor who says, “Back in our day, we just worked, and we never complained.”
Look at the current situation that residents are facing now, with housing and rent prices and increasing costs of childcare. Sprinkle in some inflation, poor hospital staffing, increasing workload, and add in the fact that the average first-year resident salary in 2023 was around $64,000.
Now, if you look back to 2012, the average salary was around $55,000. If you adjust that for inflation, it would be around $75,000 today, which is more than what the average resident is getting paid.
Then, there are hospital administrators who say that the hospital does not have the money to meet these demands; meanwhile, hospital graduate medical education (GME) offices receive about $150,000 of Medicare funds per resident.
Obviously, there are additional costs when it comes to training and supporting residents. In general, unionizing freaks out the people handling all the cash.
There’s also the threat of a strike, which no hospital wants on their public record. A recent highly publicized event happened at New York’s Elmhurst Hospital, when 160 residents went on strike for 3 days until a deal was made.
Critics of unionizing also cite a particular study in JAMA, which included a survey of 5700 general surgery residents at 285 programs. It found that while unions helped with vacation time and housing stipends, the unions were not associated with improved burnout rates, suicidality, job satisfaction, duty hour violations, mistreatment, educational environment, or salary.
Now, granted, this isn’t the strongest study. It only sampled one group of residents, so I wouldn’t generalize these findings, but it’s still commonly cited by anti-union advocates.
Another potential downside, which is purely anecdotal because I can’t find any data to support this, is potential retaliation against residents or harm to the attending-resident relationship.
I’m an attending. I don’t really understand this one. I don’t exactly own stock in my hospital, nor am I making millions of dollars by siphoning GME money. I’m just trying to focus on educating and supporting my residents the best I can.
Dr. Patel is Clinical Instructor, Department of Pediatrics, Columbia University College of Physicians and Surgeons; Pediatric Hospitalist, Morgan Stanley Children’s Hospital of NewYork–Presbyterian, and Benioff Children’s Hospital, University of California San Francisco. He disclosed ties with Medumo Inc.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Hospital administrators and some department heads have been vocal about the potential for unions to affect both the attending-resident relationship and the ability for residents to directly discuss concerns and educational plans.
Sometimes, there are institution-specific issues as well. One example was at Loma Linda. They argued that unionization would go against their religious principles. They filed a lawsuit. That didn’t go through, and the residents won a few months later.
I know there’s always that one senior, older doctor who says, “Back in our day, we just worked, and we never complained.”
Look at the current situation that residents are facing now, with housing and rent prices and increasing costs of childcare. Sprinkle in some inflation, poor hospital staffing, increasing workload, and add in the fact that the average first-year resident salary in 2023 was around $64,000.
Now, if you look back to 2012, the average salary was around $55,000. If you adjust that for inflation, it would be around $75,000 today, which is more than what the average resident is getting paid.
Then, there are hospital administrators who say that the hospital does not have the money to meet these demands; meanwhile, hospital graduate medical education (GME) offices receive about $150,000 of Medicare funds per resident.
Obviously, there are additional costs when it comes to training and supporting residents. In general, unionizing freaks out the people handling all the cash.
There’s also the threat of a strike, which no hospital wants on their public record. A recent highly publicized event happened at New York’s Elmhurst Hospital, when 160 residents went on strike for 3 days until a deal was made.
Critics of unionizing also cite a particular study in JAMA, which included a survey of 5700 general surgery residents at 285 programs. It found that while unions helped with vacation time and housing stipends, the unions were not associated with improved burnout rates, suicidality, job satisfaction, duty hour violations, mistreatment, educational environment, or salary.
Now, granted, this isn’t the strongest study. It only sampled one group of residents, so I wouldn’t generalize these findings, but it’s still commonly cited by anti-union advocates.
Another potential downside, which is purely anecdotal because I can’t find any data to support this, is potential retaliation against residents or harm to the attending-resident relationship.
I’m an attending. I don’t really understand this one. I don’t exactly own stock in my hospital, nor am I making millions of dollars by siphoning GME money. I’m just trying to focus on educating and supporting my residents the best I can.
Dr. Patel is Clinical Instructor, Department of Pediatrics, Columbia University College of Physicians and Surgeons; Pediatric Hospitalist, Morgan Stanley Children’s Hospital of NewYork–Presbyterian, and Benioff Children’s Hospital, University of California San Francisco. He disclosed ties with Medumo Inc.
A version of this article first appeared on Medscape.com.
This transcript has been edited for clarity.
Hospital administrators and some department heads have been vocal about the potential for unions to affect both the attending-resident relationship and the ability for residents to directly discuss concerns and educational plans.
Sometimes, there are institution-specific issues as well. One example was at Loma Linda. They argued that unionization would go against their religious principles. They filed a lawsuit. That didn’t go through, and the residents won a few months later.
I know there’s always that one senior, older doctor who says, “Back in our day, we just worked, and we never complained.”
Look at the current situation that residents are facing now, with housing and rent prices and increasing costs of childcare. Sprinkle in some inflation, poor hospital staffing, increasing workload, and add in the fact that the average first-year resident salary in 2023 was around $64,000.
Now, if you look back to 2012, the average salary was around $55,000. If you adjust that for inflation, it would be around $75,000 today, which is more than what the average resident is getting paid.
Then, there are hospital administrators who say that the hospital does not have the money to meet these demands; meanwhile, hospital graduate medical education (GME) offices receive about $150,000 of Medicare funds per resident.
Obviously, there are additional costs when it comes to training and supporting residents. In general, unionizing freaks out the people handling all the cash.
There’s also the threat of a strike, which no hospital wants on their public record. A recent highly publicized event happened at New York’s Elmhurst Hospital, when 160 residents went on strike for 3 days until a deal was made.
Critics of unionizing also cite a particular study in JAMA, which included a survey of 5700 general surgery residents at 285 programs. It found that while unions helped with vacation time and housing stipends, the unions were not associated with improved burnout rates, suicidality, job satisfaction, duty hour violations, mistreatment, educational environment, or salary.
Now, granted, this isn’t the strongest study. It only sampled one group of residents, so I wouldn’t generalize these findings, but it’s still commonly cited by anti-union advocates.
Another potential downside, which is purely anecdotal because I can’t find any data to support this, is potential retaliation against residents or harm to the attending-resident relationship.
I’m an attending. I don’t really understand this one. I don’t exactly own stock in my hospital, nor am I making millions of dollars by siphoning GME money. I’m just trying to focus on educating and supporting my residents the best I can.
Dr. Patel is Clinical Instructor, Department of Pediatrics, Columbia University College of Physicians and Surgeons; Pediatric Hospitalist, Morgan Stanley Children’s Hospital of NewYork–Presbyterian, and Benioff Children’s Hospital, University of California San Francisco. He disclosed ties with Medumo Inc.
A version of this article first appeared on Medscape.com.