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Routine pharmacogenetic testing in psychiatry not indicated
LAS VEGAS –
“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”
According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”
Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”
Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.
“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.
The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.
Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.
“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”
Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.
In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.
Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.
LAS VEGAS –
“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”
According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”
Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”
Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.
“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.
The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.
Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.
“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”
Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.
In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.
Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.
LAS VEGAS –
“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”
According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”
Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”
Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.
“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.
The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.
Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.
“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”
Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.
In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.
Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.
REPORTING FROM NPA 2022
One-third of psoriatic arthritis patients could have metabolic syndrome, data analysis finds
of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.
Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.
However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.
For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.
The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.
The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.
Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).
The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).
Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”
“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.
The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.
However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.
“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.
The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.
of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.
Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.
However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.
For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.
The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.
The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.
Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).
The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).
Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”
“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.
The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.
However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.
“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.
The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.
of 724 individuals, as did approximately 23%-63% of patients across multiple studies, investigators from Spain report.
Previous studies of people with PsA in particular suggest they are at an increased risk of cardiovascular disease and have a higher prevalence of metabolic syndrome, prompting recommendations on cardiovascular risk management for patients with PsA, wrote the authors, Ana Urruticoechea-Arana, MD, of the department of rheumatology, Hospital Can Misses, Ibiza, Spain, and colleagues.
However, assessing the prevalence of metabolic syndrome remains a challenge because the definition varies across studies, they noted.
For a more thorough assessment of the prevalence of metabolic syndrome in this population, the researchers conducted a study using two sources: a systematic literature review of 18 studies published up to March 2019, and data on patients with PsA enrolled in the CARMA (Spanish Cardiovascular in Rheumatology) project, a longitudinal cohort observational study of adults with inflammatory diseases in Spain. The findings were published March 1 in the Journal of Clinical Rheumatology.
The literature review included a total of a total of 2,452 patients with PsA, with a mean age between 42 and 59 years, and a mean disease duration ranging from 3 to 14 years.
The definitions of metabolic syndrome varied; the most common was the definition from the National Cholesterol Education Program (NECP ATP III). Other definitions used in the studies included those issued by the International Diabetes Federation, the World Health Organization, and the American Heart Association.
Across these studies, the rate of metabolic syndrome ranged from 23.5% to 62.9%. Prevalence was similar between men and women. One study that included patients with a PsA disease duration of only 3 years showed a prevalence of 38%, similar to the average prevalence overall. Another study showed a significantly higher prevalence of metabolic syndrome in patients with PsA and cutaneous psoriasis, compared with those without psoriasis (40.8% vs. 13.16%; P = .006).
The CARMA study included 724 patients with PsA; 45.4% were women and 21.8% were smokers. The mean age of the population in this study was 51 years, and the mean disease duration was 9 years. Overall, 222 patients (30.7%) met at least three criteria for metabolic syndrome, based on the NCEP ATP III definition. The most common abnormal findings for traditional cardiovascular risk factors in the CARMA cohort were high blood pressure (66.8%), hyperglycemia (42.6%), and hypertriglyceridemia (30.6%).
Despite the variation in prevalence of metabolic syndrome, depending on the definition used, the authors wrote, “It can be stated that the rate of [metabolic syndrome] in patients with PsA is in general very high, especially if we take into account the mean age of patients included in the studies.”
“These findings support the hypotheses that this increase in the inflammatory pathway in PsA may contribute a higher risk of cardiovascular events and [metabolic syndrome] in patients with PsA than patients with psoriasis alone, the risk being even higher in severe PsA,” and that insulin resistance, metabolic syndrome, and atherosclerotic events “may have a common inflammatory basis,” the researchers wrote in their discussion of the results.
The study findings were limited by several factors, most importantly the variation in definitions of metabolic syndrome in the literature review, which limits the generalizability of the results, the researchers said. Limitations of the CARMA study include the focus only on patients who were being cared for in hospitals, which might yield an overestimation of metabolic syndrome, they added.
However, the results support findings from previous studies and highlight the need for proper assessment of body weight and cardiovascular risk factors in patients with PsA at the onset of disease, they said.
“Furthermore, it is necessary to conduct more research to standardize (and modify as appropriate) the definition of [metabolic syndrome] and establish the best strategy for managing it in these patients,” they concluded.
The study was funded by an independent grant from UCB Pharma. One author disclosed receiving grants from Pfizer, Abbvie, Novartis, Roche, UCB, Sanofi, BMS, Lilly, MSD, and Janssen. Lead author Dr. Urruticoechea-Arana and the other authors had no disclosures.
FROM JOURNAL OF CLINICAL RHEUMATOLOGY
ARBs and cancer risk: New meta-analysis raises questions again
The debate on whether the popular class of antihypertensive drugs, angiotensin receptor blockers (ARBs), may be associated with an increased risk for cancer has been reopened with the publication of a new meta-analysis.
The analysis found an increasing risk for cancer, and specifically lung cancer, with increasing cumulative exposure to these drugs.
The findings are reported in a study published online in PLOS ONE.
The author of this new meta-analysis is Ilke Sipahi, MD, a cardiologist from Acibadem University Medical School, Istanbul, who previously raised this issue in an initial meta-analysis published in 2010.
“The new meta-analysis is important because it is the first study to investigate whether there is a dose response in the association between ARBs and cancer,” Dr. Sipahi told this news organization.
“I found a clear signal of increased risk of cancer as exposure to ARBs increased, and the association started to become significant when the maximum dose was taken for 3 years,” he added.
Dr. Sipahi explained that in the first meta-analysis published in Lancet Oncology, he and his colleagues reported an increased cancer risk with ARBs based on observations from high-exposure trials – those that included higher doses of ARBs with a long duration of follow-up.
Following this publication, an investigation by the U.S. Food and Drug Administration refuted the risk, and a collaboration of ARB trial investigators also performed an analysis published in the Journal of Hypertension (2011. doi: 10.1097/HJH.0b013e328344a7de), which again did not show an increased risk for cancer with use of ARBs.
Dr. Sipahi claims that those analyses by the FDA and the ARB Trialists Collaboration, which were all trial-level meta-analyses, diluted the “high exposure” data (including higher doses taken for longer periods of time) with a large amount of other data on much lower exposures (lower doses and/or shorter time periods).
“The overall risk would then inevitably become nonsignificant. These analyses also did not look at different exposure levels,” he says.
“For cancer, the degree of exposure is obviously very important. The risk associated with smoking 2 or 3 cigarettes a day for a year is very different from that of smoking 2 packs a day for 40 years. The same principle applies to taking a medication,” Dr. Sipahi asserts.
From these latest data, he estimates that 120 patients needed to be treated with the maximal daily dose of an ARB for 4.7 years for one excess cancer diagnosis, and 464 patients needed to be treated for one excess lung cancer.
“Given that at least 200 million individuals are being treated with an ARB globally, approximately 1.7 million excess cancers (and 430,000 lung cancers) in 4.6 years could be potentially caused by this class of drugs,” he suggests.
For the current analysis, Dr. Sipahi used trial-level data taken from the paper by the ARB Trialists Collaboration and investigated the effect of exposure to ARBs – including both the dose taken and the length of treatment – on risk for cancer. He performed metaregression analyses that he says has not been done before.
“I mathematically quantitated the degree of exposure in each trial. And when the degree of exposure was correlated with risk of cancer, there was a significant association.”
The new meta-analysis includes 15 randomized controlled trials. The two coprimary outcomes were the relationship between cumulative exposure to ARBs and risk for all cancers combined and the relationship between cumulative exposure and risk for lung cancer.
In the trials, 74,021 patients were randomly assigned to an ARB, resulting in a total cumulative exposure of 172,389 person-years of exposure to daily high dose (or equivalent), and 61,197 patients were randomly assigned to control.
Results showed a highly significant correlation between the degree of cumulative exposure to ARBs and risk for all cancers combined (slope = 0.07; 95% confidence interval, 0.03-0.11; P < .001) and also lung cancer (slope = 0.16; 95% CI, 0.05-0.27; P = .003).
In trials where the cumulative exposure was greater than 3 years of exposure to daily high dose, there was a statistically significant increase in risk for all cancers combined (risk ratio, 1.11; 95% CI, 1.03-1.19; P = .006).
There was also a statistically significant increase in risk for lung cancers in trials where the cumulative exposure was greater than 2.5 years (RR, 1.21; 95% CI, 1.02-1.44; P = .03).
In trials with lower cumulative exposure to ARBs, there was no increased risk either for all cancers combined or lung cancer.
Dr. Sipahi reports that the cumulative exposure-risk relationship with ARBs was independent of background angiotensin-converting enzyme (ACE) inhibitor treatment or the type of control (placebo or nonplacebo control).
But he acknowledges that since this is a trial-level analysis, the effects of patient characteristics such as age and smoking status could not be examined because of lack of patient-level data.
Dr. Sipahi says he does not know the mechanism behind these findings, but he draws attention to the recent withdrawal of several thousand lots of ARB formulations because of the presence of potentially carcinogenic impurities that have been suggested to be a byproduct of ARB synthesis.
He also claims that unlike some other classes of antihypertensives, ARBs have not been shown to reduce the risk for MI, leading him to conclude that “other classes of antihypertensives with good safety and efficacy data (such as ACE-inhibitors, calcium-channel blockers or others) should become the preferred first-line agents in the treatment of hypertension.”
Dr. Sipahi wants the FDA to reinvestigate the issue of ARBs and cancer risk using individual patient data. “They already have the patient-level data from the trials. They should look at it more carefully and look at exposure levels and how they relate to cancer risk,” he said. “And the fact that there have been studies linking high ARB exposure levels to increased cancer risk should at least get a warning on the drug labels.”
A ‘clear increase’ in risk
Dr. Sipahi also points out that a link between ARBs and cancer has been found in another meta-analysis performed in 2013 by senior FDA analyst Thomas Marciniak, MD.
“Because he worked at the FDA, [Dr.] Marciniak had access to individual patent data. This is the best type of analysis and generally produces more accurate results than a trial-level meta-analysis,” Dr. Sipahi commented.
Dr. Marciniak’s analysis, which is available on the FDA website as part of another document, was not officially published elsewhere, and no further action has been taken on the issue.
Contacted by this news organization, Dr. Marciniak, who has now retired from the FDA, said he not only conducted a patient-level meta-analysis but also followed up adverse effects reported in the trials that could have been a symptom of cancer to establish further whether the patient was later diagnosed with cancer or not.
“I used every scrap of information sent in, including serious adverse event reports. I saw a clear increase in lung cancer risk with the ARBs,” Dr. Marciniak said. He did not, however, perform a dose-response relationship analysis.
Asked why his analysis and those from Dr. Sipahi reach different conclusions to those from the ARB Trialists Collaboration and the official FDA investigations, Dr. Marciniak said: “It may be that there were too many low-exposure trials that just washed out the difference. But trial data generally do not capture adverse events such as cancer, which takes a long time to develop, very well, and if you’re not really looking for it, you’re probably not going to find it.”
Dr. Marciniak said that Dr. Sipahi’s current findings are in line with his results. “Finding a dose response, to me, is extremely compelling, and I think the signal here is real,” he commented. “I think this new paper from Dr. Sipahi verifies what I found. I think the FDA should now release all individual patient data it has.”
Contacted for comment, an FDA spokesperson said, “Generally the FDA does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”
They added: “The FDA has ongoing assessment, surveillance, compliance, and pharmaceutical quality efforts across every product area, and we will continue to work with drug manufacturers to ensure safe, effective, and high-quality drugs for the American public. When we identify new and previously unrecognized risks to safety and quality, we react swiftly to resolve the problem, as we have done in responding to the recent findings of nitrosamines in certain medicines.”
Analysis ‘should be taken seriously’
Commenting on this new study, Steve Nissen, MD, a key figure in analyzing such complex data and who has himself uncovered problems with high-profile drugs in the past, says the current analysis should be taken seriously.
Dr. Nissen, who was Dr. Sipahi’s senior during his post-doc position at the Cleveland Clinic, wrote an editorial accompanying Dr. Sipahi’s first paper and calling for urgent regulatory review of the evidence.
He says the new findings add to previous evidence suggesting a possible risk for cancer with ARBs.
“[Dr.] Sipahi is a capable researcher, and this analysis needs to be taken seriously, but it needs to be verified. It is not possible to draw a strong conclusion on this analysis, as it is not based on individual patient data, but I don’t think it should be ignored,” Dr. Nissen stated.
“I will say again what I said 12 years ago – that the regulatory agencies need to carefully review all their data in a very detailed way. The FDA and EMA have access to the individual patient data and are both very capable of doing the required analyses.”
Limitations of trial-level analysis
Asked to evaluate the statistics in the current paper, Andrew Althouse, PhD, an assistant professor of medicine at the University of Pittsburgh, and a clinical trial statistician, explained that the best way to do a thorough analysis of the relationship between ARB exposure and risk for incident cancer would involve the use of patient-level data.
“As such data were not available to Dr. Sipahi, I believe he is doing as well as he can. But without full access to individual patient-level data from the respective trials, it is difficult to support any firm conclusions,” Dr. Althouse said in an interview.
He suggested that the meta-regression analyses used in the paper were unable to properly estimate the relationship between ARB exposure and risk for incident cancer.
“Taken at face value, the current analysis suggests that [in] trials with longer follow-up duration (and therefore greater cumulative exposure to ARB for the treatment group), the risk of developing cancer for patients in the ARB group versus the non-ARB group was progressively higher. But this study doesn’t take into account the actual amount of follow-up time for individual patients or potential differences in the amount of follow-up time between the two groups in each trial,” he noted.
Dr. Althouse says this raises the possibility of “competing risks” or the idea that if ARBs reduce cardiovascular disease and cardiovascular death, then there would be more patients remaining in that arm who could go on to develop cancer. “So a crude count of the number of cancer cases may look as though patients receiving ARBs are ‘more likely’ to develop cancer, but this is a mirage.”
He added: “When there are some patients dying during the study, the only way to tell whether the intervention actually increased the risk of other health-related complications is to have an analysis that properly accounts for each patient’s time-at-risk of the outcome. Unfortunately, properly analyzing this requires the use of patient-level data.”
Cardiologists skeptical?
Cardiology experts asked for thoughts on the new meta-analysis were also cautious to read too much into the findings.
Franz Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “Perhaps one would simply ignore this rambling, cherrypicking-based condemnation of ARBs if it were not for the powerful negative connotation of the word cancer. Thus, the meta-analysis of Dr. Sipahi purporting that ARBs could be increasing the development of cancers in a cumulative way is of concern to both physicians and patients.”
But, raising a similar point to Dr. Althouse about competing risks, Dr. Messerli said: “We have to consider that as one gets older, the cardiovascular disease state and cancer state will compete with each other for the outcome of death. The better that therapies protect against cardiovascular death, the more they will increase life expectancy and thus the risk of cancer.”
He also added that “in head-to-head comparisons with ACE inhibitors, ARBs showed similar efficacy in terms of death, CV mortality, MI, stroke, and end-stage kidney disease, so can we agree that the attempt of Dr. Sipahi to disparage ARBs as a class is much ado about nothing?”
Dr. Nissen, however, said he views the idea of competing risk as “a bit of a stretch” in this case. “Although ARBs are effective antihypertensive drugs, I would say there is very little evidence that they would prolong survival versus other antihypertensives.”
Dr. Sipahi also claims that this argument is not relevant to the current analysis. “ARBs did not increase survival in any of the high-exposure trials that showed an excess in cancers. Therefore, competing outcomes, or ‘survival bias’ to be more specific, is not a possibility here,” he says.
George Bakris, MD, professor of medicine at the University of Chicago Medicine, noted that while the current study shows a slight increase in cancer incidence, especially lung cancer, among those taking ARBs for more than 3 years, it “totally ignores the overwhelming cardiovascular risk reduction seen in the trials.”
“Moreover,” he adds, “the author notes that the findings were independent of ACE-inhibitors, but he can’t rule out smoking and age as factors, two major risk factors for cancer and lung cancer, specifically. Thus, as typical of these types of analyses, the associations are probably true/true unrelated or, at best, partially related.”
Dr. Bakris referred to the potentially carcinogenic nitrosamine and azido compounds found in several ARB formulations that have resulted in recalls.
“At any stage of drug synthesis throughout each product’s lifetime, these impurities may evolve if an amine reacts with a nitrosating agent coexisting under appropriate conditions,” he said. “Drug regulatory authorities worldwide have established stringent guidelines on nitrosamine contamination for all drug products. The studies noted in the author’s analysis were done well before these guidelines were implemented. Hence, many of the issues raised by the authors using trials from 10-20 years ago are not of significant concern.”
Still, the cardiology experts all agreed on one thing – that patients should continue to take ARBs as prescribed.
Noting that worldwide authorities are now addressing the issue of possible carcinogen contamination, Dr. Bakris stressed that patients “should not panic and should not stop their meds.”
Dr. Nissen added: “What we don’t want is for patents who are taking ARBs to stop taking these medications – hypertension is a deadly disorder, and these drugs have proven cardiovascular benefits.”
Dr. Sipahi received no specific funding for this work. He reports receiving lecture honoraria from Novartis, Boehringer Ingelheim, Sanofi, Sandoz, Bristol-Myers Squibb, Bayer, Pfizer, Ranbaxy, Servier, and ARIS and served on advisory boards for Novartis, Sanofi, Servier, Bristol-Myers Squibb, Pfizer, Bayer and I.E. Ulagay. The other commenters do not report any relevant disclosures.
A version of this article first appeared on Medscape.com.
The debate on whether the popular class of antihypertensive drugs, angiotensin receptor blockers (ARBs), may be associated with an increased risk for cancer has been reopened with the publication of a new meta-analysis.
The analysis found an increasing risk for cancer, and specifically lung cancer, with increasing cumulative exposure to these drugs.
The findings are reported in a study published online in PLOS ONE.
The author of this new meta-analysis is Ilke Sipahi, MD, a cardiologist from Acibadem University Medical School, Istanbul, who previously raised this issue in an initial meta-analysis published in 2010.
“The new meta-analysis is important because it is the first study to investigate whether there is a dose response in the association between ARBs and cancer,” Dr. Sipahi told this news organization.
“I found a clear signal of increased risk of cancer as exposure to ARBs increased, and the association started to become significant when the maximum dose was taken for 3 years,” he added.
Dr. Sipahi explained that in the first meta-analysis published in Lancet Oncology, he and his colleagues reported an increased cancer risk with ARBs based on observations from high-exposure trials – those that included higher doses of ARBs with a long duration of follow-up.
Following this publication, an investigation by the U.S. Food and Drug Administration refuted the risk, and a collaboration of ARB trial investigators also performed an analysis published in the Journal of Hypertension (2011. doi: 10.1097/HJH.0b013e328344a7de), which again did not show an increased risk for cancer with use of ARBs.
Dr. Sipahi claims that those analyses by the FDA and the ARB Trialists Collaboration, which were all trial-level meta-analyses, diluted the “high exposure” data (including higher doses taken for longer periods of time) with a large amount of other data on much lower exposures (lower doses and/or shorter time periods).
“The overall risk would then inevitably become nonsignificant. These analyses also did not look at different exposure levels,” he says.
“For cancer, the degree of exposure is obviously very important. The risk associated with smoking 2 or 3 cigarettes a day for a year is very different from that of smoking 2 packs a day for 40 years. The same principle applies to taking a medication,” Dr. Sipahi asserts.
From these latest data, he estimates that 120 patients needed to be treated with the maximal daily dose of an ARB for 4.7 years for one excess cancer diagnosis, and 464 patients needed to be treated for one excess lung cancer.
“Given that at least 200 million individuals are being treated with an ARB globally, approximately 1.7 million excess cancers (and 430,000 lung cancers) in 4.6 years could be potentially caused by this class of drugs,” he suggests.
For the current analysis, Dr. Sipahi used trial-level data taken from the paper by the ARB Trialists Collaboration and investigated the effect of exposure to ARBs – including both the dose taken and the length of treatment – on risk for cancer. He performed metaregression analyses that he says has not been done before.
“I mathematically quantitated the degree of exposure in each trial. And when the degree of exposure was correlated with risk of cancer, there was a significant association.”
The new meta-analysis includes 15 randomized controlled trials. The two coprimary outcomes were the relationship between cumulative exposure to ARBs and risk for all cancers combined and the relationship between cumulative exposure and risk for lung cancer.
In the trials, 74,021 patients were randomly assigned to an ARB, resulting in a total cumulative exposure of 172,389 person-years of exposure to daily high dose (or equivalent), and 61,197 patients were randomly assigned to control.
Results showed a highly significant correlation between the degree of cumulative exposure to ARBs and risk for all cancers combined (slope = 0.07; 95% confidence interval, 0.03-0.11; P < .001) and also lung cancer (slope = 0.16; 95% CI, 0.05-0.27; P = .003).
In trials where the cumulative exposure was greater than 3 years of exposure to daily high dose, there was a statistically significant increase in risk for all cancers combined (risk ratio, 1.11; 95% CI, 1.03-1.19; P = .006).
There was also a statistically significant increase in risk for lung cancers in trials where the cumulative exposure was greater than 2.5 years (RR, 1.21; 95% CI, 1.02-1.44; P = .03).
In trials with lower cumulative exposure to ARBs, there was no increased risk either for all cancers combined or lung cancer.
Dr. Sipahi reports that the cumulative exposure-risk relationship with ARBs was independent of background angiotensin-converting enzyme (ACE) inhibitor treatment or the type of control (placebo or nonplacebo control).
But he acknowledges that since this is a trial-level analysis, the effects of patient characteristics such as age and smoking status could not be examined because of lack of patient-level data.
Dr. Sipahi says he does not know the mechanism behind these findings, but he draws attention to the recent withdrawal of several thousand lots of ARB formulations because of the presence of potentially carcinogenic impurities that have been suggested to be a byproduct of ARB synthesis.
He also claims that unlike some other classes of antihypertensives, ARBs have not been shown to reduce the risk for MI, leading him to conclude that “other classes of antihypertensives with good safety and efficacy data (such as ACE-inhibitors, calcium-channel blockers or others) should become the preferred first-line agents in the treatment of hypertension.”
Dr. Sipahi wants the FDA to reinvestigate the issue of ARBs and cancer risk using individual patient data. “They already have the patient-level data from the trials. They should look at it more carefully and look at exposure levels and how they relate to cancer risk,” he said. “And the fact that there have been studies linking high ARB exposure levels to increased cancer risk should at least get a warning on the drug labels.”
A ‘clear increase’ in risk
Dr. Sipahi also points out that a link between ARBs and cancer has been found in another meta-analysis performed in 2013 by senior FDA analyst Thomas Marciniak, MD.
“Because he worked at the FDA, [Dr.] Marciniak had access to individual patent data. This is the best type of analysis and generally produces more accurate results than a trial-level meta-analysis,” Dr. Sipahi commented.
Dr. Marciniak’s analysis, which is available on the FDA website as part of another document, was not officially published elsewhere, and no further action has been taken on the issue.
Contacted by this news organization, Dr. Marciniak, who has now retired from the FDA, said he not only conducted a patient-level meta-analysis but also followed up adverse effects reported in the trials that could have been a symptom of cancer to establish further whether the patient was later diagnosed with cancer or not.
“I used every scrap of information sent in, including serious adverse event reports. I saw a clear increase in lung cancer risk with the ARBs,” Dr. Marciniak said. He did not, however, perform a dose-response relationship analysis.
Asked why his analysis and those from Dr. Sipahi reach different conclusions to those from the ARB Trialists Collaboration and the official FDA investigations, Dr. Marciniak said: “It may be that there were too many low-exposure trials that just washed out the difference. But trial data generally do not capture adverse events such as cancer, which takes a long time to develop, very well, and if you’re not really looking for it, you’re probably not going to find it.”
Dr. Marciniak said that Dr. Sipahi’s current findings are in line with his results. “Finding a dose response, to me, is extremely compelling, and I think the signal here is real,” he commented. “I think this new paper from Dr. Sipahi verifies what I found. I think the FDA should now release all individual patient data it has.”
Contacted for comment, an FDA spokesperson said, “Generally the FDA does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”
They added: “The FDA has ongoing assessment, surveillance, compliance, and pharmaceutical quality efforts across every product area, and we will continue to work with drug manufacturers to ensure safe, effective, and high-quality drugs for the American public. When we identify new and previously unrecognized risks to safety and quality, we react swiftly to resolve the problem, as we have done in responding to the recent findings of nitrosamines in certain medicines.”
Analysis ‘should be taken seriously’
Commenting on this new study, Steve Nissen, MD, a key figure in analyzing such complex data and who has himself uncovered problems with high-profile drugs in the past, says the current analysis should be taken seriously.
Dr. Nissen, who was Dr. Sipahi’s senior during his post-doc position at the Cleveland Clinic, wrote an editorial accompanying Dr. Sipahi’s first paper and calling for urgent regulatory review of the evidence.
He says the new findings add to previous evidence suggesting a possible risk for cancer with ARBs.
“[Dr.] Sipahi is a capable researcher, and this analysis needs to be taken seriously, but it needs to be verified. It is not possible to draw a strong conclusion on this analysis, as it is not based on individual patient data, but I don’t think it should be ignored,” Dr. Nissen stated.
“I will say again what I said 12 years ago – that the regulatory agencies need to carefully review all their data in a very detailed way. The FDA and EMA have access to the individual patient data and are both very capable of doing the required analyses.”
Limitations of trial-level analysis
Asked to evaluate the statistics in the current paper, Andrew Althouse, PhD, an assistant professor of medicine at the University of Pittsburgh, and a clinical trial statistician, explained that the best way to do a thorough analysis of the relationship between ARB exposure and risk for incident cancer would involve the use of patient-level data.
“As such data were not available to Dr. Sipahi, I believe he is doing as well as he can. But without full access to individual patient-level data from the respective trials, it is difficult to support any firm conclusions,” Dr. Althouse said in an interview.
He suggested that the meta-regression analyses used in the paper were unable to properly estimate the relationship between ARB exposure and risk for incident cancer.
“Taken at face value, the current analysis suggests that [in] trials with longer follow-up duration (and therefore greater cumulative exposure to ARB for the treatment group), the risk of developing cancer for patients in the ARB group versus the non-ARB group was progressively higher. But this study doesn’t take into account the actual amount of follow-up time for individual patients or potential differences in the amount of follow-up time between the two groups in each trial,” he noted.
Dr. Althouse says this raises the possibility of “competing risks” or the idea that if ARBs reduce cardiovascular disease and cardiovascular death, then there would be more patients remaining in that arm who could go on to develop cancer. “So a crude count of the number of cancer cases may look as though patients receiving ARBs are ‘more likely’ to develop cancer, but this is a mirage.”
He added: “When there are some patients dying during the study, the only way to tell whether the intervention actually increased the risk of other health-related complications is to have an analysis that properly accounts for each patient’s time-at-risk of the outcome. Unfortunately, properly analyzing this requires the use of patient-level data.”
Cardiologists skeptical?
Cardiology experts asked for thoughts on the new meta-analysis were also cautious to read too much into the findings.
Franz Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “Perhaps one would simply ignore this rambling, cherrypicking-based condemnation of ARBs if it were not for the powerful negative connotation of the word cancer. Thus, the meta-analysis of Dr. Sipahi purporting that ARBs could be increasing the development of cancers in a cumulative way is of concern to both physicians and patients.”
But, raising a similar point to Dr. Althouse about competing risks, Dr. Messerli said: “We have to consider that as one gets older, the cardiovascular disease state and cancer state will compete with each other for the outcome of death. The better that therapies protect against cardiovascular death, the more they will increase life expectancy and thus the risk of cancer.”
He also added that “in head-to-head comparisons with ACE inhibitors, ARBs showed similar efficacy in terms of death, CV mortality, MI, stroke, and end-stage kidney disease, so can we agree that the attempt of Dr. Sipahi to disparage ARBs as a class is much ado about nothing?”
Dr. Nissen, however, said he views the idea of competing risk as “a bit of a stretch” in this case. “Although ARBs are effective antihypertensive drugs, I would say there is very little evidence that they would prolong survival versus other antihypertensives.”
Dr. Sipahi also claims that this argument is not relevant to the current analysis. “ARBs did not increase survival in any of the high-exposure trials that showed an excess in cancers. Therefore, competing outcomes, or ‘survival bias’ to be more specific, is not a possibility here,” he says.
George Bakris, MD, professor of medicine at the University of Chicago Medicine, noted that while the current study shows a slight increase in cancer incidence, especially lung cancer, among those taking ARBs for more than 3 years, it “totally ignores the overwhelming cardiovascular risk reduction seen in the trials.”
“Moreover,” he adds, “the author notes that the findings were independent of ACE-inhibitors, but he can’t rule out smoking and age as factors, two major risk factors for cancer and lung cancer, specifically. Thus, as typical of these types of analyses, the associations are probably true/true unrelated or, at best, partially related.”
Dr. Bakris referred to the potentially carcinogenic nitrosamine and azido compounds found in several ARB formulations that have resulted in recalls.
“At any stage of drug synthesis throughout each product’s lifetime, these impurities may evolve if an amine reacts with a nitrosating agent coexisting under appropriate conditions,” he said. “Drug regulatory authorities worldwide have established stringent guidelines on nitrosamine contamination for all drug products. The studies noted in the author’s analysis were done well before these guidelines were implemented. Hence, many of the issues raised by the authors using trials from 10-20 years ago are not of significant concern.”
Still, the cardiology experts all agreed on one thing – that patients should continue to take ARBs as prescribed.
Noting that worldwide authorities are now addressing the issue of possible carcinogen contamination, Dr. Bakris stressed that patients “should not panic and should not stop their meds.”
Dr. Nissen added: “What we don’t want is for patents who are taking ARBs to stop taking these medications – hypertension is a deadly disorder, and these drugs have proven cardiovascular benefits.”
Dr. Sipahi received no specific funding for this work. He reports receiving lecture honoraria from Novartis, Boehringer Ingelheim, Sanofi, Sandoz, Bristol-Myers Squibb, Bayer, Pfizer, Ranbaxy, Servier, and ARIS and served on advisory boards for Novartis, Sanofi, Servier, Bristol-Myers Squibb, Pfizer, Bayer and I.E. Ulagay. The other commenters do not report any relevant disclosures.
A version of this article first appeared on Medscape.com.
The debate on whether the popular class of antihypertensive drugs, angiotensin receptor blockers (ARBs), may be associated with an increased risk for cancer has been reopened with the publication of a new meta-analysis.
The analysis found an increasing risk for cancer, and specifically lung cancer, with increasing cumulative exposure to these drugs.
The findings are reported in a study published online in PLOS ONE.
The author of this new meta-analysis is Ilke Sipahi, MD, a cardiologist from Acibadem University Medical School, Istanbul, who previously raised this issue in an initial meta-analysis published in 2010.
“The new meta-analysis is important because it is the first study to investigate whether there is a dose response in the association between ARBs and cancer,” Dr. Sipahi told this news organization.
“I found a clear signal of increased risk of cancer as exposure to ARBs increased, and the association started to become significant when the maximum dose was taken for 3 years,” he added.
Dr. Sipahi explained that in the first meta-analysis published in Lancet Oncology, he and his colleagues reported an increased cancer risk with ARBs based on observations from high-exposure trials – those that included higher doses of ARBs with a long duration of follow-up.
Following this publication, an investigation by the U.S. Food and Drug Administration refuted the risk, and a collaboration of ARB trial investigators also performed an analysis published in the Journal of Hypertension (2011. doi: 10.1097/HJH.0b013e328344a7de), which again did not show an increased risk for cancer with use of ARBs.
Dr. Sipahi claims that those analyses by the FDA and the ARB Trialists Collaboration, which were all trial-level meta-analyses, diluted the “high exposure” data (including higher doses taken for longer periods of time) with a large amount of other data on much lower exposures (lower doses and/or shorter time periods).
“The overall risk would then inevitably become nonsignificant. These analyses also did not look at different exposure levels,” he says.
“For cancer, the degree of exposure is obviously very important. The risk associated with smoking 2 or 3 cigarettes a day for a year is very different from that of smoking 2 packs a day for 40 years. The same principle applies to taking a medication,” Dr. Sipahi asserts.
From these latest data, he estimates that 120 patients needed to be treated with the maximal daily dose of an ARB for 4.7 years for one excess cancer diagnosis, and 464 patients needed to be treated for one excess lung cancer.
“Given that at least 200 million individuals are being treated with an ARB globally, approximately 1.7 million excess cancers (and 430,000 lung cancers) in 4.6 years could be potentially caused by this class of drugs,” he suggests.
For the current analysis, Dr. Sipahi used trial-level data taken from the paper by the ARB Trialists Collaboration and investigated the effect of exposure to ARBs – including both the dose taken and the length of treatment – on risk for cancer. He performed metaregression analyses that he says has not been done before.
“I mathematically quantitated the degree of exposure in each trial. And when the degree of exposure was correlated with risk of cancer, there was a significant association.”
The new meta-analysis includes 15 randomized controlled trials. The two coprimary outcomes were the relationship between cumulative exposure to ARBs and risk for all cancers combined and the relationship between cumulative exposure and risk for lung cancer.
In the trials, 74,021 patients were randomly assigned to an ARB, resulting in a total cumulative exposure of 172,389 person-years of exposure to daily high dose (or equivalent), and 61,197 patients were randomly assigned to control.
Results showed a highly significant correlation between the degree of cumulative exposure to ARBs and risk for all cancers combined (slope = 0.07; 95% confidence interval, 0.03-0.11; P < .001) and also lung cancer (slope = 0.16; 95% CI, 0.05-0.27; P = .003).
In trials where the cumulative exposure was greater than 3 years of exposure to daily high dose, there was a statistically significant increase in risk for all cancers combined (risk ratio, 1.11; 95% CI, 1.03-1.19; P = .006).
There was also a statistically significant increase in risk for lung cancers in trials where the cumulative exposure was greater than 2.5 years (RR, 1.21; 95% CI, 1.02-1.44; P = .03).
In trials with lower cumulative exposure to ARBs, there was no increased risk either for all cancers combined or lung cancer.
Dr. Sipahi reports that the cumulative exposure-risk relationship with ARBs was independent of background angiotensin-converting enzyme (ACE) inhibitor treatment or the type of control (placebo or nonplacebo control).
But he acknowledges that since this is a trial-level analysis, the effects of patient characteristics such as age and smoking status could not be examined because of lack of patient-level data.
Dr. Sipahi says he does not know the mechanism behind these findings, but he draws attention to the recent withdrawal of several thousand lots of ARB formulations because of the presence of potentially carcinogenic impurities that have been suggested to be a byproduct of ARB synthesis.
He also claims that unlike some other classes of antihypertensives, ARBs have not been shown to reduce the risk for MI, leading him to conclude that “other classes of antihypertensives with good safety and efficacy data (such as ACE-inhibitors, calcium-channel blockers or others) should become the preferred first-line agents in the treatment of hypertension.”
Dr. Sipahi wants the FDA to reinvestigate the issue of ARBs and cancer risk using individual patient data. “They already have the patient-level data from the trials. They should look at it more carefully and look at exposure levels and how they relate to cancer risk,” he said. “And the fact that there have been studies linking high ARB exposure levels to increased cancer risk should at least get a warning on the drug labels.”
A ‘clear increase’ in risk
Dr. Sipahi also points out that a link between ARBs and cancer has been found in another meta-analysis performed in 2013 by senior FDA analyst Thomas Marciniak, MD.
“Because he worked at the FDA, [Dr.] Marciniak had access to individual patent data. This is the best type of analysis and generally produces more accurate results than a trial-level meta-analysis,” Dr. Sipahi commented.
Dr. Marciniak’s analysis, which is available on the FDA website as part of another document, was not officially published elsewhere, and no further action has been taken on the issue.
Contacted by this news organization, Dr. Marciniak, who has now retired from the FDA, said he not only conducted a patient-level meta-analysis but also followed up adverse effects reported in the trials that could have been a symptom of cancer to establish further whether the patient was later diagnosed with cancer or not.
“I used every scrap of information sent in, including serious adverse event reports. I saw a clear increase in lung cancer risk with the ARBs,” Dr. Marciniak said. He did not, however, perform a dose-response relationship analysis.
Asked why his analysis and those from Dr. Sipahi reach different conclusions to those from the ARB Trialists Collaboration and the official FDA investigations, Dr. Marciniak said: “It may be that there were too many low-exposure trials that just washed out the difference. But trial data generally do not capture adverse events such as cancer, which takes a long time to develop, very well, and if you’re not really looking for it, you’re probably not going to find it.”
Dr. Marciniak said that Dr. Sipahi’s current findings are in line with his results. “Finding a dose response, to me, is extremely compelling, and I think the signal here is real,” he commented. “I think this new paper from Dr. Sipahi verifies what I found. I think the FDA should now release all individual patient data it has.”
Contacted for comment, an FDA spokesperson said, “Generally the FDA does not comment on specific studies but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”
They added: “The FDA has ongoing assessment, surveillance, compliance, and pharmaceutical quality efforts across every product area, and we will continue to work with drug manufacturers to ensure safe, effective, and high-quality drugs for the American public. When we identify new and previously unrecognized risks to safety and quality, we react swiftly to resolve the problem, as we have done in responding to the recent findings of nitrosamines in certain medicines.”
Analysis ‘should be taken seriously’
Commenting on this new study, Steve Nissen, MD, a key figure in analyzing such complex data and who has himself uncovered problems with high-profile drugs in the past, says the current analysis should be taken seriously.
Dr. Nissen, who was Dr. Sipahi’s senior during his post-doc position at the Cleveland Clinic, wrote an editorial accompanying Dr. Sipahi’s first paper and calling for urgent regulatory review of the evidence.
He says the new findings add to previous evidence suggesting a possible risk for cancer with ARBs.
“[Dr.] Sipahi is a capable researcher, and this analysis needs to be taken seriously, but it needs to be verified. It is not possible to draw a strong conclusion on this analysis, as it is not based on individual patient data, but I don’t think it should be ignored,” Dr. Nissen stated.
“I will say again what I said 12 years ago – that the regulatory agencies need to carefully review all their data in a very detailed way. The FDA and EMA have access to the individual patient data and are both very capable of doing the required analyses.”
Limitations of trial-level analysis
Asked to evaluate the statistics in the current paper, Andrew Althouse, PhD, an assistant professor of medicine at the University of Pittsburgh, and a clinical trial statistician, explained that the best way to do a thorough analysis of the relationship between ARB exposure and risk for incident cancer would involve the use of patient-level data.
“As such data were not available to Dr. Sipahi, I believe he is doing as well as he can. But without full access to individual patient-level data from the respective trials, it is difficult to support any firm conclusions,” Dr. Althouse said in an interview.
He suggested that the meta-regression analyses used in the paper were unable to properly estimate the relationship between ARB exposure and risk for incident cancer.
“Taken at face value, the current analysis suggests that [in] trials with longer follow-up duration (and therefore greater cumulative exposure to ARB for the treatment group), the risk of developing cancer for patients in the ARB group versus the non-ARB group was progressively higher. But this study doesn’t take into account the actual amount of follow-up time for individual patients or potential differences in the amount of follow-up time between the two groups in each trial,” he noted.
Dr. Althouse says this raises the possibility of “competing risks” or the idea that if ARBs reduce cardiovascular disease and cardiovascular death, then there would be more patients remaining in that arm who could go on to develop cancer. “So a crude count of the number of cancer cases may look as though patients receiving ARBs are ‘more likely’ to develop cancer, but this is a mirage.”
He added: “When there are some patients dying during the study, the only way to tell whether the intervention actually increased the risk of other health-related complications is to have an analysis that properly accounts for each patient’s time-at-risk of the outcome. Unfortunately, properly analyzing this requires the use of patient-level data.”
Cardiologists skeptical?
Cardiology experts asked for thoughts on the new meta-analysis were also cautious to read too much into the findings.
Franz Messerli, MD, professor of medicine at the University of Bern, Switzerland, commented: “Perhaps one would simply ignore this rambling, cherrypicking-based condemnation of ARBs if it were not for the powerful negative connotation of the word cancer. Thus, the meta-analysis of Dr. Sipahi purporting that ARBs could be increasing the development of cancers in a cumulative way is of concern to both physicians and patients.”
But, raising a similar point to Dr. Althouse about competing risks, Dr. Messerli said: “We have to consider that as one gets older, the cardiovascular disease state and cancer state will compete with each other for the outcome of death. The better that therapies protect against cardiovascular death, the more they will increase life expectancy and thus the risk of cancer.”
He also added that “in head-to-head comparisons with ACE inhibitors, ARBs showed similar efficacy in terms of death, CV mortality, MI, stroke, and end-stage kidney disease, so can we agree that the attempt of Dr. Sipahi to disparage ARBs as a class is much ado about nothing?”
Dr. Nissen, however, said he views the idea of competing risk as “a bit of a stretch” in this case. “Although ARBs are effective antihypertensive drugs, I would say there is very little evidence that they would prolong survival versus other antihypertensives.”
Dr. Sipahi also claims that this argument is not relevant to the current analysis. “ARBs did not increase survival in any of the high-exposure trials that showed an excess in cancers. Therefore, competing outcomes, or ‘survival bias’ to be more specific, is not a possibility here,” he says.
George Bakris, MD, professor of medicine at the University of Chicago Medicine, noted that while the current study shows a slight increase in cancer incidence, especially lung cancer, among those taking ARBs for more than 3 years, it “totally ignores the overwhelming cardiovascular risk reduction seen in the trials.”
“Moreover,” he adds, “the author notes that the findings were independent of ACE-inhibitors, but he can’t rule out smoking and age as factors, two major risk factors for cancer and lung cancer, specifically. Thus, as typical of these types of analyses, the associations are probably true/true unrelated or, at best, partially related.”
Dr. Bakris referred to the potentially carcinogenic nitrosamine and azido compounds found in several ARB formulations that have resulted in recalls.
“At any stage of drug synthesis throughout each product’s lifetime, these impurities may evolve if an amine reacts with a nitrosating agent coexisting under appropriate conditions,” he said. “Drug regulatory authorities worldwide have established stringent guidelines on nitrosamine contamination for all drug products. The studies noted in the author’s analysis were done well before these guidelines were implemented. Hence, many of the issues raised by the authors using trials from 10-20 years ago are not of significant concern.”
Still, the cardiology experts all agreed on one thing – that patients should continue to take ARBs as prescribed.
Noting that worldwide authorities are now addressing the issue of possible carcinogen contamination, Dr. Bakris stressed that patients “should not panic and should not stop their meds.”
Dr. Nissen added: “What we don’t want is for patents who are taking ARBs to stop taking these medications – hypertension is a deadly disorder, and these drugs have proven cardiovascular benefits.”
Dr. Sipahi received no specific funding for this work. He reports receiving lecture honoraria from Novartis, Boehringer Ingelheim, Sanofi, Sandoz, Bristol-Myers Squibb, Bayer, Pfizer, Ranbaxy, Servier, and ARIS and served on advisory boards for Novartis, Sanofi, Servier, Bristol-Myers Squibb, Pfizer, Bayer and I.E. Ulagay. The other commenters do not report any relevant disclosures.
A version of this article first appeared on Medscape.com.
Beware of the latest TikTok trend: Nasal spray tans
Although nasal spray tanning is being described as a new “viral” trend, it seems to have gotten its start as early as the spring of 2021. The tanning method appears to be especially popular in the United Kingdom, where self-tanning product brands have TikTok videos promoting nasal sprays.
The rising concerns of this and other viral TikTok trends has now prompted a bipartisan group of seven state attorneys general to launch an investigation.
“As children and teens already grapple with issues of anxiety, social pressure, and depression, we cannot allow social media to further harm their physical health and mental wellbeing,” Massachusetts Attorney General Maura Healey, a Democrat, said in a statement. “State attorneys general have an imperative to protect young people and seek more information about how companies like TikTok are influencing their daily lives.”
Ms. Healey, along with colleagues from California, Florida, Kentucky, Nebraska, New Jersey, Tennessee, and Vermont, will whether Chinese-based TikTok violates state consumer protection laws.
The trend of people shooting spray tan up their nose is just the latest in a long line of so-called TikTok challenges that have caused controversy, and often, injury.
In a February TikTok, put out by the British company So Tanned (@_sotanned), a young woman appears with text stating that she uses nasal spray “morning and night” and then adds self-tanning oral drops a half hour before getting into a tanning bed.
But, dermatologist Lily Talakoub, MD, of McLean, Va., posted a TikTok with the bold warning “DO NOT USE NASAL TANNING SPRAY!” In the video, the white coat–clad Dr. Talakoub is in the foreground of the TikTok made by @Sashawoodx.
“Don’t try this at home,” said Dr. Talakoub.
“Don’t try this even if you think it can make you tanner. It can cause nausea, vomiting, very bad side effects,” she said, adding “this can be very dangerous to your health.”
It’s also worth mentioning that self-tanning products are not approved by the Food and Drug Administration for inhalation.
Still, another U.K. company, 2btanned, posted a TikTok showing a user spraying the product up his nose and, in the comments, @2btanned suggested that the spray should be used at least a week or two before sun exposure “in order to get full effects.”
@Sashawoodx tells her viewers: “Don’t walk ... RUN for these products,” as she shows herself in several different outfits, squirting 2btanned spray up her nose. As of March 2, the TikTok video had been viewed over 212,000 times.
TikTokker @giannaarose, who has 125,000 followers, said in a video that she uses two to three sprays up the nose before stepping into the tanning bed. A commenter said, “this is scary but where do I buy it”.
The main ingredient in self-tanning products is dihydroxyacetone, or DHA. DHA, which is FDA-approved for use on skin, causes a chemical reaction when heat is applied, and a pigment is deposited on the skin.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said, given that self-tanning products were never meant to be inhaled and that nasal sprays of any kind must be approved by the FDA, a company promoting the products is engaged in a dangerous game.
“People could go to jail over this,” said Dr. Friedman. What’s more, the products are unlikely to produce a tan.
“Because of the way self-tanners work, it would make no sense,” said Dr. Friedman.
“It’s purely a camouflage,” he said, adding that it does not produce melanin. Self-tanners were never intended to be inhaled, “so who knows what those ingredients would do to a different anatomical site like the inner passages of the nose.”
At a minimum, spraying into the nose could at cause irritation. But it could also potentially lead to acute or long-term damage, he said.
Some other spray ingredients, such as tyrosine and tyrosinase, are involved in producing melanin, but they only act within skin cells. If sprayed into the nose, the ingredients might produce melanin inside the nose, but not on the skin.
“This is not going to work,” said Dr. Friedman. “If anything, it could be dangerous.”
He added that there’s no such thing as a safe tan, and that self-tanning products offer no protection from dangerous ultraviolet rays. The nasal sprays are “quick fixes” that are not going to work.
“At the end of the day, just don’t inhale,” Dr. Friedman said.
A version of this article first appeared on WebMD.com.
Although nasal spray tanning is being described as a new “viral” trend, it seems to have gotten its start as early as the spring of 2021. The tanning method appears to be especially popular in the United Kingdom, where self-tanning product brands have TikTok videos promoting nasal sprays.
The rising concerns of this and other viral TikTok trends has now prompted a bipartisan group of seven state attorneys general to launch an investigation.
“As children and teens already grapple with issues of anxiety, social pressure, and depression, we cannot allow social media to further harm their physical health and mental wellbeing,” Massachusetts Attorney General Maura Healey, a Democrat, said in a statement. “State attorneys general have an imperative to protect young people and seek more information about how companies like TikTok are influencing their daily lives.”
Ms. Healey, along with colleagues from California, Florida, Kentucky, Nebraska, New Jersey, Tennessee, and Vermont, will whether Chinese-based TikTok violates state consumer protection laws.
The trend of people shooting spray tan up their nose is just the latest in a long line of so-called TikTok challenges that have caused controversy, and often, injury.
In a February TikTok, put out by the British company So Tanned (@_sotanned), a young woman appears with text stating that she uses nasal spray “morning and night” and then adds self-tanning oral drops a half hour before getting into a tanning bed.
But, dermatologist Lily Talakoub, MD, of McLean, Va., posted a TikTok with the bold warning “DO NOT USE NASAL TANNING SPRAY!” In the video, the white coat–clad Dr. Talakoub is in the foreground of the TikTok made by @Sashawoodx.
“Don’t try this at home,” said Dr. Talakoub.
“Don’t try this even if you think it can make you tanner. It can cause nausea, vomiting, very bad side effects,” she said, adding “this can be very dangerous to your health.”
It’s also worth mentioning that self-tanning products are not approved by the Food and Drug Administration for inhalation.
Still, another U.K. company, 2btanned, posted a TikTok showing a user spraying the product up his nose and, in the comments, @2btanned suggested that the spray should be used at least a week or two before sun exposure “in order to get full effects.”
@Sashawoodx tells her viewers: “Don’t walk ... RUN for these products,” as she shows herself in several different outfits, squirting 2btanned spray up her nose. As of March 2, the TikTok video had been viewed over 212,000 times.
TikTokker @giannaarose, who has 125,000 followers, said in a video that she uses two to three sprays up the nose before stepping into the tanning bed. A commenter said, “this is scary but where do I buy it”.
The main ingredient in self-tanning products is dihydroxyacetone, or DHA. DHA, which is FDA-approved for use on skin, causes a chemical reaction when heat is applied, and a pigment is deposited on the skin.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said, given that self-tanning products were never meant to be inhaled and that nasal sprays of any kind must be approved by the FDA, a company promoting the products is engaged in a dangerous game.
“People could go to jail over this,” said Dr. Friedman. What’s more, the products are unlikely to produce a tan.
“Because of the way self-tanners work, it would make no sense,” said Dr. Friedman.
“It’s purely a camouflage,” he said, adding that it does not produce melanin. Self-tanners were never intended to be inhaled, “so who knows what those ingredients would do to a different anatomical site like the inner passages of the nose.”
At a minimum, spraying into the nose could at cause irritation. But it could also potentially lead to acute or long-term damage, he said.
Some other spray ingredients, such as tyrosine and tyrosinase, are involved in producing melanin, but they only act within skin cells. If sprayed into the nose, the ingredients might produce melanin inside the nose, but not on the skin.
“This is not going to work,” said Dr. Friedman. “If anything, it could be dangerous.”
He added that there’s no such thing as a safe tan, and that self-tanning products offer no protection from dangerous ultraviolet rays. The nasal sprays are “quick fixes” that are not going to work.
“At the end of the day, just don’t inhale,” Dr. Friedman said.
A version of this article first appeared on WebMD.com.
Although nasal spray tanning is being described as a new “viral” trend, it seems to have gotten its start as early as the spring of 2021. The tanning method appears to be especially popular in the United Kingdom, where self-tanning product brands have TikTok videos promoting nasal sprays.
The rising concerns of this and other viral TikTok trends has now prompted a bipartisan group of seven state attorneys general to launch an investigation.
“As children and teens already grapple with issues of anxiety, social pressure, and depression, we cannot allow social media to further harm their physical health and mental wellbeing,” Massachusetts Attorney General Maura Healey, a Democrat, said in a statement. “State attorneys general have an imperative to protect young people and seek more information about how companies like TikTok are influencing their daily lives.”
Ms. Healey, along with colleagues from California, Florida, Kentucky, Nebraska, New Jersey, Tennessee, and Vermont, will whether Chinese-based TikTok violates state consumer protection laws.
The trend of people shooting spray tan up their nose is just the latest in a long line of so-called TikTok challenges that have caused controversy, and often, injury.
In a February TikTok, put out by the British company So Tanned (@_sotanned), a young woman appears with text stating that she uses nasal spray “morning and night” and then adds self-tanning oral drops a half hour before getting into a tanning bed.
But, dermatologist Lily Talakoub, MD, of McLean, Va., posted a TikTok with the bold warning “DO NOT USE NASAL TANNING SPRAY!” In the video, the white coat–clad Dr. Talakoub is in the foreground of the TikTok made by @Sashawoodx.
“Don’t try this at home,” said Dr. Talakoub.
“Don’t try this even if you think it can make you tanner. It can cause nausea, vomiting, very bad side effects,” she said, adding “this can be very dangerous to your health.”
It’s also worth mentioning that self-tanning products are not approved by the Food and Drug Administration for inhalation.
Still, another U.K. company, 2btanned, posted a TikTok showing a user spraying the product up his nose and, in the comments, @2btanned suggested that the spray should be used at least a week or two before sun exposure “in order to get full effects.”
@Sashawoodx tells her viewers: “Don’t walk ... RUN for these products,” as she shows herself in several different outfits, squirting 2btanned spray up her nose. As of March 2, the TikTok video had been viewed over 212,000 times.
TikTokker @giannaarose, who has 125,000 followers, said in a video that she uses two to three sprays up the nose before stepping into the tanning bed. A commenter said, “this is scary but where do I buy it”.
The main ingredient in self-tanning products is dihydroxyacetone, or DHA. DHA, which is FDA-approved for use on skin, causes a chemical reaction when heat is applied, and a pigment is deposited on the skin.
Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, said, given that self-tanning products were never meant to be inhaled and that nasal sprays of any kind must be approved by the FDA, a company promoting the products is engaged in a dangerous game.
“People could go to jail over this,” said Dr. Friedman. What’s more, the products are unlikely to produce a tan.
“Because of the way self-tanners work, it would make no sense,” said Dr. Friedman.
“It’s purely a camouflage,” he said, adding that it does not produce melanin. Self-tanners were never intended to be inhaled, “so who knows what those ingredients would do to a different anatomical site like the inner passages of the nose.”
At a minimum, spraying into the nose could at cause irritation. But it could also potentially lead to acute or long-term damage, he said.
Some other spray ingredients, such as tyrosine and tyrosinase, are involved in producing melanin, but they only act within skin cells. If sprayed into the nose, the ingredients might produce melanin inside the nose, but not on the skin.
“This is not going to work,” said Dr. Friedman. “If anything, it could be dangerous.”
He added that there’s no such thing as a safe tan, and that self-tanning products offer no protection from dangerous ultraviolet rays. The nasal sprays are “quick fixes” that are not going to work.
“At the end of the day, just don’t inhale,” Dr. Friedman said.
A version of this article first appeared on WebMD.com.
DSM-5 update: What’s new?
Ahead of its official release on March 18, the new Diagnostic and Statistical Manual of Mental Disorders, which is in the form of a textbook, is already drawing some criticism.
It also includes symptom codes for suicidal behavior and nonsuicidal self-injury, clarifying modifications to criteria sets for more than 70 disorders, including autism spectrum disorder; changes in terminology for gender dysphoria; and a comprehensive review of the impact of racism and discrimination on the diagnosis and manifestations of mental disorders.
The Text Revision is a compilation of iterative changes that have been made online on a rolling basis since the DSM-5 was first published in 2013.
“The goal of the Text Revision was to allow a thorough revision of the text, not the criteria,” Paul Appelbaum, MD, chair of the APA’s DSM steering committee, told this news organization.
For the Text Revision, some 200 experts across a variety of APA working groups recommended changes to the text based on a comprehensive literature review, said Appelbaum, who is the Elizabeth K. Dollard Professor of Psychiatry, Medicine and Law, and director of the division of law, ethics and psychiatry at Columbia University, New York.
However, there’s not a lot that’s new, in part, because there have been few therapeutic advances.
Money maker?
Allen Frances, MD, chair of the DSM-4 task force and professor and chair emeritus of psychiatry at Duke University, Durham, N.C., said the APA is publishing the Text Revision “just to make money. They’re very anxious to do anything that will increase sales and having a revision forces some people, especially in institutions, to buy the book, even though it may not have anything substantive to add to the original.”
Dr. Frances told this news organization that when the APA published the first DSM in the late 1970s, “it became an instantaneous best-seller, to everyone’s surprise.”
The APA would not comment on how many of the $170 (list price) volumes it sells or how much those sales contribute to its budget.
Dr. Appelbaum acknowledged, “at any point in time, the canonical version is the online version.” However, it’s clear from DSM-5 sales “that many people still value having a hard copy of the DSM available to them.”
Prolonged grief: Timely or overkill?
Persistent complex bereavement disorder (PCBD) was listed as a “condition for further study” in DSM-5. After a 2019 workshop aimed at getting consensus for diagnosis criteria, the APA board approved the new prolonged grief disorder in October 2020, and the APA assembly approved the new disorder in November 2020.
Given the 950,000 deaths from COVID-19 over the past 2 years, inclusion of prolonged grief disorder in the DSM-5 may arrive at just the right time.
The diagnostic criteria for PCBD include:
- The development of a persistent grief response (longer than a year for adults and 6 months for children and adolescents) characterized by one or both of the following symptoms, which have been present most days to a clinically significant degree, and have occurred nearly every day for at least the last month: intense yearning/longing for the deceased person; preoccupation with thoughts or memories of the deceased person.
- Since the death, at least three symptoms present most days to a clinically significant degree, and occurring nearly every day for at least the last month, including identity disruption, marked sense of disbelief about the death, avoidance of reminders that the person is dead, intense emotional pain related to the death, difficulty reintegrating into one’s relationships and activities after the death, emotional numbness, feeling that life is meaningless as a result of the death, and intense loneliness as a result of the death.
- The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
- The duration and severity of the bereavement reaction clearly exceed expected social, cultural, or religious norms for the individual’s culture and context.
- The symptoms are not better explained by another mental disorder, such as major depressive disorder (MDD) or PTSD, and are not attributable to the physiological effects of a substance or another medical condition.
Dr. Frances said he believes creating a new diagnosis pathologizes grief. In DSM-3 and DSM-4, an exception was made under the diagnosis of MDD for individuals who had recently lost a loved one. “We wanted to have at least an opportunity for people to grieve without being stigmatized, mislabeled, and overtreated with medication.”
DSM-5 removed the bereavement exclusion. After 2 weeks, people who are grieving and have particular symptoms could receive a diagnosis of MDD, said Dr. Frances. He believes the exclusion should have been broadened to cover anyone experiencing a major loss – such as a job loss or divorce. If someone is having prolonged symptoms that interfere with functioning, they should get an MDD diagnosis.
The new disorder “doesn’t solve anything, it just adds to the confusion and stigmatization, and it’s part of a kind of creeping medical imperialization of everyday life, where everything has to have a mental disorder label,” Dr. Frances said.
However, Dr. Appelbaum countered that “the criteria for prolonged grief disorder are constructed in such a way as to make every effort to exclude people who are going through a normal grieving process.”
“Part of the purpose of the data analyses was to ensure the criteria that were adopted would, in fact, effectively distinguish between what anybody goes through, say when someone close to you dies, and this unusual prolonged grieving process without end that affects a much smaller number of people but which really can be crippling for them,” he added.
The Text Revision adds new symptom codes for suicidal behavior and nonsuicidal self-injury, which appear in the chapter, “Other Conditions That May Be a Focus of Clinical Attention,” said Dr. Appelbaum.
“Both suicidal behavior and nonsuicidal self-injury seem pretty persuasively to fall into that category – something a clinician would want to know about, pay attention to, and factor into treatment planning, although they are behaviors that cross many diagnostic categories,” he added.
Codes also provide a systematic way of ascertaining the incidence and prevalence of such behaviors, said Dr. Appelbaum.
Changes to gender terminology
The Text Revision also tweaks some terminology with respect to transgender individuals. The term “desired gender” is now “experienced gender”, the term “cross-sex medical procedure” is now “gender-affirming medical procedure”, and the terms “natal male/natal female” are now “individual assigned male/female at birth”.
Dr. Frances said that the existence of gender dysphoria as a diagnosis has been a matter of controversy ever since it was first included.
“The transgender community has had mixed feelings on whether there should be anything at all in the manual,” he said. On one hand is the argument that gender dysphoria should be removed because it’s not really a psychiatric issue.
“We seriously considered eliminating it altogether in DSM-4,” said Dr. Frances.
However, an argument in favor of keeping it was that if the diagnosis was removed, it would mean that people could not receive treatment. “There’s no right argument for this dilemma,” he said.
Dr. Frances, who has been a frequent critic of DSM-5, said he believes the manual continues to miss opportunities to tighten criteria for many diagnoses, including ADHD and autism spectrum disorder.
“There’s a consistent pattern of taking behaviors and symptoms of behaviors that are on the border with normality and expanding the definition of mental disorder and reducing the realm of normality,” he said.
That has consequences, Dr. Frances added. “When someone gets a diagnosis that they need to get, it’s the beginning of a much better future. When someone gets a diagnosis that’s a mislabel that they don’t need, it has all harms and no benefits. It’s stigmatizing, leads to too much treatment, the wrong treatment, and it’s much more harmful than helpful.”
A version of this article first appeared on Medscape.com.
Ahead of its official release on March 18, the new Diagnostic and Statistical Manual of Mental Disorders, which is in the form of a textbook, is already drawing some criticism.
It also includes symptom codes for suicidal behavior and nonsuicidal self-injury, clarifying modifications to criteria sets for more than 70 disorders, including autism spectrum disorder; changes in terminology for gender dysphoria; and a comprehensive review of the impact of racism and discrimination on the diagnosis and manifestations of mental disorders.
The Text Revision is a compilation of iterative changes that have been made online on a rolling basis since the DSM-5 was first published in 2013.
“The goal of the Text Revision was to allow a thorough revision of the text, not the criteria,” Paul Appelbaum, MD, chair of the APA’s DSM steering committee, told this news organization.
For the Text Revision, some 200 experts across a variety of APA working groups recommended changes to the text based on a comprehensive literature review, said Appelbaum, who is the Elizabeth K. Dollard Professor of Psychiatry, Medicine and Law, and director of the division of law, ethics and psychiatry at Columbia University, New York.
However, there’s not a lot that’s new, in part, because there have been few therapeutic advances.
Money maker?
Allen Frances, MD, chair of the DSM-4 task force and professor and chair emeritus of psychiatry at Duke University, Durham, N.C., said the APA is publishing the Text Revision “just to make money. They’re very anxious to do anything that will increase sales and having a revision forces some people, especially in institutions, to buy the book, even though it may not have anything substantive to add to the original.”
Dr. Frances told this news organization that when the APA published the first DSM in the late 1970s, “it became an instantaneous best-seller, to everyone’s surprise.”
The APA would not comment on how many of the $170 (list price) volumes it sells or how much those sales contribute to its budget.
Dr. Appelbaum acknowledged, “at any point in time, the canonical version is the online version.” However, it’s clear from DSM-5 sales “that many people still value having a hard copy of the DSM available to them.”
Prolonged grief: Timely or overkill?
Persistent complex bereavement disorder (PCBD) was listed as a “condition for further study” in DSM-5. After a 2019 workshop aimed at getting consensus for diagnosis criteria, the APA board approved the new prolonged grief disorder in October 2020, and the APA assembly approved the new disorder in November 2020.
Given the 950,000 deaths from COVID-19 over the past 2 years, inclusion of prolonged grief disorder in the DSM-5 may arrive at just the right time.
The diagnostic criteria for PCBD include:
- The development of a persistent grief response (longer than a year for adults and 6 months for children and adolescents) characterized by one or both of the following symptoms, which have been present most days to a clinically significant degree, and have occurred nearly every day for at least the last month: intense yearning/longing for the deceased person; preoccupation with thoughts or memories of the deceased person.
- Since the death, at least three symptoms present most days to a clinically significant degree, and occurring nearly every day for at least the last month, including identity disruption, marked sense of disbelief about the death, avoidance of reminders that the person is dead, intense emotional pain related to the death, difficulty reintegrating into one’s relationships and activities after the death, emotional numbness, feeling that life is meaningless as a result of the death, and intense loneliness as a result of the death.
- The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
- The duration and severity of the bereavement reaction clearly exceed expected social, cultural, or religious norms for the individual’s culture and context.
- The symptoms are not better explained by another mental disorder, such as major depressive disorder (MDD) or PTSD, and are not attributable to the physiological effects of a substance or another medical condition.
Dr. Frances said he believes creating a new diagnosis pathologizes grief. In DSM-3 and DSM-4, an exception was made under the diagnosis of MDD for individuals who had recently lost a loved one. “We wanted to have at least an opportunity for people to grieve without being stigmatized, mislabeled, and overtreated with medication.”
DSM-5 removed the bereavement exclusion. After 2 weeks, people who are grieving and have particular symptoms could receive a diagnosis of MDD, said Dr. Frances. He believes the exclusion should have been broadened to cover anyone experiencing a major loss – such as a job loss or divorce. If someone is having prolonged symptoms that interfere with functioning, they should get an MDD diagnosis.
The new disorder “doesn’t solve anything, it just adds to the confusion and stigmatization, and it’s part of a kind of creeping medical imperialization of everyday life, where everything has to have a mental disorder label,” Dr. Frances said.
However, Dr. Appelbaum countered that “the criteria for prolonged grief disorder are constructed in such a way as to make every effort to exclude people who are going through a normal grieving process.”
“Part of the purpose of the data analyses was to ensure the criteria that were adopted would, in fact, effectively distinguish between what anybody goes through, say when someone close to you dies, and this unusual prolonged grieving process without end that affects a much smaller number of people but which really can be crippling for them,” he added.
The Text Revision adds new symptom codes for suicidal behavior and nonsuicidal self-injury, which appear in the chapter, “Other Conditions That May Be a Focus of Clinical Attention,” said Dr. Appelbaum.
“Both suicidal behavior and nonsuicidal self-injury seem pretty persuasively to fall into that category – something a clinician would want to know about, pay attention to, and factor into treatment planning, although they are behaviors that cross many diagnostic categories,” he added.
Codes also provide a systematic way of ascertaining the incidence and prevalence of such behaviors, said Dr. Appelbaum.
Changes to gender terminology
The Text Revision also tweaks some terminology with respect to transgender individuals. The term “desired gender” is now “experienced gender”, the term “cross-sex medical procedure” is now “gender-affirming medical procedure”, and the terms “natal male/natal female” are now “individual assigned male/female at birth”.
Dr. Frances said that the existence of gender dysphoria as a diagnosis has been a matter of controversy ever since it was first included.
“The transgender community has had mixed feelings on whether there should be anything at all in the manual,” he said. On one hand is the argument that gender dysphoria should be removed because it’s not really a psychiatric issue.
“We seriously considered eliminating it altogether in DSM-4,” said Dr. Frances.
However, an argument in favor of keeping it was that if the diagnosis was removed, it would mean that people could not receive treatment. “There’s no right argument for this dilemma,” he said.
Dr. Frances, who has been a frequent critic of DSM-5, said he believes the manual continues to miss opportunities to tighten criteria for many diagnoses, including ADHD and autism spectrum disorder.
“There’s a consistent pattern of taking behaviors and symptoms of behaviors that are on the border with normality and expanding the definition of mental disorder and reducing the realm of normality,” he said.
That has consequences, Dr. Frances added. “When someone gets a diagnosis that they need to get, it’s the beginning of a much better future. When someone gets a diagnosis that’s a mislabel that they don’t need, it has all harms and no benefits. It’s stigmatizing, leads to too much treatment, the wrong treatment, and it’s much more harmful than helpful.”
A version of this article first appeared on Medscape.com.
Ahead of its official release on March 18, the new Diagnostic and Statistical Manual of Mental Disorders, which is in the form of a textbook, is already drawing some criticism.
It also includes symptom codes for suicidal behavior and nonsuicidal self-injury, clarifying modifications to criteria sets for more than 70 disorders, including autism spectrum disorder; changes in terminology for gender dysphoria; and a comprehensive review of the impact of racism and discrimination on the diagnosis and manifestations of mental disorders.
The Text Revision is a compilation of iterative changes that have been made online on a rolling basis since the DSM-5 was first published in 2013.
“The goal of the Text Revision was to allow a thorough revision of the text, not the criteria,” Paul Appelbaum, MD, chair of the APA’s DSM steering committee, told this news organization.
For the Text Revision, some 200 experts across a variety of APA working groups recommended changes to the text based on a comprehensive literature review, said Appelbaum, who is the Elizabeth K. Dollard Professor of Psychiatry, Medicine and Law, and director of the division of law, ethics and psychiatry at Columbia University, New York.
However, there’s not a lot that’s new, in part, because there have been few therapeutic advances.
Money maker?
Allen Frances, MD, chair of the DSM-4 task force and professor and chair emeritus of psychiatry at Duke University, Durham, N.C., said the APA is publishing the Text Revision “just to make money. They’re very anxious to do anything that will increase sales and having a revision forces some people, especially in institutions, to buy the book, even though it may not have anything substantive to add to the original.”
Dr. Frances told this news organization that when the APA published the first DSM in the late 1970s, “it became an instantaneous best-seller, to everyone’s surprise.”
The APA would not comment on how many of the $170 (list price) volumes it sells or how much those sales contribute to its budget.
Dr. Appelbaum acknowledged, “at any point in time, the canonical version is the online version.” However, it’s clear from DSM-5 sales “that many people still value having a hard copy of the DSM available to them.”
Prolonged grief: Timely or overkill?
Persistent complex bereavement disorder (PCBD) was listed as a “condition for further study” in DSM-5. After a 2019 workshop aimed at getting consensus for diagnosis criteria, the APA board approved the new prolonged grief disorder in October 2020, and the APA assembly approved the new disorder in November 2020.
Given the 950,000 deaths from COVID-19 over the past 2 years, inclusion of prolonged grief disorder in the DSM-5 may arrive at just the right time.
The diagnostic criteria for PCBD include:
- The development of a persistent grief response (longer than a year for adults and 6 months for children and adolescents) characterized by one or both of the following symptoms, which have been present most days to a clinically significant degree, and have occurred nearly every day for at least the last month: intense yearning/longing for the deceased person; preoccupation with thoughts or memories of the deceased person.
- Since the death, at least three symptoms present most days to a clinically significant degree, and occurring nearly every day for at least the last month, including identity disruption, marked sense of disbelief about the death, avoidance of reminders that the person is dead, intense emotional pain related to the death, difficulty reintegrating into one’s relationships and activities after the death, emotional numbness, feeling that life is meaningless as a result of the death, and intense loneliness as a result of the death.
- The disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of functioning.
- The duration and severity of the bereavement reaction clearly exceed expected social, cultural, or religious norms for the individual’s culture and context.
- The symptoms are not better explained by another mental disorder, such as major depressive disorder (MDD) or PTSD, and are not attributable to the physiological effects of a substance or another medical condition.
Dr. Frances said he believes creating a new diagnosis pathologizes grief. In DSM-3 and DSM-4, an exception was made under the diagnosis of MDD for individuals who had recently lost a loved one. “We wanted to have at least an opportunity for people to grieve without being stigmatized, mislabeled, and overtreated with medication.”
DSM-5 removed the bereavement exclusion. After 2 weeks, people who are grieving and have particular symptoms could receive a diagnosis of MDD, said Dr. Frances. He believes the exclusion should have been broadened to cover anyone experiencing a major loss – such as a job loss or divorce. If someone is having prolonged symptoms that interfere with functioning, they should get an MDD diagnosis.
The new disorder “doesn’t solve anything, it just adds to the confusion and stigmatization, and it’s part of a kind of creeping medical imperialization of everyday life, where everything has to have a mental disorder label,” Dr. Frances said.
However, Dr. Appelbaum countered that “the criteria for prolonged grief disorder are constructed in such a way as to make every effort to exclude people who are going through a normal grieving process.”
“Part of the purpose of the data analyses was to ensure the criteria that were adopted would, in fact, effectively distinguish between what anybody goes through, say when someone close to you dies, and this unusual prolonged grieving process without end that affects a much smaller number of people but which really can be crippling for them,” he added.
The Text Revision adds new symptom codes for suicidal behavior and nonsuicidal self-injury, which appear in the chapter, “Other Conditions That May Be a Focus of Clinical Attention,” said Dr. Appelbaum.
“Both suicidal behavior and nonsuicidal self-injury seem pretty persuasively to fall into that category – something a clinician would want to know about, pay attention to, and factor into treatment planning, although they are behaviors that cross many diagnostic categories,” he added.
Codes also provide a systematic way of ascertaining the incidence and prevalence of such behaviors, said Dr. Appelbaum.
Changes to gender terminology
The Text Revision also tweaks some terminology with respect to transgender individuals. The term “desired gender” is now “experienced gender”, the term “cross-sex medical procedure” is now “gender-affirming medical procedure”, and the terms “natal male/natal female” are now “individual assigned male/female at birth”.
Dr. Frances said that the existence of gender dysphoria as a diagnosis has been a matter of controversy ever since it was first included.
“The transgender community has had mixed feelings on whether there should be anything at all in the manual,” he said. On one hand is the argument that gender dysphoria should be removed because it’s not really a psychiatric issue.
“We seriously considered eliminating it altogether in DSM-4,” said Dr. Frances.
However, an argument in favor of keeping it was that if the diagnosis was removed, it would mean that people could not receive treatment. “There’s no right argument for this dilemma,” he said.
Dr. Frances, who has been a frequent critic of DSM-5, said he believes the manual continues to miss opportunities to tighten criteria for many diagnoses, including ADHD and autism spectrum disorder.
“There’s a consistent pattern of taking behaviors and symptoms of behaviors that are on the border with normality and expanding the definition of mental disorder and reducing the realm of normality,” he said.
That has consequences, Dr. Frances added. “When someone gets a diagnosis that they need to get, it’s the beginning of a much better future. When someone gets a diagnosis that’s a mislabel that they don’t need, it has all harms and no benefits. It’s stigmatizing, leads to too much treatment, the wrong treatment, and it’s much more harmful than helpful.”
A version of this article first appeared on Medscape.com.
A First Look at the VA MISSION Act Veteran Health Administration Medical School Scholarship and Loan Repayment Programs
As one of 4 statutory missions, the US Department of Veterans Affairs (VA) educates and trains health professionals to enhance the quality of and timely access to care provided to veterans within the Veterans Health Administration (VHA). To achieve its mission to
Despite its long-term success affiliating with medical schools, VA has continued to be challenged by physician staff shortages with wide variability in the number and specialty of available health care professionals across facilities.3,4 A 2020 VA Office of Inspector General report on VHA occupational staffing shortages concluded that numerous physician specialties were difficult to recruit due to a lack of qualified applicants, noncompetitive salary, and less desirable geographic locations.3
Federal health professions scholarship programs and loan repayment programs have long been used to address physician shortages.4 Focusing on physician shortages in underserved areas in the US, the Emergency Health Personnel Act of 1970 and its subsequent amendments paved the way for various federal medical school scholarship and loan repayment programs.5 Similarly, physician shortages in the armed forces were mitigated through the Uniformed Services Health Professions Revitalization Act of 1972 (USHPRA).6,7
In 2018, Congress passed the VA MISSION (Maintaining Internal Systems and Strengthening Integrated Outside Networks) Act, which included sections designed to alleviate physician shortages in the VHA.8 These sections authorized scholarships similar to those offered by the US Department of Defense (DoD) and loan repayment programs. Section 301 created the Health Professions Scholarship Program (HPSP), which offers scholarships for physicians and dentists. Section 302 increased the maximum debt reduction through the Education Debt Reduction Program (EDRP). Section 303 authorizes the Specialty Education Loan Repayment Program (SELRP), which provides for repayment of educational loans for physicians in specialties deemed necessary for VA. Finally, Section 304 created the Veterans Healing Veterans (VHV), a pilot scholarship specifically for veteran medical students.
Program Characteristics
Health Professions Scholarship
The VA HPSP is a program for physicians and dentists that extends from 2020 to 2033. The HPSP funds the costs of tuition, fees, and provides a stipend with a service obligation of 18 months for each year of support. The program is authorized for 10 years and must provide a minimum of 50 scholarships annually for physicians or dentists based on VHA needs. Applications are screened based on criteria that include a commitment to rural or underserved populations, veteran status, grade point average, essays, and letters of recommendation. Although the minimum required number of scholarships annually is 50, VA anticipates providing 1000 scholarships over 10 years with an aim to significantly increase the number physicians at VHA facilities (Table 1).
Implemented in 2020, the VHV was a 1-year pilot program. It offered scholarships to 2 veterans attending medical school at each of the 5 Teague-Cranston and the 4 Historically Black College and University (HBCU) medical schools (Table 2). The intent of the program was to determine the feasibility of increasing the pool of veteran physicians at VHA. Eligible applicants were notified of the scholarship opportunity through the American Medical College Application Service or through the medical school. Applicants must have separated from military service within the preceding 10 years of being admitted to medical school. In exchange for full tuition, fees, a monthly stipend, and rotation travel costs, the recipients accepted a 4-year clinical service obligation at VA facilities after completing their residency training.
Specialty Education Loan Repayment
The SELRP is a loan repayment program available to recently graduated physicians. Applicants must have graduated from an accredited medical or osteopathic school, matched to an accredited residency program and be ≥ 2 years from completion of residency. The specialties qualifying for SELRP are determined through an analysis of succession planning by the VA Office of Workforce Management and Consulting and change based on VA physician workforce needs. The SELRP provides loan repayment in the amount of $40,000 per year for up to 4 years, with a service obligation of 1 year for each $40,000 of support. In April 2021, VA began accepting applications from the eligible specialties of family medicine, internal medicine, gastroenterology, psychiatry, emergency medicine, and geriatrics.
Education Debt Reduction
The EDRP offers debt relief to clinicians in the most difficult to recruit professions, including physicians (generalists and specialists), registered nurses, licensed practical nurses, social workers, and psychologists. The list of difficult to recruit positions is developed annually by VA facilities. Annual reimbursements through the program may be used for tuition and expenses, such as fees, books, supplies, equipment, and other materials. In 2018, through the MISSION Act Section 302, the annual loan repayment was increased from $24,000 to $40,000, and the maximum level of support was increased from $120,000 to $200,000 over 5 years. Recipients receive reimbursement for loan repayment at the end of each year or service period and recipients are not required to remain in VA for 5 years.
Program Results
Health Professions Scholarship
For academic years 2020/2021 and 2021/2022, 126 HPSP applications from both allopathic and osteopathic schools were submitted and 51 scholarships were awarded (Table 3). Assuming an average residency length of 4 years, VHA estimates that these awards will yield 204 service-year equivalents by 2029.
Veterans Healing Veterans
In the VHV program, scholarship recipients came from 5 Teague-Cranston schools; 2 at University of South Carolina, 2 at East Tennessee State University, 2 at Wright State University, 1 at Texas A&M College of Medicine, 1 at Marshall University; and 3 HBCUs; 2 at Howard University, 1 at Morehouse School of Medicine and 1 at Meharry Medical College. The Charles R. Drew University of Medicine and Science did not nominate any students for the scholarship. Assuming all recipients complete postgraduate training, the VHV scholarship program will provide an additional 12 veteran physicians to serve at VA for at least 4 years each (48 service years).
Specialty Education Loan Repayment
Fourteen applicants have been approved, including 5 in psychiatry, 4 in family medicine, 3 in internal medicine, 1 in emergency medicine, and 1 in geriatrics. The mean loan repayment is anticipated to be $110,000 and equating to 38.5 VA service years or a mean of 2.3 years of service obligation per individual for the first cohort. The program has no termination date, and with continued funding, VA anticipates granting 100 loan repayments annually.
Education Debt Reduction
Since 2018, 1,546 VA physicians have received EDRP awards. Due to the increased reimbursement provided through the MISSION Act, average physician award amounts have increased from $96,090 in 2018 to $142,557 in 2019 and $148,302 in 2020.
Conclusions
The VA physician scholarship and loan repayment programs outlined in the MISSION Act build on the success of existing federal scholarship programs by providing opportunities for physician trainees to alleviate educational debt and explore a VA health professions career.
Looking ahead, VA must focus on measuring the success of the MISSION scholarship and loan repayment programs by tracking rates of acceptance and student graduation, residency and fellowship completion, and placement in VA medical facilities—both for the service obligation and future employment. Ultimately, the total impact on VA staffing, especially at rural and underresourced sites, will determine the success of the MISSION programs.
1. VA Policy Memorandum #2. Policy in Association of Veterans’ Hospitals with Medical Schools. US Department of Veterans Affairs. January 20, 1946. Accessed February 17, 2022. https://www.va.gov/oaa/Archive/PolicyMemo2.pdf 2. Gilman SC, Chang BK, Zeiss RA, Dougherty MB, Marks WJ, Ludke DA, Cox M. “The academic mission of the Department of Veterans Affairs.” In: Praeger Handbook of Veterans’ Health: History, Challenges, Issues, and Developments. Praeger; 2012:53-82.
3. Office of Inspector General, Veterans Health Administration OIG Determination of VHA Occupational Staffing Shortages FY2020. US Department of Veterans Affairs. Published September 23, 2020. Accessed February 17, 2022. https://www.va.gov/oig/pubs/VAOIG-20-01249-259.pdf
4. Hussey PS, Ringel J, et al. Resources and capabilities of the Department of Veterans Affairs to provide timely and accessible care to veterans. Rand Health Q. 2015;5(4). Accessed February 17, 2022. https://www.rand.org/content/dam/rand/pubs/research_reports/RR1100/RR1165z2/RAND_RR1165z2.pdf
5. Lynch A, Best T, Gutierrez SC, Daily JA. What Should I Do With My Student Loans? A Proposed Strategy for Educational Debt Management. J Grad Med Educ. 2018;10(1):11-15. doi:10.4300/JGME-D-17-00279.1
6. The Uniformed Services Health Professions Revitalization Act of 1972, PL 92-426. US Government Publishing Office. Published 1972. Accessed February 17, 2022. https://www.govinfo.gov/content/pkg/STATUTE-86/pdf/STATUTE-86-Pg713.pdf
7. Armed Forces Health Professions Financial Assistance Programs, 10 USC § 105 (2006).
8. ‘‘VA Maintaining Internal Systems and Strengthening Integrated Outside Networks Act of 2018’’. H.R. 5674. 115th Congress; Report No. 115-671, Part 1. May 3, 2018. Accessed February 17, 2022. https://www.congress.gov/115/bills/hr5674/BILLS-115hr5674rh.pdf
As one of 4 statutory missions, the US Department of Veterans Affairs (VA) educates and trains health professionals to enhance the quality of and timely access to care provided to veterans within the Veterans Health Administration (VHA). To achieve its mission to
Despite its long-term success affiliating with medical schools, VA has continued to be challenged by physician staff shortages with wide variability in the number and specialty of available health care professionals across facilities.3,4 A 2020 VA Office of Inspector General report on VHA occupational staffing shortages concluded that numerous physician specialties were difficult to recruit due to a lack of qualified applicants, noncompetitive salary, and less desirable geographic locations.3
Federal health professions scholarship programs and loan repayment programs have long been used to address physician shortages.4 Focusing on physician shortages in underserved areas in the US, the Emergency Health Personnel Act of 1970 and its subsequent amendments paved the way for various federal medical school scholarship and loan repayment programs.5 Similarly, physician shortages in the armed forces were mitigated through the Uniformed Services Health Professions Revitalization Act of 1972 (USHPRA).6,7
In 2018, Congress passed the VA MISSION (Maintaining Internal Systems and Strengthening Integrated Outside Networks) Act, which included sections designed to alleviate physician shortages in the VHA.8 These sections authorized scholarships similar to those offered by the US Department of Defense (DoD) and loan repayment programs. Section 301 created the Health Professions Scholarship Program (HPSP), which offers scholarships for physicians and dentists. Section 302 increased the maximum debt reduction through the Education Debt Reduction Program (EDRP). Section 303 authorizes the Specialty Education Loan Repayment Program (SELRP), which provides for repayment of educational loans for physicians in specialties deemed necessary for VA. Finally, Section 304 created the Veterans Healing Veterans (VHV), a pilot scholarship specifically for veteran medical students.
Program Characteristics
Health Professions Scholarship
The VA HPSP is a program for physicians and dentists that extends from 2020 to 2033. The HPSP funds the costs of tuition, fees, and provides a stipend with a service obligation of 18 months for each year of support. The program is authorized for 10 years and must provide a minimum of 50 scholarships annually for physicians or dentists based on VHA needs. Applications are screened based on criteria that include a commitment to rural or underserved populations, veteran status, grade point average, essays, and letters of recommendation. Although the minimum required number of scholarships annually is 50, VA anticipates providing 1000 scholarships over 10 years with an aim to significantly increase the number physicians at VHA facilities (Table 1).
Implemented in 2020, the VHV was a 1-year pilot program. It offered scholarships to 2 veterans attending medical school at each of the 5 Teague-Cranston and the 4 Historically Black College and University (HBCU) medical schools (Table 2). The intent of the program was to determine the feasibility of increasing the pool of veteran physicians at VHA. Eligible applicants were notified of the scholarship opportunity through the American Medical College Application Service or through the medical school. Applicants must have separated from military service within the preceding 10 years of being admitted to medical school. In exchange for full tuition, fees, a monthly stipend, and rotation travel costs, the recipients accepted a 4-year clinical service obligation at VA facilities after completing their residency training.
Specialty Education Loan Repayment
The SELRP is a loan repayment program available to recently graduated physicians. Applicants must have graduated from an accredited medical or osteopathic school, matched to an accredited residency program and be ≥ 2 years from completion of residency. The specialties qualifying for SELRP are determined through an analysis of succession planning by the VA Office of Workforce Management and Consulting and change based on VA physician workforce needs. The SELRP provides loan repayment in the amount of $40,000 per year for up to 4 years, with a service obligation of 1 year for each $40,000 of support. In April 2021, VA began accepting applications from the eligible specialties of family medicine, internal medicine, gastroenterology, psychiatry, emergency medicine, and geriatrics.
Education Debt Reduction
The EDRP offers debt relief to clinicians in the most difficult to recruit professions, including physicians (generalists and specialists), registered nurses, licensed practical nurses, social workers, and psychologists. The list of difficult to recruit positions is developed annually by VA facilities. Annual reimbursements through the program may be used for tuition and expenses, such as fees, books, supplies, equipment, and other materials. In 2018, through the MISSION Act Section 302, the annual loan repayment was increased from $24,000 to $40,000, and the maximum level of support was increased from $120,000 to $200,000 over 5 years. Recipients receive reimbursement for loan repayment at the end of each year or service period and recipients are not required to remain in VA for 5 years.
Program Results
Health Professions Scholarship
For academic years 2020/2021 and 2021/2022, 126 HPSP applications from both allopathic and osteopathic schools were submitted and 51 scholarships were awarded (Table 3). Assuming an average residency length of 4 years, VHA estimates that these awards will yield 204 service-year equivalents by 2029.
Veterans Healing Veterans
In the VHV program, scholarship recipients came from 5 Teague-Cranston schools; 2 at University of South Carolina, 2 at East Tennessee State University, 2 at Wright State University, 1 at Texas A&M College of Medicine, 1 at Marshall University; and 3 HBCUs; 2 at Howard University, 1 at Morehouse School of Medicine and 1 at Meharry Medical College. The Charles R. Drew University of Medicine and Science did not nominate any students for the scholarship. Assuming all recipients complete postgraduate training, the VHV scholarship program will provide an additional 12 veteran physicians to serve at VA for at least 4 years each (48 service years).
Specialty Education Loan Repayment
Fourteen applicants have been approved, including 5 in psychiatry, 4 in family medicine, 3 in internal medicine, 1 in emergency medicine, and 1 in geriatrics. The mean loan repayment is anticipated to be $110,000 and equating to 38.5 VA service years or a mean of 2.3 years of service obligation per individual for the first cohort. The program has no termination date, and with continued funding, VA anticipates granting 100 loan repayments annually.
Education Debt Reduction
Since 2018, 1,546 VA physicians have received EDRP awards. Due to the increased reimbursement provided through the MISSION Act, average physician award amounts have increased from $96,090 in 2018 to $142,557 in 2019 and $148,302 in 2020.
Conclusions
The VA physician scholarship and loan repayment programs outlined in the MISSION Act build on the success of existing federal scholarship programs by providing opportunities for physician trainees to alleviate educational debt and explore a VA health professions career.
Looking ahead, VA must focus on measuring the success of the MISSION scholarship and loan repayment programs by tracking rates of acceptance and student graduation, residency and fellowship completion, and placement in VA medical facilities—both for the service obligation and future employment. Ultimately, the total impact on VA staffing, especially at rural and underresourced sites, will determine the success of the MISSION programs.
As one of 4 statutory missions, the US Department of Veterans Affairs (VA) educates and trains health professionals to enhance the quality of and timely access to care provided to veterans within the Veterans Health Administration (VHA). To achieve its mission to
Despite its long-term success affiliating with medical schools, VA has continued to be challenged by physician staff shortages with wide variability in the number and specialty of available health care professionals across facilities.3,4 A 2020 VA Office of Inspector General report on VHA occupational staffing shortages concluded that numerous physician specialties were difficult to recruit due to a lack of qualified applicants, noncompetitive salary, and less desirable geographic locations.3
Federal health professions scholarship programs and loan repayment programs have long been used to address physician shortages.4 Focusing on physician shortages in underserved areas in the US, the Emergency Health Personnel Act of 1970 and its subsequent amendments paved the way for various federal medical school scholarship and loan repayment programs.5 Similarly, physician shortages in the armed forces were mitigated through the Uniformed Services Health Professions Revitalization Act of 1972 (USHPRA).6,7
In 2018, Congress passed the VA MISSION (Maintaining Internal Systems and Strengthening Integrated Outside Networks) Act, which included sections designed to alleviate physician shortages in the VHA.8 These sections authorized scholarships similar to those offered by the US Department of Defense (DoD) and loan repayment programs. Section 301 created the Health Professions Scholarship Program (HPSP), which offers scholarships for physicians and dentists. Section 302 increased the maximum debt reduction through the Education Debt Reduction Program (EDRP). Section 303 authorizes the Specialty Education Loan Repayment Program (SELRP), which provides for repayment of educational loans for physicians in specialties deemed necessary for VA. Finally, Section 304 created the Veterans Healing Veterans (VHV), a pilot scholarship specifically for veteran medical students.
Program Characteristics
Health Professions Scholarship
The VA HPSP is a program for physicians and dentists that extends from 2020 to 2033. The HPSP funds the costs of tuition, fees, and provides a stipend with a service obligation of 18 months for each year of support. The program is authorized for 10 years and must provide a minimum of 50 scholarships annually for physicians or dentists based on VHA needs. Applications are screened based on criteria that include a commitment to rural or underserved populations, veteran status, grade point average, essays, and letters of recommendation. Although the minimum required number of scholarships annually is 50, VA anticipates providing 1000 scholarships over 10 years with an aim to significantly increase the number physicians at VHA facilities (Table 1).
Implemented in 2020, the VHV was a 1-year pilot program. It offered scholarships to 2 veterans attending medical school at each of the 5 Teague-Cranston and the 4 Historically Black College and University (HBCU) medical schools (Table 2). The intent of the program was to determine the feasibility of increasing the pool of veteran physicians at VHA. Eligible applicants were notified of the scholarship opportunity through the American Medical College Application Service or through the medical school. Applicants must have separated from military service within the preceding 10 years of being admitted to medical school. In exchange for full tuition, fees, a monthly stipend, and rotation travel costs, the recipients accepted a 4-year clinical service obligation at VA facilities after completing their residency training.
Specialty Education Loan Repayment
The SELRP is a loan repayment program available to recently graduated physicians. Applicants must have graduated from an accredited medical or osteopathic school, matched to an accredited residency program and be ≥ 2 years from completion of residency. The specialties qualifying for SELRP are determined through an analysis of succession planning by the VA Office of Workforce Management and Consulting and change based on VA physician workforce needs. The SELRP provides loan repayment in the amount of $40,000 per year for up to 4 years, with a service obligation of 1 year for each $40,000 of support. In April 2021, VA began accepting applications from the eligible specialties of family medicine, internal medicine, gastroenterology, psychiatry, emergency medicine, and geriatrics.
Education Debt Reduction
The EDRP offers debt relief to clinicians in the most difficult to recruit professions, including physicians (generalists and specialists), registered nurses, licensed practical nurses, social workers, and psychologists. The list of difficult to recruit positions is developed annually by VA facilities. Annual reimbursements through the program may be used for tuition and expenses, such as fees, books, supplies, equipment, and other materials. In 2018, through the MISSION Act Section 302, the annual loan repayment was increased from $24,000 to $40,000, and the maximum level of support was increased from $120,000 to $200,000 over 5 years. Recipients receive reimbursement for loan repayment at the end of each year or service period and recipients are not required to remain in VA for 5 years.
Program Results
Health Professions Scholarship
For academic years 2020/2021 and 2021/2022, 126 HPSP applications from both allopathic and osteopathic schools were submitted and 51 scholarships were awarded (Table 3). Assuming an average residency length of 4 years, VHA estimates that these awards will yield 204 service-year equivalents by 2029.
Veterans Healing Veterans
In the VHV program, scholarship recipients came from 5 Teague-Cranston schools; 2 at University of South Carolina, 2 at East Tennessee State University, 2 at Wright State University, 1 at Texas A&M College of Medicine, 1 at Marshall University; and 3 HBCUs; 2 at Howard University, 1 at Morehouse School of Medicine and 1 at Meharry Medical College. The Charles R. Drew University of Medicine and Science did not nominate any students for the scholarship. Assuming all recipients complete postgraduate training, the VHV scholarship program will provide an additional 12 veteran physicians to serve at VA for at least 4 years each (48 service years).
Specialty Education Loan Repayment
Fourteen applicants have been approved, including 5 in psychiatry, 4 in family medicine, 3 in internal medicine, 1 in emergency medicine, and 1 in geriatrics. The mean loan repayment is anticipated to be $110,000 and equating to 38.5 VA service years or a mean of 2.3 years of service obligation per individual for the first cohort. The program has no termination date, and with continued funding, VA anticipates granting 100 loan repayments annually.
Education Debt Reduction
Since 2018, 1,546 VA physicians have received EDRP awards. Due to the increased reimbursement provided through the MISSION Act, average physician award amounts have increased from $96,090 in 2018 to $142,557 in 2019 and $148,302 in 2020.
Conclusions
The VA physician scholarship and loan repayment programs outlined in the MISSION Act build on the success of existing federal scholarship programs by providing opportunities for physician trainees to alleviate educational debt and explore a VA health professions career.
Looking ahead, VA must focus on measuring the success of the MISSION scholarship and loan repayment programs by tracking rates of acceptance and student graduation, residency and fellowship completion, and placement in VA medical facilities—both for the service obligation and future employment. Ultimately, the total impact on VA staffing, especially at rural and underresourced sites, will determine the success of the MISSION programs.
1. VA Policy Memorandum #2. Policy in Association of Veterans’ Hospitals with Medical Schools. US Department of Veterans Affairs. January 20, 1946. Accessed February 17, 2022. https://www.va.gov/oaa/Archive/PolicyMemo2.pdf 2. Gilman SC, Chang BK, Zeiss RA, Dougherty MB, Marks WJ, Ludke DA, Cox M. “The academic mission of the Department of Veterans Affairs.” In: Praeger Handbook of Veterans’ Health: History, Challenges, Issues, and Developments. Praeger; 2012:53-82.
3. Office of Inspector General, Veterans Health Administration OIG Determination of VHA Occupational Staffing Shortages FY2020. US Department of Veterans Affairs. Published September 23, 2020. Accessed February 17, 2022. https://www.va.gov/oig/pubs/VAOIG-20-01249-259.pdf
4. Hussey PS, Ringel J, et al. Resources and capabilities of the Department of Veterans Affairs to provide timely and accessible care to veterans. Rand Health Q. 2015;5(4). Accessed February 17, 2022. https://www.rand.org/content/dam/rand/pubs/research_reports/RR1100/RR1165z2/RAND_RR1165z2.pdf
5. Lynch A, Best T, Gutierrez SC, Daily JA. What Should I Do With My Student Loans? A Proposed Strategy for Educational Debt Management. J Grad Med Educ. 2018;10(1):11-15. doi:10.4300/JGME-D-17-00279.1
6. The Uniformed Services Health Professions Revitalization Act of 1972, PL 92-426. US Government Publishing Office. Published 1972. Accessed February 17, 2022. https://www.govinfo.gov/content/pkg/STATUTE-86/pdf/STATUTE-86-Pg713.pdf
7. Armed Forces Health Professions Financial Assistance Programs, 10 USC § 105 (2006).
8. ‘‘VA Maintaining Internal Systems and Strengthening Integrated Outside Networks Act of 2018’’. H.R. 5674. 115th Congress; Report No. 115-671, Part 1. May 3, 2018. Accessed February 17, 2022. https://www.congress.gov/115/bills/hr5674/BILLS-115hr5674rh.pdf
1. VA Policy Memorandum #2. Policy in Association of Veterans’ Hospitals with Medical Schools. US Department of Veterans Affairs. January 20, 1946. Accessed February 17, 2022. https://www.va.gov/oaa/Archive/PolicyMemo2.pdf 2. Gilman SC, Chang BK, Zeiss RA, Dougherty MB, Marks WJ, Ludke DA, Cox M. “The academic mission of the Department of Veterans Affairs.” In: Praeger Handbook of Veterans’ Health: History, Challenges, Issues, and Developments. Praeger; 2012:53-82.
3. Office of Inspector General, Veterans Health Administration OIG Determination of VHA Occupational Staffing Shortages FY2020. US Department of Veterans Affairs. Published September 23, 2020. Accessed February 17, 2022. https://www.va.gov/oig/pubs/VAOIG-20-01249-259.pdf
4. Hussey PS, Ringel J, et al. Resources and capabilities of the Department of Veterans Affairs to provide timely and accessible care to veterans. Rand Health Q. 2015;5(4). Accessed February 17, 2022. https://www.rand.org/content/dam/rand/pubs/research_reports/RR1100/RR1165z2/RAND_RR1165z2.pdf
5. Lynch A, Best T, Gutierrez SC, Daily JA. What Should I Do With My Student Loans? A Proposed Strategy for Educational Debt Management. J Grad Med Educ. 2018;10(1):11-15. doi:10.4300/JGME-D-17-00279.1
6. The Uniformed Services Health Professions Revitalization Act of 1972, PL 92-426. US Government Publishing Office. Published 1972. Accessed February 17, 2022. https://www.govinfo.gov/content/pkg/STATUTE-86/pdf/STATUTE-86-Pg713.pdf
7. Armed Forces Health Professions Financial Assistance Programs, 10 USC § 105 (2006).
8. ‘‘VA Maintaining Internal Systems and Strengthening Integrated Outside Networks Act of 2018’’. H.R. 5674. 115th Congress; Report No. 115-671, Part 1. May 3, 2018. Accessed February 17, 2022. https://www.congress.gov/115/bills/hr5674/BILLS-115hr5674rh.pdf
Telescoping Stents to Maintain a 3-Way Patency of the Airway
There are several malignant and nonmalignant conditions that can lead to central airway obstruction (CAO) resulting in lobar collapse. The clinical consequences range from significant dyspnea to respiratory failure. Airway stenting has been used to maintain patency of obstructed airways and relieve symptoms. Before lung cancer screening became more common, approximately 10% of lung cancers at presentation had evidence of CAO.1
On occasion, an endobronchial malignancy involves the right mainstem (RMS) bronchus near the orifice of the right upper lobe (RUL).2 Such strategically located lesions pose a challenge to relieve the RMS obstruction through stenting, securing airway patency into the bronchus intermedius (BI) while avoiding obstruction of the RUL bronchus. The use of endobronchial silicone stents, hybrid covered stents, as well as self-expanding metal stents (SEMS) is an established mode of relieving CAO due to malignant disease.3 We reviewed the literature for approaches that were available before and after the date of the index case reported here.
Case Presentation
A 65-year-old veteran with a history of smoking presented to a US Department of Veterans Affairs Medical Center (VAMC) in 2011, with hemoptysis of 2-week duration. Computed tomography (CT) of the chest revealed a 5.3 × 4.2 × 6.5 cm right mediastinal mass and a 3.0 × 2.8 × 3 cm right hilar mass. Flexible bronchoscopy revealed > 80% occlusion of the RMS and BI due to a medially located mass sparing the RUL orifice, which was patent (Figure 1). Airways distal to the BI were free of disease. Endobronchial biopsies revealed poorly differentiated non-small cell carcinoma of the lung. The patient was referred to the interventional pulmonary service for further airway management.
Under general anesthesia and through a size-9 endotracheal tube, piecemeal debulking of the mass using a cryoprobe was performed. Argon photocoagulation (APC) was used to control bleeding. Balloon bronchoplasty was performed next with pulmonary Boston Scientific CRE balloon at the BI and the RMS bronchus. Under fluoroscopic guidance, a 12 × 30 mm self-expanding hybrid Merit Medical AERO stent was placed distally into the BI. Next, a 14 × 30 mm AERO stent was placed proximally in the RMS bronchus with its distal end telescoped into the smaller distal stent for a distance of 3 to 4 mm at a slanted angle. The overlap was deliberately performed at the level of RUL takeoff. Forcing the distal end of the proximal larger stent into a smaller stent created mechanical stress. The angled alignment channeled this mechanical stress so that the distal end of the proximal stent flared open laterally into the RUL orifice to allow for ventilation (Figure 2). On follow-up 6 months later, all 3 airways remained patent with stents in place (Figure 3).
The patient returned to the VAMC and underwent chemotherapy with carboplatin and paclitaxel cycles that were completed in May 2012, as well as completing 6300 centigray (cGy) of radiation to the area. This led to regression of the tumor permitting removal of the proximal stent in October 2012. Unfortunately, upon follow-up in July 2013, a hypermetabolic lesion in the right upper posterior chest was noted to be eroding the third rib. Biopsy proved it to be poorly differentiated non-small cell lung cancer. Palliative external beam radiation was used to treat this lesion with a total of 3780 cGy completed by the end of August 2013.
Sadly, the patient was admitted later in 2013 with worsening cough and shortness of breath. Chest and abdominal CTs showed an increase in the size of the right apical mass, and mediastinal lymphadenopathy, as well as innumerable nodules in the left lung. The mass had recurred and extended distal to the stent into the lower and middle lobes. New liver nodule and lytic lesion within left ischial tuberosity, T12, L1, and S1 vertebral bodies were noted. The pulmonary service reached out to us via email and we recommended either additional chemoradiotherapy or palliative care. At that point the tumor was widespread and resistant to therapy. It extended beyond the central airways making airway debulking futile. Stents are palliative in nature and we believed that the initial stenting allowed the patient to get chemoradiation by improving functional status through preventing collapse of the right lung. As a result, the patient had about 19 months of a remission period with quality of life. The patient ultimately died under the care of palliative care in inpatient hospice setting.
Literature Review
A literature review revealed multiple approaches to preserving a 3-way patent airway at the takeoff of the RUL (Table). One approach to alleviating such an obstruction favors placing a straight silicone stent from the RMS into the BI, closing off the orifice of the RUL (Figure 4A).4 However, this entails sacrificing ventilation of the RUL. An alternative suggested by Peled and colleagues was carried out successfully in 3 patients. After placing a stent to relieve the obstruction, a Nd:YAG laser is used to create a window in the stent in proximity to the RUL orifice, which allows preservation or ventilations to the RUL (Figure 4B).5
A third effective approach utilizes silicone Y stents, which are usually employed for relief of obstruction at the level of the main carina.6,7 Instead of deploying them at the main carina, they would be deployed at the secondary carina, which the RUL makes with the BI, often with customized cutting for adjustment of the stent limbs to the appropriate size of the RUL and BI (Figure 4C). This approach has been successfully used to maintain RUL ventilation.2
A fourth technique involves using an Oki stent, a dedicated bifurcated silicone stent, which was first described in 2013. It is designed for the RMS bronchus around the RUL and BI bifurcation, enabling the stent to maintain airway patency in the right lung without affecting the trachea and carina (Figure 4D). The arm located in the RUL prevents migration.8 A fifth technique involves deploying a precisely selected Oki stent specially modified based on a printed 3-dimensional (3D) model of the airways after computer-aided simulation.9A sixth technique employs de novo custom printing stents based on 3D models of the tracheobronchial tree constructed based on CT imaging. This approach creates more accurately fitting stents.1
Discussion
The RUL contributes roughly 5 to 10% of the total oxygenation capacity of the lung.10 In patients with lung cancer and limited pulmonary reserve, preserving ventilation to the RUL can be clinically important. The chosen method to relieve endobronchial obstruction depends on several variables, including expertise, ability of the patient to undergo general anesthesia for rigid or flexible bronchoscopy, stent availability, and airway anatomy.
This case illustrates a new method to deal with lesions close to the RUL orifice. This maneuver may not be possible with all types of stents. AERO stents are fully covered (Figure 4E). In contrast, stents that are uncovered at both distal ends, such as a Boston Scientific Ultraflex stent, may not be adequate for such a maneuver. Intercalating uncovered ends of SEMS may allow for tumor in-growth through the uncovered metal mesh near the RUL orifice and may paradoxically compromise both the RUL and BI. The diameter of AERO stents is slightly larger at its ends.11 This helps prevent migration, which in this case maintained the crucial overlap of the stents. On the other hand, use of AERO stents may be associated with a higher risk of infection.12 Precise measurements of the airway diameter are essential given the difference in internal and external stent diameter with silicone stents.
Silicone stents migrate more readily than SEMS and may not be well suited for the procedure we performed. In our case, we wished to maintain ventilation for the RUL; hence, we elected not to bypass it with a silicone stent. We did not have access to a YAG. Moreover, laser carries more energy than APC. Nd:YAG laser has been reported to cause airway fire when used with silicone stents.13 Several authors have reported the use of silicone Y stents at the primary or secondary carina to preserve luminal patency.6,7 Airway anatomy and the angle of the Y may require modification of these stents prior to their use. Cutting stents may compromise their integrity. The bifurcating limb prevents migration which can be a significant concern with the tubular silicone stents. An important consideration for patients in advanced stages of malignancy is that placement of such stent requires undergoing general anesthesia and rigid bronchoscopy, unlike with AERO and metal stents that can be deployed with fiberoptic bronchoscopy under moderate sedation. As such, we did not elect to use a silicone Y stent. Accumulation of secretions or formation of granulation tissue at the orifices can result in recurrence of obstruction.14
Advances in 3D printing seem to be the future of customized airway stenting. This could help clinicians overcome the challenges of improperly sized stents and distorted airway anatomy. Cases have reported successful use of 3D-printed patient-specific airway prostheses.15,16 However, their use is not common practice, as there is a limited amount of materials that are flexible, biocompatible, and approved by the US Food and Drug Administration (FDA) for medical use. Infection control is another layer of consideration in such stents. Standardization of materials and regulation of personalized devices and their cleansing protocols is neccesary.17 At the time of this case, Oki stents and 3D printing were not available in the market. This report provides a viable alternative to use AERO stents for this maneuver.
Conclusions
Patients presenting with malignant CAO near the RUL require a personalized approach to treatment, considering their overall health, functional status, nature and location of CAO, and degree of symptoms. Once a decision is made to stent the airway, careful assessment of airway anatomy, delineation of obstruction, available expertise, and types of stents available needs to be made to preserve ventilation to the nondiseased RUL. Airway stents are expensive and need to be used wisely for palliation and allowing for a quality life while the patient receives more definitive targeted therapy.
Acknowledgments
The authors would like to gratefully acknowledge Dr Jenny Kim, who referred the patient to the interventional service and helped obtain consent for publishing the case.
1. Criner GJ, Eberhardt R, Fernandez-Bussy S, et al. Interventional bronchoscopy. Am J Respir Crit Care Med. 2020;202(1):29-50. doi:10.1164/rccm.201907-1292SO
2. Oki M, Saka H, Kitagawa C, Kogure Y. Silicone y-stent placement on the carina between bronchus to the right upper lobe and bronchus intermedius. Ann Thorac Surg. 2009;87(3):971-974. doi:10.1016/j.athoracsur.2008.06.049
3. Ernst A, Feller-Kopman D, Becker HD, Mehta AC. Central airway obstruction. Am J Respir Crit Care Med. 2004;169(12):1278-1297. doi:10.1164/rccm.200210-1181SO
4. Liu Y-H, Wu Y-C, Hsieh M-J, Ko P-J. Straight bronchial stent placement across the right upper lobe bronchus: A simple alternative for the management of airway obstruction around the carina and right main bronchus. J Thorac Cardiovasc Surg. 2011;141(1):303-305.e1.doi:10.1016/j.jtcvs.2010.06.015
5. Peled N, Shitrit D, Bendayan D, Kramer MR. Right upper lobe ‘window’ in right main bronchus stenting. Eur J Cardiothorac Surg. 2006;30(4):680-682. doi:10.1016/j.ejcts.2006.07.020
6. Dumon J-F, Dumon MC. Dumon-Novatech Y-stents: a four-year experience with 50 tracheobronchial tumors involving the carina. J Bronchol. 2000;7(1):26-32 doi:10.1097/00128594-200007000-00005
7. Dutau H, Toutblanc B, Lamb C, Seijo L. Use of the Dumon Y-stent in the management of malignant disease involving the carina: a retrospective review of 86 patients. Chest. 2004;126(3):951-958. doi:10.1378/chest.126.3.951
8. Dalar L, Abul Y. Safety and efficacy of Oki stenting used to treat obstructions in the right mainstem bronchus. J Bronchol Interv Pulmonol. 2018;25(3):212-217. doi:10.1097/LBR.0000000000000486
9. Guibert N, Moreno B, Plat G, Didier A, Mazieres J, Hermant C. Stenting of complex malignant central-airway obstruction guided by a three-dimensional printed model of the airways. Ann Thorac Surg. 2017;103(4):e357-e359. doi:10.1016/j.athoracsur.2016.09.082
10. Win T, Tasker AD, Groves AM, et al. Ventilation-perfusion scintigraphy to predict postoperative pulmonary function in lung cancer patients undergoing pneumonectomy. AJR Am J Roentgenol. 2006;187(5):1260-1265. doi:10.2214/AJR.04.1973
11. Mehta AC. AERO self-expanding hybrid stent for airway stenosis. Expert Rev Med Devices. 2008;5(5):553-557. doi:10.1586/17434440.5.5.553
12. Ost DE, Shah AM, Lei X, et al. Respiratory infections increase the risk of granulation tissue formation following airway stenting in patients with malignant airway obstruction. Chest. 2012;141(6):1473-1481. doi:10.1378/chest.11-2005
13. Scherer TA. Nd-YAG laser ignition of silicone endobronchial stents. Chest. 2000;117(5):1449-1454. doi:10.1378/chest.117.5.1449
14. Folch E, Keyes C. Airway stents. Ann Cardiothorac Surg. 2018;7(2):273-283. doi:10.21037/acs.2018.03.08
15. Cheng GZ, Folch E, Brik R, et al. Three-dimensional modeled T-tube design and insertion in a patient with tracheal dehiscence. Chest. 2015;148(4):e106-e108. doi:10.1378/chest.15-0240
16. Tam MD, Laycock SD, Jayne D, Babar J, Noble B. 3-D printouts of the tracheobronchial tree generated from CT images as an aid to management in a case of tracheobronchial chondromalacia caused by relapsing polychondritis. J Radiol Case Rep. 2013;7(8):34-43. Published 2013 Aug 1. doi:10.3941/jrcr.v7i8.1390
17. Alraiyes AH, Avasarala SK, Machuzak MS, Gildea TR. 3D printing for airway disease. AME Med J. 2019;4:14. doi:10.21037/amj.2019.01.05
There are several malignant and nonmalignant conditions that can lead to central airway obstruction (CAO) resulting in lobar collapse. The clinical consequences range from significant dyspnea to respiratory failure. Airway stenting has been used to maintain patency of obstructed airways and relieve symptoms. Before lung cancer screening became more common, approximately 10% of lung cancers at presentation had evidence of CAO.1
On occasion, an endobronchial malignancy involves the right mainstem (RMS) bronchus near the orifice of the right upper lobe (RUL).2 Such strategically located lesions pose a challenge to relieve the RMS obstruction through stenting, securing airway patency into the bronchus intermedius (BI) while avoiding obstruction of the RUL bronchus. The use of endobronchial silicone stents, hybrid covered stents, as well as self-expanding metal stents (SEMS) is an established mode of relieving CAO due to malignant disease.3 We reviewed the literature for approaches that were available before and after the date of the index case reported here.
Case Presentation
A 65-year-old veteran with a history of smoking presented to a US Department of Veterans Affairs Medical Center (VAMC) in 2011, with hemoptysis of 2-week duration. Computed tomography (CT) of the chest revealed a 5.3 × 4.2 × 6.5 cm right mediastinal mass and a 3.0 × 2.8 × 3 cm right hilar mass. Flexible bronchoscopy revealed > 80% occlusion of the RMS and BI due to a medially located mass sparing the RUL orifice, which was patent (Figure 1). Airways distal to the BI were free of disease. Endobronchial biopsies revealed poorly differentiated non-small cell carcinoma of the lung. The patient was referred to the interventional pulmonary service for further airway management.
Under general anesthesia and through a size-9 endotracheal tube, piecemeal debulking of the mass using a cryoprobe was performed. Argon photocoagulation (APC) was used to control bleeding. Balloon bronchoplasty was performed next with pulmonary Boston Scientific CRE balloon at the BI and the RMS bronchus. Under fluoroscopic guidance, a 12 × 30 mm self-expanding hybrid Merit Medical AERO stent was placed distally into the BI. Next, a 14 × 30 mm AERO stent was placed proximally in the RMS bronchus with its distal end telescoped into the smaller distal stent for a distance of 3 to 4 mm at a slanted angle. The overlap was deliberately performed at the level of RUL takeoff. Forcing the distal end of the proximal larger stent into a smaller stent created mechanical stress. The angled alignment channeled this mechanical stress so that the distal end of the proximal stent flared open laterally into the RUL orifice to allow for ventilation (Figure 2). On follow-up 6 months later, all 3 airways remained patent with stents in place (Figure 3).
The patient returned to the VAMC and underwent chemotherapy with carboplatin and paclitaxel cycles that were completed in May 2012, as well as completing 6300 centigray (cGy) of radiation to the area. This led to regression of the tumor permitting removal of the proximal stent in October 2012. Unfortunately, upon follow-up in July 2013, a hypermetabolic lesion in the right upper posterior chest was noted to be eroding the third rib. Biopsy proved it to be poorly differentiated non-small cell lung cancer. Palliative external beam radiation was used to treat this lesion with a total of 3780 cGy completed by the end of August 2013.
Sadly, the patient was admitted later in 2013 with worsening cough and shortness of breath. Chest and abdominal CTs showed an increase in the size of the right apical mass, and mediastinal lymphadenopathy, as well as innumerable nodules in the left lung. The mass had recurred and extended distal to the stent into the lower and middle lobes. New liver nodule and lytic lesion within left ischial tuberosity, T12, L1, and S1 vertebral bodies were noted. The pulmonary service reached out to us via email and we recommended either additional chemoradiotherapy or palliative care. At that point the tumor was widespread and resistant to therapy. It extended beyond the central airways making airway debulking futile. Stents are palliative in nature and we believed that the initial stenting allowed the patient to get chemoradiation by improving functional status through preventing collapse of the right lung. As a result, the patient had about 19 months of a remission period with quality of life. The patient ultimately died under the care of palliative care in inpatient hospice setting.
Literature Review
A literature review revealed multiple approaches to preserving a 3-way patent airway at the takeoff of the RUL (Table). One approach to alleviating such an obstruction favors placing a straight silicone stent from the RMS into the BI, closing off the orifice of the RUL (Figure 4A).4 However, this entails sacrificing ventilation of the RUL. An alternative suggested by Peled and colleagues was carried out successfully in 3 patients. After placing a stent to relieve the obstruction, a Nd:YAG laser is used to create a window in the stent in proximity to the RUL orifice, which allows preservation or ventilations to the RUL (Figure 4B).5
A third effective approach utilizes silicone Y stents, which are usually employed for relief of obstruction at the level of the main carina.6,7 Instead of deploying them at the main carina, they would be deployed at the secondary carina, which the RUL makes with the BI, often with customized cutting for adjustment of the stent limbs to the appropriate size of the RUL and BI (Figure 4C). This approach has been successfully used to maintain RUL ventilation.2
A fourth technique involves using an Oki stent, a dedicated bifurcated silicone stent, which was first described in 2013. It is designed for the RMS bronchus around the RUL and BI bifurcation, enabling the stent to maintain airway patency in the right lung without affecting the trachea and carina (Figure 4D). The arm located in the RUL prevents migration.8 A fifth technique involves deploying a precisely selected Oki stent specially modified based on a printed 3-dimensional (3D) model of the airways after computer-aided simulation.9A sixth technique employs de novo custom printing stents based on 3D models of the tracheobronchial tree constructed based on CT imaging. This approach creates more accurately fitting stents.1
Discussion
The RUL contributes roughly 5 to 10% of the total oxygenation capacity of the lung.10 In patients with lung cancer and limited pulmonary reserve, preserving ventilation to the RUL can be clinically important. The chosen method to relieve endobronchial obstruction depends on several variables, including expertise, ability of the patient to undergo general anesthesia for rigid or flexible bronchoscopy, stent availability, and airway anatomy.
This case illustrates a new method to deal with lesions close to the RUL orifice. This maneuver may not be possible with all types of stents. AERO stents are fully covered (Figure 4E). In contrast, stents that are uncovered at both distal ends, such as a Boston Scientific Ultraflex stent, may not be adequate for such a maneuver. Intercalating uncovered ends of SEMS may allow for tumor in-growth through the uncovered metal mesh near the RUL orifice and may paradoxically compromise both the RUL and BI. The diameter of AERO stents is slightly larger at its ends.11 This helps prevent migration, which in this case maintained the crucial overlap of the stents. On the other hand, use of AERO stents may be associated with a higher risk of infection.12 Precise measurements of the airway diameter are essential given the difference in internal and external stent diameter with silicone stents.
Silicone stents migrate more readily than SEMS and may not be well suited for the procedure we performed. In our case, we wished to maintain ventilation for the RUL; hence, we elected not to bypass it with a silicone stent. We did not have access to a YAG. Moreover, laser carries more energy than APC. Nd:YAG laser has been reported to cause airway fire when used with silicone stents.13 Several authors have reported the use of silicone Y stents at the primary or secondary carina to preserve luminal patency.6,7 Airway anatomy and the angle of the Y may require modification of these stents prior to their use. Cutting stents may compromise their integrity. The bifurcating limb prevents migration which can be a significant concern with the tubular silicone stents. An important consideration for patients in advanced stages of malignancy is that placement of such stent requires undergoing general anesthesia and rigid bronchoscopy, unlike with AERO and metal stents that can be deployed with fiberoptic bronchoscopy under moderate sedation. As such, we did not elect to use a silicone Y stent. Accumulation of secretions or formation of granulation tissue at the orifices can result in recurrence of obstruction.14
Advances in 3D printing seem to be the future of customized airway stenting. This could help clinicians overcome the challenges of improperly sized stents and distorted airway anatomy. Cases have reported successful use of 3D-printed patient-specific airway prostheses.15,16 However, their use is not common practice, as there is a limited amount of materials that are flexible, biocompatible, and approved by the US Food and Drug Administration (FDA) for medical use. Infection control is another layer of consideration in such stents. Standardization of materials and regulation of personalized devices and their cleansing protocols is neccesary.17 At the time of this case, Oki stents and 3D printing were not available in the market. This report provides a viable alternative to use AERO stents for this maneuver.
Conclusions
Patients presenting with malignant CAO near the RUL require a personalized approach to treatment, considering their overall health, functional status, nature and location of CAO, and degree of symptoms. Once a decision is made to stent the airway, careful assessment of airway anatomy, delineation of obstruction, available expertise, and types of stents available needs to be made to preserve ventilation to the nondiseased RUL. Airway stents are expensive and need to be used wisely for palliation and allowing for a quality life while the patient receives more definitive targeted therapy.
Acknowledgments
The authors would like to gratefully acknowledge Dr Jenny Kim, who referred the patient to the interventional service and helped obtain consent for publishing the case.
There are several malignant and nonmalignant conditions that can lead to central airway obstruction (CAO) resulting in lobar collapse. The clinical consequences range from significant dyspnea to respiratory failure. Airway stenting has been used to maintain patency of obstructed airways and relieve symptoms. Before lung cancer screening became more common, approximately 10% of lung cancers at presentation had evidence of CAO.1
On occasion, an endobronchial malignancy involves the right mainstem (RMS) bronchus near the orifice of the right upper lobe (RUL).2 Such strategically located lesions pose a challenge to relieve the RMS obstruction through stenting, securing airway patency into the bronchus intermedius (BI) while avoiding obstruction of the RUL bronchus. The use of endobronchial silicone stents, hybrid covered stents, as well as self-expanding metal stents (SEMS) is an established mode of relieving CAO due to malignant disease.3 We reviewed the literature for approaches that were available before and after the date of the index case reported here.
Case Presentation
A 65-year-old veteran with a history of smoking presented to a US Department of Veterans Affairs Medical Center (VAMC) in 2011, with hemoptysis of 2-week duration. Computed tomography (CT) of the chest revealed a 5.3 × 4.2 × 6.5 cm right mediastinal mass and a 3.0 × 2.8 × 3 cm right hilar mass. Flexible bronchoscopy revealed > 80% occlusion of the RMS and BI due to a medially located mass sparing the RUL orifice, which was patent (Figure 1). Airways distal to the BI were free of disease. Endobronchial biopsies revealed poorly differentiated non-small cell carcinoma of the lung. The patient was referred to the interventional pulmonary service for further airway management.
Under general anesthesia and through a size-9 endotracheal tube, piecemeal debulking of the mass using a cryoprobe was performed. Argon photocoagulation (APC) was used to control bleeding. Balloon bronchoplasty was performed next with pulmonary Boston Scientific CRE balloon at the BI and the RMS bronchus. Under fluoroscopic guidance, a 12 × 30 mm self-expanding hybrid Merit Medical AERO stent was placed distally into the BI. Next, a 14 × 30 mm AERO stent was placed proximally in the RMS bronchus with its distal end telescoped into the smaller distal stent for a distance of 3 to 4 mm at a slanted angle. The overlap was deliberately performed at the level of RUL takeoff. Forcing the distal end of the proximal larger stent into a smaller stent created mechanical stress. The angled alignment channeled this mechanical stress so that the distal end of the proximal stent flared open laterally into the RUL orifice to allow for ventilation (Figure 2). On follow-up 6 months later, all 3 airways remained patent with stents in place (Figure 3).
The patient returned to the VAMC and underwent chemotherapy with carboplatin and paclitaxel cycles that were completed in May 2012, as well as completing 6300 centigray (cGy) of radiation to the area. This led to regression of the tumor permitting removal of the proximal stent in October 2012. Unfortunately, upon follow-up in July 2013, a hypermetabolic lesion in the right upper posterior chest was noted to be eroding the third rib. Biopsy proved it to be poorly differentiated non-small cell lung cancer. Palliative external beam radiation was used to treat this lesion with a total of 3780 cGy completed by the end of August 2013.
Sadly, the patient was admitted later in 2013 with worsening cough and shortness of breath. Chest and abdominal CTs showed an increase in the size of the right apical mass, and mediastinal lymphadenopathy, as well as innumerable nodules in the left lung. The mass had recurred and extended distal to the stent into the lower and middle lobes. New liver nodule and lytic lesion within left ischial tuberosity, T12, L1, and S1 vertebral bodies were noted. The pulmonary service reached out to us via email and we recommended either additional chemoradiotherapy or palliative care. At that point the tumor was widespread and resistant to therapy. It extended beyond the central airways making airway debulking futile. Stents are palliative in nature and we believed that the initial stenting allowed the patient to get chemoradiation by improving functional status through preventing collapse of the right lung. As a result, the patient had about 19 months of a remission period with quality of life. The patient ultimately died under the care of palliative care in inpatient hospice setting.
Literature Review
A literature review revealed multiple approaches to preserving a 3-way patent airway at the takeoff of the RUL (Table). One approach to alleviating such an obstruction favors placing a straight silicone stent from the RMS into the BI, closing off the orifice of the RUL (Figure 4A).4 However, this entails sacrificing ventilation of the RUL. An alternative suggested by Peled and colleagues was carried out successfully in 3 patients. After placing a stent to relieve the obstruction, a Nd:YAG laser is used to create a window in the stent in proximity to the RUL orifice, which allows preservation or ventilations to the RUL (Figure 4B).5
A third effective approach utilizes silicone Y stents, which are usually employed for relief of obstruction at the level of the main carina.6,7 Instead of deploying them at the main carina, they would be deployed at the secondary carina, which the RUL makes with the BI, often with customized cutting for adjustment of the stent limbs to the appropriate size of the RUL and BI (Figure 4C). This approach has been successfully used to maintain RUL ventilation.2
A fourth technique involves using an Oki stent, a dedicated bifurcated silicone stent, which was first described in 2013. It is designed for the RMS bronchus around the RUL and BI bifurcation, enabling the stent to maintain airway patency in the right lung without affecting the trachea and carina (Figure 4D). The arm located in the RUL prevents migration.8 A fifth technique involves deploying a precisely selected Oki stent specially modified based on a printed 3-dimensional (3D) model of the airways after computer-aided simulation.9A sixth technique employs de novo custom printing stents based on 3D models of the tracheobronchial tree constructed based on CT imaging. This approach creates more accurately fitting stents.1
Discussion
The RUL contributes roughly 5 to 10% of the total oxygenation capacity of the lung.10 In patients with lung cancer and limited pulmonary reserve, preserving ventilation to the RUL can be clinically important. The chosen method to relieve endobronchial obstruction depends on several variables, including expertise, ability of the patient to undergo general anesthesia for rigid or flexible bronchoscopy, stent availability, and airway anatomy.
This case illustrates a new method to deal with lesions close to the RUL orifice. This maneuver may not be possible with all types of stents. AERO stents are fully covered (Figure 4E). In contrast, stents that are uncovered at both distal ends, such as a Boston Scientific Ultraflex stent, may not be adequate for such a maneuver. Intercalating uncovered ends of SEMS may allow for tumor in-growth through the uncovered metal mesh near the RUL orifice and may paradoxically compromise both the RUL and BI. The diameter of AERO stents is slightly larger at its ends.11 This helps prevent migration, which in this case maintained the crucial overlap of the stents. On the other hand, use of AERO stents may be associated with a higher risk of infection.12 Precise measurements of the airway diameter are essential given the difference in internal and external stent diameter with silicone stents.
Silicone stents migrate more readily than SEMS and may not be well suited for the procedure we performed. In our case, we wished to maintain ventilation for the RUL; hence, we elected not to bypass it with a silicone stent. We did not have access to a YAG. Moreover, laser carries more energy than APC. Nd:YAG laser has been reported to cause airway fire when used with silicone stents.13 Several authors have reported the use of silicone Y stents at the primary or secondary carina to preserve luminal patency.6,7 Airway anatomy and the angle of the Y may require modification of these stents prior to their use. Cutting stents may compromise their integrity. The bifurcating limb prevents migration which can be a significant concern with the tubular silicone stents. An important consideration for patients in advanced stages of malignancy is that placement of such stent requires undergoing general anesthesia and rigid bronchoscopy, unlike with AERO and metal stents that can be deployed with fiberoptic bronchoscopy under moderate sedation. As such, we did not elect to use a silicone Y stent. Accumulation of secretions or formation of granulation tissue at the orifices can result in recurrence of obstruction.14
Advances in 3D printing seem to be the future of customized airway stenting. This could help clinicians overcome the challenges of improperly sized stents and distorted airway anatomy. Cases have reported successful use of 3D-printed patient-specific airway prostheses.15,16 However, their use is not common practice, as there is a limited amount of materials that are flexible, biocompatible, and approved by the US Food and Drug Administration (FDA) for medical use. Infection control is another layer of consideration in such stents. Standardization of materials and regulation of personalized devices and their cleansing protocols is neccesary.17 At the time of this case, Oki stents and 3D printing were not available in the market. This report provides a viable alternative to use AERO stents for this maneuver.
Conclusions
Patients presenting with malignant CAO near the RUL require a personalized approach to treatment, considering their overall health, functional status, nature and location of CAO, and degree of symptoms. Once a decision is made to stent the airway, careful assessment of airway anatomy, delineation of obstruction, available expertise, and types of stents available needs to be made to preserve ventilation to the nondiseased RUL. Airway stents are expensive and need to be used wisely for palliation and allowing for a quality life while the patient receives more definitive targeted therapy.
Acknowledgments
The authors would like to gratefully acknowledge Dr Jenny Kim, who referred the patient to the interventional service and helped obtain consent for publishing the case.
1. Criner GJ, Eberhardt R, Fernandez-Bussy S, et al. Interventional bronchoscopy. Am J Respir Crit Care Med. 2020;202(1):29-50. doi:10.1164/rccm.201907-1292SO
2. Oki M, Saka H, Kitagawa C, Kogure Y. Silicone y-stent placement on the carina between bronchus to the right upper lobe and bronchus intermedius. Ann Thorac Surg. 2009;87(3):971-974. doi:10.1016/j.athoracsur.2008.06.049
3. Ernst A, Feller-Kopman D, Becker HD, Mehta AC. Central airway obstruction. Am J Respir Crit Care Med. 2004;169(12):1278-1297. doi:10.1164/rccm.200210-1181SO
4. Liu Y-H, Wu Y-C, Hsieh M-J, Ko P-J. Straight bronchial stent placement across the right upper lobe bronchus: A simple alternative for the management of airway obstruction around the carina and right main bronchus. J Thorac Cardiovasc Surg. 2011;141(1):303-305.e1.doi:10.1016/j.jtcvs.2010.06.015
5. Peled N, Shitrit D, Bendayan D, Kramer MR. Right upper lobe ‘window’ in right main bronchus stenting. Eur J Cardiothorac Surg. 2006;30(4):680-682. doi:10.1016/j.ejcts.2006.07.020
6. Dumon J-F, Dumon MC. Dumon-Novatech Y-stents: a four-year experience with 50 tracheobronchial tumors involving the carina. J Bronchol. 2000;7(1):26-32 doi:10.1097/00128594-200007000-00005
7. Dutau H, Toutblanc B, Lamb C, Seijo L. Use of the Dumon Y-stent in the management of malignant disease involving the carina: a retrospective review of 86 patients. Chest. 2004;126(3):951-958. doi:10.1378/chest.126.3.951
8. Dalar L, Abul Y. Safety and efficacy of Oki stenting used to treat obstructions in the right mainstem bronchus. J Bronchol Interv Pulmonol. 2018;25(3):212-217. doi:10.1097/LBR.0000000000000486
9. Guibert N, Moreno B, Plat G, Didier A, Mazieres J, Hermant C. Stenting of complex malignant central-airway obstruction guided by a three-dimensional printed model of the airways. Ann Thorac Surg. 2017;103(4):e357-e359. doi:10.1016/j.athoracsur.2016.09.082
10. Win T, Tasker AD, Groves AM, et al. Ventilation-perfusion scintigraphy to predict postoperative pulmonary function in lung cancer patients undergoing pneumonectomy. AJR Am J Roentgenol. 2006;187(5):1260-1265. doi:10.2214/AJR.04.1973
11. Mehta AC. AERO self-expanding hybrid stent for airway stenosis. Expert Rev Med Devices. 2008;5(5):553-557. doi:10.1586/17434440.5.5.553
12. Ost DE, Shah AM, Lei X, et al. Respiratory infections increase the risk of granulation tissue formation following airway stenting in patients with malignant airway obstruction. Chest. 2012;141(6):1473-1481. doi:10.1378/chest.11-2005
13. Scherer TA. Nd-YAG laser ignition of silicone endobronchial stents. Chest. 2000;117(5):1449-1454. doi:10.1378/chest.117.5.1449
14. Folch E, Keyes C. Airway stents. Ann Cardiothorac Surg. 2018;7(2):273-283. doi:10.21037/acs.2018.03.08
15. Cheng GZ, Folch E, Brik R, et al. Three-dimensional modeled T-tube design and insertion in a patient with tracheal dehiscence. Chest. 2015;148(4):e106-e108. doi:10.1378/chest.15-0240
16. Tam MD, Laycock SD, Jayne D, Babar J, Noble B. 3-D printouts of the tracheobronchial tree generated from CT images as an aid to management in a case of tracheobronchial chondromalacia caused by relapsing polychondritis. J Radiol Case Rep. 2013;7(8):34-43. Published 2013 Aug 1. doi:10.3941/jrcr.v7i8.1390
17. Alraiyes AH, Avasarala SK, Machuzak MS, Gildea TR. 3D printing for airway disease. AME Med J. 2019;4:14. doi:10.21037/amj.2019.01.05
1. Criner GJ, Eberhardt R, Fernandez-Bussy S, et al. Interventional bronchoscopy. Am J Respir Crit Care Med. 2020;202(1):29-50. doi:10.1164/rccm.201907-1292SO
2. Oki M, Saka H, Kitagawa C, Kogure Y. Silicone y-stent placement on the carina between bronchus to the right upper lobe and bronchus intermedius. Ann Thorac Surg. 2009;87(3):971-974. doi:10.1016/j.athoracsur.2008.06.049
3. Ernst A, Feller-Kopman D, Becker HD, Mehta AC. Central airway obstruction. Am J Respir Crit Care Med. 2004;169(12):1278-1297. doi:10.1164/rccm.200210-1181SO
4. Liu Y-H, Wu Y-C, Hsieh M-J, Ko P-J. Straight bronchial stent placement across the right upper lobe bronchus: A simple alternative for the management of airway obstruction around the carina and right main bronchus. J Thorac Cardiovasc Surg. 2011;141(1):303-305.e1.doi:10.1016/j.jtcvs.2010.06.015
5. Peled N, Shitrit D, Bendayan D, Kramer MR. Right upper lobe ‘window’ in right main bronchus stenting. Eur J Cardiothorac Surg. 2006;30(4):680-682. doi:10.1016/j.ejcts.2006.07.020
6. Dumon J-F, Dumon MC. Dumon-Novatech Y-stents: a four-year experience with 50 tracheobronchial tumors involving the carina. J Bronchol. 2000;7(1):26-32 doi:10.1097/00128594-200007000-00005
7. Dutau H, Toutblanc B, Lamb C, Seijo L. Use of the Dumon Y-stent in the management of malignant disease involving the carina: a retrospective review of 86 patients. Chest. 2004;126(3):951-958. doi:10.1378/chest.126.3.951
8. Dalar L, Abul Y. Safety and efficacy of Oki stenting used to treat obstructions in the right mainstem bronchus. J Bronchol Interv Pulmonol. 2018;25(3):212-217. doi:10.1097/LBR.0000000000000486
9. Guibert N, Moreno B, Plat G, Didier A, Mazieres J, Hermant C. Stenting of complex malignant central-airway obstruction guided by a three-dimensional printed model of the airways. Ann Thorac Surg. 2017;103(4):e357-e359. doi:10.1016/j.athoracsur.2016.09.082
10. Win T, Tasker AD, Groves AM, et al. Ventilation-perfusion scintigraphy to predict postoperative pulmonary function in lung cancer patients undergoing pneumonectomy. AJR Am J Roentgenol. 2006;187(5):1260-1265. doi:10.2214/AJR.04.1973
11. Mehta AC. AERO self-expanding hybrid stent for airway stenosis. Expert Rev Med Devices. 2008;5(5):553-557. doi:10.1586/17434440.5.5.553
12. Ost DE, Shah AM, Lei X, et al. Respiratory infections increase the risk of granulation tissue formation following airway stenting in patients with malignant airway obstruction. Chest. 2012;141(6):1473-1481. doi:10.1378/chest.11-2005
13. Scherer TA. Nd-YAG laser ignition of silicone endobronchial stents. Chest. 2000;117(5):1449-1454. doi:10.1378/chest.117.5.1449
14. Folch E, Keyes C. Airway stents. Ann Cardiothorac Surg. 2018;7(2):273-283. doi:10.21037/acs.2018.03.08
15. Cheng GZ, Folch E, Brik R, et al. Three-dimensional modeled T-tube design and insertion in a patient with tracheal dehiscence. Chest. 2015;148(4):e106-e108. doi:10.1378/chest.15-0240
16. Tam MD, Laycock SD, Jayne D, Babar J, Noble B. 3-D printouts of the tracheobronchial tree generated from CT images as an aid to management in a case of tracheobronchial chondromalacia caused by relapsing polychondritis. J Radiol Case Rep. 2013;7(8):34-43. Published 2013 Aug 1. doi:10.3941/jrcr.v7i8.1390
17. Alraiyes AH, Avasarala SK, Machuzak MS, Gildea TR. 3D printing for airway disease. AME Med J. 2019;4:14. doi:10.21037/amj.2019.01.05
A Pioneer in Women’s Federal Practice
March is Women’s History Month. Many women have served in all branches of government health care over centuries and are worthy of celebrating. These nurses, physicians, pharmacists, and other allied health professionals devoted their time and talents, compassion, and competence to deliver and improve the care of wounded service members, disabled veterans, and the underresourced in our communities. To honor the collective contribution of women to federal practice in the Indian Health Service, Public Health Service Core, US Department of Veterans Affairs (VA) and the US Department of Defense, this column examines one pioneer in women’s federal practice—Margaret D. Craighill, MD—who epitomizes the spirit of the selfless dedication that generations of women have given to public service. Craighill is an ideal choice to represent this noble cadre of women as her career spanned active military duty, public health, and the Veterans Health Administration.
Craighill was a graduate of several of the finest institutions of medical training in the United States. Born in Southport, North Carolina, in 1898, she earned her undergraduate degree Phi Beta Kappa and master’s degree from the University of Wisconsin.2 She set her sights on becoming a physician at a period in American history when many prominent medical schools accepted few women. A marked exception—due to the fund raising and lobbying of influential women—was the prestigious Johns Hopkins University School of Medicine.3 She graduated in 1924 and held a postgraduate position at Yale Medical School. She then worked as a physiologist at a military arsenal, a pathologist, a general surgeon, and completed a residency in obstetrics and gynecology. This broad training gave her the diverse expertise she would need for her future work.4
Craighill came from a military family: Her father was a colonel in the engineering corps, and her grandfather rose to become chief engineer of the Army.5 Along with many of America’s best and brightest, Craighill left her successful medical career as dean of the Women’s Medical College of Pennsylvania to join the war effort. Author Alan G. Knight points out, more than in civilian medicine, gender stereotypes kept women from entering the military: Women were expected and accepted as nurses, not doctors.5 But in 1943 Congress passed and President Roosevelt signed the Sparkman-Johnson Bill, enabling women to enter the then all-male Army and Navy Medical Corps. Craighill took advantage of this opportunity and accepted an appointment to the Women’s Army Corps (WAC) as a major in 1943 at age 45 years, becoming the first woman physician to be commissioned an officer in the Army.
Major Craighill’s initial assignment was to the Office of the Surgeon General in the Preventive Medicine Division as the consultant for health and welfare of women. Here, she served as liaison to another innovation in women’s history in military medicine—the WAC. Journeying 56,000 miles to war zones in multiple countries, she assessed the health of 160,000 Army nurses and other staff whose focus was public health and infectious disease and hygiene. The history of women in medicine in and out of federal service is marked by overcoming innumerable biases and barriers. Craighill faced the prevailing presumption that women were unfit for military duty. In an early example of evidence-based medicine, she disproved this theory, showing that women were faring well doing hard jobs in tough environments.4
Their fortitude is more remarkable considering induction examinations for women during World War II were cursory and not tailored to address women’s health care needs. Based on her visits to WACs in theater and at home, Craighill observed recruits suffering from previously undiagnosed gynecologic and psychiatric conditions that adversely affected their health and function. She advocated for comprehensive standardized examinations that would detect many of these disorders.5
Craighill promoted other prejudices of her era. WAC command wanted to win public approval of women in the service and was concerned that lesbian relationships and “heterosexual promiscuity” would damage their public relations aims. They pressured Craighill to develop induction examinations that would screen lesbians and women with behavioral problems. She urged tolerance of homosexual behavior until it was proven.
Though clearly discriminatory and personally offensive to gay persons in federal service, we must recognize that only last year did the Pentagon move to overturn the prior administration’s prohibition against transgender persons serving in uniform.6 In this light Craighill, as the first female physician-leader in a 1940s military, adopted a relatively progressive stance.
Craighill rose to the rank of lieutenant colonel and received the Legion of Merit award for her exemplary wartime service. In 1945, she earned another first when she was appointed to be a consultant on the medical care of women veterans. For women veterans, gaining access to newly earned benefits and receiving appropriate care were serious problems that Craighill worked to solve. For many women veterans, those challenges remain, and Craighill’s legacy summons us to take up the charge to empower women in federal health professions to enhance the quality of care women veterans receive in all sectors of US medicine.
Critics and advocates agree that the VA still has a long way to go to achieve equity and excellence in our care for women veterans.7,8 Craighill’s position stands as a landmark in this effort. During her VA tenure, Craighill entered a residency in the first class of the Menninger School of Psychiatry in Topeka, Kansas, and completed psychoanalytic training. Her wartime experiences had convinced her of the need to provide high-quality mental health care to women veterans. She put her new psychosomatic knowledge and skills to use, serving as the chief of a women’s health clinic at the VA Hospital in Topeka and published several important scholarly papers.5,9Craighill went on to have a distinguished career in academic medicine, underscoring the long and valuable relationship of US medicine and the scholarly medical community. Once her psychiatric training was finished, she returned to private practice, ending her career as chief psychiatrist at Connecticut College for Women.
Craighill made a significant contribution to the role of women in federal practice. She was a visionary in her conviction that women, whether physicians, nurses, or other health care professionals, had the gifts and the grit to serve with distinction and valor and that their military service entitled them in war and peace to gender-sensitive health care. As the epigraph for this editorial shows, Craighill knew the path for women in federal practice or service while not easy is well worth treading. Her pioneering career can inspire all those women who today and in the future choose to follow in her footsteps.
1. Bellafaire J, Graf MH. Women Doctors in War. Texas A&M University Press; 2009:61.
2. Nuland SB. Doctors: The Biography of Medicine. Alfred A. Knopf; 1988:399-405.
3. Dr. Margaret D. Craighill, at 78, former dean of medical college. Obituary. New York Times, July 26, 1977. Accessed February 24, 2022. https://www.nytimes.com/1977/07/26/archives/dr-margaret-d-craighill-at-78-former-dean-of-medical-college.html
4. US Library of Medicine. Changing the face of medicine: Dr. Margaret D. Craighill. Updated June 03, 2015. Accessed February 23, 2022. https://cfmedicine.nlm.nih.gov/physicians/biography_72.html
5. Knight AG. Dr. Margaret D. Craighill, M.D. On Point. 2018;23(4):19-22. Accessed February 24, 2022. https://www.jstor.org/stable/26478427.
6. Wamsley L. Pentagon releases new policies enabling transgender people to serve in the military. Updated March 31, 2021. Accessed February 23, 2022. https://www.npr.org/2021/03/31/983118029/pentagon-releases-new-policies-enabling-transgender-people-to-serve-in-the-milit
7. Shane L. Is VA shortchanging women’s health programs. Military Times. Published February 28, 2019. Accessed February 24, 2022. https://www.militarytimes.com/news/pentagon-congress/2019/02/28/is-va-spending-enough-on-womens-health-programs
8. Marshall V, Stryczek KC, Haverhals L, et al. The focus they deserve: improving women veterans’ health care access. Womens Health Issues. 2021;31(4):399-407. doi:10.1016/j.whi.2020.12.011
9. Craighill MD. Psychiatric aspects of women serving in the Army. Am J Psychiatry. 1947;104(4):226-230. doi:10.1176/ajp.104.4.226
March is Women’s History Month. Many women have served in all branches of government health care over centuries and are worthy of celebrating. These nurses, physicians, pharmacists, and other allied health professionals devoted their time and talents, compassion, and competence to deliver and improve the care of wounded service members, disabled veterans, and the underresourced in our communities. To honor the collective contribution of women to federal practice in the Indian Health Service, Public Health Service Core, US Department of Veterans Affairs (VA) and the US Department of Defense, this column examines one pioneer in women’s federal practice—Margaret D. Craighill, MD—who epitomizes the spirit of the selfless dedication that generations of women have given to public service. Craighill is an ideal choice to represent this noble cadre of women as her career spanned active military duty, public health, and the Veterans Health Administration.
Craighill was a graduate of several of the finest institutions of medical training in the United States. Born in Southport, North Carolina, in 1898, she earned her undergraduate degree Phi Beta Kappa and master’s degree from the University of Wisconsin.2 She set her sights on becoming a physician at a period in American history when many prominent medical schools accepted few women. A marked exception—due to the fund raising and lobbying of influential women—was the prestigious Johns Hopkins University School of Medicine.3 She graduated in 1924 and held a postgraduate position at Yale Medical School. She then worked as a physiologist at a military arsenal, a pathologist, a general surgeon, and completed a residency in obstetrics and gynecology. This broad training gave her the diverse expertise she would need for her future work.4
Craighill came from a military family: Her father was a colonel in the engineering corps, and her grandfather rose to become chief engineer of the Army.5 Along with many of America’s best and brightest, Craighill left her successful medical career as dean of the Women’s Medical College of Pennsylvania to join the war effort. Author Alan G. Knight points out, more than in civilian medicine, gender stereotypes kept women from entering the military: Women were expected and accepted as nurses, not doctors.5 But in 1943 Congress passed and President Roosevelt signed the Sparkman-Johnson Bill, enabling women to enter the then all-male Army and Navy Medical Corps. Craighill took advantage of this opportunity and accepted an appointment to the Women’s Army Corps (WAC) as a major in 1943 at age 45 years, becoming the first woman physician to be commissioned an officer in the Army.
Major Craighill’s initial assignment was to the Office of the Surgeon General in the Preventive Medicine Division as the consultant for health and welfare of women. Here, she served as liaison to another innovation in women’s history in military medicine—the WAC. Journeying 56,000 miles to war zones in multiple countries, she assessed the health of 160,000 Army nurses and other staff whose focus was public health and infectious disease and hygiene. The history of women in medicine in and out of federal service is marked by overcoming innumerable biases and barriers. Craighill faced the prevailing presumption that women were unfit for military duty. In an early example of evidence-based medicine, she disproved this theory, showing that women were faring well doing hard jobs in tough environments.4
Their fortitude is more remarkable considering induction examinations for women during World War II were cursory and not tailored to address women’s health care needs. Based on her visits to WACs in theater and at home, Craighill observed recruits suffering from previously undiagnosed gynecologic and psychiatric conditions that adversely affected their health and function. She advocated for comprehensive standardized examinations that would detect many of these disorders.5
Craighill promoted other prejudices of her era. WAC command wanted to win public approval of women in the service and was concerned that lesbian relationships and “heterosexual promiscuity” would damage their public relations aims. They pressured Craighill to develop induction examinations that would screen lesbians and women with behavioral problems. She urged tolerance of homosexual behavior until it was proven.
Though clearly discriminatory and personally offensive to gay persons in federal service, we must recognize that only last year did the Pentagon move to overturn the prior administration’s prohibition against transgender persons serving in uniform.6 In this light Craighill, as the first female physician-leader in a 1940s military, adopted a relatively progressive stance.
Craighill rose to the rank of lieutenant colonel and received the Legion of Merit award for her exemplary wartime service. In 1945, she earned another first when she was appointed to be a consultant on the medical care of women veterans. For women veterans, gaining access to newly earned benefits and receiving appropriate care were serious problems that Craighill worked to solve. For many women veterans, those challenges remain, and Craighill’s legacy summons us to take up the charge to empower women in federal health professions to enhance the quality of care women veterans receive in all sectors of US medicine.
Critics and advocates agree that the VA still has a long way to go to achieve equity and excellence in our care for women veterans.7,8 Craighill’s position stands as a landmark in this effort. During her VA tenure, Craighill entered a residency in the first class of the Menninger School of Psychiatry in Topeka, Kansas, and completed psychoanalytic training. Her wartime experiences had convinced her of the need to provide high-quality mental health care to women veterans. She put her new psychosomatic knowledge and skills to use, serving as the chief of a women’s health clinic at the VA Hospital in Topeka and published several important scholarly papers.5,9Craighill went on to have a distinguished career in academic medicine, underscoring the long and valuable relationship of US medicine and the scholarly medical community. Once her psychiatric training was finished, she returned to private practice, ending her career as chief psychiatrist at Connecticut College for Women.
Craighill made a significant contribution to the role of women in federal practice. She was a visionary in her conviction that women, whether physicians, nurses, or other health care professionals, had the gifts and the grit to serve with distinction and valor and that their military service entitled them in war and peace to gender-sensitive health care. As the epigraph for this editorial shows, Craighill knew the path for women in federal practice or service while not easy is well worth treading. Her pioneering career can inspire all those women who today and in the future choose to follow in her footsteps.
March is Women’s History Month. Many women have served in all branches of government health care over centuries and are worthy of celebrating. These nurses, physicians, pharmacists, and other allied health professionals devoted their time and talents, compassion, and competence to deliver and improve the care of wounded service members, disabled veterans, and the underresourced in our communities. To honor the collective contribution of women to federal practice in the Indian Health Service, Public Health Service Core, US Department of Veterans Affairs (VA) and the US Department of Defense, this column examines one pioneer in women’s federal practice—Margaret D. Craighill, MD—who epitomizes the spirit of the selfless dedication that generations of women have given to public service. Craighill is an ideal choice to represent this noble cadre of women as her career spanned active military duty, public health, and the Veterans Health Administration.
Craighill was a graduate of several of the finest institutions of medical training in the United States. Born in Southport, North Carolina, in 1898, she earned her undergraduate degree Phi Beta Kappa and master’s degree from the University of Wisconsin.2 She set her sights on becoming a physician at a period in American history when many prominent medical schools accepted few women. A marked exception—due to the fund raising and lobbying of influential women—was the prestigious Johns Hopkins University School of Medicine.3 She graduated in 1924 and held a postgraduate position at Yale Medical School. She then worked as a physiologist at a military arsenal, a pathologist, a general surgeon, and completed a residency in obstetrics and gynecology. This broad training gave her the diverse expertise she would need for her future work.4
Craighill came from a military family: Her father was a colonel in the engineering corps, and her grandfather rose to become chief engineer of the Army.5 Along with many of America’s best and brightest, Craighill left her successful medical career as dean of the Women’s Medical College of Pennsylvania to join the war effort. Author Alan G. Knight points out, more than in civilian medicine, gender stereotypes kept women from entering the military: Women were expected and accepted as nurses, not doctors.5 But in 1943 Congress passed and President Roosevelt signed the Sparkman-Johnson Bill, enabling women to enter the then all-male Army and Navy Medical Corps. Craighill took advantage of this opportunity and accepted an appointment to the Women’s Army Corps (WAC) as a major in 1943 at age 45 years, becoming the first woman physician to be commissioned an officer in the Army.
Major Craighill’s initial assignment was to the Office of the Surgeon General in the Preventive Medicine Division as the consultant for health and welfare of women. Here, she served as liaison to another innovation in women’s history in military medicine—the WAC. Journeying 56,000 miles to war zones in multiple countries, she assessed the health of 160,000 Army nurses and other staff whose focus was public health and infectious disease and hygiene. The history of women in medicine in and out of federal service is marked by overcoming innumerable biases and barriers. Craighill faced the prevailing presumption that women were unfit for military duty. In an early example of evidence-based medicine, she disproved this theory, showing that women were faring well doing hard jobs in tough environments.4
Their fortitude is more remarkable considering induction examinations for women during World War II were cursory and not tailored to address women’s health care needs. Based on her visits to WACs in theater and at home, Craighill observed recruits suffering from previously undiagnosed gynecologic and psychiatric conditions that adversely affected their health and function. She advocated for comprehensive standardized examinations that would detect many of these disorders.5
Craighill promoted other prejudices of her era. WAC command wanted to win public approval of women in the service and was concerned that lesbian relationships and “heterosexual promiscuity” would damage their public relations aims. They pressured Craighill to develop induction examinations that would screen lesbians and women with behavioral problems. She urged tolerance of homosexual behavior until it was proven.
Though clearly discriminatory and personally offensive to gay persons in federal service, we must recognize that only last year did the Pentagon move to overturn the prior administration’s prohibition against transgender persons serving in uniform.6 In this light Craighill, as the first female physician-leader in a 1940s military, adopted a relatively progressive stance.
Craighill rose to the rank of lieutenant colonel and received the Legion of Merit award for her exemplary wartime service. In 1945, she earned another first when she was appointed to be a consultant on the medical care of women veterans. For women veterans, gaining access to newly earned benefits and receiving appropriate care were serious problems that Craighill worked to solve. For many women veterans, those challenges remain, and Craighill’s legacy summons us to take up the charge to empower women in federal health professions to enhance the quality of care women veterans receive in all sectors of US medicine.
Critics and advocates agree that the VA still has a long way to go to achieve equity and excellence in our care for women veterans.7,8 Craighill’s position stands as a landmark in this effort. During her VA tenure, Craighill entered a residency in the first class of the Menninger School of Psychiatry in Topeka, Kansas, and completed psychoanalytic training. Her wartime experiences had convinced her of the need to provide high-quality mental health care to women veterans. She put her new psychosomatic knowledge and skills to use, serving as the chief of a women’s health clinic at the VA Hospital in Topeka and published several important scholarly papers.5,9Craighill went on to have a distinguished career in academic medicine, underscoring the long and valuable relationship of US medicine and the scholarly medical community. Once her psychiatric training was finished, she returned to private practice, ending her career as chief psychiatrist at Connecticut College for Women.
Craighill made a significant contribution to the role of women in federal practice. She was a visionary in her conviction that women, whether physicians, nurses, or other health care professionals, had the gifts and the grit to serve with distinction and valor and that their military service entitled them in war and peace to gender-sensitive health care. As the epigraph for this editorial shows, Craighill knew the path for women in federal practice or service while not easy is well worth treading. Her pioneering career can inspire all those women who today and in the future choose to follow in her footsteps.
1. Bellafaire J, Graf MH. Women Doctors in War. Texas A&M University Press; 2009:61.
2. Nuland SB. Doctors: The Biography of Medicine. Alfred A. Knopf; 1988:399-405.
3. Dr. Margaret D. Craighill, at 78, former dean of medical college. Obituary. New York Times, July 26, 1977. Accessed February 24, 2022. https://www.nytimes.com/1977/07/26/archives/dr-margaret-d-craighill-at-78-former-dean-of-medical-college.html
4. US Library of Medicine. Changing the face of medicine: Dr. Margaret D. Craighill. Updated June 03, 2015. Accessed February 23, 2022. https://cfmedicine.nlm.nih.gov/physicians/biography_72.html
5. Knight AG. Dr. Margaret D. Craighill, M.D. On Point. 2018;23(4):19-22. Accessed February 24, 2022. https://www.jstor.org/stable/26478427.
6. Wamsley L. Pentagon releases new policies enabling transgender people to serve in the military. Updated March 31, 2021. Accessed February 23, 2022. https://www.npr.org/2021/03/31/983118029/pentagon-releases-new-policies-enabling-transgender-people-to-serve-in-the-milit
7. Shane L. Is VA shortchanging women’s health programs. Military Times. Published February 28, 2019. Accessed February 24, 2022. https://www.militarytimes.com/news/pentagon-congress/2019/02/28/is-va-spending-enough-on-womens-health-programs
8. Marshall V, Stryczek KC, Haverhals L, et al. The focus they deserve: improving women veterans’ health care access. Womens Health Issues. 2021;31(4):399-407. doi:10.1016/j.whi.2020.12.011
9. Craighill MD. Psychiatric aspects of women serving in the Army. Am J Psychiatry. 1947;104(4):226-230. doi:10.1176/ajp.104.4.226
1. Bellafaire J, Graf MH. Women Doctors in War. Texas A&M University Press; 2009:61.
2. Nuland SB. Doctors: The Biography of Medicine. Alfred A. Knopf; 1988:399-405.
3. Dr. Margaret D. Craighill, at 78, former dean of medical college. Obituary. New York Times, July 26, 1977. Accessed February 24, 2022. https://www.nytimes.com/1977/07/26/archives/dr-margaret-d-craighill-at-78-former-dean-of-medical-college.html
4. US Library of Medicine. Changing the face of medicine: Dr. Margaret D. Craighill. Updated June 03, 2015. Accessed February 23, 2022. https://cfmedicine.nlm.nih.gov/physicians/biography_72.html
5. Knight AG. Dr. Margaret D. Craighill, M.D. On Point. 2018;23(4):19-22. Accessed February 24, 2022. https://www.jstor.org/stable/26478427.
6. Wamsley L. Pentagon releases new policies enabling transgender people to serve in the military. Updated March 31, 2021. Accessed February 23, 2022. https://www.npr.org/2021/03/31/983118029/pentagon-releases-new-policies-enabling-transgender-people-to-serve-in-the-milit
7. Shane L. Is VA shortchanging women’s health programs. Military Times. Published February 28, 2019. Accessed February 24, 2022. https://www.militarytimes.com/news/pentagon-congress/2019/02/28/is-va-spending-enough-on-womens-health-programs
8. Marshall V, Stryczek KC, Haverhals L, et al. The focus they deserve: improving women veterans’ health care access. Womens Health Issues. 2021;31(4):399-407. doi:10.1016/j.whi.2020.12.011
9. Craighill MD. Psychiatric aspects of women serving in the Army. Am J Psychiatry. 1947;104(4):226-230. doi:10.1176/ajp.104.4.226
Is a progression-free survival benefit alone really worth $10,000 a month?
In the field of lung cancer, and more broadly in oncology, many of our biggest advances in 2021 have come as clinically meaningful improvements in surrogate endpoints – disease-free survival, progression-free survival, and sometimes even pathologic complete response rate.
I have historically been most compelled to consider new findings to be practice-changing when they improve overall survival or quality of life – the endpoints that translate to direct benefits for patients. However, I also feel it is appropriate to call surrogate endpoints practice-changing when they can predict improvements in overall survival or quality of life.
Take the PACIFIC trial, which assessed maintenance durvalumab after concurrent chemoradiation for unresectable stage III non–small cell lung cancer (NSCLC).
Back in 2017, I was initially unconvinced by the interim phase 3 data that were presented in a press release that highlighted the disease-free survival benefit. However, after examining additional data more closely, I saw the dramatic improvement in time to distant relapse or death was overwhelmingly likely to predict an improvement in overall survival – a benefit that the data subsequently bore out.
More recently, the disease-free survival results for adjuvant osimertinib in resected endothelial growth factor receptor mutation–positive NSCLC and adjuvant atezolizumab in resected programmed death-ligand 1–positive stage II-IIIA NSCLC have led to excitement about Food and Drug Administration approvals for these therapies. Although there is reason to be cautious about the likelihood of an overall survival benefit with either therapy – particularly for patients with low programmed death-ligand 1 who receive atezolizumab – I think that the results are promising enough to discuss these treatment options with appropriate patients.
Some argue, however, that overall survival is not necessarily a critical goal and that certain surrogate endpoints are inherently beneficial. Patients and oncologists may, for instance, view delaying disease progression as a win, even if overall survival remains the same.
I appreciate the view that favorable scan results are an achievement, even without a survival benefit. Patients appreciate the good news, and it is gratifying for us to deliver it. However, what remains unspoken is whether the benefit can be provided at a reasonable value given the financial costs associated with the new treatment.
In the United States, we consider the physician-patient relationship to be autonomous and even revered, but we conveniently ignore the fact that both are deciding on treatments that are funded by people who are not represented in the room. And in a health care system that fails to cover basic cancer care needs as well as other critical, high-value interventions for both the uninsured and underinsured, we should acknowledge that our decisions redirect limited resources from others.
Is it the best use of $10,000 per month for a new drug that improves disease-free survival but not overall survival?
At the same time, we also have to remain vigilant and reflect on whether we are echoing the marketing messages of the companies selling these treatments. Having recently watched the excellent Hulu series Dopesick, which realistically portrays the medical community’s egregious overuse of Oxycontin at the behest of Purdue Pharmaceuticals, it is striking to see how effectively the pharmaceutical industry can co-opt stakeholders. Very few physicians or patients have expertise in health care policy with broad societal perspective, yet subspecialists offer edicts as if society should dedicate unlimited resources first and foremost to our career focus or personal cause.
I certainly appreciate the appeal of surrogate endpoints in a world in which we hope to offer novel therapies to patients in a timely fashion. In the next few years, some of our most promising data in oncology will demand that we consider whether surrogate endpoints are practice-changing. We are facing a fundamental question: Are we using these surrogate endpoints to predict overall survival or quality of life or do these endpoints stand on their own as practice-changing metrics?
We need to acknowledge that our primary clinical focus is not the only one that deserves our attention, particularly when our treatment decisions are, in fact, spending other people’s money. We should be asking not whether we prefer to deliver good news after a scan, but whether that alone is enough to justify the high cost of a new treatment without an overall survival benefit.
Dr. West disclosed serving as a director, officer, partner, employee, adviser, consultant, or trustee for Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, and Merck; serving as a speaker or a member of a speakers bureau for Ariad/Takeda, AstraZeneca, and Genentech/Roche; and receiving income from Eli Lilly. A version of this article first appeared on Medscape.com.
In the field of lung cancer, and more broadly in oncology, many of our biggest advances in 2021 have come as clinically meaningful improvements in surrogate endpoints – disease-free survival, progression-free survival, and sometimes even pathologic complete response rate.
I have historically been most compelled to consider new findings to be practice-changing when they improve overall survival or quality of life – the endpoints that translate to direct benefits for patients. However, I also feel it is appropriate to call surrogate endpoints practice-changing when they can predict improvements in overall survival or quality of life.
Take the PACIFIC trial, which assessed maintenance durvalumab after concurrent chemoradiation for unresectable stage III non–small cell lung cancer (NSCLC).
Back in 2017, I was initially unconvinced by the interim phase 3 data that were presented in a press release that highlighted the disease-free survival benefit. However, after examining additional data more closely, I saw the dramatic improvement in time to distant relapse or death was overwhelmingly likely to predict an improvement in overall survival – a benefit that the data subsequently bore out.
More recently, the disease-free survival results for adjuvant osimertinib in resected endothelial growth factor receptor mutation–positive NSCLC and adjuvant atezolizumab in resected programmed death-ligand 1–positive stage II-IIIA NSCLC have led to excitement about Food and Drug Administration approvals for these therapies. Although there is reason to be cautious about the likelihood of an overall survival benefit with either therapy – particularly for patients with low programmed death-ligand 1 who receive atezolizumab – I think that the results are promising enough to discuss these treatment options with appropriate patients.
Some argue, however, that overall survival is not necessarily a critical goal and that certain surrogate endpoints are inherently beneficial. Patients and oncologists may, for instance, view delaying disease progression as a win, even if overall survival remains the same.
I appreciate the view that favorable scan results are an achievement, even without a survival benefit. Patients appreciate the good news, and it is gratifying for us to deliver it. However, what remains unspoken is whether the benefit can be provided at a reasonable value given the financial costs associated with the new treatment.
In the United States, we consider the physician-patient relationship to be autonomous and even revered, but we conveniently ignore the fact that both are deciding on treatments that are funded by people who are not represented in the room. And in a health care system that fails to cover basic cancer care needs as well as other critical, high-value interventions for both the uninsured and underinsured, we should acknowledge that our decisions redirect limited resources from others.
Is it the best use of $10,000 per month for a new drug that improves disease-free survival but not overall survival?
At the same time, we also have to remain vigilant and reflect on whether we are echoing the marketing messages of the companies selling these treatments. Having recently watched the excellent Hulu series Dopesick, which realistically portrays the medical community’s egregious overuse of Oxycontin at the behest of Purdue Pharmaceuticals, it is striking to see how effectively the pharmaceutical industry can co-opt stakeholders. Very few physicians or patients have expertise in health care policy with broad societal perspective, yet subspecialists offer edicts as if society should dedicate unlimited resources first and foremost to our career focus or personal cause.
I certainly appreciate the appeal of surrogate endpoints in a world in which we hope to offer novel therapies to patients in a timely fashion. In the next few years, some of our most promising data in oncology will demand that we consider whether surrogate endpoints are practice-changing. We are facing a fundamental question: Are we using these surrogate endpoints to predict overall survival or quality of life or do these endpoints stand on their own as practice-changing metrics?
We need to acknowledge that our primary clinical focus is not the only one that deserves our attention, particularly when our treatment decisions are, in fact, spending other people’s money. We should be asking not whether we prefer to deliver good news after a scan, but whether that alone is enough to justify the high cost of a new treatment without an overall survival benefit.
Dr. West disclosed serving as a director, officer, partner, employee, adviser, consultant, or trustee for Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, and Merck; serving as a speaker or a member of a speakers bureau for Ariad/Takeda, AstraZeneca, and Genentech/Roche; and receiving income from Eli Lilly. A version of this article first appeared on Medscape.com.
In the field of lung cancer, and more broadly in oncology, many of our biggest advances in 2021 have come as clinically meaningful improvements in surrogate endpoints – disease-free survival, progression-free survival, and sometimes even pathologic complete response rate.
I have historically been most compelled to consider new findings to be practice-changing when they improve overall survival or quality of life – the endpoints that translate to direct benefits for patients. However, I also feel it is appropriate to call surrogate endpoints practice-changing when they can predict improvements in overall survival or quality of life.
Take the PACIFIC trial, which assessed maintenance durvalumab after concurrent chemoradiation for unresectable stage III non–small cell lung cancer (NSCLC).
Back in 2017, I was initially unconvinced by the interim phase 3 data that were presented in a press release that highlighted the disease-free survival benefit. However, after examining additional data more closely, I saw the dramatic improvement in time to distant relapse or death was overwhelmingly likely to predict an improvement in overall survival – a benefit that the data subsequently bore out.
More recently, the disease-free survival results for adjuvant osimertinib in resected endothelial growth factor receptor mutation–positive NSCLC and adjuvant atezolizumab in resected programmed death-ligand 1–positive stage II-IIIA NSCLC have led to excitement about Food and Drug Administration approvals for these therapies. Although there is reason to be cautious about the likelihood of an overall survival benefit with either therapy – particularly for patients with low programmed death-ligand 1 who receive atezolizumab – I think that the results are promising enough to discuss these treatment options with appropriate patients.
Some argue, however, that overall survival is not necessarily a critical goal and that certain surrogate endpoints are inherently beneficial. Patients and oncologists may, for instance, view delaying disease progression as a win, even if overall survival remains the same.
I appreciate the view that favorable scan results are an achievement, even without a survival benefit. Patients appreciate the good news, and it is gratifying for us to deliver it. However, what remains unspoken is whether the benefit can be provided at a reasonable value given the financial costs associated with the new treatment.
In the United States, we consider the physician-patient relationship to be autonomous and even revered, but we conveniently ignore the fact that both are deciding on treatments that are funded by people who are not represented in the room. And in a health care system that fails to cover basic cancer care needs as well as other critical, high-value interventions for both the uninsured and underinsured, we should acknowledge that our decisions redirect limited resources from others.
Is it the best use of $10,000 per month for a new drug that improves disease-free survival but not overall survival?
At the same time, we also have to remain vigilant and reflect on whether we are echoing the marketing messages of the companies selling these treatments. Having recently watched the excellent Hulu series Dopesick, which realistically portrays the medical community’s egregious overuse of Oxycontin at the behest of Purdue Pharmaceuticals, it is striking to see how effectively the pharmaceutical industry can co-opt stakeholders. Very few physicians or patients have expertise in health care policy with broad societal perspective, yet subspecialists offer edicts as if society should dedicate unlimited resources first and foremost to our career focus or personal cause.
I certainly appreciate the appeal of surrogate endpoints in a world in which we hope to offer novel therapies to patients in a timely fashion. In the next few years, some of our most promising data in oncology will demand that we consider whether surrogate endpoints are practice-changing. We are facing a fundamental question: Are we using these surrogate endpoints to predict overall survival or quality of life or do these endpoints stand on their own as practice-changing metrics?
We need to acknowledge that our primary clinical focus is not the only one that deserves our attention, particularly when our treatment decisions are, in fact, spending other people’s money. We should be asking not whether we prefer to deliver good news after a scan, but whether that alone is enough to justify the high cost of a new treatment without an overall survival benefit.
Dr. West disclosed serving as a director, officer, partner, employee, adviser, consultant, or trustee for Ariad/Takeda, Bristol-Myers Squibb, Boehringer Ingelheim, Spectrum, AstraZeneca, Celgene, Genentech/Roche, Pfizer, and Merck; serving as a speaker or a member of a speakers bureau for Ariad/Takeda, AstraZeneca, and Genentech/Roche; and receiving income from Eli Lilly. A version of this article first appeared on Medscape.com.
Aaron Rodgers’s Panchakarma ‘cleanse’ is a dangerous play
Green Bay Packers quarterback Aaron Rodgers recently made headlines when he said he finished a 12-day detoxification process that is said to cleanse the body from within.
Registered dietitians who spoke to this news organizastion about the Panchakarma cleanse were quick to debunk it.
“There is no scientific evidence that supports a cleanse,” says Jessica DeGore, a registered dietitian and owner of Pittsburgh-based Dietitian Jess. “Our kidneys, GI systems, and liver all work to keep us healthy and rid us of toxins.”
The Panchakarma cleanse has roots in the ancient Indian alternative medicine approach known as ayurveda. Its 12-day approach includes such actions as self-induced vomiting; enemas; “nasya,” which means eliminating toxins through the nose; and even bloodletting in an effort to “detoxify” the blood.
All of it is misguided, says Alyssa Pike, a registered dietitian and senior manager of nutrition communications at the International Food Information Council.
“Certainly, there are medical procedures that require a fast of some kind for an extended period, and some choose to engage in a fast for religious or spiritual reasons,” she says, “but those are both very different from doing a voluntary ‘cleanse’ or ‘detox’ diet for purported health benefits.”
In fact, the idea that our bodies are full of “toxins” is simply incorrect.
“There isn’t a real medical definition of the word ‘toxins,’” says Ms. DeGore. “If you really had toxins in your body, you’d need emergency medical care, not a cleanse.”
Harmful advice
The entire notion of cleansing, whether Mr. Rodgers’s favored method or another, has gathered steam in the past few decades as celebrities like Gwyneth Paltrow peddle their favored methods for health.
“It’s easy for people to buy into these ideas when they see beautiful celebrities touting their methods for taking care of themselves,” says Ms. DeGore. “But behind the scenes, they receive support we can’t see or access to keep them well.”
Fans of Mr. Rodgers, Ms. Paltrow, and the like easily forget that these public figures have no medical credentials to support what they are pushing. And the celebrities often profit from their claims in the form of books and products related to them, leaving them anything but an unbiased resource.
In the case of Mr. Rodgers’s Panchakarma cleanse, there are real health risks in following its principles, says registered dietitian nutritionist Tiffany Godwin, director of nutrition and wellness at Connections Wellness Group.
“From a medical standpoint, engaging in activities such as induced vomiting, forced diarrhea, and enema use pose a high risk of extreme dehydration,” she says. “Dehydration can lead to fatigue, headaches, and dizziness at best. At worst, it can lead to seizures, kidney failure, coma, and death.”
Also, a cleanse that is designed to rid your body of toxins may introduce them to your body if you are using herbal medicines.
“Some of the products used in ayurvedic medicine contain herbs, metals, minerals, or other materials that may be harmful if used improperly,” Ms. Pike explains. “Ayurvedic medicines are regulated as dietary supplements rather than as drugs in the United States, so they are not required to meet the safety and efficacy standards for conventional medicines.”
When it comes to ayurveda, which is based on ancient writings that rely on a “natural” or holistic approach to physical and mental health, there is scant research or clinical trials in Western medical journals to support the approach. So people interested in following the practices should always consult with a doctor before trying them.
Mr. Rodgers’s approach includes a “nasal herbal remedy,” for instance.
“Tread very lightly with herbs and supplements,” advises Ms. DeGore. “We have the FDA to put drugs through a rigorous process before they approve them. These supplements are unregulated and don’t go through the same processes.”
Another danger is that when “cleansing,” you are starving your body of the nutrients it needs.
“When we vomit, or have diarrhea, we are not simply losing a mass amount of fluid from our bodies, but we are also losing essential electrolytes and minerals,” says Ms. Godwin.
Instead, say the registered dietitians, you can help your body by feeding it what it really needs.
“Eating plenty of fiber-rich foods such as fruits, veggies, beans, legumes, and whole grains, for example, keeps our GI tract moving and grooving, creating an ideal environment for our gut to use the useful things, and get rid of the not so useful,” says Ms. Godwin. “These systems can be compromised in different disease states, such as liver disease, kidney disease, and other GI disorders like Crohn’s or ulcerative colitis. With these disease states, however, cleanses can be even more harmful.”
Cleansing practices can also be a very slippery slope for people struggling with disordered eating.
“When celebrities promote these cleanses, they often bring in impressionable people,” says Ms. DeGore. “These approaches are stripping your body of nutritional needs and inducing disruptive behaviors. Ironically, they will slow down your metabolism, eventually leading to weight gain when you return to normal eating.”
With the Panchakarma cleanse, the 12-day length of cleansing is particularly alarming, says Ms. DeGore.
“Even after 5 days, you cannot think clearly and will have nasty side effects,” she says.
At the end of the day, whether it’s Mr. Rodgers, Ms. Paltrow, or another celebrity, all of the dietitians recommend steering clear of their advice when it comes to health and nutrition.
“Be wary of celebrities, influencers, or anyone who tries to persuade you to try an extreme cleanse or ‘too good to be true’ diet,” says Ms. Pike. “These can be dangerous for your health, physically and mentally.”
A version of this article first appeared on WebMD.com.
Green Bay Packers quarterback Aaron Rodgers recently made headlines when he said he finished a 12-day detoxification process that is said to cleanse the body from within.
Registered dietitians who spoke to this news organizastion about the Panchakarma cleanse were quick to debunk it.
“There is no scientific evidence that supports a cleanse,” says Jessica DeGore, a registered dietitian and owner of Pittsburgh-based Dietitian Jess. “Our kidneys, GI systems, and liver all work to keep us healthy and rid us of toxins.”
The Panchakarma cleanse has roots in the ancient Indian alternative medicine approach known as ayurveda. Its 12-day approach includes such actions as self-induced vomiting; enemas; “nasya,” which means eliminating toxins through the nose; and even bloodletting in an effort to “detoxify” the blood.
All of it is misguided, says Alyssa Pike, a registered dietitian and senior manager of nutrition communications at the International Food Information Council.
“Certainly, there are medical procedures that require a fast of some kind for an extended period, and some choose to engage in a fast for religious or spiritual reasons,” she says, “but those are both very different from doing a voluntary ‘cleanse’ or ‘detox’ diet for purported health benefits.”
In fact, the idea that our bodies are full of “toxins” is simply incorrect.
“There isn’t a real medical definition of the word ‘toxins,’” says Ms. DeGore. “If you really had toxins in your body, you’d need emergency medical care, not a cleanse.”
Harmful advice
The entire notion of cleansing, whether Mr. Rodgers’s favored method or another, has gathered steam in the past few decades as celebrities like Gwyneth Paltrow peddle their favored methods for health.
“It’s easy for people to buy into these ideas when they see beautiful celebrities touting their methods for taking care of themselves,” says Ms. DeGore. “But behind the scenes, they receive support we can’t see or access to keep them well.”
Fans of Mr. Rodgers, Ms. Paltrow, and the like easily forget that these public figures have no medical credentials to support what they are pushing. And the celebrities often profit from their claims in the form of books and products related to them, leaving them anything but an unbiased resource.
In the case of Mr. Rodgers’s Panchakarma cleanse, there are real health risks in following its principles, says registered dietitian nutritionist Tiffany Godwin, director of nutrition and wellness at Connections Wellness Group.
“From a medical standpoint, engaging in activities such as induced vomiting, forced diarrhea, and enema use pose a high risk of extreme dehydration,” she says. “Dehydration can lead to fatigue, headaches, and dizziness at best. At worst, it can lead to seizures, kidney failure, coma, and death.”
Also, a cleanse that is designed to rid your body of toxins may introduce them to your body if you are using herbal medicines.
“Some of the products used in ayurvedic medicine contain herbs, metals, minerals, or other materials that may be harmful if used improperly,” Ms. Pike explains. “Ayurvedic medicines are regulated as dietary supplements rather than as drugs in the United States, so they are not required to meet the safety and efficacy standards for conventional medicines.”
When it comes to ayurveda, which is based on ancient writings that rely on a “natural” or holistic approach to physical and mental health, there is scant research or clinical trials in Western medical journals to support the approach. So people interested in following the practices should always consult with a doctor before trying them.
Mr. Rodgers’s approach includes a “nasal herbal remedy,” for instance.
“Tread very lightly with herbs and supplements,” advises Ms. DeGore. “We have the FDA to put drugs through a rigorous process before they approve them. These supplements are unregulated and don’t go through the same processes.”
Another danger is that when “cleansing,” you are starving your body of the nutrients it needs.
“When we vomit, or have diarrhea, we are not simply losing a mass amount of fluid from our bodies, but we are also losing essential electrolytes and minerals,” says Ms. Godwin.
Instead, say the registered dietitians, you can help your body by feeding it what it really needs.
“Eating plenty of fiber-rich foods such as fruits, veggies, beans, legumes, and whole grains, for example, keeps our GI tract moving and grooving, creating an ideal environment for our gut to use the useful things, and get rid of the not so useful,” says Ms. Godwin. “These systems can be compromised in different disease states, such as liver disease, kidney disease, and other GI disorders like Crohn’s or ulcerative colitis. With these disease states, however, cleanses can be even more harmful.”
Cleansing practices can also be a very slippery slope for people struggling with disordered eating.
“When celebrities promote these cleanses, they often bring in impressionable people,” says Ms. DeGore. “These approaches are stripping your body of nutritional needs and inducing disruptive behaviors. Ironically, they will slow down your metabolism, eventually leading to weight gain when you return to normal eating.”
With the Panchakarma cleanse, the 12-day length of cleansing is particularly alarming, says Ms. DeGore.
“Even after 5 days, you cannot think clearly and will have nasty side effects,” she says.
At the end of the day, whether it’s Mr. Rodgers, Ms. Paltrow, or another celebrity, all of the dietitians recommend steering clear of their advice when it comes to health and nutrition.
“Be wary of celebrities, influencers, or anyone who tries to persuade you to try an extreme cleanse or ‘too good to be true’ diet,” says Ms. Pike. “These can be dangerous for your health, physically and mentally.”
A version of this article first appeared on WebMD.com.
Green Bay Packers quarterback Aaron Rodgers recently made headlines when he said he finished a 12-day detoxification process that is said to cleanse the body from within.
Registered dietitians who spoke to this news organizastion about the Panchakarma cleanse were quick to debunk it.
“There is no scientific evidence that supports a cleanse,” says Jessica DeGore, a registered dietitian and owner of Pittsburgh-based Dietitian Jess. “Our kidneys, GI systems, and liver all work to keep us healthy and rid us of toxins.”
The Panchakarma cleanse has roots in the ancient Indian alternative medicine approach known as ayurveda. Its 12-day approach includes such actions as self-induced vomiting; enemas; “nasya,” which means eliminating toxins through the nose; and even bloodletting in an effort to “detoxify” the blood.
All of it is misguided, says Alyssa Pike, a registered dietitian and senior manager of nutrition communications at the International Food Information Council.
“Certainly, there are medical procedures that require a fast of some kind for an extended period, and some choose to engage in a fast for religious or spiritual reasons,” she says, “but those are both very different from doing a voluntary ‘cleanse’ or ‘detox’ diet for purported health benefits.”
In fact, the idea that our bodies are full of “toxins” is simply incorrect.
“There isn’t a real medical definition of the word ‘toxins,’” says Ms. DeGore. “If you really had toxins in your body, you’d need emergency medical care, not a cleanse.”
Harmful advice
The entire notion of cleansing, whether Mr. Rodgers’s favored method or another, has gathered steam in the past few decades as celebrities like Gwyneth Paltrow peddle their favored methods for health.
“It’s easy for people to buy into these ideas when they see beautiful celebrities touting their methods for taking care of themselves,” says Ms. DeGore. “But behind the scenes, they receive support we can’t see or access to keep them well.”
Fans of Mr. Rodgers, Ms. Paltrow, and the like easily forget that these public figures have no medical credentials to support what they are pushing. And the celebrities often profit from their claims in the form of books and products related to them, leaving them anything but an unbiased resource.
In the case of Mr. Rodgers’s Panchakarma cleanse, there are real health risks in following its principles, says registered dietitian nutritionist Tiffany Godwin, director of nutrition and wellness at Connections Wellness Group.
“From a medical standpoint, engaging in activities such as induced vomiting, forced diarrhea, and enema use pose a high risk of extreme dehydration,” she says. “Dehydration can lead to fatigue, headaches, and dizziness at best. At worst, it can lead to seizures, kidney failure, coma, and death.”
Also, a cleanse that is designed to rid your body of toxins may introduce them to your body if you are using herbal medicines.
“Some of the products used in ayurvedic medicine contain herbs, metals, minerals, or other materials that may be harmful if used improperly,” Ms. Pike explains. “Ayurvedic medicines are regulated as dietary supplements rather than as drugs in the United States, so they are not required to meet the safety and efficacy standards for conventional medicines.”
When it comes to ayurveda, which is based on ancient writings that rely on a “natural” or holistic approach to physical and mental health, there is scant research or clinical trials in Western medical journals to support the approach. So people interested in following the practices should always consult with a doctor before trying them.
Mr. Rodgers’s approach includes a “nasal herbal remedy,” for instance.
“Tread very lightly with herbs and supplements,” advises Ms. DeGore. “We have the FDA to put drugs through a rigorous process before they approve them. These supplements are unregulated and don’t go through the same processes.”
Another danger is that when “cleansing,” you are starving your body of the nutrients it needs.
“When we vomit, or have diarrhea, we are not simply losing a mass amount of fluid from our bodies, but we are also losing essential electrolytes and minerals,” says Ms. Godwin.
Instead, say the registered dietitians, you can help your body by feeding it what it really needs.
“Eating plenty of fiber-rich foods such as fruits, veggies, beans, legumes, and whole grains, for example, keeps our GI tract moving and grooving, creating an ideal environment for our gut to use the useful things, and get rid of the not so useful,” says Ms. Godwin. “These systems can be compromised in different disease states, such as liver disease, kidney disease, and other GI disorders like Crohn’s or ulcerative colitis. With these disease states, however, cleanses can be even more harmful.”
Cleansing practices can also be a very slippery slope for people struggling with disordered eating.
“When celebrities promote these cleanses, they often bring in impressionable people,” says Ms. DeGore. “These approaches are stripping your body of nutritional needs and inducing disruptive behaviors. Ironically, they will slow down your metabolism, eventually leading to weight gain when you return to normal eating.”
With the Panchakarma cleanse, the 12-day length of cleansing is particularly alarming, says Ms. DeGore.
“Even after 5 days, you cannot think clearly and will have nasty side effects,” she says.
At the end of the day, whether it’s Mr. Rodgers, Ms. Paltrow, or another celebrity, all of the dietitians recommend steering clear of their advice when it comes to health and nutrition.
“Be wary of celebrities, influencers, or anyone who tries to persuade you to try an extreme cleanse or ‘too good to be true’ diet,” says Ms. Pike. “These can be dangerous for your health, physically and mentally.”
A version of this article first appeared on WebMD.com.