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Physician: The nicotine, not the flavors, needs regulation
While most of the recent legislative action on e-cigarettes and other electronic nicotine delivery systems are focusing on the flavors that are appealing, especially to children,
Michael B. Siegel, MD, MPH, a physician and professor at Boston University School of Public Health, said the turning point in the spike in youth e-cigarettes occurred when products like Juul, Sourin, Smok, and Phix were introduced into the market.
Prior to that, he noted that, in 2014, citing that year’s National Youth Tobacco Survey from the Centers for Disease Control and Prevention, 74% of nonsmoking youth e-cigarette users reported using e-cigarettes no more than once per week, while only 4% reported daily use. By 2018, 12% of nonsmoking youth e-cigarette users were using e-cigarettes daily, while 42% of nonsmoking e-cigarette use was no more than once a week, according to that year’s CDC survey.
“All of these brands use a different nicotine formulation from virtually all other e-cigarettes,” Dr. Siegel testified Oct. 16 at a House Energy and Commerce Health Subcommittee hearing. “They use a nicotine salt at very high concentrations.”
His written testimony notes that Juul and similar products use nicotine salt at concentrations of 50 mg/mL, whereas most other e-cigarette products have nicotine concentrations that are less than 25 mg/mL.
“The use of nicotine salts allows nicotine to be absorbed into the bloodstream much more quickly, simulating the pattern you get with a real cigarette,” he continued. “That is why so many youth are now addicted to vaping. It is not the flavors. It’s the nicotine.”
Susanne Tanski, MD, testifying on behalf of the American Academy of Pediatrics agreed with Dr. Siegel that the Food and Drug Administration needs to be doing more to regulate the amount of nicotine that these products are releasing and that the introduction of nicotine salt was a significant cause of addiction.
However, she also targeted flavors as a key issue.
“There is reasonable concern that flavors may also modify the addictiveness of e-cigarettes, but with the thousands of flavor combinations on the market, there has not been specific research yet to test this hypothesis,” Dr. Tanksi, a pediatrician at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., noted in her written testimony. “We know that flavors unto themselves are pleasurable. If you link a pleasurable flavor with a buzz of nicotine from a powerful nicotine delivery system such as the newer e-cigarettes, perhaps this is even more behaviorally and biologically reinforcing to drive the addictiveness of this new generation of products.”
Other panelists also expressed concern about the flavoring of e-cigarettes.
Subcommittee Chair Anna Eshoo (D-Calif.) noted that “flavor is very attractive. It really drives our eating habits and other habits.” She then asked whether “e-cigarettes’ sweet flavors have contributed to youth tobacco use.”
Matthew L. Myers, president of the Campaign for Tobacco-Free Kids, responded by saying that all “of the evidence is that they are the driving force of that and that it has gotten worse over the last 4 years.”
He also noted that while youth use of flavored products has spiked in the last 4 years, there really has not been any growth in adult usage of flavored tobacco.
“What it shows is the introduction of all these flavors has fueled a youth epidemic, but it has had no impact whatsoever” on adults. “Indeed, before Juul was introduced, the most popular e-cigarette flavor was tobacco. So, for smokers who want to quit, that was a viable option until Juul changed the market.”
The subcommittee hearing was held to solicit opinions on H.R. 2339, the “Reversing the Youth Tobacco Epidemic Act of 2019.” Among the provisions in the bill are raising the minimum age of purchasing all tobacco and nicotine products to age 21 years, requiring health warning labels on e-cigarette products, placing restrictions on advertising that are similar to those on smoking products, and prohibiting Internet sales of e-cigarettes.
Dr. Siegel voiced his approval for the bill, providing the provision that bans all flavored tobacco products was removed.
He noted that the current epidemic of vaping illness and deaths recently has not been caused primarily from legit e-cigarette and other vaping products, but rather from black market, THC-laced vaping cartridges.
“A ban on flavored e-cigarettes would create a public health disaster because it would create a new black market for flavored e-liquids,” he testified. “It is nearly certain that we would see more outbreaks similar to what we are seeing now with these tainted THC vape cartridges.”
He continued: “Banning flavored e-liquids is not going to do anything to curtail this respiratory disease outbreak, but it may make the outbreak worse. Why? Because the supply of e-liquids that youth are vaping is going to transition from one dominated by nicotine products to one dominated by THC products, exactly the products that are causing this outbreak.”
Dr. Siegel also spoke to the potential effect it might have on adult smokers who have abandoned combustible tobacco products in favor of e-cigarettes.
“More than 2 million adult smokers in the U.S. have quit smoking completely by switching to flavored electronic cigarettes,” he said. “If these products are banned, many of these ex-smokers will return to cigarette smoking. Most of those who don’t will turn to a new potentially dangerous black market that will be created by this legislation.”
Dr. Tanski, on the other hand, called the provision banning all flavored tobacco products, including menthol, “the single most important policy that Congress can pass to address the youth tobacco epidemic, and a step that Congress took years ago for other flavored cigarettes.”
While most of the recent legislative action on e-cigarettes and other electronic nicotine delivery systems are focusing on the flavors that are appealing, especially to children,
Michael B. Siegel, MD, MPH, a physician and professor at Boston University School of Public Health, said the turning point in the spike in youth e-cigarettes occurred when products like Juul, Sourin, Smok, and Phix were introduced into the market.
Prior to that, he noted that, in 2014, citing that year’s National Youth Tobacco Survey from the Centers for Disease Control and Prevention, 74% of nonsmoking youth e-cigarette users reported using e-cigarettes no more than once per week, while only 4% reported daily use. By 2018, 12% of nonsmoking youth e-cigarette users were using e-cigarettes daily, while 42% of nonsmoking e-cigarette use was no more than once a week, according to that year’s CDC survey.
“All of these brands use a different nicotine formulation from virtually all other e-cigarettes,” Dr. Siegel testified Oct. 16 at a House Energy and Commerce Health Subcommittee hearing. “They use a nicotine salt at very high concentrations.”
His written testimony notes that Juul and similar products use nicotine salt at concentrations of 50 mg/mL, whereas most other e-cigarette products have nicotine concentrations that are less than 25 mg/mL.
“The use of nicotine salts allows nicotine to be absorbed into the bloodstream much more quickly, simulating the pattern you get with a real cigarette,” he continued. “That is why so many youth are now addicted to vaping. It is not the flavors. It’s the nicotine.”
Susanne Tanski, MD, testifying on behalf of the American Academy of Pediatrics agreed with Dr. Siegel that the Food and Drug Administration needs to be doing more to regulate the amount of nicotine that these products are releasing and that the introduction of nicotine salt was a significant cause of addiction.
However, she also targeted flavors as a key issue.
“There is reasonable concern that flavors may also modify the addictiveness of e-cigarettes, but with the thousands of flavor combinations on the market, there has not been specific research yet to test this hypothesis,” Dr. Tanksi, a pediatrician at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., noted in her written testimony. “We know that flavors unto themselves are pleasurable. If you link a pleasurable flavor with a buzz of nicotine from a powerful nicotine delivery system such as the newer e-cigarettes, perhaps this is even more behaviorally and biologically reinforcing to drive the addictiveness of this new generation of products.”
Other panelists also expressed concern about the flavoring of e-cigarettes.
Subcommittee Chair Anna Eshoo (D-Calif.) noted that “flavor is very attractive. It really drives our eating habits and other habits.” She then asked whether “e-cigarettes’ sweet flavors have contributed to youth tobacco use.”
Matthew L. Myers, president of the Campaign for Tobacco-Free Kids, responded by saying that all “of the evidence is that they are the driving force of that and that it has gotten worse over the last 4 years.”
He also noted that while youth use of flavored products has spiked in the last 4 years, there really has not been any growth in adult usage of flavored tobacco.
“What it shows is the introduction of all these flavors has fueled a youth epidemic, but it has had no impact whatsoever” on adults. “Indeed, before Juul was introduced, the most popular e-cigarette flavor was tobacco. So, for smokers who want to quit, that was a viable option until Juul changed the market.”
The subcommittee hearing was held to solicit opinions on H.R. 2339, the “Reversing the Youth Tobacco Epidemic Act of 2019.” Among the provisions in the bill are raising the minimum age of purchasing all tobacco and nicotine products to age 21 years, requiring health warning labels on e-cigarette products, placing restrictions on advertising that are similar to those on smoking products, and prohibiting Internet sales of e-cigarettes.
Dr. Siegel voiced his approval for the bill, providing the provision that bans all flavored tobacco products was removed.
He noted that the current epidemic of vaping illness and deaths recently has not been caused primarily from legit e-cigarette and other vaping products, but rather from black market, THC-laced vaping cartridges.
“A ban on flavored e-cigarettes would create a public health disaster because it would create a new black market for flavored e-liquids,” he testified. “It is nearly certain that we would see more outbreaks similar to what we are seeing now with these tainted THC vape cartridges.”
He continued: “Banning flavored e-liquids is not going to do anything to curtail this respiratory disease outbreak, but it may make the outbreak worse. Why? Because the supply of e-liquids that youth are vaping is going to transition from one dominated by nicotine products to one dominated by THC products, exactly the products that are causing this outbreak.”
Dr. Siegel also spoke to the potential effect it might have on adult smokers who have abandoned combustible tobacco products in favor of e-cigarettes.
“More than 2 million adult smokers in the U.S. have quit smoking completely by switching to flavored electronic cigarettes,” he said. “If these products are banned, many of these ex-smokers will return to cigarette smoking. Most of those who don’t will turn to a new potentially dangerous black market that will be created by this legislation.”
Dr. Tanski, on the other hand, called the provision banning all flavored tobacco products, including menthol, “the single most important policy that Congress can pass to address the youth tobacco epidemic, and a step that Congress took years ago for other flavored cigarettes.”
While most of the recent legislative action on e-cigarettes and other electronic nicotine delivery systems are focusing on the flavors that are appealing, especially to children,
Michael B. Siegel, MD, MPH, a physician and professor at Boston University School of Public Health, said the turning point in the spike in youth e-cigarettes occurred when products like Juul, Sourin, Smok, and Phix were introduced into the market.
Prior to that, he noted that, in 2014, citing that year’s National Youth Tobacco Survey from the Centers for Disease Control and Prevention, 74% of nonsmoking youth e-cigarette users reported using e-cigarettes no more than once per week, while only 4% reported daily use. By 2018, 12% of nonsmoking youth e-cigarette users were using e-cigarettes daily, while 42% of nonsmoking e-cigarette use was no more than once a week, according to that year’s CDC survey.
“All of these brands use a different nicotine formulation from virtually all other e-cigarettes,” Dr. Siegel testified Oct. 16 at a House Energy and Commerce Health Subcommittee hearing. “They use a nicotine salt at very high concentrations.”
His written testimony notes that Juul and similar products use nicotine salt at concentrations of 50 mg/mL, whereas most other e-cigarette products have nicotine concentrations that are less than 25 mg/mL.
“The use of nicotine salts allows nicotine to be absorbed into the bloodstream much more quickly, simulating the pattern you get with a real cigarette,” he continued. “That is why so many youth are now addicted to vaping. It is not the flavors. It’s the nicotine.”
Susanne Tanski, MD, testifying on behalf of the American Academy of Pediatrics agreed with Dr. Siegel that the Food and Drug Administration needs to be doing more to regulate the amount of nicotine that these products are releasing and that the introduction of nicotine salt was a significant cause of addiction.
However, she also targeted flavors as a key issue.
“There is reasonable concern that flavors may also modify the addictiveness of e-cigarettes, but with the thousands of flavor combinations on the market, there has not been specific research yet to test this hypothesis,” Dr. Tanksi, a pediatrician at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., noted in her written testimony. “We know that flavors unto themselves are pleasurable. If you link a pleasurable flavor with a buzz of nicotine from a powerful nicotine delivery system such as the newer e-cigarettes, perhaps this is even more behaviorally and biologically reinforcing to drive the addictiveness of this new generation of products.”
Other panelists also expressed concern about the flavoring of e-cigarettes.
Subcommittee Chair Anna Eshoo (D-Calif.) noted that “flavor is very attractive. It really drives our eating habits and other habits.” She then asked whether “e-cigarettes’ sweet flavors have contributed to youth tobacco use.”
Matthew L. Myers, president of the Campaign for Tobacco-Free Kids, responded by saying that all “of the evidence is that they are the driving force of that and that it has gotten worse over the last 4 years.”
He also noted that while youth use of flavored products has spiked in the last 4 years, there really has not been any growth in adult usage of flavored tobacco.
“What it shows is the introduction of all these flavors has fueled a youth epidemic, but it has had no impact whatsoever” on adults. “Indeed, before Juul was introduced, the most popular e-cigarette flavor was tobacco. So, for smokers who want to quit, that was a viable option until Juul changed the market.”
The subcommittee hearing was held to solicit opinions on H.R. 2339, the “Reversing the Youth Tobacco Epidemic Act of 2019.” Among the provisions in the bill are raising the minimum age of purchasing all tobacco and nicotine products to age 21 years, requiring health warning labels on e-cigarette products, placing restrictions on advertising that are similar to those on smoking products, and prohibiting Internet sales of e-cigarettes.
Dr. Siegel voiced his approval for the bill, providing the provision that bans all flavored tobacco products was removed.
He noted that the current epidemic of vaping illness and deaths recently has not been caused primarily from legit e-cigarette and other vaping products, but rather from black market, THC-laced vaping cartridges.
“A ban on flavored e-cigarettes would create a public health disaster because it would create a new black market for flavored e-liquids,” he testified. “It is nearly certain that we would see more outbreaks similar to what we are seeing now with these tainted THC vape cartridges.”
He continued: “Banning flavored e-liquids is not going to do anything to curtail this respiratory disease outbreak, but it may make the outbreak worse. Why? Because the supply of e-liquids that youth are vaping is going to transition from one dominated by nicotine products to one dominated by THC products, exactly the products that are causing this outbreak.”
Dr. Siegel also spoke to the potential effect it might have on adult smokers who have abandoned combustible tobacco products in favor of e-cigarettes.
“More than 2 million adult smokers in the U.S. have quit smoking completely by switching to flavored electronic cigarettes,” he said. “If these products are banned, many of these ex-smokers will return to cigarette smoking. Most of those who don’t will turn to a new potentially dangerous black market that will be created by this legislation.”
Dr. Tanski, on the other hand, called the provision banning all flavored tobacco products, including menthol, “the single most important policy that Congress can pass to address the youth tobacco epidemic, and a step that Congress took years ago for other flavored cigarettes.”
REPORTING FROM A HOUSE ENERGY AND COMMERCE HEALTH SUBCOMMITTEE HEARING
Vaping-linked lung injuries near 1,500
according to the latest update provided by the Centers for Disease Control and Prevention. Thirty-three deaths have been confirmed.
E-cigarette–linked lung injuries, now called EVALI, occurred in all U.S. states (except Alaska), the District of Columbia, and the U.S. Virgin Islands. Seventy percent of patients are male, and 79% are under age 35 years.
Information on the substances used over the previous 3 months before symptom onset was available for 849 patients and included the following:
- 78% reported using THC-containing products, with or without nicotine-containing products;
- 31% reported exclusive use of THC-containing products;
- 58% reported using nicotine-containing products, with or without THC-containing products; and
- 10% reported exclusive use of nicotine-containing products.
CDC is now doing additional testing on available samples for chemical in the bronchoalveolar lavage fluid, blood, or urine, as well as lung biopsy or autopsy specimens. CDC is also validating methods for aerosol emission testing of case-associated product samples from vaping products and e-liquids.
In a related development, JUUL, maker of e-cigarette products, has announced that it will suspend the sale of nontobacco, nonmenthol flavors (mango, creme, fruit, and cucumber) in the United States, pending review by the Food and Drug Administration. The JUUL announcement comes in advance of an expected FDA ban on flavored e-cigarettes.
The CDC continues its investigation into EVALI but stated, “Since the specific cause or causes of lung injury are not yet known, the only way to assure that you are not at risk while the investigation continues is to consider refraining from use of all e-cigarette, or vaping, products.”
For more information and resources visit For the Public, For Healthcare Providers, and For State and Local Health Departments pages, as well as the CDC’s Publications and Resources page.
according to the latest update provided by the Centers for Disease Control and Prevention. Thirty-three deaths have been confirmed.
E-cigarette–linked lung injuries, now called EVALI, occurred in all U.S. states (except Alaska), the District of Columbia, and the U.S. Virgin Islands. Seventy percent of patients are male, and 79% are under age 35 years.
Information on the substances used over the previous 3 months before symptom onset was available for 849 patients and included the following:
- 78% reported using THC-containing products, with or without nicotine-containing products;
- 31% reported exclusive use of THC-containing products;
- 58% reported using nicotine-containing products, with or without THC-containing products; and
- 10% reported exclusive use of nicotine-containing products.
CDC is now doing additional testing on available samples for chemical in the bronchoalveolar lavage fluid, blood, or urine, as well as lung biopsy or autopsy specimens. CDC is also validating methods for aerosol emission testing of case-associated product samples from vaping products and e-liquids.
In a related development, JUUL, maker of e-cigarette products, has announced that it will suspend the sale of nontobacco, nonmenthol flavors (mango, creme, fruit, and cucumber) in the United States, pending review by the Food and Drug Administration. The JUUL announcement comes in advance of an expected FDA ban on flavored e-cigarettes.
The CDC continues its investigation into EVALI but stated, “Since the specific cause or causes of lung injury are not yet known, the only way to assure that you are not at risk while the investigation continues is to consider refraining from use of all e-cigarette, or vaping, products.”
For more information and resources visit For the Public, For Healthcare Providers, and For State and Local Health Departments pages, as well as the CDC’s Publications and Resources page.
according to the latest update provided by the Centers for Disease Control and Prevention. Thirty-three deaths have been confirmed.
E-cigarette–linked lung injuries, now called EVALI, occurred in all U.S. states (except Alaska), the District of Columbia, and the U.S. Virgin Islands. Seventy percent of patients are male, and 79% are under age 35 years.
Information on the substances used over the previous 3 months before symptom onset was available for 849 patients and included the following:
- 78% reported using THC-containing products, with or without nicotine-containing products;
- 31% reported exclusive use of THC-containing products;
- 58% reported using nicotine-containing products, with or without THC-containing products; and
- 10% reported exclusive use of nicotine-containing products.
CDC is now doing additional testing on available samples for chemical in the bronchoalveolar lavage fluid, blood, or urine, as well as lung biopsy or autopsy specimens. CDC is also validating methods for aerosol emission testing of case-associated product samples from vaping products and e-liquids.
In a related development, JUUL, maker of e-cigarette products, has announced that it will suspend the sale of nontobacco, nonmenthol flavors (mango, creme, fruit, and cucumber) in the United States, pending review by the Food and Drug Administration. The JUUL announcement comes in advance of an expected FDA ban on flavored e-cigarettes.
The CDC continues its investigation into EVALI but stated, “Since the specific cause or causes of lung injury are not yet known, the only way to assure that you are not at risk while the investigation continues is to consider refraining from use of all e-cigarette, or vaping, products.”
For more information and resources visit For the Public, For Healthcare Providers, and For State and Local Health Departments pages, as well as the CDC’s Publications and Resources page.
High burden of mental health symptoms in teens with insomnia
Adolescents diagnosed with insomnia have a high prevalence of concurrent mental health disorders and should be screened for them, according to new research.
For a study published in the Journal of Clinical Sleep Medicine, Tori R. Van Dyk, PhD, of Loma Linda (Calif.) University, and colleagues, enrolled 376 adolescents aged 11-18 years (mean age 14.5, 55% female) diagnosed with primary insomnia and referred to a sleep clinic. Subjects were evaluated using two validated questionnaires used to measure sleep disorders in adolescents, while caregivers reported and mental health diagnoses and symptoms using a standard behavioral checklist for adolescents.
Dr. Van Dyk and colleagues found that 75% of subjects had at least one or more parent-reported mental health diagnosis, most commonly anxiety, mood disorders, and ADHD. Some 64% had a clinical elevation of mental health symptoms on evaluation, most commonly affective disorders, with 40% of the cohort having two or more elevations. Specific mental health symptoms were seen linked with particular sleep symptoms. A greater burden of ADHD symptoms, for example, was significantly associated with more difficulties falling asleep, maintaining sleep, and reinitiating sleep after waking at night.
A total of 15% of subjects were reported by caregivers to engage in deliberate self-harming behaviors or talking about or attempting suicide – a higher rate than in the general adolescent population. “Because youth presenting for insomnia treatment may be even more likely to engage in self-harm behavior or to be suicidal, particular attention should be paid to directly assessing for these high-risk behaviors within the context of behavioral sleep medicine evaluations,” Dr. Van Dyk and colleagues wrote in their analysis.
Although mental health symptoms have been linked to sleep problems in other studies of children and adults, “associations identified in younger youths and/or adults should not be assumed to hold true among adolescents,” the researchers wrote, adding that adolescence “is a distinctive developmental period characterized by increases in both psychopathology and sleep problems, changing biology, increasing independence, and unique social and societal demands.” The investigators noted that because pediatric sleep specialists are relatively rare, the management of adolescent sleep problems and related mental health symptoms is likely to fall on primary care and other providers who “would benefit in recognizing the relationship between sleep problems and mental health symptoms in this population.”
Dr. Van Dyk and colleagues noted among the weaknesses of their study its cross-sectional design, use of parent-reported mental health symptoms only, lack of information on medication use or mental health treatment, and the potential for selection bias toward more severe cases.
The authors disclosed no outside funding or conflicts of interest related to their study.
SOURCE: Van Dyk TR et al. J Clin Sleep Med. 2019 Sep 6. doi: 10.5664/jcsm.7970.
Adolescents diagnosed with insomnia have a high prevalence of concurrent mental health disorders and should be screened for them, according to new research.
For a study published in the Journal of Clinical Sleep Medicine, Tori R. Van Dyk, PhD, of Loma Linda (Calif.) University, and colleagues, enrolled 376 adolescents aged 11-18 years (mean age 14.5, 55% female) diagnosed with primary insomnia and referred to a sleep clinic. Subjects were evaluated using two validated questionnaires used to measure sleep disorders in adolescents, while caregivers reported and mental health diagnoses and symptoms using a standard behavioral checklist for adolescents.
Dr. Van Dyk and colleagues found that 75% of subjects had at least one or more parent-reported mental health diagnosis, most commonly anxiety, mood disorders, and ADHD. Some 64% had a clinical elevation of mental health symptoms on evaluation, most commonly affective disorders, with 40% of the cohort having two or more elevations. Specific mental health symptoms were seen linked with particular sleep symptoms. A greater burden of ADHD symptoms, for example, was significantly associated with more difficulties falling asleep, maintaining sleep, and reinitiating sleep after waking at night.
A total of 15% of subjects were reported by caregivers to engage in deliberate self-harming behaviors or talking about or attempting suicide – a higher rate than in the general adolescent population. “Because youth presenting for insomnia treatment may be even more likely to engage in self-harm behavior or to be suicidal, particular attention should be paid to directly assessing for these high-risk behaviors within the context of behavioral sleep medicine evaluations,” Dr. Van Dyk and colleagues wrote in their analysis.
Although mental health symptoms have been linked to sleep problems in other studies of children and adults, “associations identified in younger youths and/or adults should not be assumed to hold true among adolescents,” the researchers wrote, adding that adolescence “is a distinctive developmental period characterized by increases in both psychopathology and sleep problems, changing biology, increasing independence, and unique social and societal demands.” The investigators noted that because pediatric sleep specialists are relatively rare, the management of adolescent sleep problems and related mental health symptoms is likely to fall on primary care and other providers who “would benefit in recognizing the relationship between sleep problems and mental health symptoms in this population.”
Dr. Van Dyk and colleagues noted among the weaknesses of their study its cross-sectional design, use of parent-reported mental health symptoms only, lack of information on medication use or mental health treatment, and the potential for selection bias toward more severe cases.
The authors disclosed no outside funding or conflicts of interest related to their study.
SOURCE: Van Dyk TR et al. J Clin Sleep Med. 2019 Sep 6. doi: 10.5664/jcsm.7970.
Adolescents diagnosed with insomnia have a high prevalence of concurrent mental health disorders and should be screened for them, according to new research.
For a study published in the Journal of Clinical Sleep Medicine, Tori R. Van Dyk, PhD, of Loma Linda (Calif.) University, and colleagues, enrolled 376 adolescents aged 11-18 years (mean age 14.5, 55% female) diagnosed with primary insomnia and referred to a sleep clinic. Subjects were evaluated using two validated questionnaires used to measure sleep disorders in adolescents, while caregivers reported and mental health diagnoses and symptoms using a standard behavioral checklist for adolescents.
Dr. Van Dyk and colleagues found that 75% of subjects had at least one or more parent-reported mental health diagnosis, most commonly anxiety, mood disorders, and ADHD. Some 64% had a clinical elevation of mental health symptoms on evaluation, most commonly affective disorders, with 40% of the cohort having two or more elevations. Specific mental health symptoms were seen linked with particular sleep symptoms. A greater burden of ADHD symptoms, for example, was significantly associated with more difficulties falling asleep, maintaining sleep, and reinitiating sleep after waking at night.
A total of 15% of subjects were reported by caregivers to engage in deliberate self-harming behaviors or talking about or attempting suicide – a higher rate than in the general adolescent population. “Because youth presenting for insomnia treatment may be even more likely to engage in self-harm behavior or to be suicidal, particular attention should be paid to directly assessing for these high-risk behaviors within the context of behavioral sleep medicine evaluations,” Dr. Van Dyk and colleagues wrote in their analysis.
Although mental health symptoms have been linked to sleep problems in other studies of children and adults, “associations identified in younger youths and/or adults should not be assumed to hold true among adolescents,” the researchers wrote, adding that adolescence “is a distinctive developmental period characterized by increases in both psychopathology and sleep problems, changing biology, increasing independence, and unique social and societal demands.” The investigators noted that because pediatric sleep specialists are relatively rare, the management of adolescent sleep problems and related mental health symptoms is likely to fall on primary care and other providers who “would benefit in recognizing the relationship between sleep problems and mental health symptoms in this population.”
Dr. Van Dyk and colleagues noted among the weaknesses of their study its cross-sectional design, use of parent-reported mental health symptoms only, lack of information on medication use or mental health treatment, and the potential for selection bias toward more severe cases.
The authors disclosed no outside funding or conflicts of interest related to their study.
SOURCE: Van Dyk TR et al. J Clin Sleep Med. 2019 Sep 6. doi: 10.5664/jcsm.7970.
FROM THE JOURNAL OF CLINICAL SLEEP MEDICINE
Primary CNS lymphoma: R-CHOP hits back
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of non-Hodgkin lymphoma solely confined to the CNS. The majority of PCNSL histologically presents as diffuse large B-cell lymphoma (DLBCL). However, outcomes in these patients are notably inferior, compared with nodal or other extranodal DLBCL. In order to achieve long-term progression-free survival, high-dose methotrexate (HD-MTX)–based chemotherapy followed by consolidation is needed. However, this treatment is associated with high toxicity burden and it is restricted to a select patient population – the young and fit – and requires administration at specialized hematological centers.
In the 1990s, the conventional DLBCL treatment regimen with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) was tested in PCNSL patients. The results were rather disappointing. The addition of CHOP to whole brain radiation or HD-MTX could not improve survival.1-3 The reason for CHOP failure was poor CNS penetration of doxorubicin and cyclophosphamide because of their high molecular weight. Consequently, it was concluded that there is no role for CHOP-like chemotherapy in the treatment of PCNSL.4
But is this really the case? Twenty years later, this traditional view has been challenged by Andres J.M. Ferreri, MD, and colleagues in the INGRID trial.5 Dr. Ferreri presented findings from the trial at the International Conference on Malignant Lymphoma in Lugano, Switzerland, which was greeted with much excitement.6
INGRID is a phase 2 trial conducted on patients with refractory/relapsed PCNSL. It consisted of a CHOP plus rituximab (R-CHOP) regimen, which was upgraded by engineered tumor necrosis factor–alpha (TNF-alpha). The idea was to enhance the blood-brain barrier (BBB) permeability and consequently improve the efficacy of R-CHOP in PCNSL. The use of human TNF-alpha is limited by relevant toxicities. In order to avoid that, a fusion of human TNF-alpha and CNGRCG peptide (called NGR-TNF) was developed.
CNGRCG peptide is a ligand of CD13, an aminopeptidase that is expressed almost exclusively on tumor blood vessels. Preclinical data showed that binding of CNGRCG to CD13 results in targeted – local, not systemic – delivery of TNF-alpha to the tumor blood vessels. Consequently, TNF-alpha led to increased vascular permeability in tumor tissue and enabled higher penetration of chemotherapeutic agents.7,8
Altogether, 12 heavily pretreated PCNSL patients were included in the INGRID trial. Seven patients had two or more previous treatment regimens. Within this trial, patients received R-CHOP with NGR-TNF (0.8 mcg/m2) applied 2 hours prior to R-CHOP. The great majority of grade 3/4 adverse events were hematological toxicities. Importantly, no neurological side effects of any grade occurred.
The primary aim of this study was to investigate the CD13 expression on tumor tissue and provide a proof of concept for the use of NGR-TNF/R-CHOP. Indeed, CD13 expression was observed on tumor vessels in all patients. Consequently, increased BBB permeability in tumor tissue after NGR-TNF infusion was observed using dynamic contrast-enhanced MRI and by brain scintigraphy (SPECT). This was assessed 1 day after NGR-TNF/R-CHOP treatment. More importantly, this effect on BBB seems to be sustained because it was also observed after the last cycle of NGR-TNF/R-CHOP. The fact that there was no change of drug concentrations of R-CHOP components in plasma or cerebrospinal fluid suggests that the effect of NGR-TNF is restricted to tumor vessels.
The authors also reported preliminary results regarding response rates to NGR-TNF/R-CHOP. The overall response rate was 75%. Of note, six patients achieved complete remission and one patient achieved a partial remission. The median duration of response was 10 months (range, 7-14 months), and nine patients were able to proceed to consolidation treatment.
These preliminary results are encouraging and open a new window for the treatment strategies in PCNSL patients. NGR-TNF/R-CHOP treatment induced responses in 75% of these heavily pretreated patients. The low toxicity profile and feasibility of this regimen could allow clinicians to carry out this treatment approach in outpatient settings, as well as in older and comorbid patients. Extensive supportive therapy – such as intensive hydration or leucovorin-rescue by HD-MTX – is not needed.
These results will need to be confirmed through testing in a larger patient population. Dr. Ferreri and colleagues are currently conducting the extended phase of this study and aim to recruit 28 patients. If they report positive results from that study, evaluation of NGR-TNF/R-CHOP as a first-line treatment of PCNSL seems to be the next reasonable step.
Dr. Zeremski and Dr. Fischer are both in the department of hematology/oncology and affiliated with the Health Campus Immunology, Infectiology and Inflammation at Otto-von-Guericke University Magdeburg (Germany). Dr. Fischer is a member of the editorial advisory board of Hematology News. The authors reported having no conflicts of interest.
References
1. J Clin Oncol. 1996;14:556-64.
2. Cancer. 2000;89:1359-70.
3. J Neurooncol. 1996;30:257-65.
4. Guidelines on the diagnosis and management of adult patients with primary CNS lymphoma (PCNSL) and primary intra-ocular lymphoma (PIOL). British Society for Haematology/British Committee for Standards in Haematology; HO/016, 2009.
5. Blood. 2019;134:252-62.
6. Hematol Oncol. 2019; 37:159.
7. BioDrugs. 2013;27:591-603.
8. J Clin Invest. 2002;110:475-82.
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of non-Hodgkin lymphoma solely confined to the CNS. The majority of PCNSL histologically presents as diffuse large B-cell lymphoma (DLBCL). However, outcomes in these patients are notably inferior, compared with nodal or other extranodal DLBCL. In order to achieve long-term progression-free survival, high-dose methotrexate (HD-MTX)–based chemotherapy followed by consolidation is needed. However, this treatment is associated with high toxicity burden and it is restricted to a select patient population – the young and fit – and requires administration at specialized hematological centers.
In the 1990s, the conventional DLBCL treatment regimen with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) was tested in PCNSL patients. The results were rather disappointing. The addition of CHOP to whole brain radiation or HD-MTX could not improve survival.1-3 The reason for CHOP failure was poor CNS penetration of doxorubicin and cyclophosphamide because of their high molecular weight. Consequently, it was concluded that there is no role for CHOP-like chemotherapy in the treatment of PCNSL.4
But is this really the case? Twenty years later, this traditional view has been challenged by Andres J.M. Ferreri, MD, and colleagues in the INGRID trial.5 Dr. Ferreri presented findings from the trial at the International Conference on Malignant Lymphoma in Lugano, Switzerland, which was greeted with much excitement.6
INGRID is a phase 2 trial conducted on patients with refractory/relapsed PCNSL. It consisted of a CHOP plus rituximab (R-CHOP) regimen, which was upgraded by engineered tumor necrosis factor–alpha (TNF-alpha). The idea was to enhance the blood-brain barrier (BBB) permeability and consequently improve the efficacy of R-CHOP in PCNSL. The use of human TNF-alpha is limited by relevant toxicities. In order to avoid that, a fusion of human TNF-alpha and CNGRCG peptide (called NGR-TNF) was developed.
CNGRCG peptide is a ligand of CD13, an aminopeptidase that is expressed almost exclusively on tumor blood vessels. Preclinical data showed that binding of CNGRCG to CD13 results in targeted – local, not systemic – delivery of TNF-alpha to the tumor blood vessels. Consequently, TNF-alpha led to increased vascular permeability in tumor tissue and enabled higher penetration of chemotherapeutic agents.7,8
Altogether, 12 heavily pretreated PCNSL patients were included in the INGRID trial. Seven patients had two or more previous treatment regimens. Within this trial, patients received R-CHOP with NGR-TNF (0.8 mcg/m2) applied 2 hours prior to R-CHOP. The great majority of grade 3/4 adverse events were hematological toxicities. Importantly, no neurological side effects of any grade occurred.
The primary aim of this study was to investigate the CD13 expression on tumor tissue and provide a proof of concept for the use of NGR-TNF/R-CHOP. Indeed, CD13 expression was observed on tumor vessels in all patients. Consequently, increased BBB permeability in tumor tissue after NGR-TNF infusion was observed using dynamic contrast-enhanced MRI and by brain scintigraphy (SPECT). This was assessed 1 day after NGR-TNF/R-CHOP treatment. More importantly, this effect on BBB seems to be sustained because it was also observed after the last cycle of NGR-TNF/R-CHOP. The fact that there was no change of drug concentrations of R-CHOP components in plasma or cerebrospinal fluid suggests that the effect of NGR-TNF is restricted to tumor vessels.
The authors also reported preliminary results regarding response rates to NGR-TNF/R-CHOP. The overall response rate was 75%. Of note, six patients achieved complete remission and one patient achieved a partial remission. The median duration of response was 10 months (range, 7-14 months), and nine patients were able to proceed to consolidation treatment.
These preliminary results are encouraging and open a new window for the treatment strategies in PCNSL patients. NGR-TNF/R-CHOP treatment induced responses in 75% of these heavily pretreated patients. The low toxicity profile and feasibility of this regimen could allow clinicians to carry out this treatment approach in outpatient settings, as well as in older and comorbid patients. Extensive supportive therapy – such as intensive hydration or leucovorin-rescue by HD-MTX – is not needed.
These results will need to be confirmed through testing in a larger patient population. Dr. Ferreri and colleagues are currently conducting the extended phase of this study and aim to recruit 28 patients. If they report positive results from that study, evaluation of NGR-TNF/R-CHOP as a first-line treatment of PCNSL seems to be the next reasonable step.
Dr. Zeremski and Dr. Fischer are both in the department of hematology/oncology and affiliated with the Health Campus Immunology, Infectiology and Inflammation at Otto-von-Guericke University Magdeburg (Germany). Dr. Fischer is a member of the editorial advisory board of Hematology News. The authors reported having no conflicts of interest.
References
1. J Clin Oncol. 1996;14:556-64.
2. Cancer. 2000;89:1359-70.
3. J Neurooncol. 1996;30:257-65.
4. Guidelines on the diagnosis and management of adult patients with primary CNS lymphoma (PCNSL) and primary intra-ocular lymphoma (PIOL). British Society for Haematology/British Committee for Standards in Haematology; HO/016, 2009.
5. Blood. 2019;134:252-62.
6. Hematol Oncol. 2019; 37:159.
7. BioDrugs. 2013;27:591-603.
8. J Clin Invest. 2002;110:475-82.
Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of non-Hodgkin lymphoma solely confined to the CNS. The majority of PCNSL histologically presents as diffuse large B-cell lymphoma (DLBCL). However, outcomes in these patients are notably inferior, compared with nodal or other extranodal DLBCL. In order to achieve long-term progression-free survival, high-dose methotrexate (HD-MTX)–based chemotherapy followed by consolidation is needed. However, this treatment is associated with high toxicity burden and it is restricted to a select patient population – the young and fit – and requires administration at specialized hematological centers.
In the 1990s, the conventional DLBCL treatment regimen with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) was tested in PCNSL patients. The results were rather disappointing. The addition of CHOP to whole brain radiation or HD-MTX could not improve survival.1-3 The reason for CHOP failure was poor CNS penetration of doxorubicin and cyclophosphamide because of their high molecular weight. Consequently, it was concluded that there is no role for CHOP-like chemotherapy in the treatment of PCNSL.4
But is this really the case? Twenty years later, this traditional view has been challenged by Andres J.M. Ferreri, MD, and colleagues in the INGRID trial.5 Dr. Ferreri presented findings from the trial at the International Conference on Malignant Lymphoma in Lugano, Switzerland, which was greeted with much excitement.6
INGRID is a phase 2 trial conducted on patients with refractory/relapsed PCNSL. It consisted of a CHOP plus rituximab (R-CHOP) regimen, which was upgraded by engineered tumor necrosis factor–alpha (TNF-alpha). The idea was to enhance the blood-brain barrier (BBB) permeability and consequently improve the efficacy of R-CHOP in PCNSL. The use of human TNF-alpha is limited by relevant toxicities. In order to avoid that, a fusion of human TNF-alpha and CNGRCG peptide (called NGR-TNF) was developed.
CNGRCG peptide is a ligand of CD13, an aminopeptidase that is expressed almost exclusively on tumor blood vessels. Preclinical data showed that binding of CNGRCG to CD13 results in targeted – local, not systemic – delivery of TNF-alpha to the tumor blood vessels. Consequently, TNF-alpha led to increased vascular permeability in tumor tissue and enabled higher penetration of chemotherapeutic agents.7,8
Altogether, 12 heavily pretreated PCNSL patients were included in the INGRID trial. Seven patients had two or more previous treatment regimens. Within this trial, patients received R-CHOP with NGR-TNF (0.8 mcg/m2) applied 2 hours prior to R-CHOP. The great majority of grade 3/4 adverse events were hematological toxicities. Importantly, no neurological side effects of any grade occurred.
The primary aim of this study was to investigate the CD13 expression on tumor tissue and provide a proof of concept for the use of NGR-TNF/R-CHOP. Indeed, CD13 expression was observed on tumor vessels in all patients. Consequently, increased BBB permeability in tumor tissue after NGR-TNF infusion was observed using dynamic contrast-enhanced MRI and by brain scintigraphy (SPECT). This was assessed 1 day after NGR-TNF/R-CHOP treatment. More importantly, this effect on BBB seems to be sustained because it was also observed after the last cycle of NGR-TNF/R-CHOP. The fact that there was no change of drug concentrations of R-CHOP components in plasma or cerebrospinal fluid suggests that the effect of NGR-TNF is restricted to tumor vessels.
The authors also reported preliminary results regarding response rates to NGR-TNF/R-CHOP. The overall response rate was 75%. Of note, six patients achieved complete remission and one patient achieved a partial remission. The median duration of response was 10 months (range, 7-14 months), and nine patients were able to proceed to consolidation treatment.
These preliminary results are encouraging and open a new window for the treatment strategies in PCNSL patients. NGR-TNF/R-CHOP treatment induced responses in 75% of these heavily pretreated patients. The low toxicity profile and feasibility of this regimen could allow clinicians to carry out this treatment approach in outpatient settings, as well as in older and comorbid patients. Extensive supportive therapy – such as intensive hydration or leucovorin-rescue by HD-MTX – is not needed.
These results will need to be confirmed through testing in a larger patient population. Dr. Ferreri and colleagues are currently conducting the extended phase of this study and aim to recruit 28 patients. If they report positive results from that study, evaluation of NGR-TNF/R-CHOP as a first-line treatment of PCNSL seems to be the next reasonable step.
Dr. Zeremski and Dr. Fischer are both in the department of hematology/oncology and affiliated with the Health Campus Immunology, Infectiology and Inflammation at Otto-von-Guericke University Magdeburg (Germany). Dr. Fischer is a member of the editorial advisory board of Hematology News. The authors reported having no conflicts of interest.
References
1. J Clin Oncol. 1996;14:556-64.
2. Cancer. 2000;89:1359-70.
3. J Neurooncol. 1996;30:257-65.
4. Guidelines on the diagnosis and management of adult patients with primary CNS lymphoma (PCNSL) and primary intra-ocular lymphoma (PIOL). British Society for Haematology/British Committee for Standards in Haematology; HO/016, 2009.
5. Blood. 2019;134:252-62.
6. Hematol Oncol. 2019; 37:159.
7. BioDrugs. 2013;27:591-603.
8. J Clin Invest. 2002;110:475-82.
Low disease activity a valid target in early SLE, investigators say
, investigators in a small retrospective study have concluded.
Both complete remission (CR) and achievement of a lupus low disease activity state (LLDAS) were independently associated with lower accrual of early damage after 6 months of treatment, according to results of the study, reported in Arthritis Care & Research.
Patients maintaining LLDAS over the next 12 months developed considerably less damage than did those who never achieved LLDAS or who did not maintain LLDAS over time, according to the investigators, led by Alberto Floris, MD, and Matteo Piga, MD, of the AOU University Clinic of Cagliari (Italy).
Based on these findings, maintenance of both CR and LLDAS should be targeted for damage prevention, according to the authors. “Significant differences did not emerge between persistent LLDAS and CR over 12 months in preventing early damage,” they said in their report.
Their retrospective, single-center analysis included 116 adult patients with newly diagnosed SLE who had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of at least 6 at baseline and started treatment at enrollment. The mean age of this patient cohort was approximately 35 years, and about 90% were female.
After 6 months of follow-up, 42% of the cohort achieved LLDAS, defined in part as a SLEDAI-2K of 4 or less with no major organ activity or new disease activity, while 21.6% met CR criteria, which included a SLEDAI-2K of 0.
Achieving LLDAS at that 6-month time point was independently associated with lower damage accrual at 18 months (odds ratio, 0.25; 95% confidence interval, 0.06-0.99; P = .049); likewise, a 6-month CR translated into less damage at 18 months, according to multivariate analysis (OR, 0.07; 95% CI, 0.01-0.59; P = .015).
Those patients in LLDAS at 6 months who maintained that target for another 12 months had significantly less damage when compared with those who lost response or never achieved it, the investigators added.
“Losing the early attained LLDAS and CR may frustrate prevention of damage, and therefore, LLDAS and CR maintenance should be targeted since the first stage of SLE management,” the investigators said in their report.
About 54% of the patients in LLDAS at 6 months achieved CR at an 18-month follow-up time point, while about 21% remained in LLDAS and 25% went on to develop active disease, the investigators said. Among those in CR at 6 months, 60% maintained it at 18 months, while 40% worsened to either LLDAS or active disease.
Dr. Floris, Dr. Piga, and coauthors reported no funding or competing interests related to their research.
SOURCE: Floris A et al. Arthritis Care Res. 2019 Oct 10. doi: 10.1002/acr.24086.
, investigators in a small retrospective study have concluded.
Both complete remission (CR) and achievement of a lupus low disease activity state (LLDAS) were independently associated with lower accrual of early damage after 6 months of treatment, according to results of the study, reported in Arthritis Care & Research.
Patients maintaining LLDAS over the next 12 months developed considerably less damage than did those who never achieved LLDAS or who did not maintain LLDAS over time, according to the investigators, led by Alberto Floris, MD, and Matteo Piga, MD, of the AOU University Clinic of Cagliari (Italy).
Based on these findings, maintenance of both CR and LLDAS should be targeted for damage prevention, according to the authors. “Significant differences did not emerge between persistent LLDAS and CR over 12 months in preventing early damage,” they said in their report.
Their retrospective, single-center analysis included 116 adult patients with newly diagnosed SLE who had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of at least 6 at baseline and started treatment at enrollment. The mean age of this patient cohort was approximately 35 years, and about 90% were female.
After 6 months of follow-up, 42% of the cohort achieved LLDAS, defined in part as a SLEDAI-2K of 4 or less with no major organ activity or new disease activity, while 21.6% met CR criteria, which included a SLEDAI-2K of 0.
Achieving LLDAS at that 6-month time point was independently associated with lower damage accrual at 18 months (odds ratio, 0.25; 95% confidence interval, 0.06-0.99; P = .049); likewise, a 6-month CR translated into less damage at 18 months, according to multivariate analysis (OR, 0.07; 95% CI, 0.01-0.59; P = .015).
Those patients in LLDAS at 6 months who maintained that target for another 12 months had significantly less damage when compared with those who lost response or never achieved it, the investigators added.
“Losing the early attained LLDAS and CR may frustrate prevention of damage, and therefore, LLDAS and CR maintenance should be targeted since the first stage of SLE management,” the investigators said in their report.
About 54% of the patients in LLDAS at 6 months achieved CR at an 18-month follow-up time point, while about 21% remained in LLDAS and 25% went on to develop active disease, the investigators said. Among those in CR at 6 months, 60% maintained it at 18 months, while 40% worsened to either LLDAS or active disease.
Dr. Floris, Dr. Piga, and coauthors reported no funding or competing interests related to their research.
SOURCE: Floris A et al. Arthritis Care Res. 2019 Oct 10. doi: 10.1002/acr.24086.
, investigators in a small retrospective study have concluded.
Both complete remission (CR) and achievement of a lupus low disease activity state (LLDAS) were independently associated with lower accrual of early damage after 6 months of treatment, according to results of the study, reported in Arthritis Care & Research.
Patients maintaining LLDAS over the next 12 months developed considerably less damage than did those who never achieved LLDAS or who did not maintain LLDAS over time, according to the investigators, led by Alberto Floris, MD, and Matteo Piga, MD, of the AOU University Clinic of Cagliari (Italy).
Based on these findings, maintenance of both CR and LLDAS should be targeted for damage prevention, according to the authors. “Significant differences did not emerge between persistent LLDAS and CR over 12 months in preventing early damage,” they said in their report.
Their retrospective, single-center analysis included 116 adult patients with newly diagnosed SLE who had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of at least 6 at baseline and started treatment at enrollment. The mean age of this patient cohort was approximately 35 years, and about 90% were female.
After 6 months of follow-up, 42% of the cohort achieved LLDAS, defined in part as a SLEDAI-2K of 4 or less with no major organ activity or new disease activity, while 21.6% met CR criteria, which included a SLEDAI-2K of 0.
Achieving LLDAS at that 6-month time point was independently associated with lower damage accrual at 18 months (odds ratio, 0.25; 95% confidence interval, 0.06-0.99; P = .049); likewise, a 6-month CR translated into less damage at 18 months, according to multivariate analysis (OR, 0.07; 95% CI, 0.01-0.59; P = .015).
Those patients in LLDAS at 6 months who maintained that target for another 12 months had significantly less damage when compared with those who lost response or never achieved it, the investigators added.
“Losing the early attained LLDAS and CR may frustrate prevention of damage, and therefore, LLDAS and CR maintenance should be targeted since the first stage of SLE management,” the investigators said in their report.
About 54% of the patients in LLDAS at 6 months achieved CR at an 18-month follow-up time point, while about 21% remained in LLDAS and 25% went on to develop active disease, the investigators said. Among those in CR at 6 months, 60% maintained it at 18 months, while 40% worsened to either LLDAS or active disease.
Dr. Floris, Dr. Piga, and coauthors reported no funding or competing interests related to their research.
SOURCE: Floris A et al. Arthritis Care Res. 2019 Oct 10. doi: 10.1002/acr.24086.
FROM ARTHRITIS CARE & RESEARCH
‘Clean’ and ‘natural’ beauty products
Clean beauty products have taken over the skin care market. A wave of new indie brands has entered the skin care market, some of which have garnered fame from bloggers and celebrities and via social media. There has also been a shift towards larger, more-established brands developing and marketing cleaner alternatives to their established skin care lines.
As consumers, physicians, and parents, we all want nontoxic products. However, as highlighted in a recent editorial by Bruce Brod, MD, and Courtney Blair Rubin, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, the Food and Drug Administration has “failed to define clean and natural, leaving these labels open to interpretation by nondermatologist retailers, bloggers, and celebrities who have set out to define clean beauty for themselves” (JAMA Dermatol. 2019 Sep 25. doi: 10.1001/jamadermatol.2019.2724). This vague interpretation has given rise to a billion-dollar industry of products that is unregulated and may, in fact, not be safer than other products.
For the last decade, to skin care products have also been on the rise. Some of the ingredients deemed toxic include petrolatum and parabens, which have good safety profiles and clinically, are among the least allergenic ingredients in skin products, particularly among patients with the most sensitive skin. In contrast, botanical oils, essential oils, and plant-based natural fragrances are chronic culprits of contact sensitivities and severe skin allergies.
I encourage all dermatologists to read this viewpoint as this topic will inevitably be a point of discussion with many patients. Large studies and expert consensus of safety profiles of chemicals – particularly those deemed carcinogenic, endocrine disruptors, and environmental hazards – are often lacking, leading to confusion for consumers. Our professional organizations and industry should be leading the efforts to establish standardized definitions and FDA regulations of skin care products deemed clean and natural so that the differentiation between marketing taglines and true, substantiated FDA-supported claims are clearer for consumers.
Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.
Clean beauty products have taken over the skin care market. A wave of new indie brands has entered the skin care market, some of which have garnered fame from bloggers and celebrities and via social media. There has also been a shift towards larger, more-established brands developing and marketing cleaner alternatives to their established skin care lines.
As consumers, physicians, and parents, we all want nontoxic products. However, as highlighted in a recent editorial by Bruce Brod, MD, and Courtney Blair Rubin, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, the Food and Drug Administration has “failed to define clean and natural, leaving these labels open to interpretation by nondermatologist retailers, bloggers, and celebrities who have set out to define clean beauty for themselves” (JAMA Dermatol. 2019 Sep 25. doi: 10.1001/jamadermatol.2019.2724). This vague interpretation has given rise to a billion-dollar industry of products that is unregulated and may, in fact, not be safer than other products.
For the last decade, to skin care products have also been on the rise. Some of the ingredients deemed toxic include petrolatum and parabens, which have good safety profiles and clinically, are among the least allergenic ingredients in skin products, particularly among patients with the most sensitive skin. In contrast, botanical oils, essential oils, and plant-based natural fragrances are chronic culprits of contact sensitivities and severe skin allergies.
I encourage all dermatologists to read this viewpoint as this topic will inevitably be a point of discussion with many patients. Large studies and expert consensus of safety profiles of chemicals – particularly those deemed carcinogenic, endocrine disruptors, and environmental hazards – are often lacking, leading to confusion for consumers. Our professional organizations and industry should be leading the efforts to establish standardized definitions and FDA regulations of skin care products deemed clean and natural so that the differentiation between marketing taglines and true, substantiated FDA-supported claims are clearer for consumers.
Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.
Clean beauty products have taken over the skin care market. A wave of new indie brands has entered the skin care market, some of which have garnered fame from bloggers and celebrities and via social media. There has also been a shift towards larger, more-established brands developing and marketing cleaner alternatives to their established skin care lines.
As consumers, physicians, and parents, we all want nontoxic products. However, as highlighted in a recent editorial by Bruce Brod, MD, and Courtney Blair Rubin, MD, of the department of dermatology at the University of Pennsylvania, Philadelphia, the Food and Drug Administration has “failed to define clean and natural, leaving these labels open to interpretation by nondermatologist retailers, bloggers, and celebrities who have set out to define clean beauty for themselves” (JAMA Dermatol. 2019 Sep 25. doi: 10.1001/jamadermatol.2019.2724). This vague interpretation has given rise to a billion-dollar industry of products that is unregulated and may, in fact, not be safer than other products.
For the last decade, to skin care products have also been on the rise. Some of the ingredients deemed toxic include petrolatum and parabens, which have good safety profiles and clinically, are among the least allergenic ingredients in skin products, particularly among patients with the most sensitive skin. In contrast, botanical oils, essential oils, and plant-based natural fragrances are chronic culprits of contact sensitivities and severe skin allergies.
I encourage all dermatologists to read this viewpoint as this topic will inevitably be a point of discussion with many patients. Large studies and expert consensus of safety profiles of chemicals – particularly those deemed carcinogenic, endocrine disruptors, and environmental hazards – are often lacking, leading to confusion for consumers. Our professional organizations and industry should be leading the efforts to establish standardized definitions and FDA regulations of skin care products deemed clean and natural so that the differentiation between marketing taglines and true, substantiated FDA-supported claims are clearer for consumers.
Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.
Violaceous papules on calf & foot
that usually presents on the distal lower extremities or feet as red to violaceous papules, patches, and plaques.
Clinically, lesions may look similar to Kaposi sarcoma (KS). It is considered to be a variant of stasis dermatitis or severe chronic venous stasis with a more exuberant vascular proliferation of preexisting vasculature. Although the exact etiology is unknown, it is thought that chronic edema, increased venous pressure, and tissue hypoxia may induce fibroblast and vascular proliferation.
It has also been described in association with vascular anomalies, such as Klippel-Trenaunay syndrome, Stewart-Bluefarb syndrome, and Prader-Labhart-Willi syndrome, and is caused by arteriovenous fistulae. Paralysis of lower extremities and amputation stumps are predisposing factors.
KS has four clinical variants: classic KS, African endemic KS, KS in immunocompromised patients, and AIDS-related epidemic KS. All types are caused by the human herpesvirus-8 (HHV-8). Violaceous lesions generally begin as macules and may progress to nodules or tumors.
Punch biopsies were performed in our patient. Histologically, thin-walled, dilated, capillary-like structures were present with a thin layer of surrounding pericytes with reactive fibrosis, hemorrhage, hemosiderin, and a scant chronic inflammatory cell infiltrate. The endothelial cells did not show atypia or mitotic activity. Endothelial cells were positive for CD31, CD34, and CD99. Pericytes and some of the endothelial cells were positive for actin and negative for D2-40, desmin, and HHV-8. In KS, vessels appear like slitlike or jagged spaces lined by spindled endothelial cells. Mild cytologic atypia is usually present. Endothelial cells are characteristically plump. A distinguishing feature in KS is the “promontory sign,” in which new vessels protrude into the vascular space. CD34 is usually negative and HHV-8 is positive.
Acroangiodermatitis of Mali may improve when the underlying venous insufficiency is addressed with compression stockings, pumps, or vascular intervention. Laser ablation of individual lesions has been described in the literature. Dapsone, oral erythromycin, and topical corticosteroids have been reported as helpful in some patients.
This case and these photos were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
that usually presents on the distal lower extremities or feet as red to violaceous papules, patches, and plaques.
Clinically, lesions may look similar to Kaposi sarcoma (KS). It is considered to be a variant of stasis dermatitis or severe chronic venous stasis with a more exuberant vascular proliferation of preexisting vasculature. Although the exact etiology is unknown, it is thought that chronic edema, increased venous pressure, and tissue hypoxia may induce fibroblast and vascular proliferation.
It has also been described in association with vascular anomalies, such as Klippel-Trenaunay syndrome, Stewart-Bluefarb syndrome, and Prader-Labhart-Willi syndrome, and is caused by arteriovenous fistulae. Paralysis of lower extremities and amputation stumps are predisposing factors.
KS has four clinical variants: classic KS, African endemic KS, KS in immunocompromised patients, and AIDS-related epidemic KS. All types are caused by the human herpesvirus-8 (HHV-8). Violaceous lesions generally begin as macules and may progress to nodules or tumors.
Punch biopsies were performed in our patient. Histologically, thin-walled, dilated, capillary-like structures were present with a thin layer of surrounding pericytes with reactive fibrosis, hemorrhage, hemosiderin, and a scant chronic inflammatory cell infiltrate. The endothelial cells did not show atypia or mitotic activity. Endothelial cells were positive for CD31, CD34, and CD99. Pericytes and some of the endothelial cells were positive for actin and negative for D2-40, desmin, and HHV-8. In KS, vessels appear like slitlike or jagged spaces lined by spindled endothelial cells. Mild cytologic atypia is usually present. Endothelial cells are characteristically plump. A distinguishing feature in KS is the “promontory sign,” in which new vessels protrude into the vascular space. CD34 is usually negative and HHV-8 is positive.
Acroangiodermatitis of Mali may improve when the underlying venous insufficiency is addressed with compression stockings, pumps, or vascular intervention. Laser ablation of individual lesions has been described in the literature. Dapsone, oral erythromycin, and topical corticosteroids have been reported as helpful in some patients.
This case and these photos were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
that usually presents on the distal lower extremities or feet as red to violaceous papules, patches, and plaques.
Clinically, lesions may look similar to Kaposi sarcoma (KS). It is considered to be a variant of stasis dermatitis or severe chronic venous stasis with a more exuberant vascular proliferation of preexisting vasculature. Although the exact etiology is unknown, it is thought that chronic edema, increased venous pressure, and tissue hypoxia may induce fibroblast and vascular proliferation.
It has also been described in association with vascular anomalies, such as Klippel-Trenaunay syndrome, Stewart-Bluefarb syndrome, and Prader-Labhart-Willi syndrome, and is caused by arteriovenous fistulae. Paralysis of lower extremities and amputation stumps are predisposing factors.
KS has four clinical variants: classic KS, African endemic KS, KS in immunocompromised patients, and AIDS-related epidemic KS. All types are caused by the human herpesvirus-8 (HHV-8). Violaceous lesions generally begin as macules and may progress to nodules or tumors.
Punch biopsies were performed in our patient. Histologically, thin-walled, dilated, capillary-like structures were present with a thin layer of surrounding pericytes with reactive fibrosis, hemorrhage, hemosiderin, and a scant chronic inflammatory cell infiltrate. The endothelial cells did not show atypia or mitotic activity. Endothelial cells were positive for CD31, CD34, and CD99. Pericytes and some of the endothelial cells were positive for actin and negative for D2-40, desmin, and HHV-8. In KS, vessels appear like slitlike or jagged spaces lined by spindled endothelial cells. Mild cytologic atypia is usually present. Endothelial cells are characteristically plump. A distinguishing feature in KS is the “promontory sign,” in which new vessels protrude into the vascular space. CD34 is usually negative and HHV-8 is positive.
Acroangiodermatitis of Mali may improve when the underlying venous insufficiency is addressed with compression stockings, pumps, or vascular intervention. Laser ablation of individual lesions has been described in the literature. Dapsone, oral erythromycin, and topical corticosteroids have been reported as helpful in some patients.
This case and these photos were submitted by Dr. Bilu Martin.
Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].
Vitamin D deficiency appears to worsen survival in Hodgkin lymphoma
Vitamin D deficiency is associated with worse progression-free and overall survival among patients with Hodgkin lymphoma, according to new study findings.
Sven Borchmann, MD, of the University of Cologne (Germany) and German Hodgkin Study Group and coauthors conducted a case-control study of 351 patients enrolled in the German Hodgkin Study Group trials who had available baseline serum samples. Pretreatment vitamin D levels were assessed and categorized as deficient (less than 30 nmol/L), insufficient (30-49 nmol/L), or sufficient (50 nmol/L or greater). The findings were published in the Journal of Clinical Oncology.
The researchers found that before starting treatment, 50% of patients were vitamin D deficient.
Patients with baseline vitamin D deficiency had significantly lower progression-free survival – 10.2% lower at 5 years and 17.6% lower at 10 years – compared with patients with either sufficient or insufficient vitamin D levels (P less than .001). They also had 2% lower overall survival at 5 years and 11.1% lower overall survival at 10 years (P less than .001).
The researchers also conducted preclinical studies in effort to understand the effect of vitamin D on Hodgkin lymphoma cells and in Hodgkin lymphoma tumor models.
They explored the effect of vitamin D on cultured Hodgkin lymphoma cell lines and saw a dose-response effect of calcitriol in reducing cell proliferation rates. They then looked at the effect of calcitriol on cell lines that were also exposed to doxorubicin or etoposide, and found calcitriol improved the cytotoxicity of these chemotherapy agents, especially at lower doses.
Finally, they conducted an in-vivo mouse study using Hodgkin lymphoma xenografts, and looked at whether vitamin D supplementation increased the effect of doxorubicin or etoposide. This revealed that chemotherapy and vitamin D supplementation together were significantly better at controlling tumor growth, compared with monotherapy with either vitamin D or doxorubicin and compared with placebo.
“On the basis of our study results and the limited toxicity of vitamin D replacement therapy, we would advocate for vitamin D deficiency screening and replacement to be incorporated into future randomized clinical trials to properly clarify the role of vitamin D replacement in HL [Hodgkin lymphoma],” the researchers wrote. “The goal of these trials should be to determine whether vitamin D replacement in HL improves outcome.”
No study funding information was reported. Dr. Borchmann reported honoraria and research funding from Takeda. Other authors reported financial disclosures related to Takeda, Roche, Bristol-Myers Squibb, and other companies.
SOURCE: Borchmann S et al. J Clin Oncol. 2019 Oct 17. doi:10.1200/JCO.19.00985.
Vitamin D deficiency is associated with worse progression-free and overall survival among patients with Hodgkin lymphoma, according to new study findings.
Sven Borchmann, MD, of the University of Cologne (Germany) and German Hodgkin Study Group and coauthors conducted a case-control study of 351 patients enrolled in the German Hodgkin Study Group trials who had available baseline serum samples. Pretreatment vitamin D levels were assessed and categorized as deficient (less than 30 nmol/L), insufficient (30-49 nmol/L), or sufficient (50 nmol/L or greater). The findings were published in the Journal of Clinical Oncology.
The researchers found that before starting treatment, 50% of patients were vitamin D deficient.
Patients with baseline vitamin D deficiency had significantly lower progression-free survival – 10.2% lower at 5 years and 17.6% lower at 10 years – compared with patients with either sufficient or insufficient vitamin D levels (P less than .001). They also had 2% lower overall survival at 5 years and 11.1% lower overall survival at 10 years (P less than .001).
The researchers also conducted preclinical studies in effort to understand the effect of vitamin D on Hodgkin lymphoma cells and in Hodgkin lymphoma tumor models.
They explored the effect of vitamin D on cultured Hodgkin lymphoma cell lines and saw a dose-response effect of calcitriol in reducing cell proliferation rates. They then looked at the effect of calcitriol on cell lines that were also exposed to doxorubicin or etoposide, and found calcitriol improved the cytotoxicity of these chemotherapy agents, especially at lower doses.
Finally, they conducted an in-vivo mouse study using Hodgkin lymphoma xenografts, and looked at whether vitamin D supplementation increased the effect of doxorubicin or etoposide. This revealed that chemotherapy and vitamin D supplementation together were significantly better at controlling tumor growth, compared with monotherapy with either vitamin D or doxorubicin and compared with placebo.
“On the basis of our study results and the limited toxicity of vitamin D replacement therapy, we would advocate for vitamin D deficiency screening and replacement to be incorporated into future randomized clinical trials to properly clarify the role of vitamin D replacement in HL [Hodgkin lymphoma],” the researchers wrote. “The goal of these trials should be to determine whether vitamin D replacement in HL improves outcome.”
No study funding information was reported. Dr. Borchmann reported honoraria and research funding from Takeda. Other authors reported financial disclosures related to Takeda, Roche, Bristol-Myers Squibb, and other companies.
SOURCE: Borchmann S et al. J Clin Oncol. 2019 Oct 17. doi:10.1200/JCO.19.00985.
Vitamin D deficiency is associated with worse progression-free and overall survival among patients with Hodgkin lymphoma, according to new study findings.
Sven Borchmann, MD, of the University of Cologne (Germany) and German Hodgkin Study Group and coauthors conducted a case-control study of 351 patients enrolled in the German Hodgkin Study Group trials who had available baseline serum samples. Pretreatment vitamin D levels were assessed and categorized as deficient (less than 30 nmol/L), insufficient (30-49 nmol/L), or sufficient (50 nmol/L or greater). The findings were published in the Journal of Clinical Oncology.
The researchers found that before starting treatment, 50% of patients were vitamin D deficient.
Patients with baseline vitamin D deficiency had significantly lower progression-free survival – 10.2% lower at 5 years and 17.6% lower at 10 years – compared with patients with either sufficient or insufficient vitamin D levels (P less than .001). They also had 2% lower overall survival at 5 years and 11.1% lower overall survival at 10 years (P less than .001).
The researchers also conducted preclinical studies in effort to understand the effect of vitamin D on Hodgkin lymphoma cells and in Hodgkin lymphoma tumor models.
They explored the effect of vitamin D on cultured Hodgkin lymphoma cell lines and saw a dose-response effect of calcitriol in reducing cell proliferation rates. They then looked at the effect of calcitriol on cell lines that were also exposed to doxorubicin or etoposide, and found calcitriol improved the cytotoxicity of these chemotherapy agents, especially at lower doses.
Finally, they conducted an in-vivo mouse study using Hodgkin lymphoma xenografts, and looked at whether vitamin D supplementation increased the effect of doxorubicin or etoposide. This revealed that chemotherapy and vitamin D supplementation together were significantly better at controlling tumor growth, compared with monotherapy with either vitamin D or doxorubicin and compared with placebo.
“On the basis of our study results and the limited toxicity of vitamin D replacement therapy, we would advocate for vitamin D deficiency screening and replacement to be incorporated into future randomized clinical trials to properly clarify the role of vitamin D replacement in HL [Hodgkin lymphoma],” the researchers wrote. “The goal of these trials should be to determine whether vitamin D replacement in HL improves outcome.”
No study funding information was reported. Dr. Borchmann reported honoraria and research funding from Takeda. Other authors reported financial disclosures related to Takeda, Roche, Bristol-Myers Squibb, and other companies.
SOURCE: Borchmann S et al. J Clin Oncol. 2019 Oct 17. doi:10.1200/JCO.19.00985.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point:
Major finding: Patients with Hodgkin lymphoma and vitamin D deficiency had a 17.6% lower progression-free survival at 10 years, compared with patients who were not vitamin D deficient (P less than .001).
Study details: A case-control study in 351 patients with Hodgkin lymphoma.
Disclosures: No study funding information was reported. Dr. Borchmann reported honoraria and research funding from Takeda. Other authors reported financial disclosures related to Takeda, Roche, Bristol-Myers Squibb, and other companies.
Source: Borchmann S et al. J Clin Oncol. 2019 Oct 17. doi: 10.1200/JCO.19.00985.
Cell culture–based flu vaccine maintains immunogenicity
WASHINGTON – Influenza vaccines that substitute flu grown in cell-culture for the standard formulation of flu grown in eggs recently came onto the U.S. market, and new evidence confirmed that cell-grown flu works at least as well as its egg-grown counterpart for triggering immune responses.
Results from a randomized study with 148 evaluable subjects that directly compared the immune response of individuals aged 4-20 years old to the 2018-2019 commercial formulation of a mostly cell-based influenza vaccine with a commercially marketed, fully egg-based vaccine from the same vintage showed “no difference” between the two vaccines for inducing serologic titers on both the hemagluttination inhibition assay and by microneutralization, Richard K. Zimmerman, MD, said at an annual scientific meeting on infectious diseases.
The question addressed by the study was whether the primarily cell culture–grown vaccine would perform differently in children than a standard, egg-grown vaccine. “We thought that we might find something different, but we didn’t,” said Dr. Zimmerman, a professor of family medicine at the University of Pittsburgh who studies vaccines. The finding gave further support to using flu vaccines made without eggs because of their advantages over egg-based vaccines, he said in an interview.
Dr. Zimmerman cited two major, potential problems with egg-grown influenza vaccines. First, they require a big supply of eggs to manufacture, which can pose logistical challenges that are absent with cell culture–grown vaccine once the bioreactor capacity exists to produce the necessary amount of cells. This means that egg-free vaccine production can ramp up faster when a pandemic starts, he noted.
Second, over time, egg-grown vaccine strains of influenza have become increasingly adapted to grow in eggs with the result that “in some years the egg-grown virus is so different as to not work as well [Proc Natl Acad Sci. 2017 Nov;114[44]:12578-83]. With cell culture you bypass” issues of glycosylation mismatch or other antigenic problems caused by egg passage, he explained.
Dr. Zimmerman feels so strongly about the superiority of the cell-culture vaccine that “I am personally going to get a vaccine that’s not egg based,” and he advised the University of Pittsburgh Medical Center to focus its 2019-2020 flu vaccine purchase primarily on formulations made by cell culture. For the 2019-2020 season, that specifically is Flucelvax, an inactivated influenza vaccine licensed for people aged at least 4 years old, and Flublok, a recombinant flu vaccine also produced entirely in cell culture and licensed for people aged at least 18 years old. The 2019-2020 season is the first one during which the quadravalent Flucelvax vaccine has all four component strains (one H1N1, one H3N2, and two B strains) grown in cell culture.
The study run by Dr. Zimmerman and associates at the start of the 2018-2019 season used that season’s formulation of Flucelvax, which had only three of its four component strains grown in cell culture plus one strain (H1N1) grown in eggs. The Pittsburgh researchers randomized 168 individuals to receive the 2018-2019 Flucelvax vaccine or Fluzone, an entirely egg-made quadravelent vaccine, and they had analyzable results from 148 of the enrolled participants, more than 85% of whom were 9-20 years old. The study’s primary endpoint was the extent of seropositivity and seroconversion 28 days after immunization measured with both a hemagglutination inhibition assay and by a microneutralization assay. The results showed similar rates in the 75 children who received Flucelvax and the 73 who received Fluzone. For example, seropositivity against B Victoria lineage strains by the hemagglutination inhibition assay 28 days after vaccination was 76% in children who received Flucelvax, and it was 79% among those who got Fluzone, with a seroconversion rate of 34% in each of the two study subgroups.
“These findings do not say that egg-free is better, but it was certainly no worse. My guess is that in some years vaccines that are egg-free will make a big difference. In other years it may not. But you don’t know ahead of time,” Dr. Zimmerman said.
The study received no commercial funding but received free Fluzone vaccine from Sanofi Pasteur. Dr. Zimmerman had no disclosures.
WASHINGTON – Influenza vaccines that substitute flu grown in cell-culture for the standard formulation of flu grown in eggs recently came onto the U.S. market, and new evidence confirmed that cell-grown flu works at least as well as its egg-grown counterpart for triggering immune responses.
Results from a randomized study with 148 evaluable subjects that directly compared the immune response of individuals aged 4-20 years old to the 2018-2019 commercial formulation of a mostly cell-based influenza vaccine with a commercially marketed, fully egg-based vaccine from the same vintage showed “no difference” between the two vaccines for inducing serologic titers on both the hemagluttination inhibition assay and by microneutralization, Richard K. Zimmerman, MD, said at an annual scientific meeting on infectious diseases.
The question addressed by the study was whether the primarily cell culture–grown vaccine would perform differently in children than a standard, egg-grown vaccine. “We thought that we might find something different, but we didn’t,” said Dr. Zimmerman, a professor of family medicine at the University of Pittsburgh who studies vaccines. The finding gave further support to using flu vaccines made without eggs because of their advantages over egg-based vaccines, he said in an interview.
Dr. Zimmerman cited two major, potential problems with egg-grown influenza vaccines. First, they require a big supply of eggs to manufacture, which can pose logistical challenges that are absent with cell culture–grown vaccine once the bioreactor capacity exists to produce the necessary amount of cells. This means that egg-free vaccine production can ramp up faster when a pandemic starts, he noted.
Second, over time, egg-grown vaccine strains of influenza have become increasingly adapted to grow in eggs with the result that “in some years the egg-grown virus is so different as to not work as well [Proc Natl Acad Sci. 2017 Nov;114[44]:12578-83]. With cell culture you bypass” issues of glycosylation mismatch or other antigenic problems caused by egg passage, he explained.
Dr. Zimmerman feels so strongly about the superiority of the cell-culture vaccine that “I am personally going to get a vaccine that’s not egg based,” and he advised the University of Pittsburgh Medical Center to focus its 2019-2020 flu vaccine purchase primarily on formulations made by cell culture. For the 2019-2020 season, that specifically is Flucelvax, an inactivated influenza vaccine licensed for people aged at least 4 years old, and Flublok, a recombinant flu vaccine also produced entirely in cell culture and licensed for people aged at least 18 years old. The 2019-2020 season is the first one during which the quadravalent Flucelvax vaccine has all four component strains (one H1N1, one H3N2, and two B strains) grown in cell culture.
The study run by Dr. Zimmerman and associates at the start of the 2018-2019 season used that season’s formulation of Flucelvax, which had only three of its four component strains grown in cell culture plus one strain (H1N1) grown in eggs. The Pittsburgh researchers randomized 168 individuals to receive the 2018-2019 Flucelvax vaccine or Fluzone, an entirely egg-made quadravelent vaccine, and they had analyzable results from 148 of the enrolled participants, more than 85% of whom were 9-20 years old. The study’s primary endpoint was the extent of seropositivity and seroconversion 28 days after immunization measured with both a hemagglutination inhibition assay and by a microneutralization assay. The results showed similar rates in the 75 children who received Flucelvax and the 73 who received Fluzone. For example, seropositivity against B Victoria lineage strains by the hemagglutination inhibition assay 28 days after vaccination was 76% in children who received Flucelvax, and it was 79% among those who got Fluzone, with a seroconversion rate of 34% in each of the two study subgroups.
“These findings do not say that egg-free is better, but it was certainly no worse. My guess is that in some years vaccines that are egg-free will make a big difference. In other years it may not. But you don’t know ahead of time,” Dr. Zimmerman said.
The study received no commercial funding but received free Fluzone vaccine from Sanofi Pasteur. Dr. Zimmerman had no disclosures.
WASHINGTON – Influenza vaccines that substitute flu grown in cell-culture for the standard formulation of flu grown in eggs recently came onto the U.S. market, and new evidence confirmed that cell-grown flu works at least as well as its egg-grown counterpart for triggering immune responses.
Results from a randomized study with 148 evaluable subjects that directly compared the immune response of individuals aged 4-20 years old to the 2018-2019 commercial formulation of a mostly cell-based influenza vaccine with a commercially marketed, fully egg-based vaccine from the same vintage showed “no difference” between the two vaccines for inducing serologic titers on both the hemagluttination inhibition assay and by microneutralization, Richard K. Zimmerman, MD, said at an annual scientific meeting on infectious diseases.
The question addressed by the study was whether the primarily cell culture–grown vaccine would perform differently in children than a standard, egg-grown vaccine. “We thought that we might find something different, but we didn’t,” said Dr. Zimmerman, a professor of family medicine at the University of Pittsburgh who studies vaccines. The finding gave further support to using flu vaccines made without eggs because of their advantages over egg-based vaccines, he said in an interview.
Dr. Zimmerman cited two major, potential problems with egg-grown influenza vaccines. First, they require a big supply of eggs to manufacture, which can pose logistical challenges that are absent with cell culture–grown vaccine once the bioreactor capacity exists to produce the necessary amount of cells. This means that egg-free vaccine production can ramp up faster when a pandemic starts, he noted.
Second, over time, egg-grown vaccine strains of influenza have become increasingly adapted to grow in eggs with the result that “in some years the egg-grown virus is so different as to not work as well [Proc Natl Acad Sci. 2017 Nov;114[44]:12578-83]. With cell culture you bypass” issues of glycosylation mismatch or other antigenic problems caused by egg passage, he explained.
Dr. Zimmerman feels so strongly about the superiority of the cell-culture vaccine that “I am personally going to get a vaccine that’s not egg based,” and he advised the University of Pittsburgh Medical Center to focus its 2019-2020 flu vaccine purchase primarily on formulations made by cell culture. For the 2019-2020 season, that specifically is Flucelvax, an inactivated influenza vaccine licensed for people aged at least 4 years old, and Flublok, a recombinant flu vaccine also produced entirely in cell culture and licensed for people aged at least 18 years old. The 2019-2020 season is the first one during which the quadravalent Flucelvax vaccine has all four component strains (one H1N1, one H3N2, and two B strains) grown in cell culture.
The study run by Dr. Zimmerman and associates at the start of the 2018-2019 season used that season’s formulation of Flucelvax, which had only three of its four component strains grown in cell culture plus one strain (H1N1) grown in eggs. The Pittsburgh researchers randomized 168 individuals to receive the 2018-2019 Flucelvax vaccine or Fluzone, an entirely egg-made quadravelent vaccine, and they had analyzable results from 148 of the enrolled participants, more than 85% of whom were 9-20 years old. The study’s primary endpoint was the extent of seropositivity and seroconversion 28 days after immunization measured with both a hemagglutination inhibition assay and by a microneutralization assay. The results showed similar rates in the 75 children who received Flucelvax and the 73 who received Fluzone. For example, seropositivity against B Victoria lineage strains by the hemagglutination inhibition assay 28 days after vaccination was 76% in children who received Flucelvax, and it was 79% among those who got Fluzone, with a seroconversion rate of 34% in each of the two study subgroups.
“These findings do not say that egg-free is better, but it was certainly no worse. My guess is that in some years vaccines that are egg-free will make a big difference. In other years it may not. But you don’t know ahead of time,” Dr. Zimmerman said.
The study received no commercial funding but received free Fluzone vaccine from Sanofi Pasteur. Dr. Zimmerman had no disclosures.
REPORTING FROM ID WEEK 2019
Spotting immunodeficiency in the pediatric dermatology clinic
SEATTLE – Immunodeficiency in children can look much like eczematous dermatitis. Be aware of this potential diagnosis.
“Although it is important to know these are extremely rare conditions, you don’t want to miss them because you can literally change that child’s life,” Markus Boos, MD, an assistant professor of pediatrics at the University of Washington, Seattle, said in an interview at the annual Coastal Dermatology Symposium.
He outlined some key clinical features and patient history that can raise a potential red flag.
“ and you really spend time looking at the morphology and distribution of the rash,” Dr. Boos said.
The distribution of the rash also can be distinctive. For example, hyper-IgE syndrome shows up as little red pus bumps that are widespread, but specifically occur on the face and other areas that usually aren’t affected eczematous dermatitis. “You should really focus on that, and not just assume that because something [like eczematous dermatitis] is common, everything has to be that,” Dr. Boos said at the meeting, which was jointly presented by the University of Louisville and Global Academy for Medical Education.
He also warned about a false positive. You may be alerted to high eosinophil and high IgE levels determined by a primary care physician’s tests, but these aren’t necessarily a strong indicator of hyper-IgE syndrome, he said. “Many inflammatory conditions in children have high levels of both those, so they aren’t a distinguishing feature of any one of them. You can reassure a family that the child doesn’t necessarily have hyper-IgE syndrome. There’s this leap [people take] because it sounds like the name, but it’s not a very specific marker of that particular condition.”
Patient history of an immunodeficiency patient in general obviously can include a history of infections, although a high rate of ear infections is pretty typical among children. The key is to ask yourself: “At what point does it seem like something that is beyond normal?” Dr. Boos said. Infections that required hospitalizations or were invasive or required antibiotics all are potential clues. Other factors to consider include growth and development issues such as frequent diarrhea or failure to thrive, or family members with frequent infections or who died prematurely.
Hyper-IgE patients also may have a prominent forehead and chin, deep-set eyes, broad nose, thickened facial skin, or a high arched palate. These physical features become more prominent by adolescence. For a reference for physical features go to https://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-types/hyper-ige-syndrome.
Clinical features of various immunodeficiencies include the following:
- Papulopustular eruption with frequent infections and musculoskeletal changes. This presentation is suggestive of autosomal dominant hyper-IgE syndrome. These children have a “heterozygous mutation in the gene encoding the transcription factor STAT3,” according to the Immune Deficiency Foundation.
- Severe atopy with extensive warts/molluscum/herpes simplex virus. This presentation is suggestive of autosomal recessive hyper-IgE syndrome. These children have “mutations and deletions in the DOCK8 gene,” the Immune Deficiency Foundation asserts.
- Diffusely red baby. Consider immunodeficiency if the patient also has experienced failure to thrive and/or diarrhea, or has a history of infection. High IgE levels are not a strong signal of hyper-IgE syndrome.
- Severe eczematous (or psoriasiform) dermatitis with chronic diarrhea, failure to thrive, and diabetes or hypothyroidism. This presentation is suggestive of IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked).
- Atopic dermatitis with bloody diarrhea, thrombocytopenia, recurrent ear infections. This presentation is indicative of Wiskott-Aldrich syndrome.
Dr. Boos is personally familiar with primary immunodeficiencies because he works closely with an immunology clinic, which also means he has a lot of support. Most clinicians diagnosing these patients don’t. If you find yourself with a case, “call in the troops,” he advised. You should be connected to a rheumatologist when there’s evidence of autoimmune disease, and hematologists or oncologists for the treatment, which requires a bone marrow transplant in the case of autosomal recessive hyper-IgE syndrome. Otherwise treatment is largely supportive for this immunodeficiency.
Having that network can be invaluable in managing what can be a very complicated patient. “If you ever feel uncomfortable making a decision about their care, discussing it with those other providers can give you some peace of mind,” he said.
Dr. Boos disclosed that he is a clinical researcher for Regeneron. This publication and Global Academy for Medical Education are owned by the same parent company.
SEATTLE – Immunodeficiency in children can look much like eczematous dermatitis. Be aware of this potential diagnosis.
“Although it is important to know these are extremely rare conditions, you don’t want to miss them because you can literally change that child’s life,” Markus Boos, MD, an assistant professor of pediatrics at the University of Washington, Seattle, said in an interview at the annual Coastal Dermatology Symposium.
He outlined some key clinical features and patient history that can raise a potential red flag.
“ and you really spend time looking at the morphology and distribution of the rash,” Dr. Boos said.
The distribution of the rash also can be distinctive. For example, hyper-IgE syndrome shows up as little red pus bumps that are widespread, but specifically occur on the face and other areas that usually aren’t affected eczematous dermatitis. “You should really focus on that, and not just assume that because something [like eczematous dermatitis] is common, everything has to be that,” Dr. Boos said at the meeting, which was jointly presented by the University of Louisville and Global Academy for Medical Education.
He also warned about a false positive. You may be alerted to high eosinophil and high IgE levels determined by a primary care physician’s tests, but these aren’t necessarily a strong indicator of hyper-IgE syndrome, he said. “Many inflammatory conditions in children have high levels of both those, so they aren’t a distinguishing feature of any one of them. You can reassure a family that the child doesn’t necessarily have hyper-IgE syndrome. There’s this leap [people take] because it sounds like the name, but it’s not a very specific marker of that particular condition.”
Patient history of an immunodeficiency patient in general obviously can include a history of infections, although a high rate of ear infections is pretty typical among children. The key is to ask yourself: “At what point does it seem like something that is beyond normal?” Dr. Boos said. Infections that required hospitalizations or were invasive or required antibiotics all are potential clues. Other factors to consider include growth and development issues such as frequent diarrhea or failure to thrive, or family members with frequent infections or who died prematurely.
Hyper-IgE patients also may have a prominent forehead and chin, deep-set eyes, broad nose, thickened facial skin, or a high arched palate. These physical features become more prominent by adolescence. For a reference for physical features go to https://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-types/hyper-ige-syndrome.
Clinical features of various immunodeficiencies include the following:
- Papulopustular eruption with frequent infections and musculoskeletal changes. This presentation is suggestive of autosomal dominant hyper-IgE syndrome. These children have a “heterozygous mutation in the gene encoding the transcription factor STAT3,” according to the Immune Deficiency Foundation.
- Severe atopy with extensive warts/molluscum/herpes simplex virus. This presentation is suggestive of autosomal recessive hyper-IgE syndrome. These children have “mutations and deletions in the DOCK8 gene,” the Immune Deficiency Foundation asserts.
- Diffusely red baby. Consider immunodeficiency if the patient also has experienced failure to thrive and/or diarrhea, or has a history of infection. High IgE levels are not a strong signal of hyper-IgE syndrome.
- Severe eczematous (or psoriasiform) dermatitis with chronic diarrhea, failure to thrive, and diabetes or hypothyroidism. This presentation is suggestive of IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked).
- Atopic dermatitis with bloody diarrhea, thrombocytopenia, recurrent ear infections. This presentation is indicative of Wiskott-Aldrich syndrome.
Dr. Boos is personally familiar with primary immunodeficiencies because he works closely with an immunology clinic, which also means he has a lot of support. Most clinicians diagnosing these patients don’t. If you find yourself with a case, “call in the troops,” he advised. You should be connected to a rheumatologist when there’s evidence of autoimmune disease, and hematologists or oncologists for the treatment, which requires a bone marrow transplant in the case of autosomal recessive hyper-IgE syndrome. Otherwise treatment is largely supportive for this immunodeficiency.
Having that network can be invaluable in managing what can be a very complicated patient. “If you ever feel uncomfortable making a decision about their care, discussing it with those other providers can give you some peace of mind,” he said.
Dr. Boos disclosed that he is a clinical researcher for Regeneron. This publication and Global Academy for Medical Education are owned by the same parent company.
SEATTLE – Immunodeficiency in children can look much like eczematous dermatitis. Be aware of this potential diagnosis.
“Although it is important to know these are extremely rare conditions, you don’t want to miss them because you can literally change that child’s life,” Markus Boos, MD, an assistant professor of pediatrics at the University of Washington, Seattle, said in an interview at the annual Coastal Dermatology Symposium.
He outlined some key clinical features and patient history that can raise a potential red flag.
“ and you really spend time looking at the morphology and distribution of the rash,” Dr. Boos said.
The distribution of the rash also can be distinctive. For example, hyper-IgE syndrome shows up as little red pus bumps that are widespread, but specifically occur on the face and other areas that usually aren’t affected eczematous dermatitis. “You should really focus on that, and not just assume that because something [like eczematous dermatitis] is common, everything has to be that,” Dr. Boos said at the meeting, which was jointly presented by the University of Louisville and Global Academy for Medical Education.
He also warned about a false positive. You may be alerted to high eosinophil and high IgE levels determined by a primary care physician’s tests, but these aren’t necessarily a strong indicator of hyper-IgE syndrome, he said. “Many inflammatory conditions in children have high levels of both those, so they aren’t a distinguishing feature of any one of them. You can reassure a family that the child doesn’t necessarily have hyper-IgE syndrome. There’s this leap [people take] because it sounds like the name, but it’s not a very specific marker of that particular condition.”
Patient history of an immunodeficiency patient in general obviously can include a history of infections, although a high rate of ear infections is pretty typical among children. The key is to ask yourself: “At what point does it seem like something that is beyond normal?” Dr. Boos said. Infections that required hospitalizations or were invasive or required antibiotics all are potential clues. Other factors to consider include growth and development issues such as frequent diarrhea or failure to thrive, or family members with frequent infections or who died prematurely.
Hyper-IgE patients also may have a prominent forehead and chin, deep-set eyes, broad nose, thickened facial skin, or a high arched palate. These physical features become more prominent by adolescence. For a reference for physical features go to https://primaryimmune.org/about-primary-immunodeficiencies/specific-disease-types/hyper-ige-syndrome.
Clinical features of various immunodeficiencies include the following:
- Papulopustular eruption with frequent infections and musculoskeletal changes. This presentation is suggestive of autosomal dominant hyper-IgE syndrome. These children have a “heterozygous mutation in the gene encoding the transcription factor STAT3,” according to the Immune Deficiency Foundation.
- Severe atopy with extensive warts/molluscum/herpes simplex virus. This presentation is suggestive of autosomal recessive hyper-IgE syndrome. These children have “mutations and deletions in the DOCK8 gene,” the Immune Deficiency Foundation asserts.
- Diffusely red baby. Consider immunodeficiency if the patient also has experienced failure to thrive and/or diarrhea, or has a history of infection. High IgE levels are not a strong signal of hyper-IgE syndrome.
- Severe eczematous (or psoriasiform) dermatitis with chronic diarrhea, failure to thrive, and diabetes or hypothyroidism. This presentation is suggestive of IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked).
- Atopic dermatitis with bloody diarrhea, thrombocytopenia, recurrent ear infections. This presentation is indicative of Wiskott-Aldrich syndrome.
Dr. Boos is personally familiar with primary immunodeficiencies because he works closely with an immunology clinic, which also means he has a lot of support. Most clinicians diagnosing these patients don’t. If you find yourself with a case, “call in the troops,” he advised. You should be connected to a rheumatologist when there’s evidence of autoimmune disease, and hematologists or oncologists for the treatment, which requires a bone marrow transplant in the case of autosomal recessive hyper-IgE syndrome. Otherwise treatment is largely supportive for this immunodeficiency.
Having that network can be invaluable in managing what can be a very complicated patient. “If you ever feel uncomfortable making a decision about their care, discussing it with those other providers can give you some peace of mind,” he said.
Dr. Boos disclosed that he is a clinical researcher for Regeneron. This publication and Global Academy for Medical Education are owned by the same parent company.
EXPERT ANALYSIS FROM COASTAL DERM