Recent legislation to ban the sale of e-cigarettes to persons younger than 18 years of age, and to prevent distribution of free samples and placement in vending machines where teens may be present, was a major win for the fight for the health and well-being of our adolescents.¹

The electronic nicotine delivery system, or ENDS, was developed as an alternative to smoking cigarettes, reducing the intake of harmful fumes that lead to lung cancer. It was a great idea for those wishing to decrease or completely stop smoking. Its sleek design and flavor assortment made it very appealing, not only to adults, but to teenagers as well.

The history of e-cigs goes back to the 1960s when first developed, but because smoking was so socially acceptable the idea did not take hold. It wasn’t until 2003 when they started to become popular. Initially, e-cigs were met with resistance from the Food and Drug Administration, which stated that they were dangerous. But as the need for an alternative to smoking increased and preventable deaths continued to rise, there was more pressure to make them available. In 2013, sales started to skyrocket, but no restrictions for sale or product information was required. This made them readily available to teens and heralded the start of a whole new crisis. The Centers for Disease Control and Prevention reported that between 2011 and 2014, e-cig use rose from 0.6% to 5.3% among middle schoolers and from 1.5% to 16% among high school students.²

Because the marketing for e-cigs suggests they carry a reduced risk for cancer and are a healthier alternative to cigarettes, the perception is that they are not harmful. But research shows the contrary. Nicotine exposure of any level to the developing brain has been found to have negative effects, particularly in the prefrontal cortex where altered synapses have been identified.³ Symptoms of nicotine dependence at lower doses of nicotine is evident in adolescents. Long-term effects in adolescents are reported in working memory, attention, and predilection to major depressive disorder, panic disorder, academic problems, and addiction to other substances.³

The American Academy of Pediatrics 2015 statement on e-cigarettes stated increasing use by teens “threatens 5 decades of public health gains in successfully deglamorizing, restricting, and decreasing the use of tobacco products” and called for an FDA ban on the products.⁴ Although the FDA recently did place new restrictions, it will take several years for them to go fully into effect. A recent incident where a toddler ingested the liquid nicotine from an e-cig and died also brought to light other dangers of nicotine.⁵ These nicotine solutions come in colors and a variety of flavors, which makes them even more desirable to toddlers.Just one confirmed death has been reported from e-cig solution ingestion, but there has been a significant jump in calls to poison control centers associated with the liquids. Nicotine from these solutions also can be absorbed through the skin.

mauro grigollo/Thinkstock.com

More than 3 million middle and high school students were current users of e-cigarettes in 2015,¹ and e-cigs were the most commonly used tobacco product among middle and high school students that year.² Early introduction of ENDS causes a combination of early dependence and addiction with long-term impairment of cognitive skills, promoting an even more grim future for the health of our teens. Education and awareness is imperative to slow the current trends and prevent an even worse crisis than the one ENDS was created to improve.

References

1. http://www.fda.gov/TobaccoProducts/Labeling/ProductsIngredientsComponents/ucm456610.htm

2. MMWR Morb Mortal Wkly Rep. 2016 Apr 15;65(14):361-7.

3. Cold Spring Harbor Perspectives in Medicine. 2012;2(12):10.1101/cshperspect.a012120 a012120.

4. Pediatrics. 2015 Nov.10.1542/peds.2015-3222.

5. healthychildren.org

Dr. Pearce is a pediatrician in Frankfort, Ill. Email her at [email protected].

 Recent legislation to ban the sale of e-cigarettes to persons younger than 18 years of age, and to prevent distribution of free samples and placement in vending machines where teens may be present, was a major win for the fight for the health and well-being of our adolescents.¹

The electronic nicotine delivery system, or ENDS, was developed as an alternative to smoking cigarettes, reducing the intake of harmful fumes that lead to lung cancer. It was a great idea for those wishing to decrease or completely stop smoking. Its sleek design and flavor assortment made it very appealing, not only to adults, but to teenagers as well.

The history of e-cigs goes back to the 1960s when first developed, but because smoking was so socially acceptable the idea did not take hold. It wasn’t until 2003 when they started to become popular. Initially, e-cigs were met with resistance from the Food and Drug Administration, which stated that they were dangerous. But as the need for an alternative to smoking increased and preventable deaths continued to rise, there was more pressure to make them available. In 2013, sales started to skyrocket, but no restrictions for sale or product information was required. This made them readily available to teens and heralded the start of a whole new crisis. The Centers for Disease Control and Prevention reported that between 2011 and 2014, e-cig use rose from 0.6% to 5.3% among middle schoolers and from 1.5% to 16% among high school students.²

Because the marketing for e-cigs suggests they carry a reduced risk for cancer and are a healthier alternative to cigarettes, the perception is that they are not harmful. But research shows the contrary. Nicotine exposure of any level to the developing brain has been found to have negative effects, particularly in the prefrontal cortex where altered synapses have been identified.³ Symptoms of nicotine dependence at lower doses of nicotine is evident in adolescents. Long-term effects in adolescents are reported in working memory, attention, and predilection to major depressive disorder, panic disorder, academic problems, and addiction to other substances.³

The American Academy of Pediatrics 2015 statement on e-cigarettes stated increasing use by teens “threatens 5 decades of public health gains in successfully deglamorizing, restricting, and decreasing the use of tobacco products” and called for an FDA ban on the products.⁴ Although the FDA recently did place new restrictions, it will take several years for them to go fully into effect. A recent incident where a toddler ingested the liquid nicotine from an e-cig and died also brought to light other dangers of nicotine.⁵ These nicotine solutions come in colors and a variety of flavors, which makes them even more desirable to toddlers.Just one confirmed death has been reported from e-cig solution ingestion, but there has been a significant jump in calls to poison control centers associated with the liquids. Nicotine from these solutions also can be absorbed through the skin.

mauro grigollo/Thinkstock.com

More than 3 million middle and high school students were current users of e-cigarettes in 2015,¹ and e-cigs were the most commonly used tobacco product among middle and high school students that year.² Early introduction of ENDS causes a combination of early dependence and addiction with long-term impairment of cognitive skills, promoting an even more grim future for the health of our teens. Education and awareness is imperative to slow the current trends and prevent an even worse crisis than the one ENDS was created to improve.

References

1. http://www.fda.gov/TobaccoProducts/Labeling/ProductsIngredientsComponents/ucm456610.htm

2. MMWR Morb Mortal Wkly Rep. 2016 Apr 15;65(14):361-7.

3. Cold Spring Harbor Perspectives in Medicine. 2012;2(12):10.1101/cshperspect.a012120 a012120.

4. Pediatrics. 2015 Nov.10.1542/peds.2015-3222.

5. healthychildren.org

Dr. Pearce is a pediatrician in Frankfort, Ill. Email her at [email protected].

 Recent legislation to ban the sale of e-cigarettes to persons younger than 18 years of age, and to prevent distribution of free samples and placement in vending machines where teens may be present, was a major win for the fight for the health and well-being of our adolescents.¹

The electronic nicotine delivery system, or ENDS, was developed as an alternative to smoking cigarettes, reducing the intake of harmful fumes that lead to lung cancer. It was a great idea for those wishing to decrease or completely stop smoking. Its sleek design and flavor assortment made it very appealing, not only to adults, but to teenagers as well.

The history of e-cigs goes back to the 1960s when first developed, but because smoking was so socially acceptable the idea did not take hold. It wasn’t until 2003 when they started to become popular. Initially, e-cigs were met with resistance from the Food and Drug Administration, which stated that they were dangerous. But as the need for an alternative to smoking increased and preventable deaths continued to rise, there was more pressure to make them available. In 2013, sales started to skyrocket, but no restrictions for sale or product information was required. This made them readily available to teens and heralded the start of a whole new crisis. The Centers for Disease Control and Prevention reported that between 2011 and 2014, e-cig use rose from 0.6% to 5.3% among middle schoolers and from 1.5% to 16% among high school students.²

Because the marketing for e-cigs suggests they carry a reduced risk for cancer and are a healthier alternative to cigarettes, the perception is that they are not harmful. But research shows the contrary. Nicotine exposure of any level to the developing brain has been found to have negative effects, particularly in the prefrontal cortex where altered synapses have been identified.³ Symptoms of nicotine dependence at lower doses of nicotine is evident in adolescents. Long-term effects in adolescents are reported in working memory, attention, and predilection to major depressive disorder, panic disorder, academic problems, and addiction to other substances.³

The American Academy of Pediatrics 2015 statement on e-cigarettes stated increasing use by teens “threatens 5 decades of public health gains in successfully deglamorizing, restricting, and decreasing the use of tobacco products” and called for an FDA ban on the products.⁴ Although the FDA recently did place new restrictions, it will take several years for them to go fully into effect. A recent incident where a toddler ingested the liquid nicotine from an e-cig and died also brought to light other dangers of nicotine.⁵ These nicotine solutions come in colors and a variety of flavors, which makes them even more desirable to toddlers.Just one confirmed death has been reported from e-cig solution ingestion, but there has been a significant jump in calls to poison control centers associated with the liquids. Nicotine from these solutions also can be absorbed through the skin.

mauro grigollo/Thinkstock.com

More than 3 million middle and high school students were current users of e-cigarettes in 2015,¹ and e-cigs were the most commonly used tobacco product among middle and high school students that year.² Early introduction of ENDS causes a combination of early dependence and addiction with long-term impairment of cognitive skills, promoting an even more grim future for the health of our teens. Education and awareness is imperative to slow the current trends and prevent an even worse crisis than the one ENDS was created to improve.

References

1. http://www.fda.gov/TobaccoProducts/Labeling/ProductsIngredientsComponents/ucm456610.htm

2. MMWR Morb Mortal Wkly Rep. 2016 Apr 15;65(14):361-7.

3. Cold Spring Harbor Perspectives in Medicine. 2012;2(12):10.1101/cshperspect.a012120 a012120.

4. Pediatrics. 2015 Nov.10.1542/peds.2015-3222.

5. healthychildren.org

Dr. Pearce is a pediatrician in Frankfort, Ill. Email her at [email protected].

SAN DIEGO – Blood levels of infliximab rose during pregnancy, while adalimumab levels remained stable, even after researchers accounted for changes in albumin, body mass index, and C-reactive protein levels, according to a novel single-center study of 25 women with inflammatory bowel disease (IBD).

Furthermore, blood levels of both anti–tumor necrosis factor agents varied considerably among patients, reported Dr. Cynthia Seow, a gastroenterologist at the University of Calgary (Alta.). “We should consider therapeutic drug monitoring during the prepregnancy period in order to optimize the dose during pregnancy,” she said. “Therapeutic drug monitoring may also be considered for pregnant women receiving infliximab in the second trimester to guide third-trimester dosing.

Active IBD during pregnancy increases the risk of relapse and preterm birth, Dr. Seow noted at the annual Digestive Diseases Week. Thus, infliximab and adalimumab are used to keep IBD in check during pregnancy, even though they cross the placenta and reach higher levels in the cord blood and newborn (Clin Gastroenterol Hepatol. 2013 March;11[3]:286-92) than in the mother. “However, it is not known how pregnancy itself influences the pharmacokinetics of anti-TNF agents, or the implications of this on prescribed dosing,” said Dr. Seow.

Therefore, she and her colleagues analyzed blood samples from 25 women receiving stable maintenance anti-TNF therapy for IBD, who attended a median of three prenatal visits at the University of Calgary IBD Pregnancy Clinic. Fifteen women received infliximab during 15 pregnancies, and 10 women received adalimumab during 11 pregnancies. Infliximab levels were drawn at trough times, while adalimumab levels were usually drawn 3 days before the next injection. Blood samples were tested only after delivery, and anti-TNF doses were not adjusted during pregnancy.

The infliximab group included eight women with Crohn’s disease and seven women with ulcerative colitis, and the adalimumab group included nine women with Crohn’s disease and one with ulcerative colitis, said Dr. Seow. The treatment groups were similar in terms of age at diagnosis and pregnancy, time on anti-TNF agents, and average gestational age at delivery, which was 39.2 weeks (range, 38.1-40.2 weeks) for the infliximab group and 38.4 weeks (range, 37.2-39.6 weeks) for the adalimumab patients.

Median infliximab concentrations rose from 8.5 mcg/mL in the first trimester to a peak of 21 mcg/mL during the middle of the third trimester (P = .04), and then dropped to nearly preconception levels after delivery, Dr. Seow reported. “This change persisted irrespective of disease phenotype,” she added. Albumin levels correlated inversely with infliximab levels. In contrast, median adalimumab levels ranged between 8.6 and 12.2 mcg/mL during pregnancy, dropped to 6.8 mcg/mL after birth, and were unrelated to albumin levels.

Body mass index and C-reactive protein levels did not affect blood levels of either drug, and the researchers found no differences in pharmacokinetics in subgroups of patients who had only two blood draws, subtherapeutic drug levels, or consistently absent drug levels, Dr. Seow said. Three patients had detectable antibodies during pregnancy, all of whom had a stable clinical course, she said. “The antibody levels appeared to decrease as the pregnancy progressed, and then appeared to increase again after delivery.” A third of infliximab patients and nearly half of adalimumab patients were receiving combination treatments for IBD, and their anti-TNF blood levels resembled those of patients on monotherapy, she also noted.

The researchers did not test cord blood or blood sample from the newborns, but based on past evidence, fetal anti-TNF exposure has implications for current live vaccination recommendations in infants, Dr. Seow emphasized. “The long-term consequences of anti-TNF exposure remain unknown,” she concluded.

Dr. Seow disclosed ties with Janssen, AbbVie, Takeda, Shire, and Actavis.

SAN DIEGO – Blood levels of infliximab rose during pregnancy, while adalimumab levels remained stable, even after researchers accounted for changes in albumin, body mass index, and C-reactive protein levels, according to a novel single-center study of 25 women with inflammatory bowel disease (IBD).

Furthermore, blood levels of both anti–tumor necrosis factor agents varied considerably among patients, reported Dr. Cynthia Seow, a gastroenterologist at the University of Calgary (Alta.). “We should consider therapeutic drug monitoring during the prepregnancy period in order to optimize the dose during pregnancy,” she said. “Therapeutic drug monitoring may also be considered for pregnant women receiving infliximab in the second trimester to guide third-trimester dosing.

Active IBD during pregnancy increases the risk of relapse and preterm birth, Dr. Seow noted at the annual Digestive Diseases Week. Thus, infliximab and adalimumab are used to keep IBD in check during pregnancy, even though they cross the placenta and reach higher levels in the cord blood and newborn (Clin Gastroenterol Hepatol. 2013 March;11[3]:286-92) than in the mother. “However, it is not known how pregnancy itself influences the pharmacokinetics of anti-TNF agents, or the implications of this on prescribed dosing,” said Dr. Seow.

Therefore, she and her colleagues analyzed blood samples from 25 women receiving stable maintenance anti-TNF therapy for IBD, who attended a median of three prenatal visits at the University of Calgary IBD Pregnancy Clinic. Fifteen women received infliximab during 15 pregnancies, and 10 women received adalimumab during 11 pregnancies. Infliximab levels were drawn at trough times, while adalimumab levels were usually drawn 3 days before the next injection. Blood samples were tested only after delivery, and anti-TNF doses were not adjusted during pregnancy.

The infliximab group included eight women with Crohn’s disease and seven women with ulcerative colitis, and the adalimumab group included nine women with Crohn’s disease and one with ulcerative colitis, said Dr. Seow. The treatment groups were similar in terms of age at diagnosis and pregnancy, time on anti-TNF agents, and average gestational age at delivery, which was 39.2 weeks (range, 38.1-40.2 weeks) for the infliximab group and 38.4 weeks (range, 37.2-39.6 weeks) for the adalimumab patients.

Median infliximab concentrations rose from 8.5 mcg/mL in the first trimester to a peak of 21 mcg/mL during the middle of the third trimester (P = .04), and then dropped to nearly preconception levels after delivery, Dr. Seow reported. “This change persisted irrespective of disease phenotype,” she added. Albumin levels correlated inversely with infliximab levels. In contrast, median adalimumab levels ranged between 8.6 and 12.2 mcg/mL during pregnancy, dropped to 6.8 mcg/mL after birth, and were unrelated to albumin levels.

Body mass index and C-reactive protein levels did not affect blood levels of either drug, and the researchers found no differences in pharmacokinetics in subgroups of patients who had only two blood draws, subtherapeutic drug levels, or consistently absent drug levels, Dr. Seow said. Three patients had detectable antibodies during pregnancy, all of whom had a stable clinical course, she said. “The antibody levels appeared to decrease as the pregnancy progressed, and then appeared to increase again after delivery.” A third of infliximab patients and nearly half of adalimumab patients were receiving combination treatments for IBD, and their anti-TNF blood levels resembled those of patients on monotherapy, she also noted.

The researchers did not test cord blood or blood sample from the newborns, but based on past evidence, fetal anti-TNF exposure has implications for current live vaccination recommendations in infants, Dr. Seow emphasized. “The long-term consequences of anti-TNF exposure remain unknown,” she concluded.

Dr. Seow disclosed ties with Janssen, AbbVie, Takeda, Shire, and Actavis.

SAN DIEGO – Blood levels of infliximab rose during pregnancy, while adalimumab levels remained stable, even after researchers accounted for changes in albumin, body mass index, and C-reactive protein levels, according to a novel single-center study of 25 women with inflammatory bowel disease (IBD).

Furthermore, blood levels of both anti–tumor necrosis factor agents varied considerably among patients, reported Dr. Cynthia Seow, a gastroenterologist at the University of Calgary (Alta.). “We should consider therapeutic drug monitoring during the prepregnancy period in order to optimize the dose during pregnancy,” she said. “Therapeutic drug monitoring may also be considered for pregnant women receiving infliximab in the second trimester to guide third-trimester dosing.

Active IBD during pregnancy increases the risk of relapse and preterm birth, Dr. Seow noted at the annual Digestive Diseases Week. Thus, infliximab and adalimumab are used to keep IBD in check during pregnancy, even though they cross the placenta and reach higher levels in the cord blood and newborn (Clin Gastroenterol Hepatol. 2013 March;11[3]:286-92) than in the mother. “However, it is not known how pregnancy itself influences the pharmacokinetics of anti-TNF agents, or the implications of this on prescribed dosing,” said Dr. Seow.

Therefore, she and her colleagues analyzed blood samples from 25 women receiving stable maintenance anti-TNF therapy for IBD, who attended a median of three prenatal visits at the University of Calgary IBD Pregnancy Clinic. Fifteen women received infliximab during 15 pregnancies, and 10 women received adalimumab during 11 pregnancies. Infliximab levels were drawn at trough times, while adalimumab levels were usually drawn 3 days before the next injection. Blood samples were tested only after delivery, and anti-TNF doses were not adjusted during pregnancy.

The infliximab group included eight women with Crohn’s disease and seven women with ulcerative colitis, and the adalimumab group included nine women with Crohn’s disease and one with ulcerative colitis, said Dr. Seow. The treatment groups were similar in terms of age at diagnosis and pregnancy, time on anti-TNF agents, and average gestational age at delivery, which was 39.2 weeks (range, 38.1-40.2 weeks) for the infliximab group and 38.4 weeks (range, 37.2-39.6 weeks) for the adalimumab patients.

Median infliximab concentrations rose from 8.5 mcg/mL in the first trimester to a peak of 21 mcg/mL during the middle of the third trimester (P = .04), and then dropped to nearly preconception levels after delivery, Dr. Seow reported. “This change persisted irrespective of disease phenotype,” she added. Albumin levels correlated inversely with infliximab levels. In contrast, median adalimumab levels ranged between 8.6 and 12.2 mcg/mL during pregnancy, dropped to 6.8 mcg/mL after birth, and were unrelated to albumin levels.

Body mass index and C-reactive protein levels did not affect blood levels of either drug, and the researchers found no differences in pharmacokinetics in subgroups of patients who had only two blood draws, subtherapeutic drug levels, or consistently absent drug levels, Dr. Seow said. Three patients had detectable antibodies during pregnancy, all of whom had a stable clinical course, she said. “The antibody levels appeared to decrease as the pregnancy progressed, and then appeared to increase again after delivery.” A third of infliximab patients and nearly half of adalimumab patients were receiving combination treatments for IBD, and their anti-TNF blood levels resembled those of patients on monotherapy, she also noted.

The researchers did not test cord blood or blood sample from the newborns, but based on past evidence, fetal anti-TNF exposure has implications for current live vaccination recommendations in infants, Dr. Seow emphasized. “The long-term consequences of anti-TNF exposure remain unknown,” she concluded.

Dr. Seow disclosed ties with Janssen, AbbVie, Takeda, Shire, and Actavis.

The neuropeptide Y (NPY) gene appears to play an essential role in airway reactivity and may be a target for treating noneosinophilic asthma.

Higher expression of the NPY signaling molecule was seen in mice lacking Foxp1 and Foxp4 transcription factors. NPY induced noneosinophilic airway hyperreactivity by activating smooth muscle myosin light-chain phosphorylation, researchers reported in the Journal of Clinical Investigation.

Deleting the NPY gene in mice reduced airway hyperreactivity almost to normal levels, while incubating human lung tissue with recombinant NPY triggered bronchoconstriction, said Dr. Shanru Li and his associates at the University of Pennsylvania in Philadelphia. Future treatments for noneosinophilic asthma might target paracrine signaling from the airway epithelium to underlying smooth muscle.

The researchers also used transcriptome analysis to identify 10 genes that were significantly upregulated in the knockout mice and acted on airway smooth muscle cells to trigger airway hyperresponsiveness (AHR) in a paracrine manner. Among these, NPY was expressed at the highest levels, and deleting this gene in the Foxp1/Foxp4 knockout mice caused AHR to fall almost to normal levels. Incubating recombinant NPY with human and mouse lung tissue triggered marked bronchoconstriction in response to a methacholine challenge. Furthermore, phosphorylation of myosin light chain (pMLC), “a critical signaling event required for airway smooth muscle contraction,” increased with the methacholine challenge, but rose even more with concurrent exposure to NPY.

“Foxp1 and Foxp4 double mutants represent a model for noneosinophilic asthma, which remains poorly understood,” the researchers concluded. “The studies are among the first, to our knowledge, to mechanistically link a critical transcription pathway in airway epithelium that activates a paracrine response to the promotion of AHR in the absence of a Th2-induced eosinophilic inflammatory response.”

Most asthma therapies do not improve nonimmune asthma, which accounts for about half of asthma cases overall. While NPY gene variants have been linked to asthma, the specific molecular pathway was unknown, the researchers said. They found that Foxp1/4 knockout mice had greater airway smooth muscle contraction than control mice, especially after exposure to airway irritants. Notably, they did not find increased levels of the eosinophilic marker IL-13 or the neutrophilic inflammatory markers IL-17, IL-6, or keratinocyte-derived chemokine (KC) in airway epithelium from the knockout mice. “We did observe a modest increase in the numbers of neutrophils, but not macrophages, eosinophils, or lymphocytes in the bronchoalveolar lavage fluid in the Foxp1/4 knockout mutants,” they added (J Clin Invest. 2016 Apr. doi: 10.1172/JCI81389).

The National Institutes of Health funded the studies. The investigators had no disclosures.

The neuropeptide Y (NPY) gene appears to play an essential role in airway reactivity and may be a target for treating noneosinophilic asthma.

Higher expression of the NPY signaling molecule was seen in mice lacking Foxp1 and Foxp4 transcription factors. NPY induced noneosinophilic airway hyperreactivity by activating smooth muscle myosin light-chain phosphorylation, researchers reported in the Journal of Clinical Investigation.

Deleting the NPY gene in mice reduced airway hyperreactivity almost to normal levels, while incubating human lung tissue with recombinant NPY triggered bronchoconstriction, said Dr. Shanru Li and his associates at the University of Pennsylvania in Philadelphia. Future treatments for noneosinophilic asthma might target paracrine signaling from the airway epithelium to underlying smooth muscle.

The researchers also used transcriptome analysis to identify 10 genes that were significantly upregulated in the knockout mice and acted on airway smooth muscle cells to trigger airway hyperresponsiveness (AHR) in a paracrine manner. Among these, NPY was expressed at the highest levels, and deleting this gene in the Foxp1/Foxp4 knockout mice caused AHR to fall almost to normal levels. Incubating recombinant NPY with human and mouse lung tissue triggered marked bronchoconstriction in response to a methacholine challenge. Furthermore, phosphorylation of myosin light chain (pMLC), “a critical signaling event required for airway smooth muscle contraction,” increased with the methacholine challenge, but rose even more with concurrent exposure to NPY.

“Foxp1 and Foxp4 double mutants represent a model for noneosinophilic asthma, which remains poorly understood,” the researchers concluded. “The studies are among the first, to our knowledge, to mechanistically link a critical transcription pathway in airway epithelium that activates a paracrine response to the promotion of AHR in the absence of a Th2-induced eosinophilic inflammatory response.”

Most asthma therapies do not improve nonimmune asthma, which accounts for about half of asthma cases overall. While NPY gene variants have been linked to asthma, the specific molecular pathway was unknown, the researchers said. They found that Foxp1/4 knockout mice had greater airway smooth muscle contraction than control mice, especially after exposure to airway irritants. Notably, they did not find increased levels of the eosinophilic marker IL-13 or the neutrophilic inflammatory markers IL-17, IL-6, or keratinocyte-derived chemokine (KC) in airway epithelium from the knockout mice. “We did observe a modest increase in the numbers of neutrophils, but not macrophages, eosinophils, or lymphocytes in the bronchoalveolar lavage fluid in the Foxp1/4 knockout mutants,” they added (J Clin Invest. 2016 Apr. doi: 10.1172/JCI81389).

The National Institutes of Health funded the studies. The investigators had no disclosures.

The neuropeptide Y (NPY) gene appears to play an essential role in airway reactivity and may be a target for treating noneosinophilic asthma.

Higher expression of the NPY signaling molecule was seen in mice lacking Foxp1 and Foxp4 transcription factors. NPY induced noneosinophilic airway hyperreactivity by activating smooth muscle myosin light-chain phosphorylation, researchers reported in the Journal of Clinical Investigation.

Deleting the NPY gene in mice reduced airway hyperreactivity almost to normal levels, while incubating human lung tissue with recombinant NPY triggered bronchoconstriction, said Dr. Shanru Li and his associates at the University of Pennsylvania in Philadelphia. Future treatments for noneosinophilic asthma might target paracrine signaling from the airway epithelium to underlying smooth muscle.

The researchers also used transcriptome analysis to identify 10 genes that were significantly upregulated in the knockout mice and acted on airway smooth muscle cells to trigger airway hyperresponsiveness (AHR) in a paracrine manner. Among these, NPY was expressed at the highest levels, and deleting this gene in the Foxp1/Foxp4 knockout mice caused AHR to fall almost to normal levels. Incubating recombinant NPY with human and mouse lung tissue triggered marked bronchoconstriction in response to a methacholine challenge. Furthermore, phosphorylation of myosin light chain (pMLC), “a critical signaling event required for airway smooth muscle contraction,” increased with the methacholine challenge, but rose even more with concurrent exposure to NPY.

“Foxp1 and Foxp4 double mutants represent a model for noneosinophilic asthma, which remains poorly understood,” the researchers concluded. “The studies are among the first, to our knowledge, to mechanistically link a critical transcription pathway in airway epithelium that activates a paracrine response to the promotion of AHR in the absence of a Th2-induced eosinophilic inflammatory response.”

Most asthma therapies do not improve nonimmune asthma, which accounts for about half of asthma cases overall. While NPY gene variants have been linked to asthma, the specific molecular pathway was unknown, the researchers said. They found that Foxp1/4 knockout mice had greater airway smooth muscle contraction than control mice, especially after exposure to airway irritants. Notably, they did not find increased levels of the eosinophilic marker IL-13 or the neutrophilic inflammatory markers IL-17, IL-6, or keratinocyte-derived chemokine (KC) in airway epithelium from the knockout mice. “We did observe a modest increase in the numbers of neutrophils, but not macrophages, eosinophils, or lymphocytes in the bronchoalveolar lavage fluid in the Foxp1/4 knockout mutants,” they added (J Clin Invest. 2016 Apr. doi: 10.1172/JCI81389).

The National Institutes of Health funded the studies. The investigators had no disclosures.

The rate of colorectal cancer diagnosis has risen in younger patients, with later-stage tumors predominant, according to findings from a study based on the large National Cancer Database.

Over a 10-year period, the number of colorectal cancer (CRC) cases increased by 11.4% among patients younger than 50 years, which translates to an average increase of 1.28% per year, or 136 new cases each year. By contrast, the number of newly diagnosed CRC cases in those over 50 years of age, dropped by 2.5% over the same period, according to data presented in a teleconference in advance of the annual Digestive Disease Week.

More advanced cancers were diagnosed in the younger group: stage 3, in 30.6% of patients under 50 years of age vs. 25.1% in those over that age; stage 4, in 25.6% vs. 18.2%, respectively.

“Last year, colorectal cancer was the second leading cause of cancer deaths in the U.S., second only to lung cancer. The health care system has done a great deal to heighten patient awareness and increase screenings, but these efforts have focused on people over the age of 50. Our findings show that more efforts need to be aimed at younger people, a group not normally considered at risk,” said lead author Dr. Elie Sutton. “Further, it is very concerning that within younger patients, a higher percentage were diagnosed at later stages.”

The study was based on more than 1 million CRC cases in the National Cancer Database from 2004 to 2013. Factors examined included a comparison of variables between younger-onset and older-onset CRC, such as stage at diagnosis, length of inpatient hospital stay, demographics, and 30-day and 90-day mortality.

In patients for whom data on metastatic disease were available, liver metastasis was reported in 19.4% of younger-onset patients vs. 13.8% of older-onset patients (P less than .001).

As would be expected, hospital stays were shorter for younger-onset patients, who are typically more resilient than older patients. A hospital stay of 5 days or less was recorded for 56.6% of younger-onset patients vs. 43.3% of older-onset patients (P = .001).

Short-term mortality was better for younger patients. Thirty-day mortality was 0.6% for younger-onset patients vs. 3.5% for older-onset patients (P less than .001). Ninety-day mortality was reported in 1.6% vs. 6.4%, respectively (P less than .001), and 8.5% of younger-onset patients had no insurance vs. 2.8% of older-onset patients (P less than .001).

These data are not a surprise, Dr. Sutton commented, in light of the fact that another study showed a similar trend about 5 years ago. “This means we have not adequately addressed risk of CRC in young patients under the age of 50,” he said. “Health care providers should be more vigilant and encourage screening in younger patients,” he emphasized.

Future studies will look at the trends in CRC over time. “We will continue to analyze the National Cancer Database. These insights may be helpful when revisiting colorectal cancer screening guidelines,” Dr. Sutton stated.

Dr. Sutton had no relevant financial disclosures.

The rate of colorectal cancer diagnosis has risen in younger patients, with later-stage tumors predominant, according to findings from a study based on the large National Cancer Database.

Over a 10-year period, the number of colorectal cancer (CRC) cases increased by 11.4% among patients younger than 50 years, which translates to an average increase of 1.28% per year, or 136 new cases each year. By contrast, the number of newly diagnosed CRC cases in those over 50 years of age, dropped by 2.5% over the same period, according to data presented in a teleconference in advance of the annual Digestive Disease Week.

More advanced cancers were diagnosed in the younger group: stage 3, in 30.6% of patients under 50 years of age vs. 25.1% in those over that age; stage 4, in 25.6% vs. 18.2%, respectively.

“Last year, colorectal cancer was the second leading cause of cancer deaths in the U.S., second only to lung cancer. The health care system has done a great deal to heighten patient awareness and increase screenings, but these efforts have focused on people over the age of 50. Our findings show that more efforts need to be aimed at younger people, a group not normally considered at risk,” said lead author Dr. Elie Sutton. “Further, it is very concerning that within younger patients, a higher percentage were diagnosed at later stages.”

The study was based on more than 1 million CRC cases in the National Cancer Database from 2004 to 2013. Factors examined included a comparison of variables between younger-onset and older-onset CRC, such as stage at diagnosis, length of inpatient hospital stay, demographics, and 30-day and 90-day mortality.

In patients for whom data on metastatic disease were available, liver metastasis was reported in 19.4% of younger-onset patients vs. 13.8% of older-onset patients (P less than .001).

As would be expected, hospital stays were shorter for younger-onset patients, who are typically more resilient than older patients. A hospital stay of 5 days or less was recorded for 56.6% of younger-onset patients vs. 43.3% of older-onset patients (P = .001).

Short-term mortality was better for younger patients. Thirty-day mortality was 0.6% for younger-onset patients vs. 3.5% for older-onset patients (P less than .001). Ninety-day mortality was reported in 1.6% vs. 6.4%, respectively (P less than .001), and 8.5% of younger-onset patients had no insurance vs. 2.8% of older-onset patients (P less than .001).

These data are not a surprise, Dr. Sutton commented, in light of the fact that another study showed a similar trend about 5 years ago. “This means we have not adequately addressed risk of CRC in young patients under the age of 50,” he said. “Health care providers should be more vigilant and encourage screening in younger patients,” he emphasized.

Future studies will look at the trends in CRC over time. “We will continue to analyze the National Cancer Database. These insights may be helpful when revisiting colorectal cancer screening guidelines,” Dr. Sutton stated.

Dr. Sutton had no relevant financial disclosures.

The rate of colorectal cancer diagnosis has risen in younger patients, with later-stage tumors predominant, according to findings from a study based on the large National Cancer Database.

Over a 10-year period, the number of colorectal cancer (CRC) cases increased by 11.4% among patients younger than 50 years, which translates to an average increase of 1.28% per year, or 136 new cases each year. By contrast, the number of newly diagnosed CRC cases in those over 50 years of age, dropped by 2.5% over the same period, according to data presented in a teleconference in advance of the annual Digestive Disease Week.

More advanced cancers were diagnosed in the younger group: stage 3, in 30.6% of patients under 50 years of age vs. 25.1% in those over that age; stage 4, in 25.6% vs. 18.2%, respectively.

“Last year, colorectal cancer was the second leading cause of cancer deaths in the U.S., second only to lung cancer. The health care system has done a great deal to heighten patient awareness and increase screenings, but these efforts have focused on people over the age of 50. Our findings show that more efforts need to be aimed at younger people, a group not normally considered at risk,” said lead author Dr. Elie Sutton. “Further, it is very concerning that within younger patients, a higher percentage were diagnosed at later stages.”

The study was based on more than 1 million CRC cases in the National Cancer Database from 2004 to 2013. Factors examined included a comparison of variables between younger-onset and older-onset CRC, such as stage at diagnosis, length of inpatient hospital stay, demographics, and 30-day and 90-day mortality.

In patients for whom data on metastatic disease were available, liver metastasis was reported in 19.4% of younger-onset patients vs. 13.8% of older-onset patients (P less than .001).

As would be expected, hospital stays were shorter for younger-onset patients, who are typically more resilient than older patients. A hospital stay of 5 days or less was recorded for 56.6% of younger-onset patients vs. 43.3% of older-onset patients (P = .001).

Short-term mortality was better for younger patients. Thirty-day mortality was 0.6% for younger-onset patients vs. 3.5% for older-onset patients (P less than .001). Ninety-day mortality was reported in 1.6% vs. 6.4%, respectively (P less than .001), and 8.5% of younger-onset patients had no insurance vs. 2.8% of older-onset patients (P less than .001).

These data are not a surprise, Dr. Sutton commented, in light of the fact that another study showed a similar trend about 5 years ago. “This means we have not adequately addressed risk of CRC in young patients under the age of 50,” he said. “Health care providers should be more vigilant and encourage screening in younger patients,” he emphasized.

Future studies will look at the trends in CRC over time. “We will continue to analyze the National Cancer Database. These insights may be helpful when revisiting colorectal cancer screening guidelines,” Dr. Sutton stated.

Dr. Sutton had no relevant financial disclosures.

BALTIMORE – Biopsy results from a commercially available genetic test for ruling out malignancy of thyroid nodules may not provide reliable answers to clinicians and patients.

When fine-needle aspiration biopsy of thyroid nodules comes back inconclusive, clinicians have increasingly utilized the Afirma gene expression classifier (GEC) to rule out malignancy, but a retrospective analysis of almost 200 patients with indeterminate biopsy results along with a pooled analysis of 11 previous studies has raised questions about the negative predictive value of the test.

©Sebastian Kaulitzki/Fotolia

“The Afirma GEC test has substantial variability in performance,” said Dr. Zaid Al-Qurayshi of Tulane University, New Orleans, who reported the results at the annual meeting of the American Association of Endocrine Surgeons. “This variability cannot be explained based on differences in prevalence alone, but may also be the result of intrinsic test properties.”

The Afirma GEC measures the expression of 167 genes to more precisely determine the cancer risk of an indeterminate biopsied thyroid nodule and avoid unnecessary surgery. The test costs approximately $4,800 per nodule.

The researchers undertook the study in light of an American Thyroid Association (ATA) statement last year that concluded that test results are predicated on the clinician knowing the prevalence of malignancy within each indeterminate cytologic category at his/her own institution. Without this information, the performance of the diagnostic tests may vary substantially (Thyroid. 2015;25:760-8).

The single-center, retrospective cohort analysis included 192 patients with 210 indeterminate biopsy results, 145 of whom had surgery with 154 thyroid nodules. With a malignancy prevalence of 45%, the expected negative predictive value (NPV) of the test was estimated to be 85%, Dr. Al-Qurayshi said. However, the actual observed NPV was 69%. “If the prevalence was assumed to be 25%, the expected NPV was estimated to be 94%, while the observed NPV would have been 85%,” Dr. Al-Qurayshi said.

The researchers calculated the expected NPV by adopting the sensitivity and specificity rates of the test as reported in previous studies, while they calculated the observed NPV based on the actual negative rate among the Tulane cohort, Dr. Al-Qurayshi said.

Dr. Al-Qurayshi and colleagues then compared their results with pooled data from 11 other studies of the Afirma GEC. The pooled data analysis included 1,303 patients and yielded a malignancy prevalence of 31.1%, with a range of 29%-35%, and a pooled NPV of 92%, with a range of 87%-96%, Dr. Al-Qurayshi said.

“A lot of previously published studies took the sensitivity and specificity that were previously reported for granted, and now we are showing this sensitivity is all over the place,” Dr. Al-Qurayshi said. “Now, we don’t know which is the true one, and we need a larger clinical trial first to determine the true properties. Then we can ask how the prevalence in one’s institution is affecting the performance of the test.”

In an interview, Dr. Emad Kandil, senior study coauthor, also of Tulane, said the 69% NPV of the Tulane cohort puts the diagnostic scenario “back to ground zero, which is similar to what we had prior to the use of the new commercially available genetic tests.” He added, “A larger, randomized trial of the Afirma GEC test should answer those questions.”

The seminal study for the Afirma GEC, authored by Dr. Erik Alexander of Brigham and Women’s Hospital, Boston, in 2012, reported a 92% NPV with the test (N Engl J Med. 2012;367:705-15).

“The first thought was that they had different results because their population was different,” Dr. Al-Qurayshi said. “The ATA statement noted that it is the clinician’s responsibility to determine if this test is appropriate for their population or not, but the performance of the test doesn’t just depend on the population property, but it also depends on the intrinsic testing properties.”

Dr. Kandil disclosed that he has been a primary investigator in the ENHANCE multicenter study of the Afirma GEC. The other coauthors had no financial disclosures.

BALTIMORE – Biopsy results from a commercially available genetic test for ruling out malignancy of thyroid nodules may not provide reliable answers to clinicians and patients.

When fine-needle aspiration biopsy of thyroid nodules comes back inconclusive, clinicians have increasingly utilized the Afirma gene expression classifier (GEC) to rule out malignancy, but a retrospective analysis of almost 200 patients with indeterminate biopsy results along with a pooled analysis of 11 previous studies has raised questions about the negative predictive value of the test.

©Sebastian Kaulitzki/Fotolia

“The Afirma GEC test has substantial variability in performance,” said Dr. Zaid Al-Qurayshi of Tulane University, New Orleans, who reported the results at the annual meeting of the American Association of Endocrine Surgeons. “This variability cannot be explained based on differences in prevalence alone, but may also be the result of intrinsic test properties.”

The Afirma GEC measures the expression of 167 genes to more precisely determine the cancer risk of an indeterminate biopsied thyroid nodule and avoid unnecessary surgery. The test costs approximately $4,800 per nodule.

The researchers undertook the study in light of an American Thyroid Association (ATA) statement last year that concluded that test results are predicated on the clinician knowing the prevalence of malignancy within each indeterminate cytologic category at his/her own institution. Without this information, the performance of the diagnostic tests may vary substantially (Thyroid. 2015;25:760-8).

The single-center, retrospective cohort analysis included 192 patients with 210 indeterminate biopsy results, 145 of whom had surgery with 154 thyroid nodules. With a malignancy prevalence of 45%, the expected negative predictive value (NPV) of the test was estimated to be 85%, Dr. Al-Qurayshi said. However, the actual observed NPV was 69%. “If the prevalence was assumed to be 25%, the expected NPV was estimated to be 94%, while the observed NPV would have been 85%,” Dr. Al-Qurayshi said.

The researchers calculated the expected NPV by adopting the sensitivity and specificity rates of the test as reported in previous studies, while they calculated the observed NPV based on the actual negative rate among the Tulane cohort, Dr. Al-Qurayshi said.

Dr. Al-Qurayshi and colleagues then compared their results with pooled data from 11 other studies of the Afirma GEC. The pooled data analysis included 1,303 patients and yielded a malignancy prevalence of 31.1%, with a range of 29%-35%, and a pooled NPV of 92%, with a range of 87%-96%, Dr. Al-Qurayshi said.

“A lot of previously published studies took the sensitivity and specificity that were previously reported for granted, and now we are showing this sensitivity is all over the place,” Dr. Al-Qurayshi said. “Now, we don’t know which is the true one, and we need a larger clinical trial first to determine the true properties. Then we can ask how the prevalence in one’s institution is affecting the performance of the test.”

In an interview, Dr. Emad Kandil, senior study coauthor, also of Tulane, said the 69% NPV of the Tulane cohort puts the diagnostic scenario “back to ground zero, which is similar to what we had prior to the use of the new commercially available genetic tests.” He added, “A larger, randomized trial of the Afirma GEC test should answer those questions.”

The seminal study for the Afirma GEC, authored by Dr. Erik Alexander of Brigham and Women’s Hospital, Boston, in 2012, reported a 92% NPV with the test (N Engl J Med. 2012;367:705-15).

“The first thought was that they had different results because their population was different,” Dr. Al-Qurayshi said. “The ATA statement noted that it is the clinician’s responsibility to determine if this test is appropriate for their population or not, but the performance of the test doesn’t just depend on the population property, but it also depends on the intrinsic testing properties.”

Dr. Kandil disclosed that he has been a primary investigator in the ENHANCE multicenter study of the Afirma GEC. The other coauthors had no financial disclosures.

BALTIMORE – Biopsy results from a commercially available genetic test for ruling out malignancy of thyroid nodules may not provide reliable answers to clinicians and patients.

When fine-needle aspiration biopsy of thyroid nodules comes back inconclusive, clinicians have increasingly utilized the Afirma gene expression classifier (GEC) to rule out malignancy, but a retrospective analysis of almost 200 patients with indeterminate biopsy results along with a pooled analysis of 11 previous studies has raised questions about the negative predictive value of the test.

©Sebastian Kaulitzki/Fotolia

“The Afirma GEC test has substantial variability in performance,” said Dr. Zaid Al-Qurayshi of Tulane University, New Orleans, who reported the results at the annual meeting of the American Association of Endocrine Surgeons. “This variability cannot be explained based on differences in prevalence alone, but may also be the result of intrinsic test properties.”

The Afirma GEC measures the expression of 167 genes to more precisely determine the cancer risk of an indeterminate biopsied thyroid nodule and avoid unnecessary surgery. The test costs approximately $4,800 per nodule.

The researchers undertook the study in light of an American Thyroid Association (ATA) statement last year that concluded that test results are predicated on the clinician knowing the prevalence of malignancy within each indeterminate cytologic category at his/her own institution. Without this information, the performance of the diagnostic tests may vary substantially (Thyroid. 2015;25:760-8).

The single-center, retrospective cohort analysis included 192 patients with 210 indeterminate biopsy results, 145 of whom had surgery with 154 thyroid nodules. With a malignancy prevalence of 45%, the expected negative predictive value (NPV) of the test was estimated to be 85%, Dr. Al-Qurayshi said. However, the actual observed NPV was 69%. “If the prevalence was assumed to be 25%, the expected NPV was estimated to be 94%, while the observed NPV would have been 85%,” Dr. Al-Qurayshi said.

The researchers calculated the expected NPV by adopting the sensitivity and specificity rates of the test as reported in previous studies, while they calculated the observed NPV based on the actual negative rate among the Tulane cohort, Dr. Al-Qurayshi said.

Dr. Al-Qurayshi and colleagues then compared their results with pooled data from 11 other studies of the Afirma GEC. The pooled data analysis included 1,303 patients and yielded a malignancy prevalence of 31.1%, with a range of 29%-35%, and a pooled NPV of 92%, with a range of 87%-96%, Dr. Al-Qurayshi said.

“A lot of previously published studies took the sensitivity and specificity that were previously reported for granted, and now we are showing this sensitivity is all over the place,” Dr. Al-Qurayshi said. “Now, we don’t know which is the true one, and we need a larger clinical trial first to determine the true properties. Then we can ask how the prevalence in one’s institution is affecting the performance of the test.”

In an interview, Dr. Emad Kandil, senior study coauthor, also of Tulane, said the 69% NPV of the Tulane cohort puts the diagnostic scenario “back to ground zero, which is similar to what we had prior to the use of the new commercially available genetic tests.” He added, “A larger, randomized trial of the Afirma GEC test should answer those questions.”

The seminal study for the Afirma GEC, authored by Dr. Erik Alexander of Brigham and Women’s Hospital, Boston, in 2012, reported a 92% NPV with the test (N Engl J Med. 2012;367:705-15).

“The first thought was that they had different results because their population was different,” Dr. Al-Qurayshi said. “The ATA statement noted that it is the clinician’s responsibility to determine if this test is appropriate for their population or not, but the performance of the test doesn’t just depend on the population property, but it also depends on the intrinsic testing properties.”

Dr. Kandil disclosed that he has been a primary investigator in the ENHANCE multicenter study of the Afirma GEC. The other coauthors had no financial disclosures.

There has been quite a bit of discussion and controversy lately about transgender individuals. The debate has extended to the diagnosis itself and whether it should be maintained as an official entity. The previous edition of the Diagnostic and Statistical Manual included the diagnosis of gender identity disorder, which was modified to the current diagnosis of gender dysphoria that describes individuals who show a persistent desire to be the “other” gender and/or an insistence that their gender is different from their birth sex.

One question at the heart of this discussion is the degree to which psychiatric symptoms and disorders are inherent in the gender dysphoria itself or whether most, if not all, of the noted links to things like anxiety, depression, and suicidal behavior stem from the hostility and abuse that many of these youth endure.

As has been reported in the Pediatric News column LGBT Youth Consult, research is now focusing on the mental health of transgender youth, although the data are not entirely consistent. One recent study of 298 transgender women between the ages of 16 and 29 years, of whom nearly three-quarters had received crossgender hormones, showed quite high rates of psychiatric disorders including depression (35%), anxiety (8%), and substance abuse (11%).¹ Moderate to high levels of suicidality in the past month were found in 20% of the sample. Although one cannot conclude from this study that psychopathology is intrinsic to transgender individuals, it does suggest that difficulties can certainly persist among those who have socially transitioned to their affirmed gender.

In contrast, another study from the TransYouth Project showed much more hopeful results.² In this younger sample of 73 prepubescent children, 70% of whom were natal males and all of whom had been supported in the social transition to their affirmed gender at a relatively young age, levels of depressed symptoms were no different from those in 73 controls, and scores on an anxiety scale were only slightly elevated, but did not reach clinical or even subclinical levels as a group. The authors of this study concluded that psychiatric symptoms are not “synonymous” with being transgender. They suggest that supporting youth in their transition at earlier ages could possibly prevent the occurrence of mental health problems in the future.

There is wide acknowledgment that gender-nonconforming youth are at much heightened risk from what can be vicious and cruel maltreatment from peers and the wider community. Similarly, there is good consensus that “conversion therapy” approaches that actively try to discourage youth from their affirmed gender are misguided and unethical. What remains in question among well-meaning parents and clinicians alike, however, is at what age should social transition be supported and how encompassing should it be with regard to pronoun use, bathroom and dressing room access, clothing, and so on. Studies have shown that gender atypical behavior can be quite common in young children, with the vast majority eventually developing gender identities that are in line with their natal sex. Parents may worry that promoting a premature gender transition might expose their child to bullying and harassment that could otherwise be avoided. On the other hand, parents may worry that not supporting gender transition will be experienced as rejecting and critical, which could lead to increased feelings of depression and isolation. Although both views represent valid concerns, it is probably fair to say that among clinicians and researchers who work with transgender youth, there seems to be some movement toward more active acceptance and encouragement of a child’s gender expression at the time, with the understanding that for many, there can be continued movement in one’s gender “journey” across development.

Interestingly, these studies are being published in parallel with some neuroimaging research investigating sex differences with regard to the brain. A recent study from the Proceedings of the National Academy of Sciences found that, among many different regions that are known to show some sex differences with regard to size or connectivity to other regions, the typical human brain shows a “mosaic” pattern in which some regions look more typically male while others look more typically female.³

References

1. JAMA Pediatr. 2016 May 1;170(5):481-6.
2. Pediatrics. 2016;137(3):1-8.
3. PNAS. 2015;112(50):15468-73

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. Follow him on Twitter @pedipsych.

There has been quite a bit of discussion and controversy lately about transgender individuals. The debate has extended to the diagnosis itself and whether it should be maintained as an official entity. The previous edition of the Diagnostic and Statistical Manual included the diagnosis of gender identity disorder, which was modified to the current diagnosis of gender dysphoria that describes individuals who show a persistent desire to be the “other” gender and/or an insistence that their gender is different from their birth sex.

One question at the heart of this discussion is the degree to which psychiatric symptoms and disorders are inherent in the gender dysphoria itself or whether most, if not all, of the noted links to things like anxiety, depression, and suicidal behavior stem from the hostility and abuse that many of these youth endure.

As has been reported in the Pediatric News column LGBT Youth Consult, research is now focusing on the mental health of transgender youth, although the data are not entirely consistent. One recent study of 298 transgender women between the ages of 16 and 29 years, of whom nearly three-quarters had received crossgender hormones, showed quite high rates of psychiatric disorders including depression (35%), anxiety (8%), and substance abuse (11%).¹ Moderate to high levels of suicidality in the past month were found in 20% of the sample. Although one cannot conclude from this study that psychopathology is intrinsic to transgender individuals, it does suggest that difficulties can certainly persist among those who have socially transitioned to their affirmed gender.

In contrast, another study from the TransYouth Project showed much more hopeful results.² In this younger sample of 73 prepubescent children, 70% of whom were natal males and all of whom had been supported in the social transition to their affirmed gender at a relatively young age, levels of depressed symptoms were no different from those in 73 controls, and scores on an anxiety scale were only slightly elevated, but did not reach clinical or even subclinical levels as a group. The authors of this study concluded that psychiatric symptoms are not “synonymous” with being transgender. They suggest that supporting youth in their transition at earlier ages could possibly prevent the occurrence of mental health problems in the future.

There is wide acknowledgment that gender-nonconforming youth are at much heightened risk from what can be vicious and cruel maltreatment from peers and the wider community. Similarly, there is good consensus that “conversion therapy” approaches that actively try to discourage youth from their affirmed gender are misguided and unethical. What remains in question among well-meaning parents and clinicians alike, however, is at what age should social transition be supported and how encompassing should it be with regard to pronoun use, bathroom and dressing room access, clothing, and so on. Studies have shown that gender atypical behavior can be quite common in young children, with the vast majority eventually developing gender identities that are in line with their natal sex. Parents may worry that promoting a premature gender transition might expose their child to bullying and harassment that could otherwise be avoided. On the other hand, parents may worry that not supporting gender transition will be experienced as rejecting and critical, which could lead to increased feelings of depression and isolation. Although both views represent valid concerns, it is probably fair to say that among clinicians and researchers who work with transgender youth, there seems to be some movement toward more active acceptance and encouragement of a child’s gender expression at the time, with the understanding that for many, there can be continued movement in one’s gender “journey” across development.

Interestingly, these studies are being published in parallel with some neuroimaging research investigating sex differences with regard to the brain. A recent study from the Proceedings of the National Academy of Sciences found that, among many different regions that are known to show some sex differences with regard to size or connectivity to other regions, the typical human brain shows a “mosaic” pattern in which some regions look more typically male while others look more typically female.³

References

1. JAMA Pediatr. 2016 May 1;170(5):481-6.
2. Pediatrics. 2016;137(3):1-8.
3. PNAS. 2015;112(50):15468-73

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. Follow him on Twitter @pedipsych.

There has been quite a bit of discussion and controversy lately about transgender individuals. The debate has extended to the diagnosis itself and whether it should be maintained as an official entity. The previous edition of the Diagnostic and Statistical Manual included the diagnosis of gender identity disorder, which was modified to the current diagnosis of gender dysphoria that describes individuals who show a persistent desire to be the “other” gender and/or an insistence that their gender is different from their birth sex.

One question at the heart of this discussion is the degree to which psychiatric symptoms and disorders are inherent in the gender dysphoria itself or whether most, if not all, of the noted links to things like anxiety, depression, and suicidal behavior stem from the hostility and abuse that many of these youth endure.

As has been reported in the Pediatric News column LGBT Youth Consult, research is now focusing on the mental health of transgender youth, although the data are not entirely consistent. One recent study of 298 transgender women between the ages of 16 and 29 years, of whom nearly three-quarters had received crossgender hormones, showed quite high rates of psychiatric disorders including depression (35%), anxiety (8%), and substance abuse (11%).¹ Moderate to high levels of suicidality in the past month were found in 20% of the sample. Although one cannot conclude from this study that psychopathology is intrinsic to transgender individuals, it does suggest that difficulties can certainly persist among those who have socially transitioned to their affirmed gender.

In contrast, another study from the TransYouth Project showed much more hopeful results.² In this younger sample of 73 prepubescent children, 70% of whom were natal males and all of whom had been supported in the social transition to their affirmed gender at a relatively young age, levels of depressed symptoms were no different from those in 73 controls, and scores on an anxiety scale were only slightly elevated, but did not reach clinical or even subclinical levels as a group. The authors of this study concluded that psychiatric symptoms are not “synonymous” with being transgender. They suggest that supporting youth in their transition at earlier ages could possibly prevent the occurrence of mental health problems in the future.

There is wide acknowledgment that gender-nonconforming youth are at much heightened risk from what can be vicious and cruel maltreatment from peers and the wider community. Similarly, there is good consensus that “conversion therapy” approaches that actively try to discourage youth from their affirmed gender are misguided and unethical. What remains in question among well-meaning parents and clinicians alike, however, is at what age should social transition be supported and how encompassing should it be with regard to pronoun use, bathroom and dressing room access, clothing, and so on. Studies have shown that gender atypical behavior can be quite common in young children, with the vast majority eventually developing gender identities that are in line with their natal sex. Parents may worry that promoting a premature gender transition might expose their child to bullying and harassment that could otherwise be avoided. On the other hand, parents may worry that not supporting gender transition will be experienced as rejecting and critical, which could lead to increased feelings of depression and isolation. Although both views represent valid concerns, it is probably fair to say that among clinicians and researchers who work with transgender youth, there seems to be some movement toward more active acceptance and encouragement of a child’s gender expression at the time, with the understanding that for many, there can be continued movement in one’s gender “journey” across development.

Interestingly, these studies are being published in parallel with some neuroimaging research investigating sex differences with regard to the brain. A recent study from the Proceedings of the National Academy of Sciences found that, among many different regions that are known to show some sex differences with regard to size or connectivity to other regions, the typical human brain shows a “mosaic” pattern in which some regions look more typically male while others look more typically female.³

References

1. JAMA Pediatr. 2016 May 1;170(5):481-6.
2. Pediatrics. 2016;137(3):1-8.
3. PNAS. 2015;112(50):15468-73

Dr. Rettew is an associate professor of psychiatry and pediatrics at the University of Vermont, Burlington. Follow him on Twitter @pedipsych.

A gas-filled gastric balloon may promote weight loss more effectively than does its water-filled cousin, according to data from a randomized study that was presented during a teleconference in advance of the annual Digestive Disease Week. A water-filled version of the device is on the market already.

The study enrolled 387 people aged 22 to 64 years old with a body mass index (BMI) from 30 to 40 kg/m² at 15 different sites. People were randomized to the Obalon Balloon System or to a sham control group. People in the treatment group were asked to swallow three capsules: one every 3 weeks until week 12.

The balloon is contained within the capsule, and after swallowing each balloon was filled with 250 cubic centimeters (slightly more than 1 cup) of a nitrogen-based gas via a small catheter. The control group also swallowed sugar-filled capsules (sham treatment).

A total of 366 patients swallowed at least two capsules and were included in the per protocol analysis: 185 in the treatment group and 181 in the control group. All patients saw a registered dietitian every 3 weeks and also followed diet, exercise, and behavior modification lifestyle changes. Obalon balloons were removed endoscopically at week 24, when participants’ weight was assessed.

The balloon-treated group had a mean weight loss of 6.8%, compared with 3.59% in the control group. At least 5% of body weight loss was achieved by 64.3% of the balloon-treated group, compared with 32% of the control group. The balloon treatment group, but not controls, showed improvements in levels of systolic blood pressure, LDL cholesterol, and triglycerides.

The finding that obese participants who swallowed the Obalon 6-Month Balloon System lost nearly 7% of their body weight and experienced improvements in other health indicators “is important because weight loss is quite difficult to achieve and a significant number of people are not successful in achieving their weight loss goals with diet changes and exercise,” said lead author Dr. Shelby Sullivan, who presented the findings.

Adverse events were mostly mild and included diarrhea, cramping, and nausea in nine patients. No hospitalizations were required for these events. One patient with a pre-existing bleeding ulcer experienced a serious adverse event, which the investigators classified as being possibly related to treatment.

“This patient had an orthopedic procedure and was taking high doses of NSAIDs. That should have been excluded in the trial,” said Dr. Sullivan of Washington University, St. Louis.

“Treatment over time, and even with the initial swallowing of the balloon capsule is quite well tolerated, with only mild symptoms compared with other balloon systems,” she said. “Anecdotally, my impression is that patients liked the therapy because it allowed them to follow lifestyle therapy as well.”

The Obalon balloon is given in stages, giving patients’ stomachs time to adjust to the balloon. Unlike liquid-filled balloons, the gas floats up in the stomach and may cause fewer symptoms than liquid-filled balloons, she suggested.

Dr. Sullivan believes that when the Obalon system is used in the real world, it may lead to even greater weight loss. “This has been seen in other sham-controlled trials,” she noted.

Patients enrolled in the trial are being followed longitudinally and those in the sham control group are allowed to cross over to the Obalon balloons on an open-label basis.

“More than 640 million people globally have obesity, and at this time, there are more overweight than underweight people in the world. Some treatments that are alternatives to diet and exercise may be risky. Obalon swallowable balloon is a new treatment option that can help patients lose almost twice as much weight compared with lifestyle changes alone,” she said.

Dr. Sullivan received funding for this study from Obalon Therapeutics.

A gas-filled gastric balloon may promote weight loss more effectively than does its water-filled cousin, according to data from a randomized study that was presented during a teleconference in advance of the annual Digestive Disease Week. A water-filled version of the device is on the market already.

The study enrolled 387 people aged 22 to 64 years old with a body mass index (BMI) from 30 to 40 kg/m² at 15 different sites. People were randomized to the Obalon Balloon System or to a sham control group. People in the treatment group were asked to swallow three capsules: one every 3 weeks until week 12.

The balloon is contained within the capsule, and after swallowing each balloon was filled with 250 cubic centimeters (slightly more than 1 cup) of a nitrogen-based gas via a small catheter. The control group also swallowed sugar-filled capsules (sham treatment).

A total of 366 patients swallowed at least two capsules and were included in the per protocol analysis: 185 in the treatment group and 181 in the control group. All patients saw a registered dietitian every 3 weeks and also followed diet, exercise, and behavior modification lifestyle changes. Obalon balloons were removed endoscopically at week 24, when participants’ weight was assessed.

The balloon-treated group had a mean weight loss of 6.8%, compared with 3.59% in the control group. At least 5% of body weight loss was achieved by 64.3% of the balloon-treated group, compared with 32% of the control group. The balloon treatment group, but not controls, showed improvements in levels of systolic blood pressure, LDL cholesterol, and triglycerides.

The finding that obese participants who swallowed the Obalon 6-Month Balloon System lost nearly 7% of their body weight and experienced improvements in other health indicators “is important because weight loss is quite difficult to achieve and a significant number of people are not successful in achieving their weight loss goals with diet changes and exercise,” said lead author Dr. Shelby Sullivan, who presented the findings.

Adverse events were mostly mild and included diarrhea, cramping, and nausea in nine patients. No hospitalizations were required for these events. One patient with a pre-existing bleeding ulcer experienced a serious adverse event, which the investigators classified as being possibly related to treatment.

“This patient had an orthopedic procedure and was taking high doses of NSAIDs. That should have been excluded in the trial,” said Dr. Sullivan of Washington University, St. Louis.

“Treatment over time, and even with the initial swallowing of the balloon capsule is quite well tolerated, with only mild symptoms compared with other balloon systems,” she said. “Anecdotally, my impression is that patients liked the therapy because it allowed them to follow lifestyle therapy as well.”

The Obalon balloon is given in stages, giving patients’ stomachs time to adjust to the balloon. Unlike liquid-filled balloons, the gas floats up in the stomach and may cause fewer symptoms than liquid-filled balloons, she suggested.

Dr. Sullivan believes that when the Obalon system is used in the real world, it may lead to even greater weight loss. “This has been seen in other sham-controlled trials,” she noted.

Patients enrolled in the trial are being followed longitudinally and those in the sham control group are allowed to cross over to the Obalon balloons on an open-label basis.

“More than 640 million people globally have obesity, and at this time, there are more overweight than underweight people in the world. Some treatments that are alternatives to diet and exercise may be risky. Obalon swallowable balloon is a new treatment option that can help patients lose almost twice as much weight compared with lifestyle changes alone,” she said.

Dr. Sullivan received funding for this study from Obalon Therapeutics.

A gas-filled gastric balloon may promote weight loss more effectively than does its water-filled cousin, according to data from a randomized study that was presented during a teleconference in advance of the annual Digestive Disease Week. A water-filled version of the device is on the market already.

The study enrolled 387 people aged 22 to 64 years old with a body mass index (BMI) from 30 to 40 kg/m² at 15 different sites. People were randomized to the Obalon Balloon System or to a sham control group. People in the treatment group were asked to swallow three capsules: one every 3 weeks until week 12.

The balloon is contained within the capsule, and after swallowing each balloon was filled with 250 cubic centimeters (slightly more than 1 cup) of a nitrogen-based gas via a small catheter. The control group also swallowed sugar-filled capsules (sham treatment).

A total of 366 patients swallowed at least two capsules and were included in the per protocol analysis: 185 in the treatment group and 181 in the control group. All patients saw a registered dietitian every 3 weeks and also followed diet, exercise, and behavior modification lifestyle changes. Obalon balloons were removed endoscopically at week 24, when participants’ weight was assessed.

The balloon-treated group had a mean weight loss of 6.8%, compared with 3.59% in the control group. At least 5% of body weight loss was achieved by 64.3% of the balloon-treated group, compared with 32% of the control group. The balloon treatment group, but not controls, showed improvements in levels of systolic blood pressure, LDL cholesterol, and triglycerides.

The finding that obese participants who swallowed the Obalon 6-Month Balloon System lost nearly 7% of their body weight and experienced improvements in other health indicators “is important because weight loss is quite difficult to achieve and a significant number of people are not successful in achieving their weight loss goals with diet changes and exercise,” said lead author Dr. Shelby Sullivan, who presented the findings.

Adverse events were mostly mild and included diarrhea, cramping, and nausea in nine patients. No hospitalizations were required for these events. One patient with a pre-existing bleeding ulcer experienced a serious adverse event, which the investigators classified as being possibly related to treatment.

“This patient had an orthopedic procedure and was taking high doses of NSAIDs. That should have been excluded in the trial,” said Dr. Sullivan of Washington University, St. Louis.

“Treatment over time, and even with the initial swallowing of the balloon capsule is quite well tolerated, with only mild symptoms compared with other balloon systems,” she said. “Anecdotally, my impression is that patients liked the therapy because it allowed them to follow lifestyle therapy as well.”

The Obalon balloon is given in stages, giving patients’ stomachs time to adjust to the balloon. Unlike liquid-filled balloons, the gas floats up in the stomach and may cause fewer symptoms than liquid-filled balloons, she suggested.

Dr. Sullivan believes that when the Obalon system is used in the real world, it may lead to even greater weight loss. “This has been seen in other sham-controlled trials,” she noted.

Patients enrolled in the trial are being followed longitudinally and those in the sham control group are allowed to cross over to the Obalon balloons on an open-label basis.

“More than 640 million people globally have obesity, and at this time, there are more overweight than underweight people in the world. Some treatments that are alternatives to diet and exercise may be risky. Obalon swallowable balloon is a new treatment option that can help patients lose almost twice as much weight compared with lifestyle changes alone,” she said.

Dr. Sullivan received funding for this study from Obalon Therapeutics.

FLORENCE, ITALY – Influenza vaccination of heart failure patients cut their rate of hospitalization for cardiovascular disease by nearly a third during the year following vaccination in a study of more than 59,000 British heart failure patients.

Influenza vaccination of heart failure patients also cut their rate of hospitalization for respiratory infections by a statistically significant 16% during the year following vaccination, Dr. Kazem Rahimi said at a meeting held by the Heart Failure Association of the ESC.

Mitchel L. Zoler/Frontline Medical News

“In the absence of randomized trials, this [observational] study of 59,202 heart failure patients provides the most compelling evidence to date for the protective effect of influenza vaccination on hospital admissions,” said Dr. Rahimi, a cardiologist and epidemiologist who is deputy director of the George Institute for Global Health at the University of Oxford (England).

The analysis also showed that influenza vaccination of heart failure patients had no significant effect on all-cause hospitalizations.

Dr. Rahimi and his associates analyzed electronic health records from primary and secondary care settings in England during 1990-2013, from which they identified 59,202 heart failure patients with records for at least 1 year of influenza vaccination and at least 1 year without vaccination. The patients averaged 75 years old and were divided equally among women and men.

To control for potential confounding factors, they used a self-control model in which hospitalizations for each heart failure patient during the year following an influenza vaccination were compared with an adjacent year for that same patient when no vaccination occurred.

The results showed that the incidence of hospitalizations for cardiovascular diseases fell by a statistically significant 30% in the year following an influenza vaccination, compared with one or more adjacent years without vaccination. The protection again hospitalization was strongest during the second month following vaccination and then gradually waned over the ensuing year; by about 10 months following vaccination the protection effect had disappeared.

The study also looked at influenza vaccine uptake by heart failure patients through the 24-year period examined. During that time, the vaccination uptake rate rose from a low of less than 10% in 1990 to a peak rate of just over 60% in 2006, after which the rate gradually declined to a rate of just under 50% in 2013. Dr. Rahimi attributed the rise in uptake during the period from 1990 to 2006 in part to incentives that primary care physicians in England began receiving to administer influenza vaccine to their patients. “Higher uptake of annual vaccination in heart failure patients may help alleviate the burden of influenza-related hospital admissions,” he said.

Dr. Rahimi had no disclosures.

[email protected]

On Twitter @mitchelzoler

FLORENCE, ITALY – Influenza vaccination of heart failure patients cut their rate of hospitalization for cardiovascular disease by nearly a third during the year following vaccination in a study of more than 59,000 British heart failure patients.

Influenza vaccination of heart failure patients also cut their rate of hospitalization for respiratory infections by a statistically significant 16% during the year following vaccination, Dr. Kazem Rahimi said at a meeting held by the Heart Failure Association of the ESC.

Mitchel L. Zoler/Frontline Medical News

“In the absence of randomized trials, this [observational] study of 59,202 heart failure patients provides the most compelling evidence to date for the protective effect of influenza vaccination on hospital admissions,” said Dr. Rahimi, a cardiologist and epidemiologist who is deputy director of the George Institute for Global Health at the University of Oxford (England).

The analysis also showed that influenza vaccination of heart failure patients had no significant effect on all-cause hospitalizations.

Dr. Rahimi and his associates analyzed electronic health records from primary and secondary care settings in England during 1990-2013, from which they identified 59,202 heart failure patients with records for at least 1 year of influenza vaccination and at least 1 year without vaccination. The patients averaged 75 years old and were divided equally among women and men.

To control for potential confounding factors, they used a self-control model in which hospitalizations for each heart failure patient during the year following an influenza vaccination were compared with an adjacent year for that same patient when no vaccination occurred.

The results showed that the incidence of hospitalizations for cardiovascular diseases fell by a statistically significant 30% in the year following an influenza vaccination, compared with one or more adjacent years without vaccination. The protection again hospitalization was strongest during the second month following vaccination and then gradually waned over the ensuing year; by about 10 months following vaccination the protection effect had disappeared.

The study also looked at influenza vaccine uptake by heart failure patients through the 24-year period examined. During that time, the vaccination uptake rate rose from a low of less than 10% in 1990 to a peak rate of just over 60% in 2006, after which the rate gradually declined to a rate of just under 50% in 2013. Dr. Rahimi attributed the rise in uptake during the period from 1990 to 2006 in part to incentives that primary care physicians in England began receiving to administer influenza vaccine to their patients. “Higher uptake of annual vaccination in heart failure patients may help alleviate the burden of influenza-related hospital admissions,” he said.

Dr. Rahimi had no disclosures.

[email protected]

On Twitter @mitchelzoler

FLORENCE, ITALY – Influenza vaccination of heart failure patients cut their rate of hospitalization for cardiovascular disease by nearly a third during the year following vaccination in a study of more than 59,000 British heart failure patients.

Influenza vaccination of heart failure patients also cut their rate of hospitalization for respiratory infections by a statistically significant 16% during the year following vaccination, Dr. Kazem Rahimi said at a meeting held by the Heart Failure Association of the ESC.

Mitchel L. Zoler/Frontline Medical News

“In the absence of randomized trials, this [observational] study of 59,202 heart failure patients provides the most compelling evidence to date for the protective effect of influenza vaccination on hospital admissions,” said Dr. Rahimi, a cardiologist and epidemiologist who is deputy director of the George Institute for Global Health at the University of Oxford (England).

The analysis also showed that influenza vaccination of heart failure patients had no significant effect on all-cause hospitalizations.

Dr. Rahimi and his associates analyzed electronic health records from primary and secondary care settings in England during 1990-2013, from which they identified 59,202 heart failure patients with records for at least 1 year of influenza vaccination and at least 1 year without vaccination. The patients averaged 75 years old and were divided equally among women and men.

To control for potential confounding factors, they used a self-control model in which hospitalizations for each heart failure patient during the year following an influenza vaccination were compared with an adjacent year for that same patient when no vaccination occurred.

The results showed that the incidence of hospitalizations for cardiovascular diseases fell by a statistically significant 30% in the year following an influenza vaccination, compared with one or more adjacent years without vaccination. The protection again hospitalization was strongest during the second month following vaccination and then gradually waned over the ensuing year; by about 10 months following vaccination the protection effect had disappeared.

The study also looked at influenza vaccine uptake by heart failure patients through the 24-year period examined. During that time, the vaccination uptake rate rose from a low of less than 10% in 1990 to a peak rate of just over 60% in 2006, after which the rate gradually declined to a rate of just under 50% in 2013. Dr. Rahimi attributed the rise in uptake during the period from 1990 to 2006 in part to incentives that primary care physicians in England began receiving to administer influenza vaccine to their patients. “Higher uptake of annual vaccination in heart failure patients may help alleviate the burden of influenza-related hospital admissions,” he said.

Dr. Rahimi had no disclosures.

[email protected]

On Twitter @mitchelzoler

Thank You for Investing in the Future of CT Surgery

Last year, the Foundation provided research and fellowship opportunities to 134 young surgeons from five continents, launched eight new programs and the Academic Excellence Award, while maintaining our core programs. We also increased revenue by almost $900,000, allowing us to grow program funding by 39 percent.

This wouldn’t have been possible without our individual donors and corporate/organizational partners.

Read the 2015 Graham Foundation Annual Report

The AATS Graham Foundation has been hard at work over this past year to advance its mission of driving leadership in research and education through clinical and research fellowship programs. These spectacular programs are only  possible with the support of our individual donors, institutional and foundation contributors, and industry partners. Read the report here.

Check out the Donor Honor Roll

Your support is key. Help us ensure the future of the specialty.

Make a gift to the Foundation or renew your commitment

Thank You for Investing in the Future of CT Surgery

Last year, the Foundation provided research and fellowship opportunities to 134 young surgeons from five continents, launched eight new programs and the Academic Excellence Award, while maintaining our core programs. We also increased revenue by almost $900,000, allowing us to grow program funding by 39 percent.

This wouldn’t have been possible without our individual donors and corporate/organizational partners.

Read the 2015 Graham Foundation Annual Report

The AATS Graham Foundation has been hard at work over this past year to advance its mission of driving leadership in research and education through clinical and research fellowship programs. These spectacular programs are only  possible with the support of our individual donors, institutional and foundation contributors, and industry partners. Read the report here.

Check out the Donor Honor Roll

Your support is key. Help us ensure the future of the specialty.

Make a gift to the Foundation or renew your commitment

Thank You for Investing in the Future of CT Surgery

Last year, the Foundation provided research and fellowship opportunities to 134 young surgeons from five continents, launched eight new programs and the Academic Excellence Award, while maintaining our core programs. We also increased revenue by almost $900,000, allowing us to grow program funding by 39 percent.

This wouldn’t have been possible without our individual donors and corporate/organizational partners.

Read the 2015 Graham Foundation Annual Report

The AATS Graham Foundation has been hard at work over this past year to advance its mission of driving leadership in research and education through clinical and research fellowship programs. These spectacular programs are only  possible with the support of our individual donors, institutional and foundation contributors, and industry partners. Read the report here.

Check out the Donor Honor Roll

Your support is key. Help us ensure the future of the specialty.

Make a gift to the Foundation or renew your commitment

CHICAGO – Combination therapy with oxandrolone and propranolol can attenuate burn-induced growth arrest and increase growth rate in severely burned children, according to findings from a prospective, randomized clinical trial.

Of 612 children with burns over at least 30% of their total body surface area (average of more than 50%), 103 were randomized to receive treatment with both oxandrolone and propranolol, 67 received oxandrolone alone, 194 received propranolol alone, and 248 served as controls. After a minimum of 1 year of treatment, the average growth rate was 5.9 cm in the control group and 7.6 cm in the group receiving combination therapy, Dr. David N. Herndon of the University of Texas Medical Branch at Galveston reported at the annual meeting of the American Surgical Association.

“The rate of growth with combination therapy was significantly greater than with either of the individual drugs alone,” Dr. Herndon said.

Further, the period of growth arrest was significantly shorter – by 84 days – among those in the combination-treatment group, compared with those in the control group.

Study subjects were children treated at Shriners Hospitals for Children – Galveston from 1997 to 2015. Boys aged 6 months to 14 years and girls aged 6 months to 12 years were included to eliminate the variable onset of postpubescent growth delay. About two-thirds in each group were boys, and the ages in the patient groups were similar. Mortality was low and was similar across the groups, as was hospital length of stay.

Dr. Herndon and his colleagues controlled for heterogeneous burn distribution between the groups in the course of their analyses, as well as age.

In children with severe, extensive burn injury, the hypercatabolic response is mediated by increased production of catecholamines and corticosteroids, coupled with decreased production of testosterone. This contributes to growth arrest and to decreased strength for up to 2 years after burn injury, he explained. Children with burns over 50% of their total body surface routinely survive acute hospitalization but, at 3 months post injury, are thin, have difficulty walking, and require occupational and physical therapy to help them perform even the simplest activities of daily living.

At 1 year, a raised inflammatory mass covers their wounds, they experience itching, and they have, in large part, stunted growth; there is severe loss of lean body mass and strength, and fracture risk is increased, Dr. Herndon said.

In previous work, he and his colleagues showed that administration of propranolol at an average dose of 4 mg/kg per day for 1 year decreased cardiac work and resting energy expenditure while increasing peripheral lean mass. Further, they found that the testosterone analog oxandrolone, given at 0.1 mg/kg twice per day for 1 year, improved lean body mass accretion and bone mineral content.

The current study was conducted to test the effects of administering both agents in combination.

“The combined use of oxandrolone and propranolol in severely burned children confers an additional benefit on growth over either treatment alone,” Dr. Herndon said, adding that the additive effects of combination therapy may be due to the effects of oxandrolone on bone growth and the anti-inflammatory effects of propranolol.

“The additional benefits point out mechanistic changes that may be eventful in the treatment of hypermetabolism generally and in inflammatory states,” he concluded.

Dr. Herndon reported having no disclosures.

[email protected]

CHICAGO – Combination therapy with oxandrolone and propranolol can attenuate burn-induced growth arrest and increase growth rate in severely burned children, according to findings from a prospective, randomized clinical trial.

Of 612 children with burns over at least 30% of their total body surface area (average of more than 50%), 103 were randomized to receive treatment with both oxandrolone and propranolol, 67 received oxandrolone alone, 194 received propranolol alone, and 248 served as controls. After a minimum of 1 year of treatment, the average growth rate was 5.9 cm in the control group and 7.6 cm in the group receiving combination therapy, Dr. David N. Herndon of the University of Texas Medical Branch at Galveston reported at the annual meeting of the American Surgical Association.

“The rate of growth with combination therapy was significantly greater than with either of the individual drugs alone,” Dr. Herndon said.

Further, the period of growth arrest was significantly shorter – by 84 days – among those in the combination-treatment group, compared with those in the control group.

Study subjects were children treated at Shriners Hospitals for Children – Galveston from 1997 to 2015. Boys aged 6 months to 14 years and girls aged 6 months to 12 years were included to eliminate the variable onset of postpubescent growth delay. About two-thirds in each group were boys, and the ages in the patient groups were similar. Mortality was low and was similar across the groups, as was hospital length of stay.

Dr. Herndon and his colleagues controlled for heterogeneous burn distribution between the groups in the course of their analyses, as well as age.

In children with severe, extensive burn injury, the hypercatabolic response is mediated by increased production of catecholamines and corticosteroids, coupled with decreased production of testosterone. This contributes to growth arrest and to decreased strength for up to 2 years after burn injury, he explained. Children with burns over 50% of their total body surface routinely survive acute hospitalization but, at 3 months post injury, are thin, have difficulty walking, and require occupational and physical therapy to help them perform even the simplest activities of daily living.

At 1 year, a raised inflammatory mass covers their wounds, they experience itching, and they have, in large part, stunted growth; there is severe loss of lean body mass and strength, and fracture risk is increased, Dr. Herndon said.

In previous work, he and his colleagues showed that administration of propranolol at an average dose of 4 mg/kg per day for 1 year decreased cardiac work and resting energy expenditure while increasing peripheral lean mass. Further, they found that the testosterone analog oxandrolone, given at 0.1 mg/kg twice per day for 1 year, improved lean body mass accretion and bone mineral content.

The current study was conducted to test the effects of administering both agents in combination.

“The combined use of oxandrolone and propranolol in severely burned children confers an additional benefit on growth over either treatment alone,” Dr. Herndon said, adding that the additive effects of combination therapy may be due to the effects of oxandrolone on bone growth and the anti-inflammatory effects of propranolol.

“The additional benefits point out mechanistic changes that may be eventful in the treatment of hypermetabolism generally and in inflammatory states,” he concluded.

Dr. Herndon reported having no disclosures.

[email protected]

CHICAGO – Combination therapy with oxandrolone and propranolol can attenuate burn-induced growth arrest and increase growth rate in severely burned children, according to findings from a prospective, randomized clinical trial.

Of 612 children with burns over at least 30% of their total body surface area (average of more than 50%), 103 were randomized to receive treatment with both oxandrolone and propranolol, 67 received oxandrolone alone, 194 received propranolol alone, and 248 served as controls. After a minimum of 1 year of treatment, the average growth rate was 5.9 cm in the control group and 7.6 cm in the group receiving combination therapy, Dr. David N. Herndon of the University of Texas Medical Branch at Galveston reported at the annual meeting of the American Surgical Association.

“The rate of growth with combination therapy was significantly greater than with either of the individual drugs alone,” Dr. Herndon said.

Further, the period of growth arrest was significantly shorter – by 84 days – among those in the combination-treatment group, compared with those in the control group.

Study subjects were children treated at Shriners Hospitals for Children – Galveston from 1997 to 2015. Boys aged 6 months to 14 years and girls aged 6 months to 12 years were included to eliminate the variable onset of postpubescent growth delay. About two-thirds in each group were boys, and the ages in the patient groups were similar. Mortality was low and was similar across the groups, as was hospital length of stay.

Dr. Herndon and his colleagues controlled for heterogeneous burn distribution between the groups in the course of their analyses, as well as age.

In children with severe, extensive burn injury, the hypercatabolic response is mediated by increased production of catecholamines and corticosteroids, coupled with decreased production of testosterone. This contributes to growth arrest and to decreased strength for up to 2 years after burn injury, he explained. Children with burns over 50% of their total body surface routinely survive acute hospitalization but, at 3 months post injury, are thin, have difficulty walking, and require occupational and physical therapy to help them perform even the simplest activities of daily living.

At 1 year, a raised inflammatory mass covers their wounds, they experience itching, and they have, in large part, stunted growth; there is severe loss of lean body mass and strength, and fracture risk is increased, Dr. Herndon said.

In previous work, he and his colleagues showed that administration of propranolol at an average dose of 4 mg/kg per day for 1 year decreased cardiac work and resting energy expenditure while increasing peripheral lean mass. Further, they found that the testosterone analog oxandrolone, given at 0.1 mg/kg twice per day for 1 year, improved lean body mass accretion and bone mineral content.

The current study was conducted to test the effects of administering both agents in combination.

“The combined use of oxandrolone and propranolol in severely burned children confers an additional benefit on growth over either treatment alone,” Dr. Herndon said, adding that the additive effects of combination therapy may be due to the effects of oxandrolone on bone growth and the anti-inflammatory effects of propranolol.

“The additional benefits point out mechanistic changes that may be eventful in the treatment of hypermetabolism generally and in inflammatory states,” he concluded.

Dr. Herndon reported having no disclosures.

[email protected]